Prostate Cancer

Prostate cancer is the most common cancer in US males, with an estimated 313,780 new cases and 35,770 deaths in 2025.¹ Several treatment options are available for localized prostate cancer that have similar outcomes, including active surveillance for low-risk cancers, surgery, or radiotherapy.^2,3 Conventional fractionation radiotherapy (CFRT) with 40 to 45 fractions over 8 to 9 weeks has been used for decades. Over the past 2 decades, moderate hypofractionation schedules with 2.4 to 3.4 Gy per fraction over 20 to 28 fractions have become standard, as many noninferiority randomized clinical trials (RCTs) such as CHHiP (UK),⁴ PROFIT (Canada and Europe),⁵ NRG Oncology RTOG 0415 (US),⁶ HYPRO (Netherlands),^7,8 and HYPO-RT-PC (Sweden and Denmark),⁹ have shown the noninferiority of moderately hypofractionated radiotherapy compared with CFRT. Notably, most of these noninferiority studies primarily included patients with low- or intermediate-risk prostate cancer, except for the HYPO-RT-PC trial,⁹ which also included patients with intermediate- and high-risk prostate cancer.

These noninferiority studies, along with technological advances in radiotherapy, such as intensity-modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT), and image-guided radiotherapy (IGRT), paved the path to ultrahypofractionated stereotactic body radiotherapy (SBRT) that is delivered in 5 fractions of ≥ 6 Gy. This high dose per fraction may have a radiobiologic advantage over conventional fractionation. The relatively low a/ß ratio of prostate cancer, estimated to be between 1 and 2, suggests that tumor cells may be particularly sensitive to the high doses per fraction delivered in SBRT.^10-13 Compared with CFRT, SBRT-induced tumor cell death may also be mediated through different pathways; this pathway appears to be generated in a dose-dependent manner, particularly with doses > 8 Gy per fraction.^14,15 Additionally, the higher a/ß ratio for the surrounding organs at risk, such as the bladder and rectum, theoretically allows for an improved therapeutic ratio window that maximizes tumor control while minimizing damage to healthy tissues.

A substantial body of evidence from prospective studies and meta-analyses supports the use of SBRT for localized prostate cancer. HYPO-RT-PC, a significant phase 3 noninferiority study, enrolled 1200 patients with intermediate (89%) and high-risk (11%) prostate cancer randomized between 2 arms, including CFRT to 78 Gy in 39 fractions and SBRT to 42.7 Gy in 7 fractions, treated 3 days weekly. After a median follow-up of 60 months, the estimated 5-year biochemical relapse-free survival rate was 84% in both groups.⁹ This trial was notable because it was the first randomized study to demonstrate that SBRT was noninferior to CFRT in intermediate- and high-risk prostate cancer patients. Another pivotal phase 3 trial, the PACE-B study, enrolled 874 patients to compare SBRT (36.25 Gy to the prostate gland, with a secondary dose of 40 Gy to the gross tumor volume where applicable, in 5 fractions) with CFRT (78 Gy in 39 fractions) and moderately hypofractionated radiotherapy (HFRT) (62 Gy in 20 fractions) in patients with low- or intermediate-risk prostate cancer. With a 74-month median follow-up, the study reported 5-year biochemical free rates of 94.6% for CFRT and 95.8% for SBRT, confirming the noninferiority of SBRT to CFRT.¹⁵

SBRT offers short, effective, and convenient treatment to many patients with localized prostate cancer. While previous guidelines were more restrictive, the March 2026 National Comprehensive Cancer Network (NCCN) guidelines now list SBRT as a preferred treatment modality for high-risk prostate cancer.¹⁶

Given the growing body of evidence supporting the efficacy and safety of SBRT, we implemented an SBRT program in 2014 at a tertiary care center for veterans. This retrospective study was undertaken to evaluate the early efficacy and toxicity of SBRT in patients with localized prostate cancer treated at our institution, including patients across all risk stratifications.

METHODS

We identified 242 patients diagnosed with prostate cancer who underwent SBRT treatment between November 2014 and October 2024 at Overland Park Veterans Affairs Radiation Oncology Clinic. For the final analysis, 46 patients with < 2 years of follow-up and 22 patients who died from causes other than prostate cancer were excluded, resulting in a cohort of 174 patients with ≥ 24-month follow-up.

Treatment

Patients eligible for staging underwent imaging according to NCCN guidelines, including computed tomography (CT) of the abdomen and pelvis, bone scintigraphy, or, in recent years, prostate-specific membrane antigen positron emission tomography, primarily used for unfavorable intermediate-risk (UIR) and high-risk (HR) cancers. Patients with a negative staging work-up for nodal or skeletal disease were included. Prior to planning the CT simulation, patients were given bowel preparation instructions, including a low-fiber and low-gas-producing diet, simethicone, and enemas, the night before and morning of the simulation. Patients were instructed to arrive with a comfortably full bladder, having not voided for 2 to 3 hours prior to the procedure. At Kansas City Veterans Affairs Medical Center (KCVAMC), SBRT treatment was generally restricted to patients with a baseline American Urological Association symptom score of 15 to 20 out of 35 and a prostate gland size < 80 mL to minimize the risk of acute urinary toxicity. We did not use intraprostatic fiducials, hydrogel rectal spacers, or intravenous contrast agents for planning CT simulation.

Patients were placed in a supine position, and a vacuum bag was used for immobilization. Following the CT simulation, the images were transferred to the Eclipse treatment planning system. The clinical target volume (CTV) encompassed the prostate and the proximal 1.0 cm of the seminal vesicles for Gleason score (GS) 1 to 2, and the entire seminal vesicle was included for GS 3 to 5, which is consistent with KCVAMC practice and established safety protocols. The planning target volume (PTV) was created by uniformly expanding the CTV by 5 to 7 mm, except for the posterior margin, which was limited to 3 to 5 mm. When elective nodal radiotherapy was planned for HR prostate cancer, the pelvic field for CT simulation started at the L-2 upper border, with the lower border extending to the lesser trochanter. The pelvic nodes were delineated per Radiation Therapy Oncology Group (RTOG) guidelines.¹⁷ The CTV nodes (CTVn), including common iliac, external and internal iliac nodes, obturator, and presacral nodes, were created by uniformly expanding the CTVn by 2 to 3 mm. Slice-by-slice corrections were made to avoid bowel overlap in these patients.

The use of androgen deprivation therapy (ADT) for a duration of 6 to 24 months was prescribed for patients with UIR or HR prostate cancer per NCCN guidelines.¹⁶ The prescribed dose to the PTV was 36.25 to 40 Gy (40 Gy was mostly used as a boost to the dominant lesion) in 5 fractions, with each fraction ranging from 7.25 to 8 Gy. For elective nodal radiotherapy in patients at HR, the prescribed dose was 25 Gy in 5 fractions. All patients were planned for VMAT, which aims to deliver ≥ 95% of the prescription dose to 95% of the PTV. Once the physician approved the treatment plan and physics quality assessment was completed, treatments commenced on an every-other-day schedule. Patients received the same bowel preparation instructions for each treatment as for the planning CT simulation. Daily treatment accuracy was confirmed via daily 3-dimensional cone-beam CT (CBCT) for IGRT. No fiducials or hydrogel rectal spacers were used.

Follow-up Schedule and Toxicity Assessment

Follow-up assessments were conducted 4 to 6 weeks after radiation therapy and then repeated every 6 months for 2 to 5 years, and annually thereafter. At each follow-up visit, patients were evaluated for genitourinary (GU) and gastrointestinal (GI) toxicity, according to RTOG toxicity criteria. Prostate-specific antigen (PSA) levels were monitored; in patients receiving ADT, testosterone levels were also checked.

Statistical Analysis

Biochemical failure was defined using the Phoenix definition (nadir PSA + 2 ng/mL). Differences between dose cohorts were assessed using the log-rank test for survival outcomes and X² testing for categorical variables. GU and GI toxicities were summarized as cumulative incidences of RTOG grade ≥ II events. Statistical significance was set at P < .05.

RESULTS

One hundred seventy-four patients were included in the retrospective review. Patients had a median follow-up of 45 months (range, 24-111) (Figure). The median age at treatment was 74 years (range, 51-88), and the median pretreatment PSA level was 11.9 ng/mL (range, 0.6-69.5). Twenty-six patients (14.9%) had a GS 1, 77 (44.3%) had GS 2, 41 (23.6%) had GS 3, 18 (10.3%) had GS 4, and 12 (6.9%) had GS 5. Fifty-one patients (29.3%) received elective pelvic nodal radiotherapy, and 93 patients (53.4%) received ADT (Table 1).

