Doug Brunk

Immunosuppressive therapies for inflammatory bowel disease do not appear to be implicated in the increased risk for melanomas and hematologic malignancies seen in these patients, based on the results of a large database analysis and a separate meta-analysis published in the February edition of Clinical Gastroenterology and Hepatology.

The first study, based on a nationwide population-based cohort analysis conducted in Denmark, found that patients with inflammatory bowel disease (IBD) are at increased risk for cancer, in particular hematologic malignancies and melanoma at standardized incidence ratios of 1.9 and 1.4, respectively.

The second study, based on a systematic review and meta-analysis of the medical literature, found a diagnosis of Crohn’s disease or ulcerative colitis was associated with a 37% increase in the risk of developing melanoma. Melanoma risk was higher in studies performed before the introduction of biologic therapies in 1998, but not in those studies performed after 1998.

For the first study, researchers led by Dr. Michael D. Kappelman of the division of pediatric gastroenterology at the University of North Carolina at Chapel Hill used health care databases to identify patients in Denmark with a diagnosis of Crohn’s disease or ulcerative colitis from 1978 through 2010 (doi: 10.1016/j.cgh.2013.03.034). They followed the patients until the first occurrence of cancer, death, or emigration and used standardized incidence ratios (SIRs) to compare cancer incidence in patients with IBD with that expected in the general population.

"If immunosuppressive medications reduce the risk of gastrointestinal malignancy by suppressing intestinal inflammation but increase the risk of extraintestinal malignancies, IBD patients may be trading off one set of risks for another," the researchers wrote. "We therefore sought to evaluate both intestinal and extraintestinal malignancies comprehensively, as well as the occurrence of any invasive cancer, in a nationwide cohort of patients with IBD in Denmark."

The analysis included 13,756 patients with Crohn’s disease and 35,152 patients with ulcerative colitis who were followed up for a mean of nearly 8 years. After the exclusion of cancers diagnosed within 1 year of IBD diagnosis, 772 cases of invasive cancer occurred among patients with Crohn’s disease (SIR 1.3) and 2,331 occurred among patients with ulcerative colitis (SIR 1.1). Diagnosis of Crohn’s disease was weakly associated with gastrointestinal cancers (SIR 1.2) and extraintestinal cancers (SIR 1.3), with the strongest associations for hematologic malignancies (SIR 1.9), smoking-related cancers (SIR 1.5), and melanoma (SIR 1.4). Associations between ulcerative colitis and gastrointestinal and extraintestinal cancers were weaker (SIR of 1.1 for both).

The excess risk of cancer in patients with Crohn’s disease "largely is owing to extraintestinal cancers, particularly hematologic malignancies and melanoma, both of which may be related to immune suppression, and smoking-related cancers," the researchers concluded. They added that their study "provides reassuring data that the decreasing risk for gastrointestinal malignancy observed here ... has not been offset by a concomitant increase in the risk of extraintestinal or hematologic malignancies. These findings suggest that changes in the medical and surgical treatment of IBD and/or other secular trends have not substantially impacted cancer relative risk on a population basis."

The study was supported in part by grants from the National Institute for Diabetes and Digestive and Kidney Diseases, the Karen Elise Jensen Foundation, and the Clinical Epidemiological Research Foundation.

In the second study from the journal, researchers led by Dr. Suddharth Singh of the division of gastroenterology and hepatology at Mayo Clinic, Rochester, Minn., conducted a systematic literature search through March 2013 for cohort studies showing incident melanoma after IBD diagnosis and an estimate of incident rate ratio or standardized incidence rate. Case reports or case series were excluded (doi: 10.1016/j.cgh.2013.04.033).

Of the 838 studies identified, 12 that comprised 172,837 patients with IBD were included in the final analysis. The pooled crude incidence rate of melanoma among patients in the 12 studies was 27.7/100,000 person-years. This translated into a 37% increase in the risk of melanoma (risk ratio of 1.37). The increase was observed independently in the patients with Crohn’s disease (RR 1.51) and in those with ulcerative colitis (RR 1.23). In addition, the risk of melanoma was higher in studies conducted prior to 1998, when biologic therapies were introduced (RR 1.52), but not in those conducted after 1998 (RR 1.08).

"The risk of melanoma has been shown to be increased in immunosuppressed patients, including patients with a prior solid organ transplant, lymphoma, and patients with human immunodeficiency virus infection and acquired immunodeficiency syndrome. It is possible that the increased risk of melanoma observed in patients with IBD may be related to underlying immune dysfunction in these patients, resulting in altered tumor surveillance" the researchers wrote.

They hypothesized that immunosuppressive medications may increase the risk of melanoma by "down-regulation of the tumor surveillance mechanisms, increased susceptibility to infection with oncogenic viruses such as melanoma-associated retroviruses, or through direct pharmacologic effects of medications on DNA metabolism. Although thiopurine analogs have been associated with an increased risk of nonmelanoma skin cancers, our pooled analysis did not suggest an increased risk of melanoma, albeit there were a limited number of studies."

Dr. Singh and his associates acknowledged certain limitations of the analysis, including the potential for misclassification bias in the included studies and the fact that studies "did not adjust for known risk factors for melanoma, including personal history of nonmelanoma skin cancers, family history of melanoma, or sun exposure."

For the meta-analysis, one author, Dr. Edward V. Loftus, disclosed that he has consulted for and has received research support from Janssen Biotech, Abbott Laboratories, and UCB Pharma. The others had no relevant conflicts to disclose.

dbrunk@frontlinemedcom.com

Immunosuppressive therapies for inflammatory bowel disease do not appear to be implicated in the increased risk for melanomas and hematologic malignancies seen in these patients, based on the results of a large database analysis and a separate meta-analysis published in the February edition of Clinical Gastroenterology and Hepatology.

The first study, based on a nationwide population-based cohort analysis conducted in Denmark, found that patients with inflammatory bowel disease (IBD) are at increased risk for cancer, in particular hematologic malignancies and melanoma at standardized incidence ratios of 1.9 and 1.4, respectively.

The second study, based on a systematic review and meta-analysis of the medical literature, found a diagnosis of Crohn’s disease or ulcerative colitis was associated with a 37% increase in the risk of developing melanoma. Melanoma risk was higher in studies performed before the introduction of biologic therapies in 1998, but not in those studies performed after 1998.

For the first study, researchers led by Dr. Michael D. Kappelman of the division of pediatric gastroenterology at the University of North Carolina at Chapel Hill used health care databases to identify patients in Denmark with a diagnosis of Crohn’s disease or ulcerative colitis from 1978 through 2010 (doi: 10.1016/j.cgh.2013.03.034). They followed the patients until the first occurrence of cancer, death, or emigration and used standardized incidence ratios (SIRs) to compare cancer incidence in patients with IBD with that expected in the general population.

"If immunosuppressive medications reduce the risk of gastrointestinal malignancy by suppressing intestinal inflammation but increase the risk of extraintestinal malignancies, IBD patients may be trading off one set of risks for another," the researchers wrote. "We therefore sought to evaluate both intestinal and extraintestinal malignancies comprehensively, as well as the occurrence of any invasive cancer, in a nationwide cohort of patients with IBD in Denmark."

The analysis included 13,756 patients with Crohn’s disease and 35,152 patients with ulcerative colitis who were followed up for a mean of nearly 8 years. After the exclusion of cancers diagnosed within 1 year of IBD diagnosis, 772 cases of invasive cancer occurred among patients with Crohn’s disease (SIR 1.3) and 2,331 occurred among patients with ulcerative colitis (SIR 1.1). Diagnosis of Crohn’s disease was weakly associated with gastrointestinal cancers (SIR 1.2) and extraintestinal cancers (SIR 1.3), with the strongest associations for hematologic malignancies (SIR 1.9), smoking-related cancers (SIR 1.5), and melanoma (SIR 1.4). Associations between ulcerative colitis and gastrointestinal and extraintestinal cancers were weaker (SIR of 1.1 for both).

The excess risk of cancer in patients with Crohn’s disease "largely is owing to extraintestinal cancers, particularly hematologic malignancies and melanoma, both of which may be related to immune suppression, and smoking-related cancers," the researchers concluded. They added that their study "provides reassuring data that the decreasing risk for gastrointestinal malignancy observed here ... has not been offset by a concomitant increase in the risk of extraintestinal or hematologic malignancies. These findings suggest that changes in the medical and surgical treatment of IBD and/or other secular trends have not substantially impacted cancer relative risk on a population basis."

The study was supported in part by grants from the National Institute for Diabetes and Digestive and Kidney Diseases, the Karen Elise Jensen Foundation, and the Clinical Epidemiological Research Foundation.

In the second study from the journal, researchers led by Dr. Suddharth Singh of the division of gastroenterology and hepatology at Mayo Clinic, Rochester, Minn., conducted a systematic literature search through March 2013 for cohort studies showing incident melanoma after IBD diagnosis and an estimate of incident rate ratio or standardized incidence rate. Case reports or case series were excluded (doi: 10.1016/j.cgh.2013.04.033).

Of the 838 studies identified, 12 that comprised 172,837 patients with IBD were included in the final analysis. The pooled crude incidence rate of melanoma among patients in the 12 studies was 27.7/100,000 person-years. This translated into a 37% increase in the risk of melanoma (risk ratio of 1.37). The increase was observed independently in the patients with Crohn’s disease (RR 1.51) and in those with ulcerative colitis (RR 1.23). In addition, the risk of melanoma was higher in studies conducted prior to 1998, when biologic therapies were introduced (RR 1.52), but not in those conducted after 1998 (RR 1.08).

"The risk of melanoma has been shown to be increased in immunosuppressed patients, including patients with a prior solid organ transplant, lymphoma, and patients with human immunodeficiency virus infection and acquired immunodeficiency syndrome. It is possible that the increased risk of melanoma observed in patients with IBD may be related to underlying immune dysfunction in these patients, resulting in altered tumor surveillance" the researchers wrote.

