Randy Dotinga

SAN FRANCISCO – The treatment of early-stage diffuse large B-cell lymphoma (DLBCL) is evolving after decades of failed attempts to improve on the standard treatment of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), a hematologist-oncologist said at the Association of Veterans Affairs (VA) Hematology/Oncology regional meeting on lymphoma on March 21.

A combination therapy known as pola-R-CHP is now the preferred option for many patients but has limited additional benefit, said Solomon A. Graf, MD, of the University of Washington and VA Puget Sound Health Care System. Pola-R-CHP is a modified regimen of R-CHOP that replaced vincristine in R-CHOP with polatuzumab vedotin.

The keys to treatment, Graf said, include consideration of disease variations that can affect therapy efficacy and understanding the special needs of older patients.

Understanding DLBCL

DLBCL is the most common non-Hodgkin lymphoma in the US with about 30,000 new cases per year; the median age at diagnosis is 67 years, Graf said.

“The overall incidence of DLBCL has been relatively stable over the last decades,” he said. “But gratifyingly, the rate of death from this disease has steadily been declining since about the turn of the century.”

Pola-R-CHP: A New Standard, Significant Limitations

From 2002-2022, “many attempts to improve on first-line DLBCL therapy did not pan out,” Graf said, as more than a dozen large phase 3 trials failed to dethrone R-CHOP as the standard. Most of the trials attempted to add an agent to R-CHOP but showed no additional benefit.

Then, in 2021, the landmark POLARIX study was published. The double-blind, randomized trial on the new regime showed a progression-free survival benefit (PFS) vs R-CHOP (76.7% vs 70.2% at 2 years, respectively). Safety profiles were similar between the 2 combination therapies.

However, overall survival (OS) did not differ.

"Pola-R-CHP is now considered a preferred standard, despite no overall survival benefit and despite increased upfront cost,” Graf said. (A 2023 analysis found that pola-R-CHP is more cost-effective than R-CHOP in DLBCL.)

Pola-R-CHP or Not Pola-R-CHP?

Pola-R-CHP is not for all patients with DLBCL. In advanced cases, Graf said, genomic analyses provide important information that helps clinicians understand whether patients will fare better with R-CHOP. Cell-of-origin classifications include germinal center B-cell like (GCB), activated B-cell like (ABC), and unclassifiable.

“If it’s GCB type, there's no clear benefit for Pola-R-CHP,” Graf said. “On the other hand, the ABC subtype does much better when treated with Pola-R-CHP.”

Graf highlighted the recently updated VA Oncology Clinical Pathway for DLBCL, which recommends cell-of-origin testing by the Hans algorithm for certain advanced-stage patients. The guidelines suggest R-CHOP for GCB-type patients and Pola-R-CHP for non–GCB-type patients. However, he cautioned that the Hans algorithm comes with an increased risk of misclassification.

Early-Stage Disease: Radiation or No Radiation?

About 25% to 30% of patients have stage I or II disease, and the landmark 1998 SWOG trial initially suggested that 3 cycles of CHOP plus radiation had superior PFS and OS compared with 8 cycles of CHOP alone, Graf said. This trial was conducted prior to the R-CHOP era. However, follow-up revealed that the benefit vanished over time and the risk of secondary cancers grew. “Both strategies are perfectly viable, but there isn’t as much of a preference anymore,” Graf said.

A pair of recent trials – a 2019 European study and a 2020 US study – support eliminating radiation and lowering the number of cycles of therapy in certain patients, he said.

Managing Older Patients

Patients with DLBCL tend to be older, Graf said, and many have comorbidities and other limitations. A standard course of 6 cycles of therapy may be too much for them, he said. Graf highlighted the Elderly Prognostic Index, a tool created by an Italian group that allows clinicians to predict outcomes based on patient fitness levels.

Graf offered additional guidance for this population:

• Consider corticosteroids in the prephase setting, which can be “very valuable” and improve a patient’s ECOG performance status, “giving you better confidence about proceeding with more standard therapy.”
• Include anthracycline-based therapies such as R-CHOP if appropriate, such as in patients who are focused on living longer, since they “are really crucial to achieving cure in patients with DLBCL.” Graf noted that he has “a low threshold to involve cardiology if there’s anthracycline use and some underlying cardiac comorbidity.”
• Adjust dosage as appropriate: “You can adjust in the middle, be rather flexible and creative about these doses and dosing levels as you get going with your patient and see just what they can tolerate,” he said. “Sometimes you can ramp it up over the course, and sometimes you have to ramp it down to respond to toxicities.”
• Be aware that older patients are at much higher risk of suffering from toxicities due to the vincristine component of R-CHOP. These include neurotoxicities and constipation.

Graf highlighted the phase 3 Polar Bear study, which may offer more insight into therapy options in patients aged ≥ 75 years who are frail or those aged ≥ 80 years. The trial is scheduled to end in early 2027.

Graf discloses relationships with Janssen, TG Therapeutics, BeOne, AstraZeneca, Genentech, Incyte, Eli Lilly, and Pfizer.

SAN FRANCISCO – The treatment of early-stage diffuse large B-cell lymphoma (DLBCL) is evolving after decades of failed attempts to improve on the standard treatment of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), a hematologist-oncologist said at the Association of Veterans Affairs (VA) Hematology/Oncology regional meeting on lymphoma on March 21.

A combination therapy known as pola-R-CHP is now the preferred option for many patients but has limited additional benefit, said Solomon A. Graf, MD, of the University of Washington and VA Puget Sound Health Care System. Pola-R-CHP is a modified regimen of R-CHOP that replaced vincristine in R-CHOP with polatuzumab vedotin.

The keys to treatment, Graf said, include consideration of disease variations that can affect therapy efficacy and understanding the special needs of older patients.

Understanding DLBCL

DLBCL is the most common non-Hodgkin lymphoma in the US with about 30,000 new cases per year; the median age at diagnosis is 67 years, Graf said.

“The overall incidence of DLBCL has been relatively stable over the last decades,” he said. “But gratifyingly, the rate of death from this disease has steadily been declining since about the turn of the century.”

Pola-R-CHP: A New Standard, Significant Limitations

From 2002-2022, “many attempts to improve on first-line DLBCL therapy did not pan out,” Graf said, as more than a dozen large phase 3 trials failed to dethrone R-CHOP as the standard. Most of the trials attempted to add an agent to R-CHOP but showed no additional benefit.

Then, in 2021, the landmark POLARIX study was published. The double-blind, randomized trial on the new regime showed a progression-free survival benefit (PFS) vs R-CHOP (76.7% vs 70.2% at 2 years, respectively). Safety profiles were similar between the 2 combination therapies.

However, overall survival (OS) did not differ.

"Pola-R-CHP is now considered a preferred standard, despite no overall survival benefit and despite increased upfront cost,” Graf said. (A 2023 analysis found that pola-R-CHP is more cost-effective than R-CHOP in DLBCL.)

Pola-R-CHP or Not Pola-R-CHP?

Pola-R-CHP is not for all patients with DLBCL. In advanced cases, Graf said, genomic analyses provide important information that helps clinicians understand whether patients will fare better with R-CHOP. Cell-of-origin classifications include germinal center B-cell like (GCB), activated B-cell like (ABC), and unclassifiable.

“If it’s GCB type, there's no clear benefit for Pola-R-CHP,” Graf said. “On the other hand, the ABC subtype does much better when treated with Pola-R-CHP.”

Graf highlighted the recently updated VA Oncology Clinical Pathway for DLBCL, which recommends cell-of-origin testing by the Hans algorithm for certain advanced-stage patients. The guidelines suggest R-CHOP for GCB-type patients and Pola-R-CHP for non–GCB-type patients. However, he cautioned that the Hans algorithm comes with an increased risk of misclassification.

Early-Stage Disease: Radiation or No Radiation?

About 25% to 30% of patients have stage I or II disease, and the landmark 1998 SWOG trial initially suggested that 3 cycles of CHOP plus radiation had superior PFS and OS compared with 8 cycles of CHOP alone, Graf said. This trial was conducted prior to the R-CHOP era. However, follow-up revealed that the benefit vanished over time and the risk of secondary cancers grew. “Both strategies are perfectly viable, but there isn’t as much of a preference anymore,” Graf said.

A pair of recent trials – a 2019 European study and a 2020 US study – support eliminating radiation and lowering the number of cycles of therapy in certain patients, he said.

Managing Older Patients

Patients with DLBCL tend to be older, Graf said, and many have comorbidities and other limitations. A standard course of 6 cycles of therapy may be too much for them, he said. Graf highlighted the Elderly Prognostic Index, a tool created by an Italian group that allows clinicians to predict outcomes based on patient fitness levels.

Graf offered additional guidance for this population:

• Consider corticosteroids in the prephase setting, which can be “very valuable” and improve a patient’s ECOG performance status, “giving you better confidence about proceeding with more standard therapy.”
• Include anthracycline-based therapies such as R-CHOP if appropriate, such as in patients who are focused on living longer, since they “are really crucial to achieving cure in patients with DLBCL.” Graf noted that he has “a low threshold to involve cardiology if there’s anthracycline use and some underlying cardiac comorbidity.”
• Adjust dosage as appropriate: “You can adjust in the middle, be rather flexible and creative about these doses and dosing levels as you get going with your patient and see just what they can tolerate,” he said. “Sometimes you can ramp it up over the course, and sometimes you have to ramp it down to respond to toxicities.”
• Be aware that older patients are at much higher risk of suffering from toxicities due to the vincristine component of R-CHOP. These include neurotoxicities and constipation.

Graf highlighted the phase 3 Polar Bear study, which may offer more insight into therapy options in patients aged ≥ 75 years who are frail or those aged ≥ 80 years. The trial is scheduled to end in early 2027.

Graf discloses relationships with Janssen, TG Therapeutics, BeOne, AstraZeneca, Genentech, Incyte, Eli Lilly, and Pfizer.

SAN FRANCISCO – The treatment of early-stage diffuse large B-cell lymphoma (DLBCL) is evolving after decades of failed attempts to improve on the standard treatment of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), a hematologist-oncologist said at the Association of Veterans Affairs (VA) Hematology/Oncology regional meeting on lymphoma on March 21.

A combination therapy known as pola-R-CHP is now the preferred option for many patients but has limited additional benefit, said Solomon A. Graf, MD, of the University of Washington and VA Puget Sound Health Care System. Pola-R-CHP is a modified regimen of R-CHOP that replaced vincristine in R-CHOP with polatuzumab vedotin.

The keys to treatment, Graf said, include consideration of disease variations that can affect therapy efficacy and understanding the special needs of older patients.

Understanding DLBCL

DLBCL is the most common non-Hodgkin lymphoma in the US with about 30,000 new cases per year; the median age at diagnosis is 67 years, Graf said.

“The overall incidence of DLBCL has been relatively stable over the last decades,” he said. “But gratifyingly, the rate of death from this disease has steadily been declining since about the turn of the century.”

Pola-R-CHP: A New Standard, Significant Limitations

From 2002-2022, “many attempts to improve on first-line DLBCL therapy did not pan out,” Graf said, as more than a dozen large phase 3 trials failed to dethrone R-CHOP as the standard. Most of the trials attempted to add an agent to R-CHOP but showed no additional benefit.

Then, in 2021, the landmark POLARIX study was published. The double-blind, randomized trial on the new regime showed a progression-free survival benefit (PFS) vs R-CHOP (76.7% vs 70.2% at 2 years, respectively). Safety profiles were similar between the 2 combination therapies.

However, overall survival (OS) did not differ.

"Pola-R-CHP is now considered a preferred standard, despite no overall survival benefit and despite increased upfront cost,” Graf said. (A 2023 analysis found that pola-R-CHP is more cost-effective than R-CHOP in DLBCL.)

Pola-R-CHP or Not Pola-R-CHP?

Pola-R-CHP is not for all patients with DLBCL. In advanced cases, Graf said, genomic analyses provide important information that helps clinicians understand whether patients will fare better with R-CHOP. Cell-of-origin classifications include germinal center B-cell like (GCB), activated B-cell like (ABC), and unclassifiable.

“If it’s GCB type, there's no clear benefit for Pola-R-CHP,” Graf said. “On the other hand, the ABC subtype does much better when treated with Pola-R-CHP.”

Graf highlighted the recently updated VA Oncology Clinical Pathway for DLBCL, which recommends cell-of-origin testing by the Hans algorithm for certain advanced-stage patients. The guidelines suggest R-CHOP for GCB-type patients and Pola-R-CHP for non–GCB-type patients. However, he cautioned that the Hans algorithm comes with an increased risk of misclassification.

Early-Stage Disease: Radiation or No Radiation?

About 25% to 30% of patients have stage I or II disease, and the landmark 1998 SWOG trial initially suggested that 3 cycles of CHOP plus radiation had superior PFS and OS compared with 8 cycles of CHOP alone, Graf said. This trial was conducted prior to the R-CHOP era. However, follow-up revealed that the benefit vanished over time and the risk of secondary cancers grew. “Both strategies are perfectly viable, but there isn’t as much of a preference anymore,” Graf said.

A pair of recent trials – a 2019 European study and a 2020 US study – support eliminating radiation and lowering the number of cycles of therapy in certain patients, he said.

Managing Older Patients

Patients with DLBCL tend to be older, Graf said, and many have comorbidities and other limitations. A standard course of 6 cycles of therapy may be too much for them, he said. Graf highlighted the Elderly Prognostic Index, a tool created by an Italian group that allows clinicians to predict outcomes based on patient fitness levels.

Graf offered additional guidance for this population:

• Consider corticosteroids in the prephase setting, which can be “very valuable” and improve a patient’s ECOG performance status, “giving you better confidence about proceeding with more standard therapy.”
• Include anthracycline-based therapies such as R-CHOP if appropriate, such as in patients who are focused on living longer, since they “are really crucial to achieving cure in patients with DLBCL.” Graf noted that he has “a low threshold to involve cardiology if there’s anthracycline use and some underlying cardiac comorbidity.”
• Adjust dosage as appropriate: “You can adjust in the middle, be rather flexible and creative about these doses and dosing levels as you get going with your patient and see just what they can tolerate,” he said. “Sometimes you can ramp it up over the course, and sometimes you have to ramp it down to respond to toxicities.”
• Be aware that older patients are at much higher risk of suffering from toxicities due to the vincristine component of R-CHOP. These include neurotoxicities and constipation.

Graf highlighted the phase 3 Polar Bear study, which may offer more insight into therapy options in patients aged ≥ 75 years who are frail or those aged ≥ 80 years. The trial is scheduled to end in early 2027.

Graf discloses relationships with Janssen, TG Therapeutics, BeOne, AstraZeneca, Genentech, Incyte, Eli Lilly, and Pfizer.

SAN FRANCISCO – Peripheral T-cell lymphoma (PTCL) accounts for 4% of mature non-Hodgkin lymphoma cases in the US, or only about 4000 cases a year. While the number of patients is small, however, treatment for PTCL is complex due to wide variations in subtypes and survival rates, a hematologist-oncologist said at the March 21 Association of VA Hematology/Oncology (AVAHO) regional meeting on lymphoma.