At 24 months follow-up, 6 patients (3.4%) had biochemical failures. One patient died from metastatic prostate cancer, and 5 patients are living with biochemical failure (Table 2). The actuarial 5-year overall survival (OS) rate was 99.4%, and the 5-year disease-free survival (DFS) rate was 96.6%. We performed a subanalysis comparing outcomes of the 36.25 Gy vs 40 Gy SBRT cohorts. There was no statistically significant difference in DFS, OS, or the cumulative incidence of grade II/III toxicity between patients treated with 40 Gy vs 36.25 Gy. Outcomes stratified by NCCN risk groups (low, intermediate, high/very high) are detailed in Table 3. As expected, DFS was slightly lower in the high-risk group, but overall disease control remained high across all stratifications.

The cumulative incidence of RTOG grade II and higher GU toxicity was 28.2% (Table 4). This included 46 patients (26.4%) with grade II GU toxicity and 2 patients (1.2%) who developed grade III GU complications (1 requiring self-catheterization and another a suprapubic catheter for urinary retention). One patient (0.6%) treated with a 40 Gy dose regimen experienced a grade IV GU complication in the form of a rectovesical fistula necessitating surgical intervention.

The cumulative incidence of RTOG grade II or higher GI toxicity was 3.4%, and no grade III or IV gastrointestinal toxicities were observed during the follow-up period. Importantly, intraprostatic fiducials, hydrogel rectal spacers, or intravenous contrast were not routinely used in this cohort of patients.

The high rates of actuarial 5-year DFS and OS observed suggest a favorable initial response to the SBRT regimen employed at KCVAMC. However, given the potential for late recurrence in patients with prostate cancer, longer follow-up is essential to determine the durability of these outcomes. The observed GU toxicity rate of 28.2% for grade II and higher events warrants careful consideration and compares with other published data on SBRT for prostate cancer.¹⁵ The occurrence of a grade IV rectovesical fistula, although rare, is a notable adverse event that warrants discussion in the context of the treatment approach. The low incidence of grade II or higher GI toxicity is an encouraging finding, particularly given that hydrogel rectal spacers are not routinely used to minimize rectal exposure.

DISCUSSION

The primary objective of this retrospective study was to evaluate the outcomes of SBRT for patients with localized prostate cancer treated at KCVAMC and to compare these results with those reported in the literature. Our findings demonstrate promising intermediate-term efficacy, with an estimated 5-year DFS of 96.6% and OS of 99.4% at a median follow-up of 45 months. Furthermore, the observed toxicity profile appears acceptable, with a cumulative grade II and higher GU toxicity rate of 28.2% and a grade II or higher GI toxicity rate of 3.4%. Notably, these outcomes were achieved without the routine use of intraprostatic fiducials or hydrogel rectal spacers.

Two pivotal randomized phase 3 trials have established the noninferiority of ultrahypofractionated radiotherapy (UHRT) with SBRT over conventional fractionation. The HYPO-RT-PC trial compared SBRT (42.7 Gy in 7 fractions) with conventional fractionation (78 Gy in 39 fractions) in intermediate- and high-risk patients with prostate cancer and reported a 5-year biochemical relapse-free survival of 84% in both arms.⁹ The PACE-B trial, which included patients at low- and intermediate-risk, compared SBRT (36.25 Gy in 5 fractions) with conventional or moderate HFRT and reported a 5-year biochemical control rate of 95.8% in the SBRT arm and 94.6% in the control arm.¹⁵

A comprehensive review and meta-analysis of 7 phase 3 studies involving 6795 patients compared different radiotherapy regimens, namely, UHRT, HFRT, and CFRT, and reported that after 5 years, the DFS rates were 85.1% for CFRT, 86% for HFRT, and 85% for UHRT, with no significant difference in toxicity among the 3 different treatment approaches.¹⁸ This suggests that shorter, more intense radiotherapy schedules (UHRT and HFRT) may be as effective and safe as traditional, longer courses of radiation.

There are multiple published nonrandomized prospective trials in which thousands of patients with extreme hypofractionation have been treated with different doses, fractions, and techniques. While heterogeneity and limited long-term follow-up in the existing evidence are acknowledged, these data suggest that prostate SBRT provides appropriate biochemical control with few high-grade toxicities, supporting its ongoing global use and justifying further prospective investigations. Comparative data are shown in Table 5. Several ongoing studies are evaluating noninferiority, superiority, and cost-effectiveness using different methodologies (Table 6).^9,15,19-24

This study’s efficacy outcomes, particularly the high DFS rate, are consistent with the findings from these landmark trials, suggesting that the SBRT regimen used at KCVAMC is effective in achieving early disease control despite 17.2% of patients having high-risk disease. The GU toxicity observed in this study, with a 28.2% rate of grade II or higher events, is also comparable with the 26.9% reported in the 5-fraction SBRT arm of the PACE-B trial, which had a longer median follow-up of 74 months.¹⁵ It is important to note that a portion of these grade II events occurred in patients who were already on a blockers for pre-existing lower urinary tract symptoms before starting radiotherapy, which may inflate the observed cumulative acute toxicity score.

A critical comparison is how SBRT toxicity aligns with moderate hypofractionation (eg, 60 Gy in 20 fractions or 70 Gy in 28 fractions as reported by others).^4,6 Our observed grade III and higher GU toxicity rate (1.7%) and grade III and higher GI toxicity rate (0%) are highly favorable when compared with historical moderate hypofractionation data, which typically report grade III GU toxicity in the range of 2% to 3% and grade III GI toxicity around 1% to 2%. This suggests that despite the higher dose per fraction, SBRT does not necessarily lead to increased severe acute toxicity, potentially offering a superior therapeutic ratio for GI and GU sparing.

However, the occurrence of a grade IV rectovesical fistula in 1 patient (0.6%)—who received the 40 Gy dose—was a serious complication that warrants careful consideration. This rare, but severe, complication in the higher dose cohort underscores the potential for increased organ-at-risk toxicity, particularly in the absence of a hydrogel rectal spacer, which is designed to mitigate high-dose rectal exposure. While the overall rate of significant GU toxicity remains low, this event highlights the potential risks associated with SBRT. Hydrogel rectal spacers are designed to increase the distance between the prostate and the rectum, which can reduce the rectal radiation dose and potentially mitigate the risk of such fistulas. The low rate of grade II or worse GI toxicity (3.4%) in our study is noteworthy, especially considering that hydrogel spacers were not routinely used. This finding aligns with the 2.5% GI toxicity rate reported in the SBRT arm of the PACE-B trial, suggesting that careful treatment planning and delivery techniques, such as VMAT-IMRT and daily CBCT for IGRT, may contribute to minimizing GI toxicity even without the use of rectal spacers.¹⁵ The exclusive use of 3-dimensional CBCT for IGRT in our study, without the use of fiducial markers, suggests that accurate target localization can be achieved with this approach, contributing to the observed efficacy and reduced toxicity.

Strengths and Limitations

This study’s retrospective, single-center design may have introduced selection bias. The median follow-up of 45 months, while substantial, is still relatively short for assessing very late toxicities and long-term oncologic outcomes in prostate cancer, which is known for late recurrences. Additionally, the lack of a direct comparison group within KCVAMC limits the ability to definitively attribute the observed outcomes solely to SBRT treatment. However, the strengths of this study include the inclusion of a consecutive series of veteran patients with localized prostate cancer across all risk categories, providing a real-world perspective on SBRT outcomes in a diverse patient population. Furthermore, the detailed assessment of efficacy and toxicity via standardized RTOG criteria enhances the comparability of our findings with those of other published prospective studies, despite the retrospective nature of the data.

CONCLUSIONS

This single-institution retrospective analysis revealed that short-term SBRT (36.25 to 40 Gy in 5 fractions), with a minimum follow-up of 24 months and a median follow-up of 45 months, for localized prostate cancer, including patients at HR, is associated with promising early efficacy and acceptable toxicity, even in the absence of routine fiducial or hydrogel spacer use. The favorable actuarial 5-year DFS and OS rates, coupled with a manageable toxicity profile, suggest that SBRT is a safe and convenient treatment option for many patients with localized prostate cancer. However, a longer follow-up is necessary to confirm these findings and fully characterize the long-term efficacy and toxicity of this SBRT regimen. Nevertheless, the results contribute to the growing body of evidence suggesting that SBRT is a safe and convenient treatment option for many patients with localized prostate cancer.

Prostate cancer is the most common cancer in US males, with an estimated 313,780 new cases and 35,770 deaths in 2025.¹ Several treatment options are available for localized prostate cancer that have similar outcomes, including active surveillance for low-risk cancers, surgery, or radiotherapy.^2,3 Conventional fractionation radiotherapy (CFRT) with 40 to 45 fractions over 8 to 9 weeks has been used for decades. Over the past 2 decades, moderate hypofractionation schedules with 2.4 to 3.4 Gy per fraction over 20 to 28 fractions have become standard, as many noninferiority randomized clinical trials (RCTs) such as CHHiP (UK),⁴ PROFIT (Canada and Europe),⁵ NRG Oncology RTOG 0415 (US),⁶ HYPRO (Netherlands),^7,8 and HYPO-RT-PC (Sweden and Denmark),⁹ have shown the noninferiority of moderately hypofractionated radiotherapy compared with CFRT. Notably, most of these noninferiority studies primarily included patients with low- or intermediate-risk prostate cancer, except for the HYPO-RT-PC trial,⁹ which also included patients with intermediate- and high-risk prostate cancer.