They hypothesized that immunosuppressive medications may increase the risk of melanoma by "down-regulation of the tumor surveillance mechanisms, increased susceptibility to infection with oncogenic viruses such as melanoma-associated retroviruses, or through direct pharmacologic effects of medications on DNA metabolism. Although thiopurine analogs have been associated with an increased risk of nonmelanoma skin cancers, our pooled analysis did not suggest an increased risk of melanoma, albeit there were a limited number of studies."

Dr. Singh and his associates acknowledged certain limitations of the analysis, including the potential for misclassification bias in the included studies and the fact that studies "did not adjust for known risk factors for melanoma, including personal history of nonmelanoma skin cancers, family history of melanoma, or sun exposure."

For the meta-analysis, one author, Dr. Edward V. Loftus, disclosed that he has consulted for and has received research support from Janssen Biotech, Abbott Laboratories, and UCB Pharma. The others had no relevant conflicts to disclose.

dbrunk@frontlinemedcom.com

Immunosuppressive therapies for inflammatory bowel disease do not appear to be implicated in the increased risk for melanomas and hematologic malignancies seen in these patients, based on the results of a large database analysis and a separate meta-analysis published in the February edition of Clinical Gastroenterology and Hepatology.

The first study, based on a nationwide population-based cohort analysis conducted in Denmark, found that patients with inflammatory bowel disease (IBD) are at increased risk for cancer, in particular hematologic malignancies and melanoma at standardized incidence ratios of 1.9 and 1.4, respectively.

The second study, based on a systematic review and meta-analysis of the medical literature, found a diagnosis of Crohn’s disease or ulcerative colitis was associated with a 37% increase in the risk of developing melanoma. Melanoma risk was higher in studies performed before the introduction of biologic therapies in 1998, but not in those studies performed after 1998.

For the first study, researchers led by Dr. Michael D. Kappelman of the division of pediatric gastroenterology at the University of North Carolina at Chapel Hill used health care databases to identify patients in Denmark with a diagnosis of Crohn’s disease or ulcerative colitis from 1978 through 2010 (doi: 10.1016/j.cgh.2013.03.034). They followed the patients until the first occurrence of cancer, death, or emigration and used standardized incidence ratios (SIRs) to compare cancer incidence in patients with IBD with that expected in the general population.

"If immunosuppressive medications reduce the risk of gastrointestinal malignancy by suppressing intestinal inflammation but increase the risk of extraintestinal malignancies, IBD patients may be trading off one set of risks for another," the researchers wrote. "We therefore sought to evaluate both intestinal and extraintestinal malignancies comprehensively, as well as the occurrence of any invasive cancer, in a nationwide cohort of patients with IBD in Denmark."

The analysis included 13,756 patients with Crohn’s disease and 35,152 patients with ulcerative colitis who were followed up for a mean of nearly 8 years. After the exclusion of cancers diagnosed within 1 year of IBD diagnosis, 772 cases of invasive cancer occurred among patients with Crohn’s disease (SIR 1.3) and 2,331 occurred among patients with ulcerative colitis (SIR 1.1). Diagnosis of Crohn’s disease was weakly associated with gastrointestinal cancers (SIR 1.2) and extraintestinal cancers (SIR 1.3), with the strongest associations for hematologic malignancies (SIR 1.9), smoking-related cancers (SIR 1.5), and melanoma (SIR 1.4). Associations between ulcerative colitis and gastrointestinal and extraintestinal cancers were weaker (SIR of 1.1 for both).

The excess risk of cancer in patients with Crohn’s disease "largely is owing to extraintestinal cancers, particularly hematologic malignancies and melanoma, both of which may be related to immune suppression, and smoking-related cancers," the researchers concluded. They added that their study "provides reassuring data that the decreasing risk for gastrointestinal malignancy observed here ... has not been offset by a concomitant increase in the risk of extraintestinal or hematologic malignancies. These findings suggest that changes in the medical and surgical treatment of IBD and/or other secular trends have not substantially impacted cancer relative risk on a population basis."

The study was supported in part by grants from the National Institute for Diabetes and Digestive and Kidney Diseases, the Karen Elise Jensen Foundation, and the Clinical Epidemiological Research Foundation.

In the second study from the journal, researchers led by Dr. Suddharth Singh of the division of gastroenterology and hepatology at Mayo Clinic, Rochester, Minn., conducted a systematic literature search through March 2013 for cohort studies showing incident melanoma after IBD diagnosis and an estimate of incident rate ratio or standardized incidence rate. Case reports or case series were excluded (doi: 10.1016/j.cgh.2013.04.033).

Of the 838 studies identified, 12 that comprised 172,837 patients with IBD were included in the final analysis. The pooled crude incidence rate of melanoma among patients in the 12 studies was 27.7/100,000 person-years. This translated into a 37% increase in the risk of melanoma (risk ratio of 1.37). The increase was observed independently in the patients with Crohn’s disease (RR 1.51) and in those with ulcerative colitis (RR 1.23). In addition, the risk of melanoma was higher in studies conducted prior to 1998, when biologic therapies were introduced (RR 1.52), but not in those conducted after 1998 (RR 1.08).

"The risk of melanoma has been shown to be increased in immunosuppressed patients, including patients with a prior solid organ transplant, lymphoma, and patients with human immunodeficiency virus infection and acquired immunodeficiency syndrome. It is possible that the increased risk of melanoma observed in patients with IBD may be related to underlying immune dysfunction in these patients, resulting in altered tumor surveillance" the researchers wrote.

They hypothesized that immunosuppressive medications may increase the risk of melanoma by "down-regulation of the tumor surveillance mechanisms, increased susceptibility to infection with oncogenic viruses such as melanoma-associated retroviruses, or through direct pharmacologic effects of medications on DNA metabolism. Although thiopurine analogs have been associated with an increased risk of nonmelanoma skin cancers, our pooled analysis did not suggest an increased risk of melanoma, albeit there were a limited number of studies."

Dr. Singh and his associates acknowledged certain limitations of the analysis, including the potential for misclassification bias in the included studies and the fact that studies "did not adjust for known risk factors for melanoma, including personal history of nonmelanoma skin cancers, family history of melanoma, or sun exposure."

For the meta-analysis, one author, Dr. Edward V. Loftus, disclosed that he has consulted for and has received research support from Janssen Biotech, Abbott Laboratories, and UCB Pharma. The others had no relevant conflicts to disclose.

dbrunk@frontlinemedcom.com

SAN DIEGO – Expect an expanded role of immunotherapy in patients with non–small cell lung cancer, Dr. Roy S. Herbst predicted at the Joint Conference on the Molecular Origins of Lung Cancer sponsored by the American Association for Cancer Research and the International Association for the Study of Lung Cancer.

Dr. Herbst, professor of medical oncology at Yale University, New Haven, Conn., characterized immunotherapy as "probably the most exciting new and specific therapies we have for NSCLC. The extent in its response is impressive, and this is a therapy that has memory. The adaptability of immunotherapy is important as well."

He advised researchers and clinicians to consider using immunotherapy that includes CTLA-4 antibodies, PD-1 antibodies, and PD-L1 antibodies alone or together in patients with earlier stages of lung disease. Clinical studies of immunotherapy in NSCLC patients suggest that some patients don’t get better with immunotherapy, "but a lot of patients do," said Dr. Herbst. "We want to figure out who those patients are. When we see activity like this, we think, can we bring this therapy to earlier disease? These agents might have a role in maintenance therapy and adjuvant/neoadjuvant therapy. Of course, we worry about side effects such as pneumonitis, which occurs rarely, but we still hope these agents will have a benefit in the adjuvant setting. The biology speaks to that. But what about using these agents as maintenance therapy? I think that needs to be explored."

Using immunotherapy as frontline treatment in patients with stage IV lung cancer is also feasible, he said. "I’d feel much better about it if we had a marker, but we should think about some single-agent trials," he said. "Other possibilities in stage IV disease include using immunotherapy with chemotherapy and with tyrosine kinase inhibitors."

Immunotherapy-related adverse events are "not overwhelming, but they’re different than what we see with chemotherapy," Dr. Herbst continued. "For example, some of the endocrine events are not something we often see. We are working on ways to manage this."

Use of biomarkers and immune monitoring can also help clinicians gauge the efficacy of immunotherapy in their NSCLC patients. Dr. Herbst and his associates at Yale Cancer Center follow these patients with biopsies at baseline, during therapy, and at the end of therapy, "because after their therapy at 1 year or more, you wonder: Is this active tumor? Or is this necrotic tissue?" he said. "We now have ways to figure out who is responding and why they’re responding."

Another trend in the future of immunotherapy involves combining with other agents that address key mechanisms in positive and negative regulation of the immune system. Dr. Herbst explained that the biological goal of combinations with a checkpoint inhibitor include the ability to induce antigen-specific T cells, provide more antigen-presenting cells (APCs), activation/modulation of APCs, drive T-cell expansion to expand the pool of antigen-specific cells, and remove other regulatory checkpoints/suppressive factors for T-cell activation/expansion in periphery.

"The current challenge is to identify the critical deficiencies in individual patients," he said. "We have to continue to investigate the biologic significance of all potential ligand-receptor interactions in the tumor microenvironment."

Dr. Herbst disclosed that he is on the scientific advisory boards of Biothera, Diatech, Kolltan, N of 1, Novarx, and Quintiles. He also has done consulting for Ariad, Astellas, and other companies.

dbrunk@frontlinemedcom.com

This article was updated March 25, 2014.

SAN DIEGO – Expect an expanded role of immunotherapy in patients with non–small cell lung cancer, Dr. Roy S. Herbst predicted at the Joint Conference on the Molecular Origins of Lung Cancer sponsored by the American Association for Cancer Research and the International Association for the Study of Lung Cancer.

Dr. Herbst, professor of medical oncology at Yale University, New Haven, Conn., characterized immunotherapy as "probably the most exciting new and specific therapies we have for NSCLC. The extent in its response is impressive, and this is a therapy that has memory. The adaptability of immunotherapy is important as well."