Weiyun Ai, MD, PhD, a clinical professor of medicine at University of California, San Francisco who specializes in lymphoma, explained that there are multiple subtypes of PTCL based on their location within the body. Ai discussed a 2008 analysis of North American cases of PTCL and natural killer/T-cell lymphoma from 1990-2002, of which:

• 34% were PTCL, not otherwise specified;

• 16% were angioimmunoblastic T-cell lymphoma (AITL);

• 16% were anaplastic large cell lymphoma (ALCL), anaplastic lymphoma kinase (ALK)-positive;

• 7.8% were ALCL, ALK-negative;

• 5.8% were enteropathy-type;

• 5.4% were primary cutaneous ALCL; and

• 5.1% were extranodal natural killer/T-cell lymphoma, nasal type.

The remaining cases were adult T-cell leukemia/lymphoma, hepatosplenic, subcutaneous panniculitis-like, and unclassified. 

International Prognostic Index Predicts Outcomes

“The subtype with the best outcome is ALCL, ALK-positive with a 5-year overall survival rate of 70% followed by ALK-negative ALCL at 50%, and all the other common subtypes at 30%,” Ai said. 

Ai outlined the International Prognostic Index (IPI), a tool to predict clinical outcomes in patients with aggressive non-Hodgkin lymphoma based on risk factors. IPI assigns worse scores to patients aged > 60 years; patients who have higher (worse) performance scores, higher lactate dehydrogenase (LDH) levels, and more extranodal sites; and patients at stages III-IV.

First-Line Therapy: Consider Subtypes and CD30 Levels

Subtypes and CD30 expression levels are important factors in choosing therapy, Ai said, and 2019’s landmark ECHELON-2 study (updated in 2022) defines the standard. 

Newly diagnosed patients who strongly express CD30 (ie, those with both types of ALCL) are recommended to be treated with A+CHP (brentuximab vedotin [BV] plus cyclophosphamide, doxorubicin, and prednisone). 

Combination therapy of cyclophosphamide, doxorubicin, hydroxydaunorubicin, vincristine, and prednisone (CHOP) was the prior standard of care until the ECHELON-2 study, Ai said. 

That trial, which randomized 452 patients with untreated PTCL (CD30 ≥ 10%) to A+CHP or CHOP, found that 5-year progression-free rates were 51.4% vs 43.0%, respectively (hazard ratio [HR], 0.70; 95% CI, 0.53-0.91). Five-year overall survival rates were 70.1% vs. 61.0%, respectively (HR, 0.72; 95% CI, 0.53-0.99).

The threshold CD30 level at which to turn to A+CHP—1%, 5%, or 10%—“is kind of a dealer’s choice,” Ai said. Her own cutoff is 1%.

“If they're < 1%, I tend not to do it,” Ai said. “It's usually much more expensive, as you can imagine.”

If CD30 < 1%, Ai recommends CHOP or, in younger patients, CHOP plus etoposide (CHOEP).

Follow-up treatments include autologous stem cell transplant (ASCT) and observation/maintenance, depending on factors such as subtype, fitness, and remission.

Transplant: Still Relevant

When ECHELON-2 was released, some clinicians wondered if ASCT was still warranted, Ai said. A posthoc exploratory analysis found a 62% reduction in relative risk for progression in patients who underwent transplants after reaching complete remission with A+CHP. 

The findings provide support for transplant, she said. 

For transplant-ineligible patients, a small analysis of BV and CHP followed by BV maintenance showed a progression-free survival curve that appeared to plateau after 18-24 months.

“You don't see this kind of curve very often. I was quite impressed,” Ai said. “If the patient is willing and able, I will give them BV cycles.”

Ai discloses relationships with ADC, AbbVie, Acrotech, Kite, and Kyowa Kirin.

SAN FRANCISCO – Peripheral T-cell lymphoma (PTCL) accounts for 4% of mature non-Hodgkin lymphoma cases in the US, or only about 4000 cases a year. While the number of patients is small, however, treatment for PTCL is complex due to wide variations in subtypes and survival rates, a hematologist-oncologist said at the March 21 Association of VA Hematology/Oncology (AVAHO) regional meeting on lymphoma.

Weiyun Ai, MD, PhD, a clinical professor of medicine at University of California, San Francisco who specializes in lymphoma, explained that there are multiple subtypes of PTCL based on their location within the body. Ai discussed a 2008 analysis of North American cases of PTCL and natural killer/T-cell lymphoma from 1990-2002, of which:

• 34% were PTCL, not otherwise specified;

• 16% were angioimmunoblastic T-cell lymphoma (AITL);

• 16% were anaplastic large cell lymphoma (ALCL), anaplastic lymphoma kinase (ALK)-positive;

• 7.8% were ALCL, ALK-negative;

• 5.8% were enteropathy-type;

• 5.4% were primary cutaneous ALCL; and

• 5.1% were extranodal natural killer/T-cell lymphoma, nasal type.

The remaining cases were adult T-cell leukemia/lymphoma, hepatosplenic, subcutaneous panniculitis-like, and unclassified. 

International Prognostic Index Predicts Outcomes

“The subtype with the best outcome is ALCL, ALK-positive with a 5-year overall survival rate of 70% followed by ALK-negative ALCL at 50%, and all the other common subtypes at 30%,” Ai said. 

Ai outlined the International Prognostic Index (IPI), a tool to predict clinical outcomes in patients with aggressive non-Hodgkin lymphoma based on risk factors. IPI assigns worse scores to patients aged > 60 years; patients who have higher (worse) performance scores, higher lactate dehydrogenase (LDH) levels, and more extranodal sites; and patients at stages III-IV.

First-Line Therapy: Consider Subtypes and CD30 Levels

Subtypes and CD30 expression levels are important factors in choosing therapy, Ai said, and 2019’s landmark ECHELON-2 study (updated in 2022) defines the standard. 

Newly diagnosed patients who strongly express CD30 (ie, those with both types of ALCL) are recommended to be treated with A+CHP (brentuximab vedotin [BV] plus cyclophosphamide, doxorubicin, and prednisone). 

Combination therapy of cyclophosphamide, doxorubicin, hydroxydaunorubicin, vincristine, and prednisone (CHOP) was the prior standard of care until the ECHELON-2 study, Ai said. 

That trial, which randomized 452 patients with untreated PTCL (CD30 ≥ 10%) to A+CHP or CHOP, found that 5-year progression-free rates were 51.4% vs 43.0%, respectively (hazard ratio [HR], 0.70; 95% CI, 0.53-0.91). Five-year overall survival rates were 70.1% vs. 61.0%, respectively (HR, 0.72; 95% CI, 0.53-0.99).

The threshold CD30 level at which to turn to A+CHP—1%, 5%, or 10%—“is kind of a dealer’s choice,” Ai said. Her own cutoff is 1%.

“If they're < 1%, I tend not to do it,” Ai said. “It's usually much more expensive, as you can imagine.”

If CD30 < 1%, Ai recommends CHOP or, in younger patients, CHOP plus etoposide (CHOEP).

Follow-up treatments include autologous stem cell transplant (ASCT) and observation/maintenance, depending on factors such as subtype, fitness, and remission.

Transplant: Still Relevant

When ECHELON-2 was released, some clinicians wondered if ASCT was still warranted, Ai said. A posthoc exploratory analysis found a 62% reduction in relative risk for progression in patients who underwent transplants after reaching complete remission with A+CHP. 

The findings provide support for transplant, she said. 

For transplant-ineligible patients, a small analysis of BV and CHP followed by BV maintenance showed a progression-free survival curve that appeared to plateau after 18-24 months.

“You don't see this kind of curve very often. I was quite impressed,” Ai said. “If the patient is willing and able, I will give them BV cycles.”

Ai discloses relationships with ADC, AbbVie, Acrotech, Kite, and Kyowa Kirin.

SAN FRANCISCO – Peripheral T-cell lymphoma (PTCL) accounts for 4% of mature non-Hodgkin lymphoma cases in the US, or only about 4000 cases a year. While the number of patients is small, however, treatment for PTCL is complex due to wide variations in subtypes and survival rates, a hematologist-oncologist said at the March 21 Association of VA Hematology/Oncology (AVAHO) regional meeting on lymphoma.

Weiyun Ai, MD, PhD, a clinical professor of medicine at University of California, San Francisco who specializes in lymphoma, explained that there are multiple subtypes of PTCL based on their location within the body. Ai discussed a 2008 analysis of North American cases of PTCL and natural killer/T-cell lymphoma from 1990-2002, of which:

• 34% were PTCL, not otherwise specified;

• 16% were angioimmunoblastic T-cell lymphoma (AITL);

• 16% were anaplastic large cell lymphoma (ALCL), anaplastic lymphoma kinase (ALK)-positive;

• 7.8% were ALCL, ALK-negative;

• 5.8% were enteropathy-type;

• 5.4% were primary cutaneous ALCL; and

• 5.1% were extranodal natural killer/T-cell lymphoma, nasal type.

The remaining cases were adult T-cell leukemia/lymphoma, hepatosplenic, subcutaneous panniculitis-like, and unclassified. 

International Prognostic Index Predicts Outcomes

“The subtype with the best outcome is ALCL, ALK-positive with a 5-year overall survival rate of 70% followed by ALK-negative ALCL at 50%, and all the other common subtypes at 30%,” Ai said. 

Ai outlined the International Prognostic Index (IPI), a tool to predict clinical outcomes in patients with aggressive non-Hodgkin lymphoma based on risk factors. IPI assigns worse scores to patients aged > 60 years; patients who have higher (worse) performance scores, higher lactate dehydrogenase (LDH) levels, and more extranodal sites; and patients at stages III-IV.

First-Line Therapy: Consider Subtypes and CD30 Levels

Subtypes and CD30 expression levels are important factors in choosing therapy, Ai said, and 2019’s landmark ECHELON-2 study (updated in 2022) defines the standard. 

Newly diagnosed patients who strongly express CD30 (ie, those with both types of ALCL) are recommended to be treated with A+CHP (brentuximab vedotin [BV] plus cyclophosphamide, doxorubicin, and prednisone). 

Combination therapy of cyclophosphamide, doxorubicin, hydroxydaunorubicin, vincristine, and prednisone (CHOP) was the prior standard of care until the ECHELON-2 study, Ai said. 

That trial, which randomized 452 patients with untreated PTCL (CD30 ≥ 10%) to A+CHP or CHOP, found that 5-year progression-free rates were 51.4% vs 43.0%, respectively (hazard ratio [HR], 0.70; 95% CI, 0.53-0.91). Five-year overall survival rates were 70.1% vs. 61.0%, respectively (HR, 0.72; 95% CI, 0.53-0.99).

The threshold CD30 level at which to turn to A+CHP—1%, 5%, or 10%—“is kind of a dealer’s choice,” Ai said. Her own cutoff is 1%.

“If they're < 1%, I tend not to do it,” Ai said. “It's usually much more expensive, as you can imagine.”

If CD30 < 1%, Ai recommends CHOP or, in younger patients, CHOP plus etoposide (CHOEP).

Follow-up treatments include autologous stem cell transplant (ASCT) and observation/maintenance, depending on factors such as subtype, fitness, and remission.

Transplant: Still Relevant

When ECHELON-2 was released, some clinicians wondered if ASCT was still warranted, Ai said. A posthoc exploratory analysis found a 62% reduction in relative risk for progression in patients who underwent transplants after reaching complete remission with A+CHP. 

The findings provide support for transplant, she said. 

For transplant-ineligible patients, a small analysis of BV and CHP followed by BV maintenance showed a progression-free survival curve that appeared to plateau after 18-24 months.

“You don't see this kind of curve very often. I was quite impressed,” Ai said. “If the patient is willing and able, I will give them BV cycles.”

Ai discloses relationships with ADC, AbbVie, Acrotech, Kite, and Kyowa Kirin.

Anxiety, depression, and suicide rates are elevated for veterans who are survivors of testicular cancer (TC) compared with veterans without cancer, a retrospective analysis finds.

Over 5 years, the cumulative incidence of anxiety and depression was 53.4% in veterans with TC vs 35.0% in matched controls (P < .001; hazard ratio [HR], 1.66), reported Aditya Bagrodia, MD, professor of urology and radiation oncology at the University of California San Diego, et al in Cancer Medicine. The cumulative incidence of suicidality was 5.0% and 0.1%, respectively (P < .001; HR, 22.99).

“More than half of men with testicular cancer contend with these diagnoses,” Bagrodia told Federal Practitioner. “There are risk factors, including chemotherapy, being single or divorced, or unemployed.”

Patients in these groups warrant aggressive screening and intervention, Bagrodia said. TC is the most common cancer in men in the military and the most common malignancy in men aged 18 to 45 years, Bagrodia said: “The vast majority of men who have testicular cancer are curable.”

Patients, however, face an intense burden. 

“One theme that comes up consistently from patients and caregivers is centered around mental health impact, brain fog, anxiety, depression, and difficulty concentrating,” Bagrodia said. “We wanted to dig into this a little bit further. The idea is to shed light on how common these diagnoses are on these young cancer survivors and intervene so we could positively impact their quality of life.”

The study analyzed 2022 patients with TC and 6375 matched controls enrolled at the US Department of Veterans Affairs (VA) from 1990 through 2016. In the cancer cohort, the mean age at diagnosis was 42.46 years, and ages ranged from 18 to 88 years; 89.7% of patients were White, 6.0% were Black, 2.4% were other race, 1.2% were Asian/Pacific Islander, and 0.7% were Native; 6.2% were Hispanic; and 19.9% were diagnosed between 1990 and 1999.

Factors linked to higher rates of anxiety/depression among patients with TC included divorce (HR 1.15, P = .044), unemployment (HR 1.68, P < .001), and receipt of chemotherapy (HR 1.20, P < .001).

The incidence of de novo anxiety/depression was 30.1% for patients with TC vs 16.7% for controls (P < .001), and the incidence of de novo suicidality was 2.4% for patients and 0.1% for controls.

“These are men who are going to beat their cancer and go on to live for decades and decades,” Bagrodia said. “We found that the impact of a diagnosis and chemotherapy can persist beyond the initial time frame.”

It’s not clear, however, why chemotherapy boosts the risk, Bagrodia said. Clinicians who treat patients with TC should let them know that anxiety, depression, and suicidality are common and treatable concerns.

“We've got some wonderful support services, therapy, and medications that can help out with those diagnoses,” Bagrodia said.

The study authors noted limitations such as the retrospective study design and limited consideration of factors that may affect mental health.

“Additionally, the baseline rates of anxiety, depression, and suicidality are high in the VA population, which may limit ability to apply results to the civilian population,” Bagrodia said.

Genitourinary oncologist Philippe Spiess, MD, of Moffitt Cancer Center in Tampa, praised the study in an interview, saying it provides stronger evidence than previous research. 

"It's not only about screening but surveillance, because you never know what kind of challenges they have in their lives,” Spiess told Federal Practitioner, emphasizing the need for clinicians to continue to monitor patients. “They're young, they're vulnerable. Don’t assume they're going to get help somewhere else. You need to be that source that facilitates it.”

No funding is reported. Bagrodia and other authors have no disclosures. Spiess has no disclosures. 