These noninferiority studies, along with technological advances in radiotherapy, such as intensity-modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT), and image-guided radiotherapy (IGRT), paved the path to ultrahypofractionated stereotactic body radiotherapy (SBRT) that is delivered in 5 fractions of ≥ 6 Gy. This high dose per fraction may have a radiobiologic advantage over conventional fractionation. The relatively low a/ß ratio of prostate cancer, estimated to be between 1 and 2, suggests that tumor cells may be particularly sensitive to the high doses per fraction delivered in SBRT.^10-13 Compared with CFRT, SBRT-induced tumor cell death may also be mediated through different pathways; this pathway appears to be generated in a dose-dependent manner, particularly with doses > 8 Gy per fraction.^14,15 Additionally, the higher a/ß ratio for the surrounding organs at risk, such as the bladder and rectum, theoretically allows for an improved therapeutic ratio window that maximizes tumor control while minimizing damage to healthy tissues.

A substantial body of evidence from prospective studies and meta-analyses supports the use of SBRT for localized prostate cancer. HYPO-RT-PC, a significant phase 3 noninferiority study, enrolled 1200 patients with intermediate (89%) and high-risk (11%) prostate cancer randomized between 2 arms, including CFRT to 78 Gy in 39 fractions and SBRT to 42.7 Gy in 7 fractions, treated 3 days weekly. After a median follow-up of 60 months, the estimated 5-year biochemical relapse-free survival rate was 84% in both groups.⁹ This trial was notable because it was the first randomized study to demonstrate that SBRT was noninferior to CFRT in intermediate- and high-risk prostate cancer patients. Another pivotal phase 3 trial, the PACE-B study, enrolled 874 patients to compare SBRT (36.25 Gy to the prostate gland, with a secondary dose of 40 Gy to the gross tumor volume where applicable, in 5 fractions) with CFRT (78 Gy in 39 fractions) and moderately hypofractionated radiotherapy (HFRT) (62 Gy in 20 fractions) in patients with low- or intermediate-risk prostate cancer. With a 74-month median follow-up, the study reported 5-year biochemical free rates of 94.6% for CFRT and 95.8% for SBRT, confirming the noninferiority of SBRT to CFRT.¹⁵

SBRT offers short, effective, and convenient treatment to many patients with localized prostate cancer. While previous guidelines were more restrictive, the March 2026 National Comprehensive Cancer Network (NCCN) guidelines now list SBRT as a preferred treatment modality for high-risk prostate cancer.¹⁶

Given the growing body of evidence supporting the efficacy and safety of SBRT, we implemented an SBRT program in 2014 at a tertiary care center for veterans. This retrospective study was undertaken to evaluate the early efficacy and toxicity of SBRT in patients with localized prostate cancer treated at our institution, including patients across all risk stratifications.

METHODS

We identified 242 patients diagnosed with prostate cancer who underwent SBRT treatment between November 2014 and October 2024 at Overland Park Veterans Affairs Radiation Oncology Clinic. For the final analysis, 46 patients with < 2 years of follow-up and 22 patients who died from causes other than prostate cancer were excluded, resulting in a cohort of 174 patients with ≥ 24-month follow-up.

Treatment

Patients eligible for staging underwent imaging according to NCCN guidelines, including computed tomography (CT) of the abdomen and pelvis, bone scintigraphy, or, in recent years, prostate-specific membrane antigen positron emission tomography, primarily used for unfavorable intermediate-risk (UIR) and high-risk (HR) cancers. Patients with a negative staging work-up for nodal or skeletal disease were included. Prior to planning the CT simulation, patients were given bowel preparation instructions, including a low-fiber and low-gas-producing diet, simethicone, and enemas, the night before and morning of the simulation. Patients were instructed to arrive with a comfortably full bladder, having not voided for 2 to 3 hours prior to the procedure. At Kansas City Veterans Affairs Medical Center (KCVAMC), SBRT treatment was generally restricted to patients with a baseline American Urological Association symptom score of 15 to 20 out of 35 and a prostate gland size < 80 mL to minimize the risk of acute urinary toxicity. We did not use intraprostatic fiducials, hydrogel rectal spacers, or intravenous contrast agents for planning CT simulation.

Patients were placed in a supine position, and a vacuum bag was used for immobilization. Following the CT simulation, the images were transferred to the Eclipse treatment planning system. The clinical target volume (CTV) encompassed the prostate and the proximal 1.0 cm of the seminal vesicles for Gleason score (GS) 1 to 2, and the entire seminal vesicle was included for GS 3 to 5, which is consistent with KCVAMC practice and established safety protocols. The planning target volume (PTV) was created by uniformly expanding the CTV by 5 to 7 mm, except for the posterior margin, which was limited to 3 to 5 mm. When elective nodal radiotherapy was planned for HR prostate cancer, the pelvic field for CT simulation started at the L-2 upper border, with the lower border extending to the lesser trochanter. The pelvic nodes were delineated per Radiation Therapy Oncology Group (RTOG) guidelines.¹⁷ The CTV nodes (CTVn), including common iliac, external and internal iliac nodes, obturator, and presacral nodes, were created by uniformly expanding the CTVn by 2 to 3 mm. Slice-by-slice corrections were made to avoid bowel overlap in these patients.

The use of androgen deprivation therapy (ADT) for a duration of 6 to 24 months was prescribed for patients with UIR or HR prostate cancer per NCCN guidelines.¹⁶ The prescribed dose to the PTV was 36.25 to 40 Gy (40 Gy was mostly used as a boost to the dominant lesion) in 5 fractions, with each fraction ranging from 7.25 to 8 Gy. For elective nodal radiotherapy in patients at HR, the prescribed dose was 25 Gy in 5 fractions. All patients were planned for VMAT, which aims to deliver ≥ 95% of the prescription dose to 95% of the PTV. Once the physician approved the treatment plan and physics quality assessment was completed, treatments commenced on an every-other-day schedule. Patients received the same bowel preparation instructions for each treatment as for the planning CT simulation. Daily treatment accuracy was confirmed via daily 3-dimensional cone-beam CT (CBCT) for IGRT. No fiducials or hydrogel rectal spacers were used.

Follow-up Schedule and Toxicity Assessment

Follow-up assessments were conducted 4 to 6 weeks after radiation therapy and then repeated every 6 months for 2 to 5 years, and annually thereafter. At each follow-up visit, patients were evaluated for genitourinary (GU) and gastrointestinal (GI) toxicity, according to RTOG toxicity criteria. Prostate-specific antigen (PSA) levels were monitored; in patients receiving ADT, testosterone levels were also checked.

Statistical Analysis

Biochemical failure was defined using the Phoenix definition (nadir PSA + 2 ng/mL). Differences between dose cohorts were assessed using the log-rank test for survival outcomes and X² testing for categorical variables. GU and GI toxicities were summarized as cumulative incidences of RTOG grade ≥ II events. Statistical significance was set at P < .05.

RESULTS

One hundred seventy-four patients were included in the retrospective review. Patients had a median follow-up of 45 months (range, 24-111) (Figure). The median age at treatment was 74 years (range, 51-88), and the median pretreatment PSA level was 11.9 ng/mL (range, 0.6-69.5). Twenty-six patients (14.9%) had a GS 1, 77 (44.3%) had GS 2, 41 (23.6%) had GS 3, 18 (10.3%) had GS 4, and 12 (6.9%) had GS 5. Fifty-one patients (29.3%) received elective pelvic nodal radiotherapy, and 93 patients (53.4%) received ADT (Table 1).

At 24 months follow-up, 6 patients (3.4%) had biochemical failures. One patient died from metastatic prostate cancer, and 5 patients are living with biochemical failure (Table 2). The actuarial 5-year overall survival (OS) rate was 99.4%, and the 5-year disease-free survival (DFS) rate was 96.6%. We performed a subanalysis comparing outcomes of the 36.25 Gy vs 40 Gy SBRT cohorts. There was no statistically significant difference in DFS, OS, or the cumulative incidence of grade II/III toxicity between patients treated with 40 Gy vs 36.25 Gy. Outcomes stratified by NCCN risk groups (low, intermediate, high/very high) are detailed in Table 3. As expected, DFS was slightly lower in the high-risk group, but overall disease control remained high across all stratifications.

The cumulative incidence of RTOG grade II and higher GU toxicity was 28.2% (Table 4). This included 46 patients (26.4%) with grade II GU toxicity and 2 patients (1.2%) who developed grade III GU complications (1 requiring self-catheterization and another a suprapubic catheter for urinary retention). One patient (0.6%) treated with a 40 Gy dose regimen experienced a grade IV GU complication in the form of a rectovesical fistula necessitating surgical intervention.