He advised researchers and clinicians to consider using immunotherapy that includes CTLA-4 antibodies, PD-1 antibodies, and PD-L1 antibodies alone or together in patients with earlier stages of lung disease. Clinical studies of immunotherapy in NSCLC patients suggest that some patients don’t get better with immunotherapy, "but a lot of patients do," said Dr. Herbst. "We want to figure out who those patients are. When we see activity like this, we think, can we bring this therapy to earlier disease? These agents might have a role in maintenance therapy and adjuvant/neoadjuvant therapy. Of course, we worry about side effects such as pneumonitis, which occurs rarely, but we still hope these agents will have a benefit in the adjuvant setting. The biology speaks to that. But what about using these agents as maintenance therapy? I think that needs to be explored."

Using immunotherapy as frontline treatment in patients with stage IV lung cancer is also feasible, he said. "I’d feel much better about it if we had a marker, but we should think about some single-agent trials," he said. "Other possibilities in stage IV disease include using immunotherapy with chemotherapy and with tyrosine kinase inhibitors."

Immunotherapy-related adverse events are "not overwhelming, but they’re different than what we see with chemotherapy," Dr. Herbst continued. "For example, some of the endocrine events are not something we often see. We are working on ways to manage this."

Use of biomarkers and immune monitoring can also help clinicians gauge the efficacy of immunotherapy in their NSCLC patients. Dr. Herbst and his associates at Yale Cancer Center follow these patients with biopsies at baseline, during therapy, and at the end of therapy, "because after their therapy at 1 year or more, you wonder: Is this active tumor? Or is this necrotic tissue?" he said. "We now have ways to figure out who is responding and why they’re responding."

Another trend in the future of immunotherapy involves combining with other agents that address key mechanisms in positive and negative regulation of the immune system. Dr. Herbst explained that the biological goal of combinations with a checkpoint inhibitor include the ability to induce antigen-specific T cells, provide more antigen-presenting cells (APCs), activation/modulation of APCs, drive T-cell expansion to expand the pool of antigen-specific cells, and remove other regulatory checkpoints/suppressive factors for T-cell activation/expansion in periphery.

"The current challenge is to identify the critical deficiencies in individual patients," he said. "We have to continue to investigate the biologic significance of all potential ligand-receptor interactions in the tumor microenvironment."

Dr. Herbst disclosed that he is on the scientific advisory boards of Biothera, Diatech, Kolltan, N of 1, Novarx, and Quintiles. He also has done consulting for Ariad, Astellas, and other companies.

dbrunk@frontlinemedcom.com

This article was updated March 25, 2014.

SAN DIEGO – Expect an expanded role of immunotherapy in patients with non–small cell lung cancer, Dr. Roy S. Herbst predicted at the Joint Conference on the Molecular Origins of Lung Cancer sponsored by the American Association for Cancer Research and the International Association for the Study of Lung Cancer.

Dr. Herbst, professor of medical oncology at Yale University, New Haven, Conn., characterized immunotherapy as "probably the most exciting new and specific therapies we have for NSCLC. The extent in its response is impressive, and this is a therapy that has memory. The adaptability of immunotherapy is important as well."

He advised researchers and clinicians to consider using immunotherapy that includes CTLA-4 antibodies, PD-1 antibodies, and PD-L1 antibodies alone or together in patients with earlier stages of lung disease. Clinical studies of immunotherapy in NSCLC patients suggest that some patients don’t get better with immunotherapy, "but a lot of patients do," said Dr. Herbst. "We want to figure out who those patients are. When we see activity like this, we think, can we bring this therapy to earlier disease? These agents might have a role in maintenance therapy and adjuvant/neoadjuvant therapy. Of course, we worry about side effects such as pneumonitis, which occurs rarely, but we still hope these agents will have a benefit in the adjuvant setting. The biology speaks to that. But what about using these agents as maintenance therapy? I think that needs to be explored."

Using immunotherapy as frontline treatment in patients with stage IV lung cancer is also feasible, he said. "I’d feel much better about it if we had a marker, but we should think about some single-agent trials," he said. "Other possibilities in stage IV disease include using immunotherapy with chemotherapy and with tyrosine kinase inhibitors."

Immunotherapy-related adverse events are "not overwhelming, but they’re different than what we see with chemotherapy," Dr. Herbst continued. "For example, some of the endocrine events are not something we often see. We are working on ways to manage this."

Use of biomarkers and immune monitoring can also help clinicians gauge the efficacy of immunotherapy in their NSCLC patients. Dr. Herbst and his associates at Yale Cancer Center follow these patients with biopsies at baseline, during therapy, and at the end of therapy, "because after their therapy at 1 year or more, you wonder: Is this active tumor? Or is this necrotic tissue?" he said. "We now have ways to figure out who is responding and why they’re responding."

Another trend in the future of immunotherapy involves combining with other agents that address key mechanisms in positive and negative regulation of the immune system. Dr. Herbst explained that the biological goal of combinations with a checkpoint inhibitor include the ability to induce antigen-specific T cells, provide more antigen-presenting cells (APCs), activation/modulation of APCs, drive T-cell expansion to expand the pool of antigen-specific cells, and remove other regulatory checkpoints/suppressive factors for T-cell activation/expansion in periphery.

"The current challenge is to identify the critical deficiencies in individual patients," he said. "We have to continue to investigate the biologic significance of all potential ligand-receptor interactions in the tumor microenvironment."

Dr. Herbst disclosed that he is on the scientific advisory boards of Biothera, Diatech, Kolltan, N of 1, Novarx, and Quintiles. He also has done consulting for Ariad, Astellas, and other companies.

dbrunk@frontlinemedcom.com

This article was updated March 25, 2014.

SAN DIEGO – Information about prostate tumor biology obtained from a multigene assay helped investigators discriminate low- and intermediate-risk prostate cancers in the context of tumor heterogeneity and limited sampling with needle biopsies, a clinical validation study showed.

Furthermore, the information garnered from the assay might take the place of a second biopsy for identifying appropriate patients for active surveillance.

"I’d like to suggest that we are on the very front wave of a paradigm shift," Dr. Eric A. Klein said during a conference sponsored by the American Association for Cancer Research and the Prostate Cancer Foundation. "We have learned so much about the biology and genomics of prostate cancer. We’re at the point now where we can exploit that clinically and make precision decisions for our patients."

The test, known as the Oncotype DX Genomic Prostate Score (GPS), is a biopsy-based pretreatment tool of Genomic Health Inc. that can help clinicians predict which men are more likely to harbor an aggressive form of prostate cancer. It became available in May 2013.

For patients with newly diagnosed, low- or intermediate-risk prostate cancer, limited accuracy of pretreatment risk assessment has led to underuse of active surveillance and overtreatment of nonlethal cancers, with all of the accompanying morbidity and cost, said Dr. Klein, who chairs the Glickman Urological and Kidney Institute at the Cleveland Clinic and who led the GPS development studies.

"The real problem for patients in active surveillance [is that] biopsy only samples potentially the low-grade tumor," he said. "So the question that exists is, how well does the Gleason grade predict biologic potential? And how accurately does the biopsy capture the biology of the whole prostate? The answer to the second question is unknown."

He discussed efforts to develop and validate a biopsy-based gene expression profile that predicts aggressive prostate cancer in the context of tumor heterogeneity, multifocality, and biopsy undersampling, which "limit the accuracy, precision, and confidence of current risk assessment. The goal was to explore genomics on biopsy to take decision-making from average risk based on grade, stage, and PSA [prostate-specific antigen], to more precisely define individual biological risk across the spectrum of each clinical risk group."

He and his associates conducted two development studies based on patients treated between 1987 and 2007: one to identify genes predictive of clinical recurrence, prostate cancer death, and adverse pathology at prostatectomy across multiple tumor regions sampled from each patient’s prostate, and a second to confirm the predictive value of these genes in prostate biopsies.

Next, independent researchers conducted a clinical validation study, which tested needle biopsies from patients with low to intermediate clinical risk who were treated during 1997-2011. This study was led by Dr. Peter Carroll, chair of the urology department at the University of California, San Francisco, and Dr. Matthew R. Cooperberg, also of UCSF. They used reverse-transcription polymerase chain reaction testing from prostate tumor tissue to quantitate gene expression, and used Cox proportional hazards or logistic regression to analyze associations with clinical recurrence and adverse pathology.

From a cohort sampling of 441 radical prostatectomy patients in the first development study, Dr. Klein and his associates identified 288 genes that predicted metastasis or death regardless of whether the gene expression was measured in the lowest Gleason pattern present or the highest Gleason pattern present. "This was a surprising finding," he said. "It challenges some of our notions about the biology of prostate cancer. What we’re suggesting is that grade, stage, and PSA only give us so much predictive power. We now have the tools available to unleash something that we can’t see under the microscope – the biology of the tumor – in a way that’s clinically exploitable."

For the second development study, the researchers evaluated 81 predictive genes from needle biopsy tissue in 167 patients, 58 of whom had adverse pathology at prostatectomy. Multivariate analysis of both development studies revealed 17 genes representing four biological pathways (stromal response, cellular organization, androgen signaling, and proliferation) that predicted outcome. Dr. Klein characterized the 17 genes as "a window" into the entire prostate.

"There is data in the literature that suggests the genomic signal that is present in patients with metastatic or advanced disease is almost always present in the primary tumor," he said. "It won’t be true in every case, but for the vast majority of prostate cancers I think this is true. The suggestion is that by measuring gene expression in the biopsy we can capture that signal."

The clinical validation study performed at UCSF included needle biopsy tissue from 395 patients, of whom 123 had adverse pathology at time of prostatectomy. The UCSF researchers reported that the GPS algorithm assessed in biopsies with tumor length as little as 1 mm from patients suitable for active surveillance predicted adverse pathology at prostatectomy, after adjustment for conventional pretreatment factors (P less than .005). In addition, the net reclassification improvement corresponding to at least a 5% change in predicted probability of favorable pathology with the addition of GPS to the CAPRA (Cancer of the Prostate Risk Assessment) score was 0.41 (P less than .001).

The biologic information from GPS "adds to our ability to make a precision decision for the patient," Dr. Klein said. "It doesn’t replace grade stage and PSA. It doesn’t replace clinical judgment. It’s another piece of very powerful information that can influence patient decision-making."