Anxiety, depression, and suicide rates are elevated for veterans who are survivors of testicular cancer (TC) compared with veterans without cancer, a retrospective analysis finds.

Over 5 years, the cumulative incidence of anxiety and depression was 53.4% in veterans with TC vs 35.0% in matched controls (P < .001; hazard ratio [HR], 1.66), reported Aditya Bagrodia, MD, professor of urology and radiation oncology at the University of California San Diego, et al in Cancer Medicine. The cumulative incidence of suicidality was 5.0% and 0.1%, respectively (P < .001; HR, 22.99).

“More than half of men with testicular cancer contend with these diagnoses,” Bagrodia told Federal Practitioner. “There are risk factors, including chemotherapy, being single or divorced, or unemployed.”

Patients in these groups warrant aggressive screening and intervention, Bagrodia said. TC is the most common cancer in men in the military and the most common malignancy in men aged 18 to 45 years, Bagrodia said: “The vast majority of men who have testicular cancer are curable.”

Patients, however, face an intense burden. 

“One theme that comes up consistently from patients and caregivers is centered around mental health impact, brain fog, anxiety, depression, and difficulty concentrating,” Bagrodia said. “We wanted to dig into this a little bit further. The idea is to shed light on how common these diagnoses are on these young cancer survivors and intervene so we could positively impact their quality of life.”

The study analyzed 2022 patients with TC and 6375 matched controls enrolled at the US Department of Veterans Affairs (VA) from 1990 through 2016. In the cancer cohort, the mean age at diagnosis was 42.46 years, and ages ranged from 18 to 88 years; 89.7% of patients were White, 6.0% were Black, 2.4% were other race, 1.2% were Asian/Pacific Islander, and 0.7% were Native; 6.2% were Hispanic; and 19.9% were diagnosed between 1990 and 1999.

Factors linked to higher rates of anxiety/depression among patients with TC included divorce (HR 1.15, P = .044), unemployment (HR 1.68, P < .001), and receipt of chemotherapy (HR 1.20, P < .001).

The incidence of de novo anxiety/depression was 30.1% for patients with TC vs 16.7% for controls (P < .001), and the incidence of de novo suicidality was 2.4% for patients and 0.1% for controls.

“These are men who are going to beat their cancer and go on to live for decades and decades,” Bagrodia said. “We found that the impact of a diagnosis and chemotherapy can persist beyond the initial time frame.”

It’s not clear, however, why chemotherapy boosts the risk, Bagrodia said. Clinicians who treat patients with TC should let them know that anxiety, depression, and suicidality are common and treatable concerns.

“We've got some wonderful support services, therapy, and medications that can help out with those diagnoses,” Bagrodia said.

The study authors noted limitations such as the retrospective study design and limited consideration of factors that may affect mental health.

“Additionally, the baseline rates of anxiety, depression, and suicidality are high in the VA population, which may limit ability to apply results to the civilian population,” Bagrodia said.

Genitourinary oncologist Philippe Spiess, MD, of Moffitt Cancer Center in Tampa, praised the study in an interview, saying it provides stronger evidence than previous research. 

"It's not only about screening but surveillance, because you never know what kind of challenges they have in their lives,” Spiess told Federal Practitioner, emphasizing the need for clinicians to continue to monitor patients. “They're young, they're vulnerable. Don’t assume they're going to get help somewhere else. You need to be that source that facilitates it.”

No funding is reported. Bagrodia and other authors have no disclosures. Spiess has no disclosures. 

Anxiety, depression, and suicide rates are elevated for veterans who are survivors of testicular cancer (TC) compared with veterans without cancer, a retrospective analysis finds.

Over 5 years, the cumulative incidence of anxiety and depression was 53.4% in veterans with TC vs 35.0% in matched controls (P < .001; hazard ratio [HR], 1.66), reported Aditya Bagrodia, MD, professor of urology and radiation oncology at the University of California San Diego, et al in Cancer Medicine. The cumulative incidence of suicidality was 5.0% and 0.1%, respectively (P < .001; HR, 22.99).

“More than half of men with testicular cancer contend with these diagnoses,” Bagrodia told Federal Practitioner. “There are risk factors, including chemotherapy, being single or divorced, or unemployed.”

Patients in these groups warrant aggressive screening and intervention, Bagrodia said. TC is the most common cancer in men in the military and the most common malignancy in men aged 18 to 45 years, Bagrodia said: “The vast majority of men who have testicular cancer are curable.”

Patients, however, face an intense burden. 

“One theme that comes up consistently from patients and caregivers is centered around mental health impact, brain fog, anxiety, depression, and difficulty concentrating,” Bagrodia said. “We wanted to dig into this a little bit further. The idea is to shed light on how common these diagnoses are on these young cancer survivors and intervene so we could positively impact their quality of life.”

The study analyzed 2022 patients with TC and 6375 matched controls enrolled at the US Department of Veterans Affairs (VA) from 1990 through 2016. In the cancer cohort, the mean age at diagnosis was 42.46 years, and ages ranged from 18 to 88 years; 89.7% of patients were White, 6.0% were Black, 2.4% were other race, 1.2% were Asian/Pacific Islander, and 0.7% were Native; 6.2% were Hispanic; and 19.9% were diagnosed between 1990 and 1999.

Factors linked to higher rates of anxiety/depression among patients with TC included divorce (HR 1.15, P = .044), unemployment (HR 1.68, P < .001), and receipt of chemotherapy (HR 1.20, P < .001).

The incidence of de novo anxiety/depression was 30.1% for patients with TC vs 16.7% for controls (P < .001), and the incidence of de novo suicidality was 2.4% for patients and 0.1% for controls.

“These are men who are going to beat their cancer and go on to live for decades and decades,” Bagrodia said. “We found that the impact of a diagnosis and chemotherapy can persist beyond the initial time frame.”

It’s not clear, however, why chemotherapy boosts the risk, Bagrodia said. Clinicians who treat patients with TC should let them know that anxiety, depression, and suicidality are common and treatable concerns.

“We've got some wonderful support services, therapy, and medications that can help out with those diagnoses,” Bagrodia said.

The study authors noted limitations such as the retrospective study design and limited consideration of factors that may affect mental health.

“Additionally, the baseline rates of anxiety, depression, and suicidality are high in the VA population, which may limit ability to apply results to the civilian population,” Bagrodia said.

Genitourinary oncologist Philippe Spiess, MD, of Moffitt Cancer Center in Tampa, praised the study in an interview, saying it provides stronger evidence than previous research. 

"It's not only about screening but surveillance, because you never know what kind of challenges they have in their lives,” Spiess told Federal Practitioner, emphasizing the need for clinicians to continue to monitor patients. “They're young, they're vulnerable. Don’t assume they're going to get help somewhere else. You need to be that source that facilitates it.”

No funding is reported. Bagrodia and other authors have no disclosures. Spiess has no disclosures. 

A pilot program appeared to more than double the rate of germline genetic testing among veterans with metastatic prostate cancer (mPC) by using remote communication rather than relying on clinicians for in-person outreach to patients. 

Of 1952 veterans with mPC, 681 (34.9%) provided consent and 459 (23.5%) completed testing, exceeding the usual 10% to 12% of patients who undergo testing, reported Bruce Montgomery, MD, et al in Cancer.

Although testing is recommended for all patients with mPC to guide therapy and alert relatives who may be at risk, 23.5% is still an impressive number, Montgomery, an oncologist with Veterans Affairs (VA) Puget Sound Health Care System in Seattle told Federal Practitioner: “With a letter and very little money and very little real time from clinicians, we could get testing done at 3 times the rate happening out there in the big wide world,” he said. “For 2000 patients, we needed one research coordinator and a small part of a genetic counselor's time.”

According to the study, germline genetic testing—which examines inherited DNA—is now recommended for all men with mPC by the National Comprehensive Cancer Network, the American Society of Clinical Oncology, and the American Urological Association. Germline genetic testing differs from somatic testing, which seeks genetic changes in the tumors themselves.

In the VA and community at large, the percentage of men with mPC who undergo germline genetic testing is low, Montgomery said. Research suggests < 40% of patients undergo somatic testing.

Germline genetic testing only costs about 10% compared with somatic testing, Montgomery said, and can be conducted at any time. In about 10% of mPC cases, the testing provides insight into the best treatment, he said.

Montgomery noted another benefit to germline genetic testing: It can raise the alarm about pathogenic variants that could boost cancer risk in family members, allowing them to get screened and take action.

There are many reasons veterans do not get tested, Montgomery said. The process is not automatic because patient consent is needed, and clinicians often fail to ask. In some cases, veterans worry about privacy or whether they will lose service-connected benefits if their cancer is blamed on genetics.

The study focused on 2104 veterans with mPC who had already agreed to take part in the Million Veteran Program, a prospective cohort study examining genetic and nongenetic risk for disease. The genetic analysis from that project did not provide guidance about mPC, so researchers approached the veterans directly.

Patients were enrolled from February 2021 to October 2023. A total of 1952 veterans did not opt out when contacted by mail (median age, 75 years; 63% White, 25% Black; 74% urban and 24% rural). The median age of those who consented and completed testing after phone contact was 74 years; 67% of patients were White and 22% were Black; 78% of patients lived in urban communities and 20% lived in rural communities.

Fifty-nine patients (13%) had pathogenic variants, and 37 of those had variants that indicated treatment with targeted therapies. Of the 37, 14 received targeted therapy, 18 were not at the point where targeted therapy was indicated, and 5 were not treated with targeted therapy for various reasons before they died.

Twelve of the 59 patients with pathogenic variants agreed to let the study team contact their first-degree relatives. Thirty relatives underwent testing, and 10 of them were positive for the variants.

Following completion of the study, researchers examined electronic records for the 59 patients with pathogenic variants and found that 19% did not have documentation of the germline finding in the medical record. The authors cited an “urgent need” to standardize where genetic information is included in the records.

While “it seems like a very small number of patients took up testing,” Montgomery said, the study findings are promising: “If we did the same thing nationally in the VA, there would be 15,000 men with metastatic disease, and we’d be testing 5000 of them with almost no effort.”

In an interview, Susan Vadaparampil, PhD, MPH, associate center director of Community Outreach and Engagement at Moffitt Cancer Center, who studies genetic testing, praised the strengths of the study. Vadaparampil, who did not take part in the research, told Federal Practitioner that the study relies on “an intervention that could likely be incorporated into routine clinical practice, a less resource-intensive model that provides posttest counseling for those who test positive, and support to share results with family members.”

However, she said, “testing uptake was uneven based on participant sociodemographic characteristics. It's important to consider how discussions and resources to facilitate testing may need to be adapted to meet the needs of all patients.

“Strategies that facilitate clinicians’ knowledge, comfort, and consistency in discussing testing with all mPC patients are essential,” Vadaparampil added. “Simultaneously using multiple strategies targeted to different levels can further help boost uptake.”

The study was funded by the VA Office of Research and Development, Prostate Cancer Foundation, Pacific Northwest Prostate Cancer SPORE, Institute for Prostate Cancer Research, Congressionally Directed Medical Research Programs (CDMRP), and Put VA Data to Work for Veterans. 

Montgomery discloses relationships with Daiichi Sankyo, INmune Bio, Clovis, Janssen Pharmaceuticals, Johnson and Johnson, and Merck. Some other authors report various disclosures. Vadaparampil has no disclosures.

A pilot program appeared to more than double the rate of germline genetic testing among veterans with metastatic prostate cancer (mPC) by using remote communication rather than relying on clinicians for in-person outreach to patients. 

Of 1952 veterans with mPC, 681 (34.9%) provided consent and 459 (23.5%) completed testing, exceeding the usual 10% to 12% of patients who undergo testing, reported Bruce Montgomery, MD, et al in Cancer.

Although testing is recommended for all patients with mPC to guide therapy and alert relatives who may be at risk, 23.5% is still an impressive number, Montgomery, an oncologist with Veterans Affairs (VA) Puget Sound Health Care System in Seattle told Federal Practitioner: “With a letter and very little money and very little real time from clinicians, we could get testing done at 3 times the rate happening out there in the big wide world,” he said. “For 2000 patients, we needed one research coordinator and a small part of a genetic counselor's time.”

According to the study, germline genetic testing—which examines inherited DNA—is now recommended for all men with mPC by the National Comprehensive Cancer Network, the American Society of Clinical Oncology, and the American Urological Association. Germline genetic testing differs from somatic testing, which seeks genetic changes in the tumors themselves.

In the VA and community at large, the percentage of men with mPC who undergo germline genetic testing is low, Montgomery said. Research suggests < 40% of patients undergo somatic testing.

Germline genetic testing only costs about 10% compared with somatic testing, Montgomery said, and can be conducted at any time. In about 10% of mPC cases, the testing provides insight into the best treatment, he said.

Montgomery noted another benefit to germline genetic testing: It can raise the alarm about pathogenic variants that could boost cancer risk in family members, allowing them to get screened and take action.

There are many reasons veterans do not get tested, Montgomery said. The process is not automatic because patient consent is needed, and clinicians often fail to ask. In some cases, veterans worry about privacy or whether they will lose service-connected benefits if their cancer is blamed on genetics.

The study focused on 2104 veterans with mPC who had already agreed to take part in the Million Veteran Program, a prospective cohort study examining genetic and nongenetic risk for disease. The genetic analysis from that project did not provide guidance about mPC, so researchers approached the veterans directly.

Patients were enrolled from February 2021 to October 2023. A total of 1952 veterans did not opt out when contacted by mail (median age, 75 years; 63% White, 25% Black; 74% urban and 24% rural). The median age of those who consented and completed testing after phone contact was 74 years; 67% of patients were White and 22% were Black; 78% of patients lived in urban communities and 20% lived in rural communities.

Fifty-nine patients (13%) had pathogenic variants, and 37 of those had variants that indicated treatment with targeted therapies. Of the 37, 14 received targeted therapy, 18 were not at the point where targeted therapy was indicated, and 5 were not treated with targeted therapy for various reasons before they died.

Twelve of the 59 patients with pathogenic variants agreed to let the study team contact their first-degree relatives. Thirty relatives underwent testing, and 10 of them were positive for the variants.

Following completion of the study, researchers examined electronic records for the 59 patients with pathogenic variants and found that 19% did not have documentation of the germline finding in the medical record. The authors cited an “urgent need” to standardize where genetic information is included in the records.

While “it seems like a very small number of patients took up testing,” Montgomery said, the study findings are promising: “If we did the same thing nationally in the VA, there would be 15,000 men with metastatic disease, and we’d be testing 5000 of them with almost no effort.”

In an interview, Susan Vadaparampil, PhD, MPH, associate center director of Community Outreach and Engagement at Moffitt Cancer Center, who studies genetic testing, praised the strengths of the study. Vadaparampil, who did not take part in the research, told Federal Practitioner that the study relies on “an intervention that could likely be incorporated into routine clinical practice, a less resource-intensive model that provides posttest counseling for those who test positive, and support to share results with family members.”

However, she said, “testing uptake was uneven based on participant sociodemographic characteristics. It's important to consider how discussions and resources to facilitate testing may need to be adapted to meet the needs of all patients.