The cumulative incidence of RTOG grade II or higher GI toxicity was 3.4%, and no grade III or IV gastrointestinal toxicities were observed during the follow-up period. Importantly, intraprostatic fiducials, hydrogel rectal spacers, or intravenous contrast were not routinely used in this cohort of patients.

The high rates of actuarial 5-year DFS and OS observed suggest a favorable initial response to the SBRT regimen employed at KCVAMC. However, given the potential for late recurrence in patients with prostate cancer, longer follow-up is essential to determine the durability of these outcomes. The observed GU toxicity rate of 28.2% for grade II and higher events warrants careful consideration and compares with other published data on SBRT for prostate cancer.¹⁵ The occurrence of a grade IV rectovesical fistula, although rare, is a notable adverse event that warrants discussion in the context of the treatment approach. The low incidence of grade II or higher GI toxicity is an encouraging finding, particularly given that hydrogel rectal spacers are not routinely used to minimize rectal exposure.

DISCUSSION

The primary objective of this retrospective study was to evaluate the outcomes of SBRT for patients with localized prostate cancer treated at KCVAMC and to compare these results with those reported in the literature. Our findings demonstrate promising intermediate-term efficacy, with an estimated 5-year DFS of 96.6% and OS of 99.4% at a median follow-up of 45 months. Furthermore, the observed toxicity profile appears acceptable, with a cumulative grade II and higher GU toxicity rate of 28.2% and a grade II or higher GI toxicity rate of 3.4%. Notably, these outcomes were achieved without the routine use of intraprostatic fiducials or hydrogel rectal spacers.

Two pivotal randomized phase 3 trials have established the noninferiority of ultrahypofractionated radiotherapy (UHRT) with SBRT over conventional fractionation. The HYPO-RT-PC trial compared SBRT (42.7 Gy in 7 fractions) with conventional fractionation (78 Gy in 39 fractions) in intermediate- and high-risk patients with prostate cancer and reported a 5-year biochemical relapse-free survival of 84% in both arms.⁹ The PACE-B trial, which included patients at low- and intermediate-risk, compared SBRT (36.25 Gy in 5 fractions) with conventional or moderate HFRT and reported a 5-year biochemical control rate of 95.8% in the SBRT arm and 94.6% in the control arm.¹⁵

A comprehensive review and meta-analysis of 7 phase 3 studies involving 6795 patients compared different radiotherapy regimens, namely, UHRT, HFRT, and CFRT, and reported that after 5 years, the DFS rates were 85.1% for CFRT, 86% for HFRT, and 85% for UHRT, with no significant difference in toxicity among the 3 different treatment approaches.¹⁸ This suggests that shorter, more intense radiotherapy schedules (UHRT and HFRT) may be as effective and safe as traditional, longer courses of radiation.

There are multiple published nonrandomized prospective trials in which thousands of patients with extreme hypofractionation have been treated with different doses, fractions, and techniques. While heterogeneity and limited long-term follow-up in the existing evidence are acknowledged, these data suggest that prostate SBRT provides appropriate biochemical control with few high-grade toxicities, supporting its ongoing global use and justifying further prospective investigations. Comparative data are shown in Table 5. Several ongoing studies are evaluating noninferiority, superiority, and cost-effectiveness using different methodologies (Table 6).^9,15,19-24

This study’s efficacy outcomes, particularly the high DFS rate, are consistent with the findings from these landmark trials, suggesting that the SBRT regimen used at KCVAMC is effective in achieving early disease control despite 17.2% of patients having high-risk disease. The GU toxicity observed in this study, with a 28.2% rate of grade II or higher events, is also comparable with the 26.9% reported in the 5-fraction SBRT arm of the PACE-B trial, which had a longer median follow-up of 74 months.¹⁵ It is important to note that a portion of these grade II events occurred in patients who were already on a blockers for pre-existing lower urinary tract symptoms before starting radiotherapy, which may inflate the observed cumulative acute toxicity score.

A critical comparison is how SBRT toxicity aligns with moderate hypofractionation (eg, 60 Gy in 20 fractions or 70 Gy in 28 fractions as reported by others).^4,6 Our observed grade III and higher GU toxicity rate (1.7%) and grade III and higher GI toxicity rate (0%) are highly favorable when compared with historical moderate hypofractionation data, which typically report grade III GU toxicity in the range of 2% to 3% and grade III GI toxicity around 1% to 2%. This suggests that despite the higher dose per fraction, SBRT does not necessarily lead to increased severe acute toxicity, potentially offering a superior therapeutic ratio for GI and GU sparing.

However, the occurrence of a grade IV rectovesical fistula in 1 patient (0.6%)—who received the 40 Gy dose—was a serious complication that warrants careful consideration. This rare, but severe, complication in the higher dose cohort underscores the potential for increased organ-at-risk toxicity, particularly in the absence of a hydrogel rectal spacer, which is designed to mitigate high-dose rectal exposure. While the overall rate of significant GU toxicity remains low, this event highlights the potential risks associated with SBRT. Hydrogel rectal spacers are designed to increase the distance between the prostate and the rectum, which can reduce the rectal radiation dose and potentially mitigate the risk of such fistulas. The low rate of grade II or worse GI toxicity (3.4%) in our study is noteworthy, especially considering that hydrogel spacers were not routinely used. This finding aligns with the 2.5% GI toxicity rate reported in the SBRT arm of the PACE-B trial, suggesting that careful treatment planning and delivery techniques, such as VMAT-IMRT and daily CBCT for IGRT, may contribute to minimizing GI toxicity even without the use of rectal spacers.¹⁵ The exclusive use of 3-dimensional CBCT for IGRT in our study, without the use of fiducial markers, suggests that accurate target localization can be achieved with this approach, contributing to the observed efficacy and reduced toxicity.

Strengths and Limitations

This study’s retrospective, single-center design may have introduced selection bias. The median follow-up of 45 months, while substantial, is still relatively short for assessing very late toxicities and long-term oncologic outcomes in prostate cancer, which is known for late recurrences. Additionally, the lack of a direct comparison group within KCVAMC limits the ability to definitively attribute the observed outcomes solely to SBRT treatment. However, the strengths of this study include the inclusion of a consecutive series of veteran patients with localized prostate cancer across all risk categories, providing a real-world perspective on SBRT outcomes in a diverse patient population. Furthermore, the detailed assessment of efficacy and toxicity via standardized RTOG criteria enhances the comparability of our findings with those of other published prospective studies, despite the retrospective nature of the data.

CONCLUSIONS

This single-institution retrospective analysis revealed that short-term SBRT (36.25 to 40 Gy in 5 fractions), with a minimum follow-up of 24 months and a median follow-up of 45 months, for localized prostate cancer, including patients at HR, is associated with promising early efficacy and acceptable toxicity, even in the absence of routine fiducial or hydrogel spacer use. The favorable actuarial 5-year DFS and OS rates, coupled with a manageable toxicity profile, suggest that SBRT is a safe and convenient treatment option for many patients with localized prostate cancer. However, a longer follow-up is necessary to confirm these findings and fully characterize the long-term efficacy and toxicity of this SBRT regimen. Nevertheless, the results contribute to the growing body of evidence suggesting that SBRT is a safe and convenient treatment option for many patients with localized prostate cancer.

Prostate cancer is the most common cancer in US males, with an estimated 313,780 new cases and 35,770 deaths in 2025.¹ Several treatment options are available for localized prostate cancer that have similar outcomes, including active surveillance for low-risk cancers, surgery, or radiotherapy.^2,3 Conventional fractionation radiotherapy (CFRT) with 40 to 45 fractions over 8 to 9 weeks has been used for decades. Over the past 2 decades, moderate hypofractionation schedules with 2.4 to 3.4 Gy per fraction over 20 to 28 fractions have become standard, as many noninferiority randomized clinical trials (RCTs) such as CHHiP (UK),⁴ PROFIT (Canada and Europe),⁵ NRG Oncology RTOG 0415 (US),⁶ HYPRO (Netherlands),^7,8 and HYPO-RT-PC (Sweden and Denmark),⁹ have shown the noninferiority of moderately hypofractionated radiotherapy compared with CFRT. Notably, most of these noninferiority studies primarily included patients with low- or intermediate-risk prostate cancer, except for the HYPO-RT-PC trial,⁹ which also included patients with intermediate- and high-risk prostate cancer.

These noninferiority studies, along with technological advances in radiotherapy, such as intensity-modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT), and image-guided radiotherapy (IGRT), paved the path to ultrahypofractionated stereotactic body radiotherapy (SBRT) that is delivered in 5 fractions of ≥ 6 Gy. This high dose per fraction may have a radiobiologic advantage over conventional fractionation. The relatively low a/ß ratio of prostate cancer, estimated to be between 1 and 2, suggests that tumor cells may be particularly sensitive to the high doses per fraction delivered in SBRT.^10-13 Compared with CFRT, SBRT-induced tumor cell death may also be mediated through different pathways; this pathway appears to be generated in a dose-dependent manner, particularly with doses > 8 Gy per fraction.^14,15 Additionally, the higher a/ß ratio for the surrounding organs at risk, such as the bladder and rectum, theoretically allows for an improved therapeutic ratio window that maximizes tumor control while minimizing damage to healthy tissues.