He went on to note that a test like the GPS could reduce the burden of determining eligibility for active surveillance. "Typically, in most practices, if you’re going to be considered for active surveillance after initial biopsy that shows low-grade disease, you have a second biopsy," Dr. Klein said. "I believe that the rationale is established that you could substitute this kind of biomarker for a second biopsy."

Dr. Klein disclosed that he has received research support and/or consulting fees from Genomic Health, GenomeDx Biosciences, and Metamark.

dbrunk@frontlinemedcom.com

SAN DIEGO – Information about prostate tumor biology obtained from a multigene assay helped investigators discriminate low- and intermediate-risk prostate cancers in the context of tumor heterogeneity and limited sampling with needle biopsies, a clinical validation study showed.

Furthermore, the information garnered from the assay might take the place of a second biopsy for identifying appropriate patients for active surveillance.

"I’d like to suggest that we are on the very front wave of a paradigm shift," Dr. Eric A. Klein said during a conference sponsored by the American Association for Cancer Research and the Prostate Cancer Foundation. "We have learned so much about the biology and genomics of prostate cancer. We’re at the point now where we can exploit that clinically and make precision decisions for our patients."

The test, known as the Oncotype DX Genomic Prostate Score (GPS), is a biopsy-based pretreatment tool of Genomic Health Inc. that can help clinicians predict which men are more likely to harbor an aggressive form of prostate cancer. It became available in May 2013.

For patients with newly diagnosed, low- or intermediate-risk prostate cancer, limited accuracy of pretreatment risk assessment has led to underuse of active surveillance and overtreatment of nonlethal cancers, with all of the accompanying morbidity and cost, said Dr. Klein, who chairs the Glickman Urological and Kidney Institute at the Cleveland Clinic and who led the GPS development studies.

"The real problem for patients in active surveillance [is that] biopsy only samples potentially the low-grade tumor," he said. "So the question that exists is, how well does the Gleason grade predict biologic potential? And how accurately does the biopsy capture the biology of the whole prostate? The answer to the second question is unknown."

He discussed efforts to develop and validate a biopsy-based gene expression profile that predicts aggressive prostate cancer in the context of tumor heterogeneity, multifocality, and biopsy undersampling, which "limit the accuracy, precision, and confidence of current risk assessment. The goal was to explore genomics on biopsy to take decision-making from average risk based on grade, stage, and PSA [prostate-specific antigen], to more precisely define individual biological risk across the spectrum of each clinical risk group."

He and his associates conducted two development studies based on patients treated between 1987 and 2007: one to identify genes predictive of clinical recurrence, prostate cancer death, and adverse pathology at prostatectomy across multiple tumor regions sampled from each patient’s prostate, and a second to confirm the predictive value of these genes in prostate biopsies.

Next, independent researchers conducted a clinical validation study, which tested needle biopsies from patients with low to intermediate clinical risk who were treated during 1997-2011. This study was led by Dr. Peter Carroll, chair of the urology department at the University of California, San Francisco, and Dr. Matthew R. Cooperberg, also of UCSF. They used reverse-transcription polymerase chain reaction testing from prostate tumor tissue to quantitate gene expression, and used Cox proportional hazards or logistic regression to analyze associations with clinical recurrence and adverse pathology.

From a cohort sampling of 441 radical prostatectomy patients in the first development study, Dr. Klein and his associates identified 288 genes that predicted metastasis or death regardless of whether the gene expression was measured in the lowest Gleason pattern present or the highest Gleason pattern present. "This was a surprising finding," he said. "It challenges some of our notions about the biology of prostate cancer. What we’re suggesting is that grade, stage, and PSA only give us so much predictive power. We now have the tools available to unleash something that we can’t see under the microscope – the biology of the tumor – in a way that’s clinically exploitable."

For the second development study, the researchers evaluated 81 predictive genes from needle biopsy tissue in 167 patients, 58 of whom had adverse pathology at prostatectomy. Multivariate analysis of both development studies revealed 17 genes representing four biological pathways (stromal response, cellular organization, androgen signaling, and proliferation) that predicted outcome. Dr. Klein characterized the 17 genes as "a window" into the entire prostate.

"There is data in the literature that suggests the genomic signal that is present in patients with metastatic or advanced disease is almost always present in the primary tumor," he said. "It won’t be true in every case, but for the vast majority of prostate cancers I think this is true. The suggestion is that by measuring gene expression in the biopsy we can capture that signal."

The clinical validation study performed at UCSF included needle biopsy tissue from 395 patients, of whom 123 had adverse pathology at time of prostatectomy. The UCSF researchers reported that the GPS algorithm assessed in biopsies with tumor length as little as 1 mm from patients suitable for active surveillance predicted adverse pathology at prostatectomy, after adjustment for conventional pretreatment factors (P less than .005). In addition, the net reclassification improvement corresponding to at least a 5% change in predicted probability of favorable pathology with the addition of GPS to the CAPRA (Cancer of the Prostate Risk Assessment) score was 0.41 (P less than .001).

The biologic information from GPS "adds to our ability to make a precision decision for the patient," Dr. Klein said. "It doesn’t replace grade stage and PSA. It doesn’t replace clinical judgment. It’s another piece of very powerful information that can influence patient decision-making."

He went on to note that a test like the GPS could reduce the burden of determining eligibility for active surveillance. "Typically, in most practices, if you’re going to be considered for active surveillance after initial biopsy that shows low-grade disease, you have a second biopsy," Dr. Klein said. "I believe that the rationale is established that you could substitute this kind of biomarker for a second biopsy."

Dr. Klein disclosed that he has received research support and/or consulting fees from Genomic Health, GenomeDx Biosciences, and Metamark.

dbrunk@frontlinemedcom.com

SAN DIEGO – Information about prostate tumor biology obtained from a multigene assay helped investigators discriminate low- and intermediate-risk prostate cancers in the context of tumor heterogeneity and limited sampling with needle biopsies, a clinical validation study showed.

Furthermore, the information garnered from the assay might take the place of a second biopsy for identifying appropriate patients for active surveillance.

"I’d like to suggest that we are on the very front wave of a paradigm shift," Dr. Eric A. Klein said during a conference sponsored by the American Association for Cancer Research and the Prostate Cancer Foundation. "We have learned so much about the biology and genomics of prostate cancer. We’re at the point now where we can exploit that clinically and make precision decisions for our patients."

The test, known as the Oncotype DX Genomic Prostate Score (GPS), is a biopsy-based pretreatment tool of Genomic Health Inc. that can help clinicians predict which men are more likely to harbor an aggressive form of prostate cancer. It became available in May 2013.

For patients with newly diagnosed, low- or intermediate-risk prostate cancer, limited accuracy of pretreatment risk assessment has led to underuse of active surveillance and overtreatment of nonlethal cancers, with all of the accompanying morbidity and cost, said Dr. Klein, who chairs the Glickman Urological and Kidney Institute at the Cleveland Clinic and who led the GPS development studies.

"The real problem for patients in active surveillance [is that] biopsy only samples potentially the low-grade tumor," he said. "So the question that exists is, how well does the Gleason grade predict biologic potential? And how accurately does the biopsy capture the biology of the whole prostate? The answer to the second question is unknown."

He discussed efforts to develop and validate a biopsy-based gene expression profile that predicts aggressive prostate cancer in the context of tumor heterogeneity, multifocality, and biopsy undersampling, which "limit the accuracy, precision, and confidence of current risk assessment. The goal was to explore genomics on biopsy to take decision-making from average risk based on grade, stage, and PSA [prostate-specific antigen], to more precisely define individual biological risk across the spectrum of each clinical risk group."

He and his associates conducted two development studies based on patients treated between 1987 and 2007: one to identify genes predictive of clinical recurrence, prostate cancer death, and adverse pathology at prostatectomy across multiple tumor regions sampled from each patient’s prostate, and a second to confirm the predictive value of these genes in prostate biopsies.

Next, independent researchers conducted a clinical validation study, which tested needle biopsies from patients with low to intermediate clinical risk who were treated during 1997-2011. This study was led by Dr. Peter Carroll, chair of the urology department at the University of California, San Francisco, and Dr. Matthew R. Cooperberg, also of UCSF. They used reverse-transcription polymerase chain reaction testing from prostate tumor tissue to quantitate gene expression, and used Cox proportional hazards or logistic regression to analyze associations with clinical recurrence and adverse pathology.

From a cohort sampling of 441 radical prostatectomy patients in the first development study, Dr. Klein and his associates identified 288 genes that predicted metastasis or death regardless of whether the gene expression was measured in the lowest Gleason pattern present or the highest Gleason pattern present. "This was a surprising finding," he said. "It challenges some of our notions about the biology of prostate cancer. What we’re suggesting is that grade, stage, and PSA only give us so much predictive power. We now have the tools available to unleash something that we can’t see under the microscope – the biology of the tumor – in a way that’s clinically exploitable."

For the second development study, the researchers evaluated 81 predictive genes from needle biopsy tissue in 167 patients, 58 of whom had adverse pathology at prostatectomy. Multivariate analysis of both development studies revealed 17 genes representing four biological pathways (stromal response, cellular organization, androgen signaling, and proliferation) that predicted outcome. Dr. Klein characterized the 17 genes as "a window" into the entire prostate.

"There is data in the literature that suggests the genomic signal that is present in patients with metastatic or advanced disease is almost always present in the primary tumor," he said. "It won’t be true in every case, but for the vast majority of prostate cancers I think this is true. The suggestion is that by measuring gene expression in the biopsy we can capture that signal."

The clinical validation study performed at UCSF included needle biopsy tissue from 395 patients, of whom 123 had adverse pathology at time of prostatectomy. The UCSF researchers reported that the GPS algorithm assessed in biopsies with tumor length as little as 1 mm from patients suitable for active surveillance predicted adverse pathology at prostatectomy, after adjustment for conventional pretreatment factors (P less than .005). In addition, the net reclassification improvement corresponding to at least a 5% change in predicted probability of favorable pathology with the addition of GPS to the CAPRA (Cancer of the Prostate Risk Assessment) score was 0.41 (P less than .001).