“Strategies that facilitate clinicians’ knowledge, comfort, and consistency in discussing testing with all mPC patients are essential,” Vadaparampil added. “Simultaneously using multiple strategies targeted to different levels can further help boost uptake.”

The study was funded by the VA Office of Research and Development, Prostate Cancer Foundation, Pacific Northwest Prostate Cancer SPORE, Institute for Prostate Cancer Research, Congressionally Directed Medical Research Programs (CDMRP), and Put VA Data to Work for Veterans. 

Montgomery discloses relationships with Daiichi Sankyo, INmune Bio, Clovis, Janssen Pharmaceuticals, Johnson and Johnson, and Merck. Some other authors report various disclosures. Vadaparampil has no disclosures.

A pilot program appeared to more than double the rate of germline genetic testing among veterans with metastatic prostate cancer (mPC) by using remote communication rather than relying on clinicians for in-person outreach to patients. 

Of 1952 veterans with mPC, 681 (34.9%) provided consent and 459 (23.5%) completed testing, exceeding the usual 10% to 12% of patients who undergo testing, reported Bruce Montgomery, MD, et al in Cancer.

Although testing is recommended for all patients with mPC to guide therapy and alert relatives who may be at risk, 23.5% is still an impressive number, Montgomery, an oncologist with Veterans Affairs (VA) Puget Sound Health Care System in Seattle told Federal Practitioner: “With a letter and very little money and very little real time from clinicians, we could get testing done at 3 times the rate happening out there in the big wide world,” he said. “For 2000 patients, we needed one research coordinator and a small part of a genetic counselor's time.”

According to the study, germline genetic testing—which examines inherited DNA—is now recommended for all men with mPC by the National Comprehensive Cancer Network, the American Society of Clinical Oncology, and the American Urological Association. Germline genetic testing differs from somatic testing, which seeks genetic changes in the tumors themselves.

In the VA and community at large, the percentage of men with mPC who undergo germline genetic testing is low, Montgomery said. Research suggests < 40% of patients undergo somatic testing.

Germline genetic testing only costs about 10% compared with somatic testing, Montgomery said, and can be conducted at any time. In about 10% of mPC cases, the testing provides insight into the best treatment, he said.

Montgomery noted another benefit to germline genetic testing: It can raise the alarm about pathogenic variants that could boost cancer risk in family members, allowing them to get screened and take action.

There are many reasons veterans do not get tested, Montgomery said. The process is not automatic because patient consent is needed, and clinicians often fail to ask. In some cases, veterans worry about privacy or whether they will lose service-connected benefits if their cancer is blamed on genetics.

The study focused on 2104 veterans with mPC who had already agreed to take part in the Million Veteran Program, a prospective cohort study examining genetic and nongenetic risk for disease. The genetic analysis from that project did not provide guidance about mPC, so researchers approached the veterans directly.

Patients were enrolled from February 2021 to October 2023. A total of 1952 veterans did not opt out when contacted by mail (median age, 75 years; 63% White, 25% Black; 74% urban and 24% rural). The median age of those who consented and completed testing after phone contact was 74 years; 67% of patients were White and 22% were Black; 78% of patients lived in urban communities and 20% lived in rural communities.

Fifty-nine patients (13%) had pathogenic variants, and 37 of those had variants that indicated treatment with targeted therapies. Of the 37, 14 received targeted therapy, 18 were not at the point where targeted therapy was indicated, and 5 were not treated with targeted therapy for various reasons before they died.

Twelve of the 59 patients with pathogenic variants agreed to let the study team contact their first-degree relatives. Thirty relatives underwent testing, and 10 of them were positive for the variants.

Following completion of the study, researchers examined electronic records for the 59 patients with pathogenic variants and found that 19% did not have documentation of the germline finding in the medical record. The authors cited an “urgent need” to standardize where genetic information is included in the records.

While “it seems like a very small number of patients took up testing,” Montgomery said, the study findings are promising: “If we did the same thing nationally in the VA, there would be 15,000 men with metastatic disease, and we’d be testing 5000 of them with almost no effort.”

In an interview, Susan Vadaparampil, PhD, MPH, associate center director of Community Outreach and Engagement at Moffitt Cancer Center, who studies genetic testing, praised the strengths of the study. Vadaparampil, who did not take part in the research, told Federal Practitioner that the study relies on “an intervention that could likely be incorporated into routine clinical practice, a less resource-intensive model that provides posttest counseling for those who test positive, and support to share results with family members.”

However, she said, “testing uptake was uneven based on participant sociodemographic characteristics. It's important to consider how discussions and resources to facilitate testing may need to be adapted to meet the needs of all patients.

“Strategies that facilitate clinicians’ knowledge, comfort, and consistency in discussing testing with all mPC patients are essential,” Vadaparampil added. “Simultaneously using multiple strategies targeted to different levels can further help boost uptake.”

The study was funded by the VA Office of Research and Development, Prostate Cancer Foundation, Pacific Northwest Prostate Cancer SPORE, Institute for Prostate Cancer Research, Congressionally Directed Medical Research Programs (CDMRP), and Put VA Data to Work for Veterans. 

Montgomery discloses relationships with Daiichi Sankyo, INmune Bio, Clovis, Janssen Pharmaceuticals, Johnson and Johnson, and Merck. Some other authors report various disclosures. Vadaparampil has no disclosures.

US service members and veterans were less likely to die than the general population from most causes of death over a 17-year period, a population-based, prospective analysis found. But there was a glaring exception: suicide by firearm.

Among 201,618 subjects tracked from 2001 to 2018 by the Millennium Cohort Study, the overall death rate was less than half that of a comparable group of US adults (standardized mortality ratios [SMR], 0.44), reported Edward J. Boyko, MD, MPH, staff physician with the Veterans Affairs (VA) Puget Sound Health Care System and professor of medicine at the University of Washington, Seattle, and colleagues in BMC Public Health. However, suicides by firearm—while rare—were more common overall (SMR, 1.42), among military men only (SMR, 1.33), and among military women only (SMR, 2.83) than civilians. 

The findings about the overall death rate may reflect the better health of those who join the military and have access to health care during and after service, Boyko told Federal Practitioner. The suicide data may reflect higher access to firearms, he said, although “more research is needed to identify what types of military exposures or physical and mental health predictors are associated with increased mortality risk due to suicide.”

The ongoing Millennium Cohort Study began in 2001 to track the health of military personnel over time. The study has spawned > 180 reports “used to inform and guide policy, guidelines, and health promotion efforts within the military and VA,” Boyko said. “As the Millennium Cohort Study approaches its 25-year anniversary, it seemed like an ideal time to assess mortality, especially cause-specific mortality, as a way to measure the impact of military service on long-term health.”

The analysis tracks 4 panels of subjects enrolled at various times between 2001 and 2013. Of the 201,619 participants, 3018 (1.5%) died by 2018. Of the 198,01 nondeceased participants, 69.2% were male; 8.1% were born before 1960, 16.1% were born from 1960 to 1969, 24.4% were born from 1970 to 1979, and 51.5% were born in or after 1980. The racial/ethnic makeup was 72.7% non-Hispanic White, 12.2% non-Hispanic Black, 7.9% Hispanic, and 7.1% other. Two-thirds (66.4%) were active duty, and 33.6% were in the Reserve or National Guard.

Of the 3018 deceased participants, 81.2% were male. In terms of birth year, 32.4% were born before 1960, 22.1% were born from 1960 to 1969, 18.2% were born from 1970 to 1979, and 27.3% were born in or after 1980. The racial/ethnic makeup was 77.7% non-Hispanic White, 11.9% non-Hispanic Black, 5.5% Hispanic, and 4.9% other. About half (51.0%) were active duty, and 49.0% were in the Reserve or National Guard.

Most deaths were due to natural causes (57.0%), followed by accident (20.1%), suicide (17.1%), operations of war (3.0%), homicide (2.1%), and other causes (1.2%). The new report noted that the Millennium Cohort Study and other research have identified a “healthy soldier effect, in which military populations tend to be healthier than the general US population.”

Boyko explained that “the fitness requirements for joining the military may favor the selection of healthier individuals from the general population. Another benefit of military service is free access to health care, especially among those on active duty, as well as eligibility for VA health care and other benefits after leaving service. This would allow for greater access to preventive care and treatments, as well as routine screening for health conditions such as cancer, diabetes, or cardiovascular disease.”

Overall suicide rates were higher among female subjects than among civilians (SMR, 1.65), but no statistically significant difference was seen in men (SMR, 0.96) or across all participants (SMR, 1.03). Regarding the large gaps in firearm suicide rates in military subjects vs civilians, Boyko said, “accessibility and familiarity with firearms, a highly lethal means of suicide, may be driving the elevated risk of suicide by firearms … prior research has found that unsecure firearms storage—such as unlocked, loaded firearms—increases the risk of suicide by firearms.”

Rachel Sayko Adams, PhD, MPH, a research associate professor with the Department of Health Law, Policy and Management at Boston University School of Public Health, is familiar with the study findings. Adams, a principal investigator at the VA Rocky Mountain Mental Illness Research, Education and Clinical Center for Suicide Prevention, told Federal Practitioner that “efforts to further develop suicide prevention programs that consider the unique needs and preferences of female service members and veterans are critical to prevent future suicide mortality in this population.”

Adams added: “Just because service members and veterans have a lower all-cause mortality rate compared to the general US population, we should not assume that they are universally low risk or that we can reduce our public health prevention efforts targeting this population.”

Boyko highlighted KeepItSecure.net, which “helps veterans and service members protect themselves and their families by making it easier to store firearms securely during stressful or high-risk periods.” The site offers practical, judgment-free guidance with powerful storytelling and public outreach, with clear, actionable steps—such as using a cable gun lock or lockbox—to lower suicide risk long before a crisis occurs. The VA, Boyko said, provides free cable gun locks nationwide.

The Millennium Cohort Study is funded by the Department of Veterans Affairs and Department of Defense Military Operational Medicine Research Program and Defense Health Program. The report authors and Adams have no disclosures. 

US service members and veterans were less likely to die than the general population from most causes of death over a 17-year period, a population-based, prospective analysis found. But there was a glaring exception: suicide by firearm.

Among 201,618 subjects tracked from 2001 to 2018 by the Millennium Cohort Study, the overall death rate was less than half that of a comparable group of US adults (standardized mortality ratios [SMR], 0.44), reported Edward J. Boyko, MD, MPH, staff physician with the Veterans Affairs (VA) Puget Sound Health Care System and professor of medicine at the University of Washington, Seattle, and colleagues in BMC Public Health. However, suicides by firearm—while rare—were more common overall (SMR, 1.42), among military men only (SMR, 1.33), and among military women only (SMR, 2.83) than civilians. 

The findings about the overall death rate may reflect the better health of those who join the military and have access to health care during and after service, Boyko told Federal Practitioner. The suicide data may reflect higher access to firearms, he said, although “more research is needed to identify what types of military exposures or physical and mental health predictors are associated with increased mortality risk due to suicide.”

The ongoing Millennium Cohort Study began in 2001 to track the health of military personnel over time. The study has spawned > 180 reports “used to inform and guide policy, guidelines, and health promotion efforts within the military and VA,” Boyko said. “As the Millennium Cohort Study approaches its 25-year anniversary, it seemed like an ideal time to assess mortality, especially cause-specific mortality, as a way to measure the impact of military service on long-term health.”

The analysis tracks 4 panels of subjects enrolled at various times between 2001 and 2013. Of the 201,619 participants, 3018 (1.5%) died by 2018. Of the 198,01 nondeceased participants, 69.2% were male; 8.1% were born before 1960, 16.1% were born from 1960 to 1969, 24.4% were born from 1970 to 1979, and 51.5% were born in or after 1980. The racial/ethnic makeup was 72.7% non-Hispanic White, 12.2% non-Hispanic Black, 7.9% Hispanic, and 7.1% other. Two-thirds (66.4%) were active duty, and 33.6% were in the Reserve or National Guard.

Of the 3018 deceased participants, 81.2% were male. In terms of birth year, 32.4% were born before 1960, 22.1% were born from 1960 to 1969, 18.2% were born from 1970 to 1979, and 27.3% were born in or after 1980. The racial/ethnic makeup was 77.7% non-Hispanic White, 11.9% non-Hispanic Black, 5.5% Hispanic, and 4.9% other. About half (51.0%) were active duty, and 49.0% were in the Reserve or National Guard.

Most deaths were due to natural causes (57.0%), followed by accident (20.1%), suicide (17.1%), operations of war (3.0%), homicide (2.1%), and other causes (1.2%). The new report noted that the Millennium Cohort Study and other research have identified a “healthy soldier effect, in which military populations tend to be healthier than the general US population.”

Boyko explained that “the fitness requirements for joining the military may favor the selection of healthier individuals from the general population. Another benefit of military service is free access to health care, especially among those on active duty, as well as eligibility for VA health care and other benefits after leaving service. This would allow for greater access to preventive care and treatments, as well as routine screening for health conditions such as cancer, diabetes, or cardiovascular disease.”

Overall suicide rates were higher among female subjects than among civilians (SMR, 1.65), but no statistically significant difference was seen in men (SMR, 0.96) or across all participants (SMR, 1.03). Regarding the large gaps in firearm suicide rates in military subjects vs civilians, Boyko said, “accessibility and familiarity with firearms, a highly lethal means of suicide, may be driving the elevated risk of suicide by firearms … prior research has found that unsecure firearms storage—such as unlocked, loaded firearms—increases the risk of suicide by firearms.”

Rachel Sayko Adams, PhD, MPH, a research associate professor with the Department of Health Law, Policy and Management at Boston University School of Public Health, is familiar with the study findings. Adams, a principal investigator at the VA Rocky Mountain Mental Illness Research, Education and Clinical Center for Suicide Prevention, told Federal Practitioner that “efforts to further develop suicide prevention programs that consider the unique needs and preferences of female service members and veterans are critical to prevent future suicide mortality in this population.”

Adams added: “Just because service members and veterans have a lower all-cause mortality rate compared to the general US population, we should not assume that they are universally low risk or that we can reduce our public health prevention efforts targeting this population.”

Boyko highlighted KeepItSecure.net, which “helps veterans and service members protect themselves and their families by making it easier to store firearms securely during stressful or high-risk periods.” The site offers practical, judgment-free guidance with powerful storytelling and public outreach, with clear, actionable steps—such as using a cable gun lock or lockbox—to lower suicide risk long before a crisis occurs. The VA, Boyko said, provides free cable gun locks nationwide.

The Millennium Cohort Study is funded by the Department of Veterans Affairs and Department of Defense Military Operational Medicine Research Program and Defense Health Program. The report authors and Adams have no disclosures. 

US service members and veterans were less likely to die than the general population from most causes of death over a 17-year period, a population-based, prospective analysis found. But there was a glaring exception: suicide by firearm.

Among 201,618 subjects tracked from 2001 to 2018 by the Millennium Cohort Study, the overall death rate was less than half that of a comparable group of US adults (standardized mortality ratios [SMR], 0.44), reported Edward J. Boyko, MD, MPH, staff physician with the Veterans Affairs (VA) Puget Sound Health Care System and professor of medicine at the University of Washington, Seattle, and colleagues in BMC Public Health. However, suicides by firearm—while rare—were more common overall (SMR, 1.42), among military men only (SMR, 1.33), and among military women only (SMR, 2.83) than civilians. 