A substantial body of evidence from prospective studies and meta-analyses supports the use of SBRT for localized prostate cancer. HYPO-RT-PC, a significant phase 3 noninferiority study, enrolled 1200 patients with intermediate (89%) and high-risk (11%) prostate cancer randomized between 2 arms, including CFRT to 78 Gy in 39 fractions and SBRT to 42.7 Gy in 7 fractions, treated 3 days weekly. After a median follow-up of 60 months, the estimated 5-year biochemical relapse-free survival rate was 84% in both groups.⁹ This trial was notable because it was the first randomized study to demonstrate that SBRT was noninferior to CFRT in intermediate- and high-risk prostate cancer patients. Another pivotal phase 3 trial, the PACE-B study, enrolled 874 patients to compare SBRT (36.25 Gy to the prostate gland, with a secondary dose of 40 Gy to the gross tumor volume where applicable, in 5 fractions) with CFRT (78 Gy in 39 fractions) and moderately hypofractionated radiotherapy (HFRT) (62 Gy in 20 fractions) in patients with low- or intermediate-risk prostate cancer. With a 74-month median follow-up, the study reported 5-year biochemical free rates of 94.6% for CFRT and 95.8% for SBRT, confirming the noninferiority of SBRT to CFRT.¹⁵

SBRT offers short, effective, and convenient treatment to many patients with localized prostate cancer. While previous guidelines were more restrictive, the March 2026 National Comprehensive Cancer Network (NCCN) guidelines now list SBRT as a preferred treatment modality for high-risk prostate cancer.¹⁶

Given the growing body of evidence supporting the efficacy and safety of SBRT, we implemented an SBRT program in 2014 at a tertiary care center for veterans. This retrospective study was undertaken to evaluate the early efficacy and toxicity of SBRT in patients with localized prostate cancer treated at our institution, including patients across all risk stratifications.

METHODS

We identified 242 patients diagnosed with prostate cancer who underwent SBRT treatment between November 2014 and October 2024 at Overland Park Veterans Affairs Radiation Oncology Clinic. For the final analysis, 46 patients with < 2 years of follow-up and 22 patients who died from causes other than prostate cancer were excluded, resulting in a cohort of 174 patients with ≥ 24-month follow-up.

Treatment

Patients eligible for staging underwent imaging according to NCCN guidelines, including computed tomography (CT) of the abdomen and pelvis, bone scintigraphy, or, in recent years, prostate-specific membrane antigen positron emission tomography, primarily used for unfavorable intermediate-risk (UIR) and high-risk (HR) cancers. Patients with a negative staging work-up for nodal or skeletal disease were included. Prior to planning the CT simulation, patients were given bowel preparation instructions, including a low-fiber and low-gas-producing diet, simethicone, and enemas, the night before and morning of the simulation. Patients were instructed to arrive with a comfortably full bladder, having not voided for 2 to 3 hours prior to the procedure. At Kansas City Veterans Affairs Medical Center (KCVAMC), SBRT treatment was generally restricted to patients with a baseline American Urological Association symptom score of 15 to 20 out of 35 and a prostate gland size < 80 mL to minimize the risk of acute urinary toxicity. We did not use intraprostatic fiducials, hydrogel rectal spacers, or intravenous contrast agents for planning CT simulation.

Patients were placed in a supine position, and a vacuum bag was used for immobilization. Following the CT simulation, the images were transferred to the Eclipse treatment planning system. The clinical target volume (CTV) encompassed the prostate and the proximal 1.0 cm of the seminal vesicles for Gleason score (GS) 1 to 2, and the entire seminal vesicle was included for GS 3 to 5, which is consistent with KCVAMC practice and established safety protocols. The planning target volume (PTV) was created by uniformly expanding the CTV by 5 to 7 mm, except for the posterior margin, which was limited to 3 to 5 mm. When elective nodal radiotherapy was planned for HR prostate cancer, the pelvic field for CT simulation started at the L-2 upper border, with the lower border extending to the lesser trochanter. The pelvic nodes were delineated per Radiation Therapy Oncology Group (RTOG) guidelines.¹⁷ The CTV nodes (CTVn), including common iliac, external and internal iliac nodes, obturator, and presacral nodes, were created by uniformly expanding the CTVn by 2 to 3 mm. Slice-by-slice corrections were made to avoid bowel overlap in these patients.

The use of androgen deprivation therapy (ADT) for a duration of 6 to 24 months was prescribed for patients with UIR or HR prostate cancer per NCCN guidelines.¹⁶ The prescribed dose to the PTV was 36.25 to 40 Gy (40 Gy was mostly used as a boost to the dominant lesion) in 5 fractions, with each fraction ranging from 7.25 to 8 Gy. For elective nodal radiotherapy in patients at HR, the prescribed dose was 25 Gy in 5 fractions. All patients were planned for VMAT, which aims to deliver ≥ 95% of the prescription dose to 95% of the PTV. Once the physician approved the treatment plan and physics quality assessment was completed, treatments commenced on an every-other-day schedule. Patients received the same bowel preparation instructions for each treatment as for the planning CT simulation. Daily treatment accuracy was confirmed via daily 3-dimensional cone-beam CT (CBCT) for IGRT. No fiducials or hydrogel rectal spacers were used.

Follow-up Schedule and Toxicity Assessment

Follow-up assessments were conducted 4 to 6 weeks after radiation therapy and then repeated every 6 months for 2 to 5 years, and annually thereafter. At each follow-up visit, patients were evaluated for genitourinary (GU) and gastrointestinal (GI) toxicity, according to RTOG toxicity criteria. Prostate-specific antigen (PSA) levels were monitored; in patients receiving ADT, testosterone levels were also checked.

Statistical Analysis

Biochemical failure was defined using the Phoenix definition (nadir PSA + 2 ng/mL). Differences between dose cohorts were assessed using the log-rank test for survival outcomes and X² testing for categorical variables. GU and GI toxicities were summarized as cumulative incidences of RTOG grade ≥ II events. Statistical significance was set at P < .05.

RESULTS

One hundred seventy-four patients were included in the retrospective review. Patients had a median follow-up of 45 months (range, 24-111) (Figure). The median age at treatment was 74 years (range, 51-88), and the median pretreatment PSA level was 11.9 ng/mL (range, 0.6-69.5). Twenty-six patients (14.9%) had a GS 1, 77 (44.3%) had GS 2, 41 (23.6%) had GS 3, 18 (10.3%) had GS 4, and 12 (6.9%) had GS 5. Fifty-one patients (29.3%) received elective pelvic nodal radiotherapy, and 93 patients (53.4%) received ADT (Table 1).

At 24 months follow-up, 6 patients (3.4%) had biochemical failures. One patient died from metastatic prostate cancer, and 5 patients are living with biochemical failure (Table 2). The actuarial 5-year overall survival (OS) rate was 99.4%, and the 5-year disease-free survival (DFS) rate was 96.6%. We performed a subanalysis comparing outcomes of the 36.25 Gy vs 40 Gy SBRT cohorts. There was no statistically significant difference in DFS, OS, or the cumulative incidence of grade II/III toxicity between patients treated with 40 Gy vs 36.25 Gy. Outcomes stratified by NCCN risk groups (low, intermediate, high/very high) are detailed in Table 3. As expected, DFS was slightly lower in the high-risk group, but overall disease control remained high across all stratifications.

The cumulative incidence of RTOG grade II and higher GU toxicity was 28.2% (Table 4). This included 46 patients (26.4%) with grade II GU toxicity and 2 patients (1.2%) who developed grade III GU complications (1 requiring self-catheterization and another a suprapubic catheter for urinary retention). One patient (0.6%) treated with a 40 Gy dose regimen experienced a grade IV GU complication in the form of a rectovesical fistula necessitating surgical intervention.

The cumulative incidence of RTOG grade II or higher GI toxicity was 3.4%, and no grade III or IV gastrointestinal toxicities were observed during the follow-up period. Importantly, intraprostatic fiducials, hydrogel rectal spacers, or intravenous contrast were not routinely used in this cohort of patients.

The high rates of actuarial 5-year DFS and OS observed suggest a favorable initial response to the SBRT regimen employed at KCVAMC. However, given the potential for late recurrence in patients with prostate cancer, longer follow-up is essential to determine the durability of these outcomes. The observed GU toxicity rate of 28.2% for grade II and higher events warrants careful consideration and compares with other published data on SBRT for prostate cancer.¹⁵ The occurrence of a grade IV rectovesical fistula, although rare, is a notable adverse event that warrants discussion in the context of the treatment approach. The low incidence of grade II or higher GI toxicity is an encouraging finding, particularly given that hydrogel rectal spacers are not routinely used to minimize rectal exposure.