The biologic information from GPS "adds to our ability to make a precision decision for the patient," Dr. Klein said. "It doesn’t replace grade stage and PSA. It doesn’t replace clinical judgment. It’s another piece of very powerful information that can influence patient decision-making."

He went on to note that a test like the GPS could reduce the burden of determining eligibility for active surveillance. "Typically, in most practices, if you’re going to be considered for active surveillance after initial biopsy that shows low-grade disease, you have a second biopsy," Dr. Klein said. "I believe that the rationale is established that you could substitute this kind of biomarker for a second biopsy."

Dr. Klein disclosed that he has received research support and/or consulting fees from Genomic Health, GenomeDx Biosciences, and Metamark.

dbrunk@frontlinemedcom.com

SAN DIEGO – Over the past 20 years, death rates from prostate cancer in the United States have declined by 39%, due largely to early detection and/or improved treatment, according to Dr. Peter R. Carroll.

"It’s important to realize that this accounts for 20% of the decrease in cancer-specific deaths in men," said Dr. Carroll, professor and chair of the department of urology at the University of California, San Francisco. "However, the Achilles’ heel of PSA [prostate-specific antigen] testing is that it does so at the risk of overdetection – detecting disease that would not have become clinically apparent over a patient’s lifetime if left untreated. In this country, detection and treatment are too tightly linked."

In addition, widespread use of serum PSA has resulted in a "dramatic stage and grade shift, with most cancers currently being detected of limited cancer grade and stage," he said. Data from his colleagues at UCSF found that between 1990 and 2012, age-adjusted death rates from prostate cancer decreased 3.96% in North America yet increased 41% worldwide. In the United States, men with nonpalpable PSA-driven cancer comprise the largest segment of prostate cancer patients. "We think that we’ve seen a leveling of overdetection, but I think we’ll see another round of overdetection, because of a lowering PSA threshold to prompt biopsy, aggressive rescreening, the use of PSA velocity at low PSA values to prompt biopsy, and the use of saturation biopsies," he said during a conference sponsored by the American Association for Cancer Research and the Prostate Cancer Foundation.

In 2012 the U.S. Preventive Services Task Force came out against prostate cancer screening, classifying it as a grade D recommendation (Ann. Intern. Med. 2012;157[2]:120-34). The magnitude of overdetection varies with time period, age, comorbidities, region, definition, and screening practices and is thought to range between 2% and 67%, Dr. Carroll said. "I think a good number is somewhere between 35% and 40%." A recently published nomogram for predicting overdiagnosis found that depending on a man’s age, Gleason score, and PSA level, the likelihood that his tumor has been overdiagnosed ranges from 2.9% to 88.1% (J. Natl. Cancer Inst. 2014 [doi:10.1093/jnci.djt367]).

If prostate cancer screening is to be undertaken, "it should only be done recognizing that selective, rather than indiscriminate, treatment should follow," Dr. Carroll said. "Such an approach has been shown to reduce mortality while managing many with active surveillance in lieu of immediate treatment" (Lancet Oncol. 2010;11[8]:725-32). At UCSF, where more than 1,000 men are on active surveillance, the 5-year treatment-free survival is 65%, the 5-year overall survival is 97%, and the 5-year prostate cancer–specific survival is 100%. "The window of opportunity for treatment appears to be open for a long period of time," he said.

Potential solutions Dr. Carroll proposed to decrease the rates of overdetection include:

• Reducing the treatment of low-risk tumors.

• Identifying high-risk populations and targeting prevention and screening efforts to those populations.

• Developing new screening markers.

• Developing clinical and patient tools to support informed decision making about prevention, screening, biopsy, and treatment.

• Changing screening guidelines.

"The single biggest predictor of risk is a baseline PSA. It trumps ethnicity and family history," Dr. Carroll said. "I think there’s a strong rationale for a baseline screening between ages 45 and 55. If you screen beyond age 70, you increase the risk of overdetection. But if you stop screening you also increase the mortality. So beyond age 70 you want to individualize, consider screening only in those with a long life expectancy, and perhaps change the rationale for biopsy. Digital rectal examination in my mind is optional as a primary screening maneuver. Screening can be done at 1- to 2-year intervals. One thing we need to get away from is using PSA velocity at low PSA levels. That drives overdetection quite a bit."

Dr. Carroll disclosed that he has received honoraria, research support, and/or consulting fees from Genomic Health, Intuitive, Janssen, and Myriad.

dbrunk@frontlinemedcom.com

SAN DIEGO – Over the past 20 years, death rates from prostate cancer in the United States have declined by 39%, due largely to early detection and/or improved treatment, according to Dr. Peter R. Carroll.

"It’s important to realize that this accounts for 20% of the decrease in cancer-specific deaths in men," said Dr. Carroll, professor and chair of the department of urology at the University of California, San Francisco. "However, the Achilles’ heel of PSA [prostate-specific antigen] testing is that it does so at the risk of overdetection – detecting disease that would not have become clinically apparent over a patient’s lifetime if left untreated. In this country, detection and treatment are too tightly linked."

In addition, widespread use of serum PSA has resulted in a "dramatic stage and grade shift, with most cancers currently being detected of limited cancer grade and stage," he said. Data from his colleagues at UCSF found that between 1990 and 2012, age-adjusted death rates from prostate cancer decreased 3.96% in North America yet increased 41% worldwide. In the United States, men with nonpalpable PSA-driven cancer comprise the largest segment of prostate cancer patients. "We think that we’ve seen a leveling of overdetection, but I think we’ll see another round of overdetection, because of a lowering PSA threshold to prompt biopsy, aggressive rescreening, the use of PSA velocity at low PSA values to prompt biopsy, and the use of saturation biopsies," he said during a conference sponsored by the American Association for Cancer Research and the Prostate Cancer Foundation.

In 2012 the U.S. Preventive Services Task Force came out against prostate cancer screening, classifying it as a grade D recommendation (Ann. Intern. Med. 2012;157[2]:120-34). The magnitude of overdetection varies with time period, age, comorbidities, region, definition, and screening practices and is thought to range between 2% and 67%, Dr. Carroll said. "I think a good number is somewhere between 35% and 40%." A recently published nomogram for predicting overdiagnosis found that depending on a man’s age, Gleason score, and PSA level, the likelihood that his tumor has been overdiagnosed ranges from 2.9% to 88.1% (J. Natl. Cancer Inst. 2014 [doi:10.1093/jnci.djt367]).

If prostate cancer screening is to be undertaken, "it should only be done recognizing that selective, rather than indiscriminate, treatment should follow," Dr. Carroll said. "Such an approach has been shown to reduce mortality while managing many with active surveillance in lieu of immediate treatment" (Lancet Oncol. 2010;11[8]:725-32). At UCSF, where more than 1,000 men are on active surveillance, the 5-year treatment-free survival is 65%, the 5-year overall survival is 97%, and the 5-year prostate cancer–specific survival is 100%. "The window of opportunity for treatment appears to be open for a long period of time," he said.

Potential solutions Dr. Carroll proposed to decrease the rates of overdetection include:

• Reducing the treatment of low-risk tumors.

• Identifying high-risk populations and targeting prevention and screening efforts to those populations.

• Developing new screening markers.

• Developing clinical and patient tools to support informed decision making about prevention, screening, biopsy, and treatment.

• Changing screening guidelines.

"The single biggest predictor of risk is a baseline PSA. It trumps ethnicity and family history," Dr. Carroll said. "I think there’s a strong rationale for a baseline screening between ages 45 and 55. If you screen beyond age 70, you increase the risk of overdetection. But if you stop screening you also increase the mortality. So beyond age 70 you want to individualize, consider screening only in those with a long life expectancy, and perhaps change the rationale for biopsy. Digital rectal examination in my mind is optional as a primary screening maneuver. Screening can be done at 1- to 2-year intervals. One thing we need to get away from is using PSA velocity at low PSA levels. That drives overdetection quite a bit."

Dr. Carroll disclosed that he has received honoraria, research support, and/or consulting fees from Genomic Health, Intuitive, Janssen, and Myriad.

dbrunk@frontlinemedcom.com

SAN DIEGO – Over the past 20 years, death rates from prostate cancer in the United States have declined by 39%, due largely to early detection and/or improved treatment, according to Dr. Peter R. Carroll.

"It’s important to realize that this accounts for 20% of the decrease in cancer-specific deaths in men," said Dr. Carroll, professor and chair of the department of urology at the University of California, San Francisco. "However, the Achilles’ heel of PSA [prostate-specific antigen] testing is that it does so at the risk of overdetection – detecting disease that would not have become clinically apparent over a patient’s lifetime if left untreated. In this country, detection and treatment are too tightly linked."

In addition, widespread use of serum PSA has resulted in a "dramatic stage and grade shift, with most cancers currently being detected of limited cancer grade and stage," he said. Data from his colleagues at UCSF found that between 1990 and 2012, age-adjusted death rates from prostate cancer decreased 3.96% in North America yet increased 41% worldwide. In the United States, men with nonpalpable PSA-driven cancer comprise the largest segment of prostate cancer patients. "We think that we’ve seen a leveling of overdetection, but I think we’ll see another round of overdetection, because of a lowering PSA threshold to prompt biopsy, aggressive rescreening, the use of PSA velocity at low PSA values to prompt biopsy, and the use of saturation biopsies," he said during a conference sponsored by the American Association for Cancer Research and the Prostate Cancer Foundation.

In 2012 the U.S. Preventive Services Task Force came out against prostate cancer screening, classifying it as a grade D recommendation (Ann. Intern. Med. 2012;157[2]:120-34). The magnitude of overdetection varies with time period, age, comorbidities, region, definition, and screening practices and is thought to range between 2% and 67%, Dr. Carroll said. "I think a good number is somewhere between 35% and 40%." A recently published nomogram for predicting overdiagnosis found that depending on a man’s age, Gleason score, and PSA level, the likelihood that his tumor has been overdiagnosed ranges from 2.9% to 88.1% (J. Natl. Cancer Inst. 2014 [doi:10.1093/jnci.djt367]).