The findings about the overall death rate may reflect the better health of those who join the military and have access to health care during and after service, Boyko told Federal Practitioner. The suicide data may reflect higher access to firearms, he said, although “more research is needed to identify what types of military exposures or physical and mental health predictors are associated with increased mortality risk due to suicide.”

The ongoing Millennium Cohort Study began in 2001 to track the health of military personnel over time. The study has spawned > 180 reports “used to inform and guide policy, guidelines, and health promotion efforts within the military and VA,” Boyko said. “As the Millennium Cohort Study approaches its 25-year anniversary, it seemed like an ideal time to assess mortality, especially cause-specific mortality, as a way to measure the impact of military service on long-term health.”

The analysis tracks 4 panels of subjects enrolled at various times between 2001 and 2013. Of the 201,619 participants, 3018 (1.5%) died by 2018. Of the 198,01 nondeceased participants, 69.2% were male; 8.1% were born before 1960, 16.1% were born from 1960 to 1969, 24.4% were born from 1970 to 1979, and 51.5% were born in or after 1980. The racial/ethnic makeup was 72.7% non-Hispanic White, 12.2% non-Hispanic Black, 7.9% Hispanic, and 7.1% other. Two-thirds (66.4%) were active duty, and 33.6% were in the Reserve or National Guard.

Of the 3018 deceased participants, 81.2% were male. In terms of birth year, 32.4% were born before 1960, 22.1% were born from 1960 to 1969, 18.2% were born from 1970 to 1979, and 27.3% were born in or after 1980. The racial/ethnic makeup was 77.7% non-Hispanic White, 11.9% non-Hispanic Black, 5.5% Hispanic, and 4.9% other. About half (51.0%) were active duty, and 49.0% were in the Reserve or National Guard.

Most deaths were due to natural causes (57.0%), followed by accident (20.1%), suicide (17.1%), operations of war (3.0%), homicide (2.1%), and other causes (1.2%). The new report noted that the Millennium Cohort Study and other research have identified a “healthy soldier effect, in which military populations tend to be healthier than the general US population.”

Boyko explained that “the fitness requirements for joining the military may favor the selection of healthier individuals from the general population. Another benefit of military service is free access to health care, especially among those on active duty, as well as eligibility for VA health care and other benefits after leaving service. This would allow for greater access to preventive care and treatments, as well as routine screening for health conditions such as cancer, diabetes, or cardiovascular disease.”

Overall suicide rates were higher among female subjects than among civilians (SMR, 1.65), but no statistically significant difference was seen in men (SMR, 0.96) or across all participants (SMR, 1.03). Regarding the large gaps in firearm suicide rates in military subjects vs civilians, Boyko said, “accessibility and familiarity with firearms, a highly lethal means of suicide, may be driving the elevated risk of suicide by firearms … prior research has found that unsecure firearms storage—such as unlocked, loaded firearms—increases the risk of suicide by firearms.”

Rachel Sayko Adams, PhD, MPH, a research associate professor with the Department of Health Law, Policy and Management at Boston University School of Public Health, is familiar with the study findings. Adams, a principal investigator at the VA Rocky Mountain Mental Illness Research, Education and Clinical Center for Suicide Prevention, told Federal Practitioner that “efforts to further develop suicide prevention programs that consider the unique needs and preferences of female service members and veterans are critical to prevent future suicide mortality in this population.”

Adams added: “Just because service members and veterans have a lower all-cause mortality rate compared to the general US population, we should not assume that they are universally low risk or that we can reduce our public health prevention efforts targeting this population.”

Boyko highlighted KeepItSecure.net, which “helps veterans and service members protect themselves and their families by making it easier to store firearms securely during stressful or high-risk periods.” The site offers practical, judgment-free guidance with powerful storytelling and public outreach, with clear, actionable steps—such as using a cable gun lock or lockbox—to lower suicide risk long before a crisis occurs. The VA, Boyko said, provides free cable gun locks nationwide.

The Millennium Cohort Study is funded by the Department of Veterans Affairs and Department of Defense Military Operational Medicine Research Program and Defense Health Program. The report authors and Adams have no disclosures. 

Veterans experiencing unstable housing, financial strain, and with poor access to health care have a higher risk of suicidal thoughts and behaviors, according to findings in a new study, leading researchers to call for additional screening to identify those in jeopardy. 

Each incremental increase in social disadvantage was tied to increases in the likelihood of recent suicidal thoughts (odds ratio [OR], 2.14), future suicidal intent (OR, 2.21), and lifetime suicide attempt (OR, 1.78) in a weighted analysis. The self-reported data was published as a cross-sectional study by Pietrzak et al in the December 2025 issue of JAMA Psychiatry.

Veterans whose social plights ranked in the worst 5% were > 20 times more likely to report suicidal thoughts and behaviors than those in the top 5%. Especially striking were the magnitudes of the associations and their persistence after adjustment for psychiatric conditions and other suicide risk factors, lead author Robert H. Pietrzak, PhD, MPH said in an interview with Federal Practitioner.

“This finding highlights how extreme cumulative disadvantage can be overwhelming,” Pietrzak said. “It suggests that suicide risk among veterans increases dramatically when multiple social stressors cluster together. Rather than any single hardship driving risk, it is the cumulative impact of social disadvantage that appears most strongly linked to elevated suicide risk.”

As Pietrzak explained, veterans account for < 7% of total US adults but about 14% of suicide deaths. “Several factors may contribute to this difference, including higher exposure to trauma, elevated rates of psychiatric conditions, challenges with reintegration into civilian life, and structural barriers to care,” Pietrzak said. “Increasingly, social and economic stressors are also recognized by experts and researchers as critical contributors to suicide risk.”

Social determinants of health (SDOH) such as unemployment and lack of access to health care have also been linked to suicide risk, he said.

“Less well understood is how multiple adverse social conditions interact and accumulate to compound suicide risk,” Pietrzak said.

The new study sought to determine the impact of SDOH as a whole, not just in isolation. The study analyzed SDOH in 5 areas—education access and quality, economic conditions, health care access and quality, neighborhood and built environment, and social and community context—via the National Health and Resilience in Veterans Study, which surveyed 4069 veterans. The participants had weighted demographics of mean age 62.2 years; 90.2% were male; and 78.1% White, 11.2% Black, 6.6% Hispanic, 4.2% other.

Past-year suicidal ideation was most highly linked to psychosocial difficulties (OR, 1.58; 95% CI, 1.43-1.75). Future suicidal intent was most highly linked to residing in a mobile home, recreational vehicle, or van (OR, 1.60; 95% CI, 1.24-2.07) in addition to psychosocial difficulties (OR, 1.45; 95% CI, 1.18-1.80). Lifetime suicidal attempt was most highly linked to history of homelessness (OR, 1.37; 95% CI, 1.22-1.55; all P < .001).

“The results of our study underscore the importance of routine, standardized screening for cumulative social disadvantage within VA and community care settings that serve veterans,” Pietrzak said.

He added that findings make it clear that “suicide prevention extends beyond mental health care. Improving the social conditions in which veterans live, work, and age is not only good public policy. It may save lives.”

Mark S. Kaplan, DrPH, a research professor of Social Welfare at the University of California at Los Angeles Luskin School of Public Affairs is familiar with the study findings and said they highlight the need to “approach the question of suicide in much wider terms as opposed to reducing it to psychiatric traits.”

J. John Mann, MD, a professor of translational neuroscience in psychiatry and radiology who studies suicide at Columbia University, New York City, said the study’s findings illustrate that clinicians must do more to understand the lives of patients outside the examination room. He predicted that more screening for social determinants of health will “enrich the amount of information that the clinician will have and lead to a more comprehensive clinical care plan.”

The US Department of Veterans Affairs supported the study. Pietrzak has no disclosures. Other study authors report various disclosures.

Veterans experiencing unstable housing, financial strain, and with poor access to health care have a higher risk of suicidal thoughts and behaviors, according to findings in a new study, leading researchers to call for additional screening to identify those in jeopardy. 

Each incremental increase in social disadvantage was tied to increases in the likelihood of recent suicidal thoughts (odds ratio [OR], 2.14), future suicidal intent (OR, 2.21), and lifetime suicide attempt (OR, 1.78) in a weighted analysis. The self-reported data was published as a cross-sectional study by Pietrzak et al in the December 2025 issue of JAMA Psychiatry.

Veterans whose social plights ranked in the worst 5% were > 20 times more likely to report suicidal thoughts and behaviors than those in the top 5%. Especially striking were the magnitudes of the associations and their persistence after adjustment for psychiatric conditions and other suicide risk factors, lead author Robert H. Pietrzak, PhD, MPH said in an interview with Federal Practitioner.

“This finding highlights how extreme cumulative disadvantage can be overwhelming,” Pietrzak said. “It suggests that suicide risk among veterans increases dramatically when multiple social stressors cluster together. Rather than any single hardship driving risk, it is the cumulative impact of social disadvantage that appears most strongly linked to elevated suicide risk.”

As Pietrzak explained, veterans account for < 7% of total US adults but about 14% of suicide deaths. “Several factors may contribute to this difference, including higher exposure to trauma, elevated rates of psychiatric conditions, challenges with reintegration into civilian life, and structural barriers to care,” Pietrzak said. “Increasingly, social and economic stressors are also recognized by experts and researchers as critical contributors to suicide risk.”

Social determinants of health (SDOH) such as unemployment and lack of access to health care have also been linked to suicide risk, he said.

“Less well understood is how multiple adverse social conditions interact and accumulate to compound suicide risk,” Pietrzak said.

The new study sought to determine the impact of SDOH as a whole, not just in isolation. The study analyzed SDOH in 5 areas—education access and quality, economic conditions, health care access and quality, neighborhood and built environment, and social and community context—via the National Health and Resilience in Veterans Study, which surveyed 4069 veterans. The participants had weighted demographics of mean age 62.2 years; 90.2% were male; and 78.1% White, 11.2% Black, 6.6% Hispanic, 4.2% other.

Past-year suicidal ideation was most highly linked to psychosocial difficulties (OR, 1.58; 95% CI, 1.43-1.75). Future suicidal intent was most highly linked to residing in a mobile home, recreational vehicle, or van (OR, 1.60; 95% CI, 1.24-2.07) in addition to psychosocial difficulties (OR, 1.45; 95% CI, 1.18-1.80). Lifetime suicidal attempt was most highly linked to history of homelessness (OR, 1.37; 95% CI, 1.22-1.55; all P < .001).

“The results of our study underscore the importance of routine, standardized screening for cumulative social disadvantage within VA and community care settings that serve veterans,” Pietrzak said.

He added that findings make it clear that “suicide prevention extends beyond mental health care. Improving the social conditions in which veterans live, work, and age is not only good public policy. It may save lives.”

Mark S. Kaplan, DrPH, a research professor of Social Welfare at the University of California at Los Angeles Luskin School of Public Affairs is familiar with the study findings and said they highlight the need to “approach the question of suicide in much wider terms as opposed to reducing it to psychiatric traits.”

J. John Mann, MD, a professor of translational neuroscience in psychiatry and radiology who studies suicide at Columbia University, New York City, said the study’s findings illustrate that clinicians must do more to understand the lives of patients outside the examination room. He predicted that more screening for social determinants of health will “enrich the amount of information that the clinician will have and lead to a more comprehensive clinical care plan.”

The US Department of Veterans Affairs supported the study. Pietrzak has no disclosures. Other study authors report various disclosures.

Veterans experiencing unstable housing, financial strain, and with poor access to health care have a higher risk of suicidal thoughts and behaviors, according to findings in a new study, leading researchers to call for additional screening to identify those in jeopardy. 

Each incremental increase in social disadvantage was tied to increases in the likelihood of recent suicidal thoughts (odds ratio [OR], 2.14), future suicidal intent (OR, 2.21), and lifetime suicide attempt (OR, 1.78) in a weighted analysis. The self-reported data was published as a cross-sectional study by Pietrzak et al in the December 2025 issue of JAMA Psychiatry.

Veterans whose social plights ranked in the worst 5% were > 20 times more likely to report suicidal thoughts and behaviors than those in the top 5%. Especially striking were the magnitudes of the associations and their persistence after adjustment for psychiatric conditions and other suicide risk factors, lead author Robert H. Pietrzak, PhD, MPH said in an interview with Federal Practitioner.

“This finding highlights how extreme cumulative disadvantage can be overwhelming,” Pietrzak said. “It suggests that suicide risk among veterans increases dramatically when multiple social stressors cluster together. Rather than any single hardship driving risk, it is the cumulative impact of social disadvantage that appears most strongly linked to elevated suicide risk.”

As Pietrzak explained, veterans account for < 7% of total US adults but about 14% of suicide deaths. “Several factors may contribute to this difference, including higher exposure to trauma, elevated rates of psychiatric conditions, challenges with reintegration into civilian life, and structural barriers to care,” Pietrzak said. “Increasingly, social and economic stressors are also recognized by experts and researchers as critical contributors to suicide risk.”

Social determinants of health (SDOH) such as unemployment and lack of access to health care have also been linked to suicide risk, he said.

“Less well understood is how multiple adverse social conditions interact and accumulate to compound suicide risk,” Pietrzak said.

The new study sought to determine the impact of SDOH as a whole, not just in isolation. The study analyzed SDOH in 5 areas—education access and quality, economic conditions, health care access and quality, neighborhood and built environment, and social and community context—via the National Health and Resilience in Veterans Study, which surveyed 4069 veterans. The participants had weighted demographics of mean age 62.2 years; 90.2% were male; and 78.1% White, 11.2% Black, 6.6% Hispanic, 4.2% other.

Past-year suicidal ideation was most highly linked to psychosocial difficulties (OR, 1.58; 95% CI, 1.43-1.75). Future suicidal intent was most highly linked to residing in a mobile home, recreational vehicle, or van (OR, 1.60; 95% CI, 1.24-2.07) in addition to psychosocial difficulties (OR, 1.45; 95% CI, 1.18-1.80). Lifetime suicidal attempt was most highly linked to history of homelessness (OR, 1.37; 95% CI, 1.22-1.55; all P < .001).

“The results of our study underscore the importance of routine, standardized screening for cumulative social disadvantage within VA and community care settings that serve veterans,” Pietrzak said.

He added that findings make it clear that “suicide prevention extends beyond mental health care. Improving the social conditions in which veterans live, work, and age is not only good public policy. It may save lives.”

Mark S. Kaplan, DrPH, a research professor of Social Welfare at the University of California at Los Angeles Luskin School of Public Affairs is familiar with the study findings and said they highlight the need to “approach the question of suicide in much wider terms as opposed to reducing it to psychiatric traits.”

J. John Mann, MD, a professor of translational neuroscience in psychiatry and radiology who studies suicide at Columbia University, New York City, said the study’s findings illustrate that clinicians must do more to understand the lives of patients outside the examination room. He predicted that more screening for social determinants of health will “enrich the amount of information that the clinician will have and lead to a more comprehensive clinical care plan.”