DISCUSSION

The primary objective of this retrospective study was to evaluate the outcomes of SBRT for patients with localized prostate cancer treated at KCVAMC and to compare these results with those reported in the literature. Our findings demonstrate promising intermediate-term efficacy, with an estimated 5-year DFS of 96.6% and OS of 99.4% at a median follow-up of 45 months. Furthermore, the observed toxicity profile appears acceptable, with a cumulative grade II and higher GU toxicity rate of 28.2% and a grade II or higher GI toxicity rate of 3.4%. Notably, these outcomes were achieved without the routine use of intraprostatic fiducials or hydrogel rectal spacers.

Two pivotal randomized phase 3 trials have established the noninferiority of ultrahypofractionated radiotherapy (UHRT) with SBRT over conventional fractionation. The HYPO-RT-PC trial compared SBRT (42.7 Gy in 7 fractions) with conventional fractionation (78 Gy in 39 fractions) in intermediate- and high-risk patients with prostate cancer and reported a 5-year biochemical relapse-free survival of 84% in both arms.⁹ The PACE-B trial, which included patients at low- and intermediate-risk, compared SBRT (36.25 Gy in 5 fractions) with conventional or moderate HFRT and reported a 5-year biochemical control rate of 95.8% in the SBRT arm and 94.6% in the control arm.¹⁵

A comprehensive review and meta-analysis of 7 phase 3 studies involving 6795 patients compared different radiotherapy regimens, namely, UHRT, HFRT, and CFRT, and reported that after 5 years, the DFS rates were 85.1% for CFRT, 86% for HFRT, and 85% for UHRT, with no significant difference in toxicity among the 3 different treatment approaches.¹⁸ This suggests that shorter, more intense radiotherapy schedules (UHRT and HFRT) may be as effective and safe as traditional, longer courses of radiation.

There are multiple published nonrandomized prospective trials in which thousands of patients with extreme hypofractionation have been treated with different doses, fractions, and techniques. While heterogeneity and limited long-term follow-up in the existing evidence are acknowledged, these data suggest that prostate SBRT provides appropriate biochemical control with few high-grade toxicities, supporting its ongoing global use and justifying further prospective investigations. Comparative data are shown in Table 5. Several ongoing studies are evaluating noninferiority, superiority, and cost-effectiveness using different methodologies (Table 6).^9,15,19-24

This study’s efficacy outcomes, particularly the high DFS rate, are consistent with the findings from these landmark trials, suggesting that the SBRT regimen used at KCVAMC is effective in achieving early disease control despite 17.2% of patients having high-risk disease. The GU toxicity observed in this study, with a 28.2% rate of grade II or higher events, is also comparable with the 26.9% reported in the 5-fraction SBRT arm of the PACE-B trial, which had a longer median follow-up of 74 months.¹⁵ It is important to note that a portion of these grade II events occurred in patients who were already on a blockers for pre-existing lower urinary tract symptoms before starting radiotherapy, which may inflate the observed cumulative acute toxicity score.

A critical comparison is how SBRT toxicity aligns with moderate hypofractionation (eg, 60 Gy in 20 fractions or 70 Gy in 28 fractions as reported by others).^4,6 Our observed grade III and higher GU toxicity rate (1.7%) and grade III and higher GI toxicity rate (0%) are highly favorable when compared with historical moderate hypofractionation data, which typically report grade III GU toxicity in the range of 2% to 3% and grade III GI toxicity around 1% to 2%. This suggests that despite the higher dose per fraction, SBRT does not necessarily lead to increased severe acute toxicity, potentially offering a superior therapeutic ratio for GI and GU sparing.

However, the occurrence of a grade IV rectovesical fistula in 1 patient (0.6%)—who received the 40 Gy dose—was a serious complication that warrants careful consideration. This rare, but severe, complication in the higher dose cohort underscores the potential for increased organ-at-risk toxicity, particularly in the absence of a hydrogel rectal spacer, which is designed to mitigate high-dose rectal exposure. While the overall rate of significant GU toxicity remains low, this event highlights the potential risks associated with SBRT. Hydrogel rectal spacers are designed to increase the distance between the prostate and the rectum, which can reduce the rectal radiation dose and potentially mitigate the risk of such fistulas. The low rate of grade II or worse GI toxicity (3.4%) in our study is noteworthy, especially considering that hydrogel spacers were not routinely used. This finding aligns with the 2.5% GI toxicity rate reported in the SBRT arm of the PACE-B trial, suggesting that careful treatment planning and delivery techniques, such as VMAT-IMRT and daily CBCT for IGRT, may contribute to minimizing GI toxicity even without the use of rectal spacers.¹⁵ The exclusive use of 3-dimensional CBCT for IGRT in our study, without the use of fiducial markers, suggests that accurate target localization can be achieved with this approach, contributing to the observed efficacy and reduced toxicity.

Strengths and Limitations

This study’s retrospective, single-center design may have introduced selection bias. The median follow-up of 45 months, while substantial, is still relatively short for assessing very late toxicities and long-term oncologic outcomes in prostate cancer, which is known for late recurrences. Additionally, the lack of a direct comparison group within KCVAMC limits the ability to definitively attribute the observed outcomes solely to SBRT treatment. However, the strengths of this study include the inclusion of a consecutive series of veteran patients with localized prostate cancer across all risk categories, providing a real-world perspective on SBRT outcomes in a diverse patient population. Furthermore, the detailed assessment of efficacy and toxicity via standardized RTOG criteria enhances the comparability of our findings with those of other published prospective studies, despite the retrospective nature of the data.

CONCLUSIONS

This single-institution retrospective analysis revealed that short-term SBRT (36.25 to 40 Gy in 5 fractions), with a minimum follow-up of 24 months and a median follow-up of 45 months, for localized prostate cancer, including patients at HR, is associated with promising early efficacy and acceptable toxicity, even in the absence of routine fiducial or hydrogel spacer use. The favorable actuarial 5-year DFS and OS rates, coupled with a manageable toxicity profile, suggest that SBRT is a safe and convenient treatment option for many patients with localized prostate cancer. However, a longer follow-up is necessary to confirm these findings and fully characterize the long-term efficacy and toxicity of this SBRT regimen. Nevertheless, the results contribute to the growing body of evidence suggesting that SBRT is a safe and convenient treatment option for many patients with localized prostate cancer.

TOPLINE:

Among 1.3 million male veterans treated for prostate cancer, 11,327 (0.86%) developed breast cancer an average of 5.4 years after initial diagnosis. Younger age at prostate cancer diagnosis, metastatic disease, androgen deprivation therapy (ADT), radiation treatment, and prolonged use of certain cardiovascular disease (CVD) medications were associated with increased risk for breast cancer.

METHODOLOGY:

• Researchers used a retrospective cohort design in Veterans Health Administration (VHA) care, pulling data from the Veterans Affairs (VA) Prostate Cancer Data Core at the VA Corporate Data Warehouse.
• Participants included 1,314,492 male veterans with prostate cancer treated at VHA facilities from January 1, 2000, to March 12, 2024.
• Exposure definitions included prostate cancer treatments (ADT, anti-androgen treatment, radiation-brachytherapy, and platinum chemotherapy) and CVD medications (furosemide, spironolactone, digoxin) captured via inpatient/outpatient/fee-based pharmacy and Current Procedural Terminology codes.
• Analysis measured time from prostate cancer diagnosis to breast cancer diagnosis, death, or March 12, 2024, applying Cox proportional hazards and Fine-Gray competing risk methods, with a sensitivity analysis adding body mass index (BMI) after excluding 71,718 missing values.

TAKEAWAY:

• Metastatic prostate cancer at diagnosis more than doubled the risk for breast cancer compared to nonmetastatic disease (hazard ratio [HR], 2.03; 95% CI, 1.90-2.17; P < .0001; subdistribution hazard ratio [SHR], 1.68; 95% CI, 1.57-1.81; P < .0001).
• Younger age at prostate cancer diagnosis was associated with increased risk for breast cancer (HR, 0.97; 95% CI, 0.97-0.98; P < .0001; SHR, 0.957; 95% CI, 0.955-0.959; P < .0001), indicating that for each additional year of age at diagnosis, the risk decreased.
• Continuation of CVD medications after prostate cancer diagnosis was associated with increased risk for breast cancer: furosemide (HR, 1.51; 95% CI, 1.39-1.63; P < .0001; SHR, 1.21; 95% CI, 1.12-1.31; P < .0001), spironolactone (HR, 1.36; 95% CI, 1.15-1.61; P = .0004; SHR, 1.23; 95% CI, 1.04-1.47; P = .0174), and digoxin (HR, 1.49; 95% CI, 1.29-1.72; P < .0001; SHR, 1.26; 95% CI, 1.10-1.46; P = .0015).
• Radiation therapy and ADT were associated with increased risk for breast cancer (radiation: HR, 1.06; 95% CI, 1.02-1.11; P = .0088; SHR, 1.10; 95% CI, 1.05-1.15; P < .0001; ADT: HR, 1.24; 95% CI, 1.17-1.32; P < .0001; SHR, 1.28; 95% CI, 1.20-1.37; P < .0001), while abiraterone was associated with decreased risk (HR, 0.36; 95% CI, 0.31-0.42; P < .0001; SHR, 0.39; 95% CI, 0.34-0.45; P < .0001).