If prostate cancer screening is to be undertaken, "it should only be done recognizing that selective, rather than indiscriminate, treatment should follow," Dr. Carroll said. "Such an approach has been shown to reduce mortality while managing many with active surveillance in lieu of immediate treatment" (Lancet Oncol. 2010;11[8]:725-32). At UCSF, where more than 1,000 men are on active surveillance, the 5-year treatment-free survival is 65%, the 5-year overall survival is 97%, and the 5-year prostate cancer–specific survival is 100%. "The window of opportunity for treatment appears to be open for a long period of time," he said.

Potential solutions Dr. Carroll proposed to decrease the rates of overdetection include:

• Reducing the treatment of low-risk tumors.

• Identifying high-risk populations and targeting prevention and screening efforts to those populations.

• Developing new screening markers.

• Developing clinical and patient tools to support informed decision making about prevention, screening, biopsy, and treatment.

• Changing screening guidelines.

"The single biggest predictor of risk is a baseline PSA. It trumps ethnicity and family history," Dr. Carroll said. "I think there’s a strong rationale for a baseline screening between ages 45 and 55. If you screen beyond age 70, you increase the risk of overdetection. But if you stop screening you also increase the mortality. So beyond age 70 you want to individualize, consider screening only in those with a long life expectancy, and perhaps change the rationale for biopsy. Digital rectal examination in my mind is optional as a primary screening maneuver. Screening can be done at 1- to 2-year intervals. One thing we need to get away from is using PSA velocity at low PSA levels. That drives overdetection quite a bit."

Dr. Carroll disclosed that he has received honoraria, research support, and/or consulting fees from Genomic Health, Intuitive, Janssen, and Myriad.

dbrunk@frontlinemedcom.com

SAN DIEGO – Now is the time for researchers and clinicians to examine strategies and interventions for preventing prostate cancer, in the opinion of Dr. Peter H. Gann.

"In the last 12 years or so we have seen a litany of failure with regard to prostate cancer prevention in trials with clinical endpoints," Dr. Gann, professor and director of pathology research at the University of Illinois at Chicago, said during a conference sponsored by the American Association for Cancer Research and the Prostate Cancer Foundation.

"With vitamin E supplementation, for example, we see a possible increased risk of prostate cancer, no effect with selenium and possibly and increased risk of diabetes, no effect from soy, and the potential impact of green tea polyphenols is unresolved."

Moreover, it’s conceivable that you might need to screen 1,500 average-risk patients to prevent one prostate cancer from occurring. "That means that preventive agents don’t have to be safe; they have to be incredibly safe if they’re going to be used in this way," Dr. Gann said.

He proposed five ways to advance prostate cancer prevention efforts:

• Develop better preclinical models. Canadian investigators have reported success with generating high fidelity patient-derived xenografts for accelerating prostate cancer discovery and drug development (Cancer Res. 2013 Dec. 19 [doi:10.1158/0008-5472.CAN-13-2921-T]). "One of the incredible things about this is that the transplantable cells can be obtained from needle biopsies," said Dr. Gann, who was not involved with the study. "Architecture and protein marker expression is preserved in these xenografts, as are other molecular characteristics of the tumor, which is fantastic."

An unrelated Australian study demonstrated that it’s possible to generate xenografts of the earlier low-to-moderate grade, localized tumors (Nat. Protoc. 2013;8:836-48). "Why is this exciting for us in prevention? More and more we’re thinking about not how to prevent things from the initiation stage but rather in terms of progression," Dr. Gann explained. "Being able to have individualized samples that we can study versus agents that may inhibit progression is a major opportunity, I think."

• Improve clinical trial design and infrastructure. The existing networks for prostate cancer prevention trials are largely undeveloped, unlike cooperative group networks available for therapeutic trials, according to Dr. Gann. "Many investigators with promising ideas do not have access to the clinical infrastructure or funding sources they need for translational research," he noted. "Moreover, the pros and cons of various available designs for phase II and III trials have not been adequately debated, amidst a shifting landscape in which some designs become less feasible as others become more feasible."

• Develop better risk stratification and patient targeting. What if clinicians could do a better job of sorting out who is truly at risk for prostate cancer? "Active surveillance cohorts are the most promising opportunity we have for prevention trials involving low-risk interventions," Dr. Gann said. Cumulative results from genome-wide association studies and the expected results from sequencing studies capable of identifying rare genetic variants with high penetrance hold promise for identifying populations for whom preventive strategies would have the most benefit, he added.

• Develop better interventional agents. To date, "I think we’ve taken a haphazard approach to identifying agents for prostate cancer prevention," Dr. Gann said. "With preclinical models lacking, sometimes they’re not vetted very well, either. We’re not going to be able to develop a rational approach to preventing prostate cancer until we have a better idea of how it all comes about. One idea is to do high throughput cell assay based drug screening, which we do for therapeutics but not for chemopreventive agents. The question is, do we have the right libraries of compounds and do we have the right readouts? I suggest that we can start with compounds, especially dietary agents that could inhibit 5-alpha reductase. We also need to think beyond a pharmacologic approach: studying the effects of diet and physical activity, for example."

• Establish better intermediate endpoints for phase II trials. A lack of intermediate endpoint biomarkers (IEBs) for phase II trials is creating a "phase II bottleneck," he said. "There is an ongoing explosion of opportunities provided by new biotechnology and computational methods, but converting these opportunities into validated IEBs for trials will take thought and planning."

Dr. Gann disclosed that he has received grant support from GlaxoSmithKline.

dbrunk@frontlinemedcom.com

SAN DIEGO – Now is the time for researchers and clinicians to examine strategies and interventions for preventing prostate cancer, in the opinion of Dr. Peter H. Gann.

"In the last 12 years or so we have seen a litany of failure with regard to prostate cancer prevention in trials with clinical endpoints," Dr. Gann, professor and director of pathology research at the University of Illinois at Chicago, said during a conference sponsored by the American Association for Cancer Research and the Prostate Cancer Foundation.

"With vitamin E supplementation, for example, we see a possible increased risk of prostate cancer, no effect with selenium and possibly and increased risk of diabetes, no effect from soy, and the potential impact of green tea polyphenols is unresolved."

Moreover, it’s conceivable that you might need to screen 1,500 average-risk patients to prevent one prostate cancer from occurring. "That means that preventive agents don’t have to be safe; they have to be incredibly safe if they’re going to be used in this way," Dr. Gann said.

He proposed five ways to advance prostate cancer prevention efforts:

• Develop better preclinical models. Canadian investigators have reported success with generating high fidelity patient-derived xenografts for accelerating prostate cancer discovery and drug development (Cancer Res. 2013 Dec. 19 [doi:10.1158/0008-5472.CAN-13-2921-T]). "One of the incredible things about this is that the transplantable cells can be obtained from needle biopsies," said Dr. Gann, who was not involved with the study. "Architecture and protein marker expression is preserved in these xenografts, as are other molecular characteristics of the tumor, which is fantastic."

An unrelated Australian study demonstrated that it’s possible to generate xenografts of the earlier low-to-moderate grade, localized tumors (Nat. Protoc. 2013;8:836-48). "Why is this exciting for us in prevention? More and more we’re thinking about not how to prevent things from the initiation stage but rather in terms of progression," Dr. Gann explained. "Being able to have individualized samples that we can study versus agents that may inhibit progression is a major opportunity, I think."

• Improve clinical trial design and infrastructure. The existing networks for prostate cancer prevention trials are largely undeveloped, unlike cooperative group networks available for therapeutic trials, according to Dr. Gann. "Many investigators with promising ideas do not have access to the clinical infrastructure or funding sources they need for translational research," he noted. "Moreover, the pros and cons of various available designs for phase II and III trials have not been adequately debated, amidst a shifting landscape in which some designs become less feasible as others become more feasible."

• Develop better risk stratification and patient targeting. What if clinicians could do a better job of sorting out who is truly at risk for prostate cancer? "Active surveillance cohorts are the most promising opportunity we have for prevention trials involving low-risk interventions," Dr. Gann said. Cumulative results from genome-wide association studies and the expected results from sequencing studies capable of identifying rare genetic variants with high penetrance hold promise for identifying populations for whom preventive strategies would have the most benefit, he added.

• Develop better interventional agents. To date, "I think we’ve taken a haphazard approach to identifying agents for prostate cancer prevention," Dr. Gann said. "With preclinical models lacking, sometimes they’re not vetted very well, either. We’re not going to be able to develop a rational approach to preventing prostate cancer until we have a better idea of how it all comes about. One idea is to do high throughput cell assay based drug screening, which we do for therapeutics but not for chemopreventive agents. The question is, do we have the right libraries of compounds and do we have the right readouts? I suggest that we can start with compounds, especially dietary agents that could inhibit 5-alpha reductase. We also need to think beyond a pharmacologic approach: studying the effects of diet and physical activity, for example."

• Establish better intermediate endpoints for phase II trials. A lack of intermediate endpoint biomarkers (IEBs) for phase II trials is creating a "phase II bottleneck," he said. "There is an ongoing explosion of opportunities provided by new biotechnology and computational methods, but converting these opportunities into validated IEBs for trials will take thought and planning."

Dr. Gann disclosed that he has received grant support from GlaxoSmithKline.

dbrunk@frontlinemedcom.com

SAN DIEGO – Now is the time for researchers and clinicians to examine strategies and interventions for preventing prostate cancer, in the opinion of Dr. Peter H. Gann.

"In the last 12 years or so we have seen a litany of failure with regard to prostate cancer prevention in trials with clinical endpoints," Dr. Gann, professor and director of pathology research at the University of Illinois at Chicago, said during a conference sponsored by the American Association for Cancer Research and the Prostate Cancer Foundation.

"With vitamin E supplementation, for example, we see a possible increased risk of prostate cancer, no effect with selenium and possibly and increased risk of diabetes, no effect from soy, and the potential impact of green tea polyphenols is unresolved."

Moreover, it’s conceivable that you might need to screen 1,500 average-risk patients to prevent one prostate cancer from occurring. "That means that preventive agents don’t have to be safe; they have to be incredibly safe if they’re going to be used in this way," Dr. Gann said.