The US Department of Veterans Affairs supported the study. Pietrzak has no disclosures. Other study authors report various disclosures.

Veterans with posttraumatic stress disorder (PTSD) were much more likely than their counterparts to be a perpetrator or victim of violence and suffer from social, legal, and financial problems, a new retrospective analysis finds.

An analysis of 62,298 matched veterans found that those newly diagnosed with PTSD were more likely to be linked to violence (adjusted odds ratio [aOR], 3.98), social problems (aOR, 2.87) legal problems (aOR, 1.75), and financial problems (aOR, 2.01), reported Ouyang et al in the November 2025 issue of the Journal of Affective Disorders.

A separate analysis of 11,758 propensity-matched veterans found that those with PTSD were more likely to experience violence (50.15% vs 11.26%), social problems (64.44% vs 25.32%), legal problems (24.84% vs 8.07%), and financial problems (48.60% vs 19.21%). 

The study does not prove that PTSD is directly linked to these problems. However, Ouyang told Federal Practitioner that the findings suggest "PTSD extends beyond psychiatric symptoms: It significantly impacts economic stability, housing security, and legal safety."

Clinicians should screen for various problems in patients with PTSD, Ouyang said, “particularly given that the risk is highest during the first year.” The study also sought to better understand the effects of PTSD over time.

“While it is established that PTSD creates serious challenges regarding employment, family dynamics, and substance use, most previous studies provided only a cross-sectional snapshot,” Ouyang said. “We aimed to understand the progression over a 10-year period.”

In addition, “previous studies relied heavily on standard diagnosis codes and missed a significant amount of unstructured data,” she said. The new study uses natural language processing, an artificial intelligence field that parses the words people use, to gain insight from clinical notes.

In the cross-sectional analysis of 62,298 veterans, including 31,149 diagnosed with PTSD in the 2011-2012 fiscal year and 31,149 without PTSD (average age 60, 91.49% male, 71.50% White and 19.27% Black), PTSD was linked to higher rates of housing instability (aOR, 1.65), barriers to care (aOR, 1.45), transitions of care (aOR, 1.58), food insecurity (aOR, 1.37), and nonspecific psychosocial needs (aOR, 1.31).

Why might PTSD be linked to violence, which was defined as perpetrated by or against the veteran?

“The primary theory centers on hyperarousal, a symptom of PTSD characterized by a state of constant high alert and anxiety,” Ouyang said. “This state creates difficulties in emotional regulation and impulse control, which can lead to aggressive reactions.”

Patients are also at risk of revictimization, Ouyang added, “where the erosion of social support networks leaves veterans more vulnerable to harm from others.”

Aspects of PTSD are also thought to contribute to problems other than violence, Ouyang said. For example, mental health struggles can make it hard to keep a job and stay financially stable “and veterans may be hesitant to seek help due to stigma until the situation becomes critical, potentially leading to housing loss.”

In terms of solutions, “clinical treatment alone is insufficient,” she said. “We recommend an integrated health care model that combines mental health treatment with referrals to social work and economic support services to address the broader determinants of well-being.”

Brian Klassen, PhD, an associate professor with the Department of Psychiatry and Behavioral Sciences at Rush University Medical Center, reviewed the study for Federal Practitioner. 

The research “underscores how problematic the diagnosis of PTSD is for folks,” said Klassen, the director of Strategic Partnership for the Road Home Program/Center for Veterans and Their Families. “It plays out in lives in trouble with relationships, work, and housing, things like that.”

How PTSD cultivates a veteran’s everyday life is important for clinicians to understand, he said. “A lot of our treatments directly target symptoms: how to help people sleep better, manage their mood. This encourages practitioners to look at the whole person,” Klassen said. “What other kind of resource needs might this person have that are related to—or maybe caused by—their PTSD diagnosis?”

These resources can “include things like job training and housing and financial assistance, maybe help to get out in the community and form relationships with people.”

The US Department of Veterans Affairs and National Institutes of Health funded the study. The study authors and Klassen have no disclosures. 

Veterans with posttraumatic stress disorder (PTSD) were much more likely than their counterparts to be a perpetrator or victim of violence and suffer from social, legal, and financial problems, a new retrospective analysis finds.

An analysis of 62,298 matched veterans found that those newly diagnosed with PTSD were more likely to be linked to violence (adjusted odds ratio [aOR], 3.98), social problems (aOR, 2.87) legal problems (aOR, 1.75), and financial problems (aOR, 2.01), reported Ouyang et al in the November 2025 issue of the Journal of Affective Disorders.

A separate analysis of 11,758 propensity-matched veterans found that those with PTSD were more likely to experience violence (50.15% vs 11.26%), social problems (64.44% vs 25.32%), legal problems (24.84% vs 8.07%), and financial problems (48.60% vs 19.21%). 

The study does not prove that PTSD is directly linked to these problems. However, Ouyang told Federal Practitioner that the findings suggest "PTSD extends beyond psychiatric symptoms: It significantly impacts economic stability, housing security, and legal safety."

Clinicians should screen for various problems in patients with PTSD, Ouyang said, “particularly given that the risk is highest during the first year.” The study also sought to better understand the effects of PTSD over time.

“While it is established that PTSD creates serious challenges regarding employment, family dynamics, and substance use, most previous studies provided only a cross-sectional snapshot,” Ouyang said. “We aimed to understand the progression over a 10-year period.”

In addition, “previous studies relied heavily on standard diagnosis codes and missed a significant amount of unstructured data,” she said. The new study uses natural language processing, an artificial intelligence field that parses the words people use, to gain insight from clinical notes.

In the cross-sectional analysis of 62,298 veterans, including 31,149 diagnosed with PTSD in the 2011-2012 fiscal year and 31,149 without PTSD (average age 60, 91.49% male, 71.50% White and 19.27% Black), PTSD was linked to higher rates of housing instability (aOR, 1.65), barriers to care (aOR, 1.45), transitions of care (aOR, 1.58), food insecurity (aOR, 1.37), and nonspecific psychosocial needs (aOR, 1.31).

Why might PTSD be linked to violence, which was defined as perpetrated by or against the veteran?

“The primary theory centers on hyperarousal, a symptom of PTSD characterized by a state of constant high alert and anxiety,” Ouyang said. “This state creates difficulties in emotional regulation and impulse control, which can lead to aggressive reactions.”

Patients are also at risk of revictimization, Ouyang added, “where the erosion of social support networks leaves veterans more vulnerable to harm from others.”

Aspects of PTSD are also thought to contribute to problems other than violence, Ouyang said. For example, mental health struggles can make it hard to keep a job and stay financially stable “and veterans may be hesitant to seek help due to stigma until the situation becomes critical, potentially leading to housing loss.”

In terms of solutions, “clinical treatment alone is insufficient,” she said. “We recommend an integrated health care model that combines mental health treatment with referrals to social work and economic support services to address the broader determinants of well-being.”

Brian Klassen, PhD, an associate professor with the Department of Psychiatry and Behavioral Sciences at Rush University Medical Center, reviewed the study for Federal Practitioner. 

The research “underscores how problematic the diagnosis of PTSD is for folks,” said Klassen, the director of Strategic Partnership for the Road Home Program/Center for Veterans and Their Families. “It plays out in lives in trouble with relationships, work, and housing, things like that.”

How PTSD cultivates a veteran’s everyday life is important for clinicians to understand, he said. “A lot of our treatments directly target symptoms: how to help people sleep better, manage their mood. This encourages practitioners to look at the whole person,” Klassen said. “What other kind of resource needs might this person have that are related to—or maybe caused by—their PTSD diagnosis?”

These resources can “include things like job training and housing and financial assistance, maybe help to get out in the community and form relationships with people.”

The US Department of Veterans Affairs and National Institutes of Health funded the study. The study authors and Klassen have no disclosures. 

Veterans with posttraumatic stress disorder (PTSD) were much more likely than their counterparts to be a perpetrator or victim of violence and suffer from social, legal, and financial problems, a new retrospective analysis finds.

An analysis of 62,298 matched veterans found that those newly diagnosed with PTSD were more likely to be linked to violence (adjusted odds ratio [aOR], 3.98), social problems (aOR, 2.87) legal problems (aOR, 1.75), and financial problems (aOR, 2.01), reported Ouyang et al in the November 2025 issue of the Journal of Affective Disorders.

A separate analysis of 11,758 propensity-matched veterans found that those with PTSD were more likely to experience violence (50.15% vs 11.26%), social problems (64.44% vs 25.32%), legal problems (24.84% vs 8.07%), and financial problems (48.60% vs 19.21%). 

The study does not prove that PTSD is directly linked to these problems. However, Ouyang told Federal Practitioner that the findings suggest "PTSD extends beyond psychiatric symptoms: It significantly impacts economic stability, housing security, and legal safety."

Clinicians should screen for various problems in patients with PTSD, Ouyang said, “particularly given that the risk is highest during the first year.” The study also sought to better understand the effects of PTSD over time.

“While it is established that PTSD creates serious challenges regarding employment, family dynamics, and substance use, most previous studies provided only a cross-sectional snapshot,” Ouyang said. “We aimed to understand the progression over a 10-year period.”

In addition, “previous studies relied heavily on standard diagnosis codes and missed a significant amount of unstructured data,” she said. The new study uses natural language processing, an artificial intelligence field that parses the words people use, to gain insight from clinical notes.

In the cross-sectional analysis of 62,298 veterans, including 31,149 diagnosed with PTSD in the 2011-2012 fiscal year and 31,149 without PTSD (average age 60, 91.49% male, 71.50% White and 19.27% Black), PTSD was linked to higher rates of housing instability (aOR, 1.65), barriers to care (aOR, 1.45), transitions of care (aOR, 1.58), food insecurity (aOR, 1.37), and nonspecific psychosocial needs (aOR, 1.31).

Why might PTSD be linked to violence, which was defined as perpetrated by or against the veteran?

“The primary theory centers on hyperarousal, a symptom of PTSD characterized by a state of constant high alert and anxiety,” Ouyang said. “This state creates difficulties in emotional regulation and impulse control, which can lead to aggressive reactions.”

Patients are also at risk of revictimization, Ouyang added, “where the erosion of social support networks leaves veterans more vulnerable to harm from others.”

Aspects of PTSD are also thought to contribute to problems other than violence, Ouyang said. For example, mental health struggles can make it hard to keep a job and stay financially stable “and veterans may be hesitant to seek help due to stigma until the situation becomes critical, potentially leading to housing loss.”

In terms of solutions, “clinical treatment alone is insufficient,” she said. “We recommend an integrated health care model that combines mental health treatment with referrals to social work and economic support services to address the broader determinants of well-being.”

Brian Klassen, PhD, an associate professor with the Department of Psychiatry and Behavioral Sciences at Rush University Medical Center, reviewed the study for Federal Practitioner. 

The research “underscores how problematic the diagnosis of PTSD is for folks,” said Klassen, the director of Strategic Partnership for the Road Home Program/Center for Veterans and Their Families. “It plays out in lives in trouble with relationships, work, and housing, things like that.”

How PTSD cultivates a veteran’s everyday life is important for clinicians to understand, he said. “A lot of our treatments directly target symptoms: how to help people sleep better, manage their mood. This encourages practitioners to look at the whole person,” Klassen said. “What other kind of resource needs might this person have that are related to—or maybe caused by—their PTSD diagnosis?”

These resources can “include things like job training and housing and financial assistance, maybe help to get out in the community and form relationships with people.”

The US Department of Veterans Affairs and National Institutes of Health funded the study. The study authors and Klassen have no disclosures. 

Abiraterone and enzalutamide showed identical survival outcomes when used as first-line treatment for metastatic hormone-sensitive prostate cancer (mHSPC), according to a new study using US Department of Veterans Affairs (VA) data. The report represents the first head-to-head clinical analysis of these commonly used androgen receptor inhibitors.

Among 1258 veterans treated with abiraterone and 311 treated with enzalutamide, median overall survival was 36.2 months for both drugs. Patients were followed for a mean of 28.7 months (abiraterone) and 30.8 months (enzalutamide), reported by Martin W. Schoen, MD, MPH, from Saint Louis University School of Medicine and the St. Louis VA Medical Center, in JAMA Network Open. 

Notably, there was no significant difference in outcomes among Black veterans, who often have poorer outcomes in prostate cancer, and in patients with cardiovascular disease.

“This is the first direct comparison of abiraterone and enzalutamide for mHSPC in a clinical practice setting,” Schoen told Federal Practitioner. “At the population level, there are no differences based on initial treatment choice.”

Abiraterone Is Preferred in the VA Due to Cost

According to Schoen, abiraterone and enzalutamide are the most commonly used androgen receptor inhibitors to treat mHSPC within the VA. A 2025 study by Schoen and colleagues found that 53.7% of veterans with mHSPC in 2022 received androgen receptor inhibitor therapy, up from 16.9% in 2017. 

“In the VA, the preference for most patients is abiraterone since it is the least expensive agent,” he said. A generic version has been available for several years.

Additionally, abiraterone “has been on the market for the longest, and therefore clinicians are familiar with its use,” Schoen said. However, “clinicians have little idea of the comparative efficacy between these 2 agents,” he added.

The authors suggest that the cost and toxicities of the medications should guide clinician decisions, Schoen said. “There is data that abiraterone may worsen diabetes, since it is given with prednisone and could increase the risk of cardiovascular events,” he said.

He added that 2 newer drugs, apalutamide and darolutamide, are also “viable options.” Chemotherapies and certain targeted drugs are also available, “but they are only used in a select group of patients.”

Outside Specialist: Diverse Study Population Is a Plus

Hematologist-oncologist Natalie Reizine, MD, of the University of Illinois College of Medicine, Chicago, who was not involved in the study, told Federal Practitioner that the real-world data are valuable given the limitations of clinical trial populations.

“It’s difficult to compare clinical trials because they enroll different groups of patients,” she said. And, she said, they often exclude patients with significant comorbidities. “If they have bad cardiovascular disease, for instance, or poorly controlled diabetes, they're excluded from the clinical trial. But in real life, many of our patients have other medical problems that we have to manage.”

Reizine also emphasized the significance of the study’s diverse patient population. “Black men are very underrepresented in clinical trials. Many clinical trials that lead to drug approval will have only few or no Black men at all, yet these drugs go on to be widely prescribed to all men with prostate cancer.”

Results Are ‘Reassuring’

Reizine described the overall study findings as “reassuring,” especially in light of “studies that show that abiraterone and prednisone may be associated with worse cardiovascular outcomes. This study showed that in this VA population, even for patients who had cardiovascular disease, there was not a difference in how they did.”

As for choosing between agents, she recommended considering comorbidities and potential drug-drug interactions. “One of the big reasons that you may not be able to safely prescribe enzalutamide, for instance, is if a patient is on an anticoagulant, which is incredibly common in cancer patients. Enzalutamide has more drug-drug interactions than abiraterone and prednisone.” 

Study Demographics and Findings

The study included all patients with mHSPC who initiated abiraterone or enzalutamide between July 2017 and April 2023.