IN PRACTICE:

"While there is a lack of data, male veterans with previous prostate cancer are at an elevated risk of breast cancer (0.87%), than their civilian counterparts (0.14%),” the authors wrote. “To address the current gap in knowledge and data, this study leveraged an existing large cohort of male veterans with prostate cancer and examined factors associated with increased risk of male breast cancer."

SOURCE:

The study was led by Erum Z. Whyne, VA North Texas Health Care System in Dallas, and Haekyung Jeon-Slaughter, University of Texas Southwestern Medical Center in Dallas. It was published online in The Prostate.

LIMITATIONS:

Though the study findings are based on large, representative data from male veterans with previously diagnosed prostate cancer, the results might not be generalizable to the overall male breast cancer population. As a retrospective cohort study, results may be biased and causality is difficult to establish. The study did not examine other known risk factors for male breast cancer incidence, such as family history, BRCA2 mutations, and military environmental exposure due to lack of data. BMI had missingness of 5.46% (n = 71,718) and was not included as a covariate in the final model, though sensitivity analysis showed it was not significantly associated with increased risk for male breast cancer.

DISCLOSURES:

The research was supported using resources and facilities of the VA Informatics and Computing Infrastructure (VINCI), VA HSR RES 13-457. The VA North Texas Health Care System Institutional Review Board approved the study and waived informed consent. No conflicts of interest were disclosed by the authors.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

TOPLINE:

Among 1.3 million male veterans treated for prostate cancer, 11,327 (0.86%) developed breast cancer an average of 5.4 years after initial diagnosis. Younger age at prostate cancer diagnosis, metastatic disease, androgen deprivation therapy (ADT), radiation treatment, and prolonged use of certain cardiovascular disease (CVD) medications were associated with increased risk for breast cancer.

METHODOLOGY:

• Researchers used a retrospective cohort design in Veterans Health Administration (VHA) care, pulling data from the Veterans Affairs (VA) Prostate Cancer Data Core at the VA Corporate Data Warehouse.
• Participants included 1,314,492 male veterans with prostate cancer treated at VHA facilities from January 1, 2000, to March 12, 2024.
• Exposure definitions included prostate cancer treatments (ADT, anti-androgen treatment, radiation-brachytherapy, and platinum chemotherapy) and CVD medications (furosemide, spironolactone, digoxin) captured via inpatient/outpatient/fee-based pharmacy and Current Procedural Terminology codes.
• Analysis measured time from prostate cancer diagnosis to breast cancer diagnosis, death, or March 12, 2024, applying Cox proportional hazards and Fine-Gray competing risk methods, with a sensitivity analysis adding body mass index (BMI) after excluding 71,718 missing values.

TAKEAWAY:

• Metastatic prostate cancer at diagnosis more than doubled the risk for breast cancer compared to nonmetastatic disease (hazard ratio [HR], 2.03; 95% CI, 1.90-2.17; P < .0001; subdistribution hazard ratio [SHR], 1.68; 95% CI, 1.57-1.81; P < .0001).
• Younger age at prostate cancer diagnosis was associated with increased risk for breast cancer (HR, 0.97; 95% CI, 0.97-0.98; P < .0001; SHR, 0.957; 95% CI, 0.955-0.959; P < .0001), indicating that for each additional year of age at diagnosis, the risk decreased.
• Continuation of CVD medications after prostate cancer diagnosis was associated with increased risk for breast cancer: furosemide (HR, 1.51; 95% CI, 1.39-1.63; P < .0001; SHR, 1.21; 95% CI, 1.12-1.31; P < .0001), spironolactone (HR, 1.36; 95% CI, 1.15-1.61; P = .0004; SHR, 1.23; 95% CI, 1.04-1.47; P = .0174), and digoxin (HR, 1.49; 95% CI, 1.29-1.72; P < .0001; SHR, 1.26; 95% CI, 1.10-1.46; P = .0015).
• Radiation therapy and ADT were associated with increased risk for breast cancer (radiation: HR, 1.06; 95% CI, 1.02-1.11; P = .0088; SHR, 1.10; 95% CI, 1.05-1.15; P < .0001; ADT: HR, 1.24; 95% CI, 1.17-1.32; P < .0001; SHR, 1.28; 95% CI, 1.20-1.37; P < .0001), while abiraterone was associated with decreased risk (HR, 0.36; 95% CI, 0.31-0.42; P < .0001; SHR, 0.39; 95% CI, 0.34-0.45; P < .0001).

IN PRACTICE:

"While there is a lack of data, male veterans with previous prostate cancer are at an elevated risk of breast cancer (0.87%), than their civilian counterparts (0.14%),” the authors wrote. “To address the current gap in knowledge and data, this study leveraged an existing large cohort of male veterans with prostate cancer and examined factors associated with increased risk of male breast cancer."

SOURCE:

The study was led by Erum Z. Whyne, VA North Texas Health Care System in Dallas, and Haekyung Jeon-Slaughter, University of Texas Southwestern Medical Center in Dallas. It was published online in The Prostate.

LIMITATIONS:

Though the study findings are based on large, representative data from male veterans with previously diagnosed prostate cancer, the results might not be generalizable to the overall male breast cancer population. As a retrospective cohort study, results may be biased and causality is difficult to establish. The study did not examine other known risk factors for male breast cancer incidence, such as family history, BRCA2 mutations, and military environmental exposure due to lack of data. BMI had missingness of 5.46% (n = 71,718) and was not included as a covariate in the final model, though sensitivity analysis showed it was not significantly associated with increased risk for male breast cancer.

DISCLOSURES:

The research was supported using resources and facilities of the VA Informatics and Computing Infrastructure (VINCI), VA HSR RES 13-457. The VA North Texas Health Care System Institutional Review Board approved the study and waived informed consent. No conflicts of interest were disclosed by the authors.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

TOPLINE:

Among 1.3 million male veterans treated for prostate cancer, 11,327 (0.86%) developed breast cancer an average of 5.4 years after initial diagnosis. Younger age at prostate cancer diagnosis, metastatic disease, androgen deprivation therapy (ADT), radiation treatment, and prolonged use of certain cardiovascular disease (CVD) medications were associated with increased risk for breast cancer.

METHODOLOGY:

• Researchers used a retrospective cohort design in Veterans Health Administration (VHA) care, pulling data from the Veterans Affairs (VA) Prostate Cancer Data Core at the VA Corporate Data Warehouse.
• Participants included 1,314,492 male veterans with prostate cancer treated at VHA facilities from January 1, 2000, to March 12, 2024.
• Exposure definitions included prostate cancer treatments (ADT, anti-androgen treatment, radiation-brachytherapy, and platinum chemotherapy) and CVD medications (furosemide, spironolactone, digoxin) captured via inpatient/outpatient/fee-based pharmacy and Current Procedural Terminology codes.
• Analysis measured time from prostate cancer diagnosis to breast cancer diagnosis, death, or March 12, 2024, applying Cox proportional hazards and Fine-Gray competing risk methods, with a sensitivity analysis adding body mass index (BMI) after excluding 71,718 missing values.

TAKEAWAY:

• Metastatic prostate cancer at diagnosis more than doubled the risk for breast cancer compared to nonmetastatic disease (hazard ratio [HR], 2.03; 95% CI, 1.90-2.17; P < .0001; subdistribution hazard ratio [SHR], 1.68; 95% CI, 1.57-1.81; P < .0001).
• Younger age at prostate cancer diagnosis was associated with increased risk for breast cancer (HR, 0.97; 95% CI, 0.97-0.98; P < .0001; SHR, 0.957; 95% CI, 0.955-0.959; P < .0001), indicating that for each additional year of age at diagnosis, the risk decreased.
• Continuation of CVD medications after prostate cancer diagnosis was associated with increased risk for breast cancer: furosemide (HR, 1.51; 95% CI, 1.39-1.63; P < .0001; SHR, 1.21; 95% CI, 1.12-1.31; P < .0001), spironolactone (HR, 1.36; 95% CI, 1.15-1.61; P = .0004; SHR, 1.23; 95% CI, 1.04-1.47; P = .0174), and digoxin (HR, 1.49; 95% CI, 1.29-1.72; P < .0001; SHR, 1.26; 95% CI, 1.10-1.46; P = .0015).
• Radiation therapy and ADT were associated with increased risk for breast cancer (radiation: HR, 1.06; 95% CI, 1.02-1.11; P = .0088; SHR, 1.10; 95% CI, 1.05-1.15; P < .0001; ADT: HR, 1.24; 95% CI, 1.17-1.32; P < .0001; SHR, 1.28; 95% CI, 1.20-1.37; P < .0001), while abiraterone was associated with decreased risk (HR, 0.36; 95% CI, 0.31-0.42; P < .0001; SHR, 0.39; 95% CI, 0.34-0.45; P < .0001).