He proposed five ways to advance prostate cancer prevention efforts:

• Develop better preclinical models. Canadian investigators have reported success with generating high fidelity patient-derived xenografts for accelerating prostate cancer discovery and drug development (Cancer Res. 2013 Dec. 19 [doi:10.1158/0008-5472.CAN-13-2921-T]). "One of the incredible things about this is that the transplantable cells can be obtained from needle biopsies," said Dr. Gann, who was not involved with the study. "Architecture and protein marker expression is preserved in these xenografts, as are other molecular characteristics of the tumor, which is fantastic."

An unrelated Australian study demonstrated that it’s possible to generate xenografts of the earlier low-to-moderate grade, localized tumors (Nat. Protoc. 2013;8:836-48). "Why is this exciting for us in prevention? More and more we’re thinking about not how to prevent things from the initiation stage but rather in terms of progression," Dr. Gann explained. "Being able to have individualized samples that we can study versus agents that may inhibit progression is a major opportunity, I think."

• Improve clinical trial design and infrastructure. The existing networks for prostate cancer prevention trials are largely undeveloped, unlike cooperative group networks available for therapeutic trials, according to Dr. Gann. "Many investigators with promising ideas do not have access to the clinical infrastructure or funding sources they need for translational research," he noted. "Moreover, the pros and cons of various available designs for phase II and III trials have not been adequately debated, amidst a shifting landscape in which some designs become less feasible as others become more feasible."

• Develop better risk stratification and patient targeting. What if clinicians could do a better job of sorting out who is truly at risk for prostate cancer? "Active surveillance cohorts are the most promising opportunity we have for prevention trials involving low-risk interventions," Dr. Gann said. Cumulative results from genome-wide association studies and the expected results from sequencing studies capable of identifying rare genetic variants with high penetrance hold promise for identifying populations for whom preventive strategies would have the most benefit, he added.

• Develop better interventional agents. To date, "I think we’ve taken a haphazard approach to identifying agents for prostate cancer prevention," Dr. Gann said. "With preclinical models lacking, sometimes they’re not vetted very well, either. We’re not going to be able to develop a rational approach to preventing prostate cancer until we have a better idea of how it all comes about. One idea is to do high throughput cell assay based drug screening, which we do for therapeutics but not for chemopreventive agents. The question is, do we have the right libraries of compounds and do we have the right readouts? I suggest that we can start with compounds, especially dietary agents that could inhibit 5-alpha reductase. We also need to think beyond a pharmacologic approach: studying the effects of diet and physical activity, for example."

• Establish better intermediate endpoints for phase II trials. A lack of intermediate endpoint biomarkers (IEBs) for phase II trials is creating a "phase II bottleneck," he said. "There is an ongoing explosion of opportunities provided by new biotechnology and computational methods, but converting these opportunities into validated IEBs for trials will take thought and planning."

Dr. Gann disclosed that he has received grant support from GlaxoSmithKline.

dbrunk@frontlinemedcom.com

SAN DIEGO – Is there a future for prostate cancer chemoprevention?

"Some people think not," Maarten C. Bosland, Ph.D., said during a conference sponsored by the American Association for Cancer Research and the Prostate Cancer Foundation. "Maybe we should just engage in more exercise and decrease our body weight."

Population studies of people who move from low-risk to high-risk countries indicate that the risk of prostate cancer – including the risk of dying from the disease – could be modified by environmental factors that are not yet understood. However, the 5-alpha reductase inhibitor trials provided proof of principle that the risk of a subset of prostate cancer can be reduced by drugs. Why, then, has the prostate cancer prevention field not moved forward?

Reasons for the current stagnation of progress include failure of the Selenium and Vitamin E Cancer Prevention Trial (SELECT) to show preventive activity of selenium and vitamin E; the failure of a high-risk phase III study to show preventive activity of selenized yeast; the refusal of the Food and Drug Administration to approve finasteride for prostate cancer prevention, and uncertainty regarding the long-term effects of treatment with 5-alpha reductase inhibitors, according to Dr. Bosland of the department of pathology at the University of Illinois at Chicago.

Then there’s the issue of clinical or biologic significance.

"Some prostate cancers start early while others start late," he explained. "In each of these categories, some of the cancers can lead to death and others won’t; they’ll remain clinically insignificant. This poses a problem in thinking about how to go about chemoprevention. We want to prevent death from prostate cancer, but the window of opportunity in which we can intervene in a chemoprevention setting is limited, and it encompasses different stages of prostate cancer. This is difficult in terms of how we conduct clinical trials and identify endpoints that are meaningful in terms of preventing death from prostate cancer."

In the case of SELECT, investigators made a direct jump to a phase III study, based on evidence from clinical trials with prostate cancer as a secondary endpoint. "I think we should go back to the traditional approach, with phase I, II, and III trials [of candidate agents for prostate cancer chemoprevention]," Dr. Bosland said.

"There were no phase II studies to support phase III trials when SELECT and other studies with selenium were started." Clinical study "needs to be driven by the biology and mechanisms of prostate cancer," he said.

Speaking in the context of clinical studies, Dr. Bosland said that researchers are challenged by the fact that prostate cancer development is complicated by a range of different pathways and multiple underlying mechanisms. "That is consistent with the enormous heterogeneity of prostate cancer morphologically, genetically, and clinically," he said. "There are several types of prostate cancer with a different frequency, time of onset, and potential to progress. This means that we need a broad spectrum of chemoprevention agents or combination of agents. Multiple preclinical models are needed to represent the different pathways/types of cancer and progression to lethality. We need to focus on the ultimate goal of preventing only aggressive lethal cancer. We don’t want to interfere with clinically insignificant cancer. It’s meaningless."

To accomplish this, Dr. Bosland recommended the development of a valid high-throughput system to identify new candidate agents for prostate cancer chemoprevention. "Markers of fatal/lethal disease need to be identified for application in clinical trials," he continued. "A systematic evaluation of the predictive value of preclinical models, phase II designs, and biomarkers is also needed."

His other recommendations include: Conduct no phase III trials before having data from phase II trials, and conduct no phase II trials before having adequate preclinical data; consider the mechanism and biology of the agent and target before embarking on clinical studies; and develop a rational identification of candidate agents based on biology, mechanism, and results of high-throughput screening. "Only if we do all of this and find the funding for it will there be a future for prostate cancer chemoprevention," Dr.Bosland concluded.

Dr. Bosland said he had no relevant financial conflicts to disclose.

dbrunk@frontlinemedcom.com

SAN DIEGO – Is there a future for prostate cancer chemoprevention?

"Some people think not," Maarten C. Bosland, Ph.D., said during a conference sponsored by the American Association for Cancer Research and the Prostate Cancer Foundation. "Maybe we should just engage in more exercise and decrease our body weight."

Population studies of people who move from low-risk to high-risk countries indicate that the risk of prostate cancer – including the risk of dying from the disease – could be modified by environmental factors that are not yet understood. However, the 5-alpha reductase inhibitor trials provided proof of principle that the risk of a subset of prostate cancer can be reduced by drugs. Why, then, has the prostate cancer prevention field not moved forward?

Reasons for the current stagnation of progress include failure of the Selenium and Vitamin E Cancer Prevention Trial (SELECT) to show preventive activity of selenium and vitamin E; the failure of a high-risk phase III study to show preventive activity of selenized yeast; the refusal of the Food and Drug Administration to approve finasteride for prostate cancer prevention, and uncertainty regarding the long-term effects of treatment with 5-alpha reductase inhibitors, according to Dr. Bosland of the department of pathology at the University of Illinois at Chicago.

Then there’s the issue of clinical or biologic significance.

"Some prostate cancers start early while others start late," he explained. "In each of these categories, some of the cancers can lead to death and others won’t; they’ll remain clinically insignificant. This poses a problem in thinking about how to go about chemoprevention. We want to prevent death from prostate cancer, but the window of opportunity in which we can intervene in a chemoprevention setting is limited, and it encompasses different stages of prostate cancer. This is difficult in terms of how we conduct clinical trials and identify endpoints that are meaningful in terms of preventing death from prostate cancer."

In the case of SELECT, investigators made a direct jump to a phase III study, based on evidence from clinical trials with prostate cancer as a secondary endpoint. "I think we should go back to the traditional approach, with phase I, II, and III trials [of candidate agents for prostate cancer chemoprevention]," Dr. Bosland said.

"There were no phase II studies to support phase III trials when SELECT and other studies with selenium were started." Clinical study "needs to be driven by the biology and mechanisms of prostate cancer," he said.

Speaking in the context of clinical studies, Dr. Bosland said that researchers are challenged by the fact that prostate cancer development is complicated by a range of different pathways and multiple underlying mechanisms. "That is consistent with the enormous heterogeneity of prostate cancer morphologically, genetically, and clinically," he said. "There are several types of prostate cancer with a different frequency, time of onset, and potential to progress. This means that we need a broad spectrum of chemoprevention agents or combination of agents. Multiple preclinical models are needed to represent the different pathways/types of cancer and progression to lethality. We need to focus on the ultimate goal of preventing only aggressive lethal cancer. We don’t want to interfere with clinically insignificant cancer. It’s meaningless."

To accomplish this, Dr. Bosland recommended the development of a valid high-throughput system to identify new candidate agents for prostate cancer chemoprevention. "Markers of fatal/lethal disease need to be identified for application in clinical trials," he continued. "A systematic evaluation of the predictive value of preclinical models, phase II designs, and biomarkers is also needed."

His other recommendations include: Conduct no phase III trials before having data from phase II trials, and conduct no phase II trials before having adequate preclinical data; consider the mechanism and biology of the agent and target before embarking on clinical studies; and develop a rational identification of candidate agents based on biology, mechanism, and results of high-throughput screening. "Only if we do all of this and find the funding for it will there be a future for prostate cancer chemoprevention," Dr.Bosland concluded.

Dr. Bosland said he had no relevant financial conflicts to disclose.

dbrunk@frontlinemedcom.com

SAN DIEGO – Is there a future for prostate cancer chemoprevention?