Median ages were 73 (abiraterone) and 74 years (enzalutamide, P = .29). Racial distribution was similar between groups: abiraterone (68.1% White, 25.0% Black, 6.9% other/unknown) and enzalutamide (66.6% White, 27.0% Black, 6.4% other/unknown; P = .74). Ethnicity was 89.2% non-Hispanic, 4.4% Hispanic, and 6.4% unknown in the abiraterone group vs 88.4% non-Hispanic, 3.5% Hispanic, and 8.0% unknown in the enzalutamide group (P = .50).

The groups had similar rates of the most common comorbidities: diabetes (40.5% vs 46.3%, respectively, P = .07), peripheral vascular disease (40.2% vs 37.6%, respectively, P = .44), and chronic pulmonary disease (37.0% vs 40.5%, P = .29).

In an inverse probability weighting analysis with abiraterone as reference, weighted median overall survival was comparable across the entire cohort (36.2 months, P = .32), Black veterans (39.7 months, P = .90), and those with cardiovascular disease (31.5 months, P = .30).

The authors noted limitations such as the observational cohort design and data constraints. 

The study was supported by the American Society of Clinical Oncology Conquer Cancer Foundation, the Prostate Cancer Foundation, and the Blavatnik Family Foundation.

Schoen discloses relationships with the Prostate Cancer Foundation, Astellas, and US Department of Defense. Other authors disclose relationships with the American Society of Clinical Oncology, Pfizer, Exelixis, Eli Lilly, Sanofi, Merck, Seagen, Bellicum, and BMS.

Outside the submitted work. Reizine discloses relationships with the US Department of Defense, Sanofi, Exelexis, Janssen, AstraZeneca, EMD Serono, Janssen, Merck, and Tempus.

Abiraterone and enzalutamide showed identical survival outcomes when used as first-line treatment for metastatic hormone-sensitive prostate cancer (mHSPC), according to a new study using US Department of Veterans Affairs (VA) data. The report represents the first head-to-head clinical analysis of these commonly used androgen receptor inhibitors.

Among 1258 veterans treated with abiraterone and 311 treated with enzalutamide, median overall survival was 36.2 months for both drugs. Patients were followed for a mean of 28.7 months (abiraterone) and 30.8 months (enzalutamide), reported by Martin W. Schoen, MD, MPH, from Saint Louis University School of Medicine and the St. Louis VA Medical Center, in JAMA Network Open. 

Notably, there was no significant difference in outcomes among Black veterans, who often have poorer outcomes in prostate cancer, and in patients with cardiovascular disease.

“This is the first direct comparison of abiraterone and enzalutamide for mHSPC in a clinical practice setting,” Schoen told Federal Practitioner. “At the population level, there are no differences based on initial treatment choice.”

Abiraterone Is Preferred in the VA Due to Cost

According to Schoen, abiraterone and enzalutamide are the most commonly used androgen receptor inhibitors to treat mHSPC within the VA. A 2025 study by Schoen and colleagues found that 53.7% of veterans with mHSPC in 2022 received androgen receptor inhibitor therapy, up from 16.9% in 2017. 

“In the VA, the preference for most patients is abiraterone since it is the least expensive agent,” he said. A generic version has been available for several years.

Additionally, abiraterone “has been on the market for the longest, and therefore clinicians are familiar with its use,” Schoen said. However, “clinicians have little idea of the comparative efficacy between these 2 agents,” he added.

The authors suggest that the cost and toxicities of the medications should guide clinician decisions, Schoen said. “There is data that abiraterone may worsen diabetes, since it is given with prednisone and could increase the risk of cardiovascular events,” he said.

He added that 2 newer drugs, apalutamide and darolutamide, are also “viable options.” Chemotherapies and certain targeted drugs are also available, “but they are only used in a select group of patients.”

Outside Specialist: Diverse Study Population Is a Plus

Hematologist-oncologist Natalie Reizine, MD, of the University of Illinois College of Medicine, Chicago, who was not involved in the study, told Federal Practitioner that the real-world data are valuable given the limitations of clinical trial populations.

“It’s difficult to compare clinical trials because they enroll different groups of patients,” she said. And, she said, they often exclude patients with significant comorbidities. “If they have bad cardiovascular disease, for instance, or poorly controlled diabetes, they're excluded from the clinical trial. But in real life, many of our patients have other medical problems that we have to manage.”

Reizine also emphasized the significance of the study’s diverse patient population. “Black men are very underrepresented in clinical trials. Many clinical trials that lead to drug approval will have only few or no Black men at all, yet these drugs go on to be widely prescribed to all men with prostate cancer.”

Results Are ‘Reassuring’

Reizine described the overall study findings as “reassuring,” especially in light of “studies that show that abiraterone and prednisone may be associated with worse cardiovascular outcomes. This study showed that in this VA population, even for patients who had cardiovascular disease, there was not a difference in how they did.”

As for choosing between agents, she recommended considering comorbidities and potential drug-drug interactions. “One of the big reasons that you may not be able to safely prescribe enzalutamide, for instance, is if a patient is on an anticoagulant, which is incredibly common in cancer patients. Enzalutamide has more drug-drug interactions than abiraterone and prednisone.” 

Study Demographics and Findings

The study included all patients with mHSPC who initiated abiraterone or enzalutamide between July 2017 and April 2023.

Median ages were 73 (abiraterone) and 74 years (enzalutamide, P = .29). Racial distribution was similar between groups: abiraterone (68.1% White, 25.0% Black, 6.9% other/unknown) and enzalutamide (66.6% White, 27.0% Black, 6.4% other/unknown; P = .74). Ethnicity was 89.2% non-Hispanic, 4.4% Hispanic, and 6.4% unknown in the abiraterone group vs 88.4% non-Hispanic, 3.5% Hispanic, and 8.0% unknown in the enzalutamide group (P = .50).

The groups had similar rates of the most common comorbidities: diabetes (40.5% vs 46.3%, respectively, P = .07), peripheral vascular disease (40.2% vs 37.6%, respectively, P = .44), and chronic pulmonary disease (37.0% vs 40.5%, P = .29).

In an inverse probability weighting analysis with abiraterone as reference, weighted median overall survival was comparable across the entire cohort (36.2 months, P = .32), Black veterans (39.7 months, P = .90), and those with cardiovascular disease (31.5 months, P = .30).

The authors noted limitations such as the observational cohort design and data constraints. 

The study was supported by the American Society of Clinical Oncology Conquer Cancer Foundation, the Prostate Cancer Foundation, and the Blavatnik Family Foundation.

Schoen discloses relationships with the Prostate Cancer Foundation, Astellas, and US Department of Defense. Other authors disclose relationships with the American Society of Clinical Oncology, Pfizer, Exelixis, Eli Lilly, Sanofi, Merck, Seagen, Bellicum, and BMS.

Outside the submitted work. Reizine discloses relationships with the US Department of Defense, Sanofi, Exelexis, Janssen, AstraZeneca, EMD Serono, Janssen, Merck, and Tempus.

Abiraterone and enzalutamide showed identical survival outcomes when used as first-line treatment for metastatic hormone-sensitive prostate cancer (mHSPC), according to a new study using US Department of Veterans Affairs (VA) data. The report represents the first head-to-head clinical analysis of these commonly used androgen receptor inhibitors.

Among 1258 veterans treated with abiraterone and 311 treated with enzalutamide, median overall survival was 36.2 months for both drugs. Patients were followed for a mean of 28.7 months (abiraterone) and 30.8 months (enzalutamide), reported by Martin W. Schoen, MD, MPH, from Saint Louis University School of Medicine and the St. Louis VA Medical Center, in JAMA Network Open. 

Notably, there was no significant difference in outcomes among Black veterans, who often have poorer outcomes in prostate cancer, and in patients with cardiovascular disease.

“This is the first direct comparison of abiraterone and enzalutamide for mHSPC in a clinical practice setting,” Schoen told Federal Practitioner. “At the population level, there are no differences based on initial treatment choice.”

Abiraterone Is Preferred in the VA Due to Cost

According to Schoen, abiraterone and enzalutamide are the most commonly used androgen receptor inhibitors to treat mHSPC within the VA. A 2025 study by Schoen and colleagues found that 53.7% of veterans with mHSPC in 2022 received androgen receptor inhibitor therapy, up from 16.9% in 2017. 

“In the VA, the preference for most patients is abiraterone since it is the least expensive agent,” he said. A generic version has been available for several years.

Additionally, abiraterone “has been on the market for the longest, and therefore clinicians are familiar with its use,” Schoen said. However, “clinicians have little idea of the comparative efficacy between these 2 agents,” he added.

The authors suggest that the cost and toxicities of the medications should guide clinician decisions, Schoen said. “There is data that abiraterone may worsen diabetes, since it is given with prednisone and could increase the risk of cardiovascular events,” he said.

He added that 2 newer drugs, apalutamide and darolutamide, are also “viable options.” Chemotherapies and certain targeted drugs are also available, “but they are only used in a select group of patients.”

Outside Specialist: Diverse Study Population Is a Plus

Hematologist-oncologist Natalie Reizine, MD, of the University of Illinois College of Medicine, Chicago, who was not involved in the study, told Federal Practitioner that the real-world data are valuable given the limitations of clinical trial populations.

“It’s difficult to compare clinical trials because they enroll different groups of patients,” she said. And, she said, they often exclude patients with significant comorbidities. “If they have bad cardiovascular disease, for instance, or poorly controlled diabetes, they're excluded from the clinical trial. But in real life, many of our patients have other medical problems that we have to manage.”

Reizine also emphasized the significance of the study’s diverse patient population. “Black men are very underrepresented in clinical trials. Many clinical trials that lead to drug approval will have only few or no Black men at all, yet these drugs go on to be widely prescribed to all men with prostate cancer.”

Results Are ‘Reassuring’

Reizine described the overall study findings as “reassuring,” especially in light of “studies that show that abiraterone and prednisone may be associated with worse cardiovascular outcomes. This study showed that in this VA population, even for patients who had cardiovascular disease, there was not a difference in how they did.”

As for choosing between agents, she recommended considering comorbidities and potential drug-drug interactions. “One of the big reasons that you may not be able to safely prescribe enzalutamide, for instance, is if a patient is on an anticoagulant, which is incredibly common in cancer patients. Enzalutamide has more drug-drug interactions than abiraterone and prednisone.” 

Study Demographics and Findings

The study included all patients with mHSPC who initiated abiraterone or enzalutamide between July 2017 and April 2023.

Median ages were 73 (abiraterone) and 74 years (enzalutamide, P = .29). Racial distribution was similar between groups: abiraterone (68.1% White, 25.0% Black, 6.9% other/unknown) and enzalutamide (66.6% White, 27.0% Black, 6.4% other/unknown; P = .74). Ethnicity was 89.2% non-Hispanic, 4.4% Hispanic, and 6.4% unknown in the abiraterone group vs 88.4% non-Hispanic, 3.5% Hispanic, and 8.0% unknown in the enzalutamide group (P = .50).

The groups had similar rates of the most common comorbidities: diabetes (40.5% vs 46.3%, respectively, P = .07), peripheral vascular disease (40.2% vs 37.6%, respectively, P = .44), and chronic pulmonary disease (37.0% vs 40.5%, P = .29).

In an inverse probability weighting analysis with abiraterone as reference, weighted median overall survival was comparable across the entire cohort (36.2 months, P = .32), Black veterans (39.7 months, P = .90), and those with cardiovascular disease (31.5 months, P = .30).

The authors noted limitations such as the observational cohort design and data constraints. 

The study was supported by the American Society of Clinical Oncology Conquer Cancer Foundation, the Prostate Cancer Foundation, and the Blavatnik Family Foundation.

Schoen discloses relationships with the Prostate Cancer Foundation, Astellas, and US Department of Defense. Other authors disclose relationships with the American Society of Clinical Oncology, Pfizer, Exelixis, Eli Lilly, Sanofi, Merck, Seagen, Bellicum, and BMS.

Outside the submitted work. Reizine discloses relationships with the US Department of Defense, Sanofi, Exelexis, Janssen, AstraZeneca, EMD Serono, Janssen, Merck, and Tempus.

PHOENIX ‑ A US Department of Veterans Affairs (VA) hospital in Tennessee has performed the first “bloodless” autologous stem cell transplant within the Veterans Health Administration, treating a 61-year-old Jehovah’s Witness patient with multiple myeloma who traveled from California for the procedure.

The case, presented at the annual meeting of the Association of VA Hematology/Oncology, stated that “we should not withhold any therapies for patients who are Jehovah’s Witnesses out of fear of them bleeding out or having complications from anemia,” said Bhagirathbhai Dholaria, MBBS, an associate professor of medicine at Vanderbilt University Medical Center who worked with the VA Tennessee Valley Healthcare System in Nashville.

While Jehovah’s Witnesses accept medical treatment, their faith forbids blood transfusions, including of preoperative autologous blood, due to its interpretation of the Bible. The faith allows individuals to decide whether to accept stem cells collected from their blood or someone else’s “provided that blood components are not intentionally collected, stored, and reinfused along with the stem cells.”

There are an estimated 1.2 million Jehovah’s Witnesses in the US. 

Traditional Stem Cell Transplants Require Blood Support

In conventional autologous stem cell transplants for multiple myeloma, high-dose chemotherapy temporarily wipes out the patient’s bone marrow for about 2 to 3 weeks, Dholaria explained. During this period, patients typically receive 2 units of packed red blood cells and platelet transfusions to prevent severe complications from anemia and low platelet counts.

“Because of this reason, Jehovah’s Witnesses have been traditionally denied these therapies,” Dholaria said.

However, bloodless autologous transplants have been performed for about 2 decades, and Vanderbilt University has been offering the procedures for about 3 years, according to Dholaria.

For the first bloodless procedure in the VA, the patient–who had an aggressive, newly diagnosed IgG kappa multiple myeloma–was evaluated.

“He had been treated by local doctors in California. Otherwise, he was actually in really good shape. Physically, he didn’t have any major issues,” Dholaria said. “So, he met the criteria for our bloodless protocol, and we decided to offer him the procedure.”

The team consulted ethics and legal departments and noted the patient’s blood product preferences in his electronic health record. The patient then underwent a preoptimization protocol that included erythropoiesis-stimulating agents, intravenous iron, and vitamin B12 supplementation to boost blood counts before the transplant, according to the case presentation. 

Special Protocol Required in ‘Bloodless’ Procedures

After stem cell collection and chemotherapy, patients undergoing bloodless procedures receive aggressive growth factor support to minimize the duration and severity of cytopenia, Dholaria said. As part of the protocol, the care team uses pediatric tubes for blood draws to minimize blood loss and monitors patients closely on cardiac monitors, he added. In addition, blood draws are only performed every 3 days. 

“We watch for any cardiac decompensation because these patients have severe anemia for a brief period of time. We make sure they don’t [have a] heart attack or arrhythmias,” Dholaria said. “Or if the platelets are too low, and they start oozing blood from the nose, gums, or gut, that needs to be dealt with accordingly.”

For bleeding complications, the team uses clotting factors and intravenous and oral medications to support remaining platelet function rather than platelet transfusions.

The patient in this case tolerated the transplant “exceptionally well with minimal complications,” according to the case presentation. He achieved full engraftment on day 14 after transplant and was discharged from inpatient care with continued monitoring through day 30.