IN PRACTICE:

"While there is a lack of data, male veterans with previous prostate cancer are at an elevated risk of breast cancer (0.87%), than their civilian counterparts (0.14%),” the authors wrote. “To address the current gap in knowledge and data, this study leveraged an existing large cohort of male veterans with prostate cancer and examined factors associated with increased risk of male breast cancer."

SOURCE:

The study was led by Erum Z. Whyne, VA North Texas Health Care System in Dallas, and Haekyung Jeon-Slaughter, University of Texas Southwestern Medical Center in Dallas. It was published online in The Prostate.

LIMITATIONS:

Though the study findings are based on large, representative data from male veterans with previously diagnosed prostate cancer, the results might not be generalizable to the overall male breast cancer population. As a retrospective cohort study, results may be biased and causality is difficult to establish. The study did not examine other known risk factors for male breast cancer incidence, such as family history, BRCA2 mutations, and military environmental exposure due to lack of data. BMI had missingness of 5.46% (n = 71,718) and was not included as a covariate in the final model, though sensitivity analysis showed it was not significantly associated with increased risk for male breast cancer.

DISCLOSURES:

The research was supported using resources and facilities of the VA Informatics and Computing Infrastructure (VINCI), VA HSR RES 13-457. The VA North Texas Health Care System Institutional Review Board approved the study and waived informed consent. No conflicts of interest were disclosed by the authors.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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.

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.

A faster, oral alternative to docetaxel is set to reach NHS clinics after the National Institute for Health and Care Excellence (NICE) recommended darolutamide (Nubeqa, Bayer) in combination with androgen deprivation therapy (ADT) for men with metastatic hormone-sensitive prostate cancer who are unable to receive or tolerate chemotherapy.

Detailed in NICE’s final draft guidance, the decision will make darolutamide available through the NHS in England and Wales to approximately 6000 patients, offering a new oral therapy for those who with limited alternatives to docetaxel or other androgen-receptor inhibitors.

 

New Option for Chemo-Ineligible Patients

Darolutamide functions by blocking hormones that fuel cancer growth, specifically depriving prostate cancer cells of testosterone required for multiplication and spread. Patients take two tablets twice daily alongside standard ADT. 

Peter Johnson, national clinical director for cancer at NHS England, welcomed the decision and expects this approval to give clinicians and their patients “more flexibility to choose the approach best suited to individual circumstances and clinical needs.”

The guidance was finalised 5 weeks ahead of the standard review timeline, underscoring NICE’s commitment to accelerating access to effective prostate cancer treatments.

 

Clinical Trial Evidence

The NICE’s decision was supported by evidence from the phase 3 ARASENS trial (N = 1306). 

The results showed that adding darolutamide to ADT and docetaxel significantly improved overall survival in metastatic hormone-sensitive prostate cancer, reducing the risk for death by 32% compared with ADT and docetaxel alone. Progression-free outcomes, measured by time to castration-resistant disease or death, also favoured darolutamide. 

A NICE network meta-analysis of the TITAN, ARCHES, LATITUDE, and STAMPEDE trials suggested that combining ADT with androgen-receptor pathway inhibitors such as apalutamide, enzalutamide, and abiraterone provides comparable survival benefits in this disease setting.

 

Cost and Implementation

NICE determined that darolutamide plus ADT delivers similar or lower overall costs to the NHS compared with apalutamide plus ADT. The list price is £4040.00 for a 28-day supply (112 × 300-mg tablets), though Bayer has agreed to a confidential commercial discount.

The guidance requires healthcare providers to use the least expensive suitable treatment option, considering administration costs, dosages, price per dose, and commercial arrangements when choosing between darolutamide plus ADT and apalutamide plus ADT. 

NHS England and integrated care boards must provide funding within 30 days of final publication, with routine commissioning beginning after this interim period.

A version of this article first appeared on Medscape.com.

A faster, oral alternative to docetaxel is set to reach NHS clinics after the National Institute for Health and Care Excellence (NICE) recommended darolutamide (Nubeqa, Bayer) in combination with androgen deprivation therapy (ADT) for men with metastatic hormone-sensitive prostate cancer who are unable to receive or tolerate chemotherapy.

Detailed in NICE’s final draft guidance, the decision will make darolutamide available through the NHS in England and Wales to approximately 6000 patients, offering a new oral therapy for those who with limited alternatives to docetaxel or other androgen-receptor inhibitors.

 

New Option for Chemo-Ineligible Patients

Darolutamide functions by blocking hormones that fuel cancer growth, specifically depriving prostate cancer cells of testosterone required for multiplication and spread. Patients take two tablets twice daily alongside standard ADT. 

Peter Johnson, national clinical director for cancer at NHS England, welcomed the decision and expects this approval to give clinicians and their patients “more flexibility to choose the approach best suited to individual circumstances and clinical needs.”

The guidance was finalised 5 weeks ahead of the standard review timeline, underscoring NICE’s commitment to accelerating access to effective prostate cancer treatments.

 

Clinical Trial Evidence

The NICE’s decision was supported by evidence from the phase 3 ARASENS trial (N = 1306). 

The results showed that adding darolutamide to ADT and docetaxel significantly improved overall survival in metastatic hormone-sensitive prostate cancer, reducing the risk for death by 32% compared with ADT and docetaxel alone. Progression-free outcomes, measured by time to castration-resistant disease or death, also favoured darolutamide. 

A NICE network meta-analysis of the TITAN, ARCHES, LATITUDE, and STAMPEDE trials suggested that combining ADT with androgen-receptor pathway inhibitors such as apalutamide, enzalutamide, and abiraterone provides comparable survival benefits in this disease setting.

 

Cost and Implementation

NICE determined that darolutamide plus ADT delivers similar or lower overall costs to the NHS compared with apalutamide plus ADT. The list price is £4040.00 for a 28-day supply (112 × 300-mg tablets), though Bayer has agreed to a confidential commercial discount.

The guidance requires healthcare providers to use the least expensive suitable treatment option, considering administration costs, dosages, price per dose, and commercial arrangements when choosing between darolutamide plus ADT and apalutamide plus ADT. 

NHS England and integrated care boards must provide funding within 30 days of final publication, with routine commissioning beginning after this interim period.

A version of this article first appeared on Medscape.com.

A faster, oral alternative to docetaxel is set to reach NHS clinics after the National Institute for Health and Care Excellence (NICE) recommended darolutamide (Nubeqa, Bayer) in combination with androgen deprivation therapy (ADT) for men with metastatic hormone-sensitive prostate cancer who are unable to receive or tolerate chemotherapy.

Detailed in NICE’s final draft guidance, the decision will make darolutamide available through the NHS in England and Wales to approximately 6000 patients, offering a new oral therapy for those who with limited alternatives to docetaxel or other androgen-receptor inhibitors.

 

New Option for Chemo-Ineligible Patients

Darolutamide functions by blocking hormones that fuel cancer growth, specifically depriving prostate cancer cells of testosterone required for multiplication and spread. Patients take two tablets twice daily alongside standard ADT. 

Peter Johnson, national clinical director for cancer at NHS England, welcomed the decision and expects this approval to give clinicians and their patients “more flexibility to choose the approach best suited to individual circumstances and clinical needs.”

The guidance was finalised 5 weeks ahead of the standard review timeline, underscoring NICE’s commitment to accelerating access to effective prostate cancer treatments.

 

Clinical Trial Evidence

The NICE’s decision was supported by evidence from the phase 3 ARASENS trial (N = 1306). 

The results showed that adding darolutamide to ADT and docetaxel significantly improved overall survival in metastatic hormone-sensitive prostate cancer, reducing the risk for death by 32% compared with ADT and docetaxel alone. Progression-free outcomes, measured by time to castration-resistant disease or death, also favoured darolutamide. 

A NICE network meta-analysis of the TITAN, ARCHES, LATITUDE, and STAMPEDE trials suggested that combining ADT with androgen-receptor pathway inhibitors such as apalutamide, enzalutamide, and abiraterone provides comparable survival benefits in this disease setting.

 

Cost and Implementation

NICE determined that darolutamide plus ADT delivers similar or lower overall costs to the NHS compared with apalutamide plus ADT. The list price is £4040.00 for a 28-day supply (112 × 300-mg tablets), though Bayer has agreed to a confidential commercial discount.

The guidance requires healthcare providers to use the least expensive suitable treatment option, considering administration costs, dosages, price per dose, and commercial arrangements when choosing between darolutamide plus ADT and apalutamide plus ADT. 

NHS England and integrated care boards must provide funding within 30 days of final publication, with routine commissioning beginning after this interim period.

A version of this article first appeared on Medscape.com.