“The patient was very compliant,” said Salyka Sengsayadeth, MD, medical director of the VA Tennessee Valley Healthcare System Stem Cell Transplant and Cellular Therapy Program and associate professor of medicine at Vanderbilt. 

“He tolerated everything that we needed to do,” she said. “He called us when he needed to call us and did everything that we asked and recommended for him.”

The patient’s roughly 30-day hospital stay matched that of typical transplant patients, Sengsayadeth noted. His myeloma responded to treatment, and he returned to California, Dholaria said.

‘Bloodless’ Procedures Not for All Stem Cell Transplants 

The case highlights the availability of stem cell transplants in the VA–they are only performed in Seattle and Nashville–and opportunities for patients who wish to avoid blood transfusions. Sengsayadeth said the bloodless protocol is available for patients without religious objections who simply prefer to avoid blood products.

Dholaria cautioned that bloodless protocol applies specifically to autologous transplants, where patients receive their own stem cells. The team does not plan to offer bloodless allogeneic transplants, which use donor stem cells for conditions like leukemia, due to higher risks. In addition, most Jehovah’s Witnesses decline allogeneic transplants because they do not accept stem cells from another person, Dholaria said.

Beyond multiple myeloma, the Tennessee Valley Healthcare System offers bloodless autologous transplants for various blood cancers, including non-Hodgkin lymphomas such as large B-cell lymphoma, follicular lymphoma, and mantle cell lymphoma, as well as lymphomas affecting the brain, Dholaria said.

Clinicians “should start thinking about this early on, as soon as the cancer diagnosis is made, to make the referral and get the patient on our radar,” Dholaria said.

Sengsayadeth said physicians within the VA typically know how to refer appropriate patients to her team. “They just send us an email or give us a call or a message to say ‘I have this patient. Do you think they’re someone I should send to you?’ We usually answer right back, and then we can proceed with the full evaluation if we think that’s a reasonable thing to do.”

‘Treated Like Family’

The patient, a Marine Corps veteran named Keith Cody, spoke about the procedure in a video interview. Cody said he was reluctant at first to undergo the procedure because he didn’t understand what it would accomplish. 

“As I was doing the massive chemo every week, and then suffering with the side effects, I decided to ask again about this procedure and how it improves my quality of life,” he said. 

At the time of the taping of the video, Cody was getting ready to go home to California. “They’ve told me that I’ll still need more time to get my energy back, but I do feel much better already,” he said.

He also praised the staff. “Everybody that we came across, I enjoyed the interactions. It’s actually sad to leave people behind that you really felt treated you like family.”

Dholaria discloses relationships with Janssen, Angiocrine, Pfizer, Poseida, MEI, Orcabio, Wugen, Allovir, Adicet, BMS, Molecular Templates, Atara, MJH, Arvinas, Janssen, ADC, Gilead, GSK, Caribou, F. Hoffmann-La Roche AG, Autolus, and Pierre Fabre.

Sengsayadeth has no disclosures. 

PHOENIX ‑ A US Department of Veterans Affairs (VA) hospital in Tennessee has performed the first “bloodless” autologous stem cell transplant within the Veterans Health Administration, treating a 61-year-old Jehovah’s Witness patient with multiple myeloma who traveled from California for the procedure.

The case, presented at the annual meeting of the Association of VA Hematology/Oncology, stated that “we should not withhold any therapies for patients who are Jehovah’s Witnesses out of fear of them bleeding out or having complications from anemia,” said Bhagirathbhai Dholaria, MBBS, an associate professor of medicine at Vanderbilt University Medical Center who worked with the VA Tennessee Valley Healthcare System in Nashville.

While Jehovah’s Witnesses accept medical treatment, their faith forbids blood transfusions, including of preoperative autologous blood, due to its interpretation of the Bible. The faith allows individuals to decide whether to accept stem cells collected from their blood or someone else’s “provided that blood components are not intentionally collected, stored, and reinfused along with the stem cells.”

There are an estimated 1.2 million Jehovah’s Witnesses in the US. 

Traditional Stem Cell Transplants Require Blood Support

In conventional autologous stem cell transplants for multiple myeloma, high-dose chemotherapy temporarily wipes out the patient’s bone marrow for about 2 to 3 weeks, Dholaria explained. During this period, patients typically receive 2 units of packed red blood cells and platelet transfusions to prevent severe complications from anemia and low platelet counts.

“Because of this reason, Jehovah’s Witnesses have been traditionally denied these therapies,” Dholaria said.

However, bloodless autologous transplants have been performed for about 2 decades, and Vanderbilt University has been offering the procedures for about 3 years, according to Dholaria.

For the first bloodless procedure in the VA, the patient–who had an aggressive, newly diagnosed IgG kappa multiple myeloma–was evaluated.

“He had been treated by local doctors in California. Otherwise, he was actually in really good shape. Physically, he didn’t have any major issues,” Dholaria said. “So, he met the criteria for our bloodless protocol, and we decided to offer him the procedure.”

The team consulted ethics and legal departments and noted the patient’s blood product preferences in his electronic health record. The patient then underwent a preoptimization protocol that included erythropoiesis-stimulating agents, intravenous iron, and vitamin B12 supplementation to boost blood counts before the transplant, according to the case presentation. 

Special Protocol Required in ‘Bloodless’ Procedures

After stem cell collection and chemotherapy, patients undergoing bloodless procedures receive aggressive growth factor support to minimize the duration and severity of cytopenia, Dholaria said. As part of the protocol, the care team uses pediatric tubes for blood draws to minimize blood loss and monitors patients closely on cardiac monitors, he added. In addition, blood draws are only performed every 3 days. 

“We watch for any cardiac decompensation because these patients have severe anemia for a brief period of time. We make sure they don’t [have a] heart attack or arrhythmias,” Dholaria said. “Or if the platelets are too low, and they start oozing blood from the nose, gums, or gut, that needs to be dealt with accordingly.”

For bleeding complications, the team uses clotting factors and intravenous and oral medications to support remaining platelet function rather than platelet transfusions.

The patient in this case tolerated the transplant “exceptionally well with minimal complications,” according to the case presentation. He achieved full engraftment on day 14 after transplant and was discharged from inpatient care with continued monitoring through day 30.

“The patient was very compliant,” said Salyka Sengsayadeth, MD, medical director of the VA Tennessee Valley Healthcare System Stem Cell Transplant and Cellular Therapy Program and associate professor of medicine at Vanderbilt. 

“He tolerated everything that we needed to do,” she said. “He called us when he needed to call us and did everything that we asked and recommended for him.”

The patient’s roughly 30-day hospital stay matched that of typical transplant patients, Sengsayadeth noted. His myeloma responded to treatment, and he returned to California, Dholaria said.

‘Bloodless’ Procedures Not for All Stem Cell Transplants 

The case highlights the availability of stem cell transplants in the VA–they are only performed in Seattle and Nashville–and opportunities for patients who wish to avoid blood transfusions. Sengsayadeth said the bloodless protocol is available for patients without religious objections who simply prefer to avoid blood products.

Dholaria cautioned that bloodless protocol applies specifically to autologous transplants, where patients receive their own stem cells. The team does not plan to offer bloodless allogeneic transplants, which use donor stem cells for conditions like leukemia, due to higher risks. In addition, most Jehovah’s Witnesses decline allogeneic transplants because they do not accept stem cells from another person, Dholaria said.

Beyond multiple myeloma, the Tennessee Valley Healthcare System offers bloodless autologous transplants for various blood cancers, including non-Hodgkin lymphomas such as large B-cell lymphoma, follicular lymphoma, and mantle cell lymphoma, as well as lymphomas affecting the brain, Dholaria said.

Clinicians “should start thinking about this early on, as soon as the cancer diagnosis is made, to make the referral and get the patient on our radar,” Dholaria said.

Sengsayadeth said physicians within the VA typically know how to refer appropriate patients to her team. “They just send us an email or give us a call or a message to say ‘I have this patient. Do you think they’re someone I should send to you?’ We usually answer right back, and then we can proceed with the full evaluation if we think that’s a reasonable thing to do.”

‘Treated Like Family’

The patient, a Marine Corps veteran named Keith Cody, spoke about the procedure in a video interview. Cody said he was reluctant at first to undergo the procedure because he didn’t understand what it would accomplish. 

“As I was doing the massive chemo every week, and then suffering with the side effects, I decided to ask again about this procedure and how it improves my quality of life,” he said. 

At the time of the taping of the video, Cody was getting ready to go home to California. “They’ve told me that I’ll still need more time to get my energy back, but I do feel much better already,” he said.

He also praised the staff. “Everybody that we came across, I enjoyed the interactions. It’s actually sad to leave people behind that you really felt treated you like family.”

Dholaria discloses relationships with Janssen, Angiocrine, Pfizer, Poseida, MEI, Orcabio, Wugen, Allovir, Adicet, BMS, Molecular Templates, Atara, MJH, Arvinas, Janssen, ADC, Gilead, GSK, Caribou, F. Hoffmann-La Roche AG, Autolus, and Pierre Fabre.

Sengsayadeth has no disclosures. 

PHOENIX ‑ A US Department of Veterans Affairs (VA) hospital in Tennessee has performed the first “bloodless” autologous stem cell transplant within the Veterans Health Administration, treating a 61-year-old Jehovah’s Witness patient with multiple myeloma who traveled from California for the procedure.

The case, presented at the annual meeting of the Association of VA Hematology/Oncology, stated that “we should not withhold any therapies for patients who are Jehovah’s Witnesses out of fear of them bleeding out or having complications from anemia,” said Bhagirathbhai Dholaria, MBBS, an associate professor of medicine at Vanderbilt University Medical Center who worked with the VA Tennessee Valley Healthcare System in Nashville.

While Jehovah’s Witnesses accept medical treatment, their faith forbids blood transfusions, including of preoperative autologous blood, due to its interpretation of the Bible. The faith allows individuals to decide whether to accept stem cells collected from their blood or someone else’s “provided that blood components are not intentionally collected, stored, and reinfused along with the stem cells.”

There are an estimated 1.2 million Jehovah’s Witnesses in the US. 

Traditional Stem Cell Transplants Require Blood Support

In conventional autologous stem cell transplants for multiple myeloma, high-dose chemotherapy temporarily wipes out the patient’s bone marrow for about 2 to 3 weeks, Dholaria explained. During this period, patients typically receive 2 units of packed red blood cells and platelet transfusions to prevent severe complications from anemia and low platelet counts.

“Because of this reason, Jehovah’s Witnesses have been traditionally denied these therapies,” Dholaria said.

However, bloodless autologous transplants have been performed for about 2 decades, and Vanderbilt University has been offering the procedures for about 3 years, according to Dholaria.

For the first bloodless procedure in the VA, the patient–who had an aggressive, newly diagnosed IgG kappa multiple myeloma–was evaluated.

“He had been treated by local doctors in California. Otherwise, he was actually in really good shape. Physically, he didn’t have any major issues,” Dholaria said. “So, he met the criteria for our bloodless protocol, and we decided to offer him the procedure.”

The team consulted ethics and legal departments and noted the patient’s blood product preferences in his electronic health record. The patient then underwent a preoptimization protocol that included erythropoiesis-stimulating agents, intravenous iron, and vitamin B12 supplementation to boost blood counts before the transplant, according to the case presentation. 

Special Protocol Required in ‘Bloodless’ Procedures

After stem cell collection and chemotherapy, patients undergoing bloodless procedures receive aggressive growth factor support to minimize the duration and severity of cytopenia, Dholaria said. As part of the protocol, the care team uses pediatric tubes for blood draws to minimize blood loss and monitors patients closely on cardiac monitors, he added. In addition, blood draws are only performed every 3 days. 

“We watch for any cardiac decompensation because these patients have severe anemia for a brief period of time. We make sure they don’t [have a] heart attack or arrhythmias,” Dholaria said. “Or if the platelets are too low, and they start oozing blood from the nose, gums, or gut, that needs to be dealt with accordingly.”

For bleeding complications, the team uses clotting factors and intravenous and oral medications to support remaining platelet function rather than platelet transfusions.

The patient in this case tolerated the transplant “exceptionally well with minimal complications,” according to the case presentation. He achieved full engraftment on day 14 after transplant and was discharged from inpatient care with continued monitoring through day 30.

“The patient was very compliant,” said Salyka Sengsayadeth, MD, medical director of the VA Tennessee Valley Healthcare System Stem Cell Transplant and Cellular Therapy Program and associate professor of medicine at Vanderbilt. 

“He tolerated everything that we needed to do,” she said. “He called us when he needed to call us and did everything that we asked and recommended for him.”

The patient’s roughly 30-day hospital stay matched that of typical transplant patients, Sengsayadeth noted. His myeloma responded to treatment, and he returned to California, Dholaria said.

‘Bloodless’ Procedures Not for All Stem Cell Transplants 

The case highlights the availability of stem cell transplants in the VA–they are only performed in Seattle and Nashville–and opportunities for patients who wish to avoid blood transfusions. Sengsayadeth said the bloodless protocol is available for patients without religious objections who simply prefer to avoid blood products.

Dholaria cautioned that bloodless protocol applies specifically to autologous transplants, where patients receive their own stem cells. The team does not plan to offer bloodless allogeneic transplants, which use donor stem cells for conditions like leukemia, due to higher risks. In addition, most Jehovah’s Witnesses decline allogeneic transplants because they do not accept stem cells from another person, Dholaria said.

Beyond multiple myeloma, the Tennessee Valley Healthcare System offers bloodless autologous transplants for various blood cancers, including non-Hodgkin lymphomas such as large B-cell lymphoma, follicular lymphoma, and mantle cell lymphoma, as well as lymphomas affecting the brain, Dholaria said.

Clinicians “should start thinking about this early on, as soon as the cancer diagnosis is made, to make the referral and get the patient on our radar,” Dholaria said.

Sengsayadeth said physicians within the VA typically know how to refer appropriate patients to her team. “They just send us an email or give us a call or a message to say ‘I have this patient. Do you think they’re someone I should send to you?’ We usually answer right back, and then we can proceed with the full evaluation if we think that’s a reasonable thing to do.”

‘Treated Like Family’

The patient, a Marine Corps veteran named Keith Cody, spoke about the procedure in a video interview. Cody said he was reluctant at first to undergo the procedure because he didn’t understand what it would accomplish. 

“As I was doing the massive chemo every week, and then suffering with the side effects, I decided to ask again about this procedure and how it improves my quality of life,” he said. 

At the time of the taping of the video, Cody was getting ready to go home to California. “They’ve told me that I’ll still need more time to get my energy back, but I do feel much better already,” he said.

He also praised the staff. “Everybody that we came across, I enjoyed the interactions. It’s actually sad to leave people behind that you really felt treated you like family.”

Dholaria discloses relationships with Janssen, Angiocrine, Pfizer, Poseida, MEI, Orcabio, Wugen, Allovir, Adicet, BMS, Molecular Templates, Atara, MJH, Arvinas, Janssen, ADC, Gilead, GSK, Caribou, F. Hoffmann-La Roche AG, Autolus, and Pierre Fabre.

Sengsayadeth has no disclosures.