"Some people think not," Maarten C. Bosland, Ph.D., said during a conference sponsored by the American Association for Cancer Research and the Prostate Cancer Foundation. "Maybe we should just engage in more exercise and decrease our body weight."

Population studies of people who move from low-risk to high-risk countries indicate that the risk of prostate cancer – including the risk of dying from the disease – could be modified by environmental factors that are not yet understood. However, the 5-alpha reductase inhibitor trials provided proof of principle that the risk of a subset of prostate cancer can be reduced by drugs. Why, then, has the prostate cancer prevention field not moved forward?

Reasons for the current stagnation of progress include failure of the Selenium and Vitamin E Cancer Prevention Trial (SELECT) to show preventive activity of selenium and vitamin E; the failure of a high-risk phase III study to show preventive activity of selenized yeast; the refusal of the Food and Drug Administration to approve finasteride for prostate cancer prevention, and uncertainty regarding the long-term effects of treatment with 5-alpha reductase inhibitors, according to Dr. Bosland of the department of pathology at the University of Illinois at Chicago.

Then there’s the issue of clinical or biologic significance.

"Some prostate cancers start early while others start late," he explained. "In each of these categories, some of the cancers can lead to death and others won’t; they’ll remain clinically insignificant. This poses a problem in thinking about how to go about chemoprevention. We want to prevent death from prostate cancer, but the window of opportunity in which we can intervene in a chemoprevention setting is limited, and it encompasses different stages of prostate cancer. This is difficult in terms of how we conduct clinical trials and identify endpoints that are meaningful in terms of preventing death from prostate cancer."

In the case of SELECT, investigators made a direct jump to a phase III study, based on evidence from clinical trials with prostate cancer as a secondary endpoint. "I think we should go back to the traditional approach, with phase I, II, and III trials [of candidate agents for prostate cancer chemoprevention]," Dr. Bosland said.

"There were no phase II studies to support phase III trials when SELECT and other studies with selenium were started." Clinical study "needs to be driven by the biology and mechanisms of prostate cancer," he said.

Speaking in the context of clinical studies, Dr. Bosland said that researchers are challenged by the fact that prostate cancer development is complicated by a range of different pathways and multiple underlying mechanisms. "That is consistent with the enormous heterogeneity of prostate cancer morphologically, genetically, and clinically," he said. "There are several types of prostate cancer with a different frequency, time of onset, and potential to progress. This means that we need a broad spectrum of chemoprevention agents or combination of agents. Multiple preclinical models are needed to represent the different pathways/types of cancer and progression to lethality. We need to focus on the ultimate goal of preventing only aggressive lethal cancer. We don’t want to interfere with clinically insignificant cancer. It’s meaningless."

To accomplish this, Dr. Bosland recommended the development of a valid high-throughput system to identify new candidate agents for prostate cancer chemoprevention. "Markers of fatal/lethal disease need to be identified for application in clinical trials," he continued. "A systematic evaluation of the predictive value of preclinical models, phase II designs, and biomarkers is also needed."

His other recommendations include: Conduct no phase III trials before having data from phase II trials, and conduct no phase II trials before having adequate preclinical data; consider the mechanism and biology of the agent and target before embarking on clinical studies; and develop a rational identification of candidate agents based on biology, mechanism, and results of high-throughput screening. "Only if we do all of this and find the funding for it will there be a future for prostate cancer chemoprevention," Dr.Bosland concluded.

Dr. Bosland said he had no relevant financial conflicts to disclose.

dbrunk@frontlinemedcom.com

SAN DIEGO – Long-term use of aspirin, other nonsteroidal anti-inflammatory drugs, or statins affected neither the levels of prostate-specific antigen nor the velocity with which those levels changed, judging from a secondary analysis from a clinical trial.

"The prevention of prostate cancer by statins, aspirin, and other NSAIDs is an important topic given the widespread use of these drugs in the general population and particularly in the population of men at risk for prostate cancer," Steven P. Stratton. Ph.D., said in an interview during a conference sponsored by the American Association for Cancer Research and the Prostate Cancer Foundation.

"A lot of scientific papers have been published linking these drugs together with cancer prevention, but results are controversial. So definitive, prospective studies in prostate cancer have to be performed before we can know for sure," he said.

In an effort to investigate the effect of these medications on markers used to assess prostate cancer risk, Dr. Stratton and his associates analyzed a population of 699 men enrolled in a phase III chemoprevention trial that was designed to investigate the effects of selenium supplementation on prostate cancer incidence.

"The selenium didn’t work, but we also asked men in this study about their use of other commonly used drugs like statins and NSAIDs; and we measured the PSA on all of these men every 6 months for 5 years," said Dr. Stratton, who chairs the Scientific Review Committee and leads the Prostate Cancer Prevention Team at the University of Arizona Cancer Center, Tucson. "We used statistical models to see if there were relationships between drug use and PSA changes over time."

Men in the study had a PSA greater than 4 ng/mL and/or a suspicious digital rectal examination and/or a PSA velocity (PSAV) of greater than 0.75 ng/mL/year, but with a negative prostate biopsy. During the course of the trial, 73 of the study participants were diagnosed with prostate cancer.

After Dr. Stratton and his associates adjusted for variables including selenium use, age, race, body mass index, and pack-years of smoking, they found that the use of aspirin, NSAIDs, or statins did not demonstrate significant associations with PSA (P = .79, .68, and .79, respectively) or PSAV (P = .23, .43, and .84, respectively). Stratification between men who developed prostate cancer during the course of the study and those with repeated negative prostate biopsies did not alter the results.

"The study wasn’t long enough, nor was it designed to detect a cancer prevention effect of these drugs, but we can say with pretty good confidence that the drug use did not impact the PSA test – a problem called ‘detection bias’ – given that we saw no differences between men taking the drugs and those who did not," Dr. Stratton said. "This is important, because if the drug interfered with the PSA test – regardless of the impact on cancer – it could reduce the usefulness of the PSA test in men taking these drugs."

He acknowledged certain limitations of the study, including the fact that it was a secondary analysis using data from a clinical trial designed for another purpose. "Also, the data on medication use were based on self-reporting by the patients rather than an examination of their medical records or more stringent methods of data collection," he said.

Dr. Stratton said he had no relevant financial conflicts to disclose.

dbrunk@frontlinemedcom.com

SAN DIEGO – Long-term use of aspirin, other nonsteroidal anti-inflammatory drugs, or statins affected neither the levels of prostate-specific antigen nor the velocity with which those levels changed, judging from a secondary analysis from a clinical trial.

"The prevention of prostate cancer by statins, aspirin, and other NSAIDs is an important topic given the widespread use of these drugs in the general population and particularly in the population of men at risk for prostate cancer," Steven P. Stratton. Ph.D., said in an interview during a conference sponsored by the American Association for Cancer Research and the Prostate Cancer Foundation.

"A lot of scientific papers have been published linking these drugs together with cancer prevention, but results are controversial. So definitive, prospective studies in prostate cancer have to be performed before we can know for sure," he said.

In an effort to investigate the effect of these medications on markers used to assess prostate cancer risk, Dr. Stratton and his associates analyzed a population of 699 men enrolled in a phase III chemoprevention trial that was designed to investigate the effects of selenium supplementation on prostate cancer incidence.

"The selenium didn’t work, but we also asked men in this study about their use of other commonly used drugs like statins and NSAIDs; and we measured the PSA on all of these men every 6 months for 5 years," said Dr. Stratton, who chairs the Scientific Review Committee and leads the Prostate Cancer Prevention Team at the University of Arizona Cancer Center, Tucson. "We used statistical models to see if there were relationships between drug use and PSA changes over time."

Men in the study had a PSA greater than 4 ng/mL and/or a suspicious digital rectal examination and/or a PSA velocity (PSAV) of greater than 0.75 ng/mL/year, but with a negative prostate biopsy. During the course of the trial, 73 of the study participants were diagnosed with prostate cancer.

After Dr. Stratton and his associates adjusted for variables including selenium use, age, race, body mass index, and pack-years of smoking, they found that the use of aspirin, NSAIDs, or statins did not demonstrate significant associations with PSA (P = .79, .68, and .79, respectively) or PSAV (P = .23, .43, and .84, respectively). Stratification between men who developed prostate cancer during the course of the study and those with repeated negative prostate biopsies did not alter the results.

"The study wasn’t long enough, nor was it designed to detect a cancer prevention effect of these drugs, but we can say with pretty good confidence that the drug use did not impact the PSA test – a problem called ‘detection bias’ – given that we saw no differences between men taking the drugs and those who did not," Dr. Stratton said. "This is important, because if the drug interfered with the PSA test – regardless of the impact on cancer – it could reduce the usefulness of the PSA test in men taking these drugs."

He acknowledged certain limitations of the study, including the fact that it was a secondary analysis using data from a clinical trial designed for another purpose. "Also, the data on medication use were based on self-reporting by the patients rather than an examination of their medical records or more stringent methods of data collection," he said.

Dr. Stratton said he had no relevant financial conflicts to disclose.

dbrunk@frontlinemedcom.com

SAN DIEGO – Long-term use of aspirin, other nonsteroidal anti-inflammatory drugs, or statins affected neither the levels of prostate-specific antigen nor the velocity with which those levels changed, judging from a secondary analysis from a clinical trial.

"The prevention of prostate cancer by statins, aspirin, and other NSAIDs is an important topic given the widespread use of these drugs in the general population and particularly in the population of men at risk for prostate cancer," Steven P. Stratton. Ph.D., said in an interview during a conference sponsored by the American Association for Cancer Research and the Prostate Cancer Foundation.

"A lot of scientific papers have been published linking these drugs together with cancer prevention, but results are controversial. So definitive, prospective studies in prostate cancer have to be performed before we can know for sure," he said.

In an effort to investigate the effect of these medications on markers used to assess prostate cancer risk, Dr. Stratton and his associates analyzed a population of 699 men enrolled in a phase III chemoprevention trial that was designed to investigate the effects of selenium supplementation on prostate cancer incidence.

"The selenium didn’t work, but we also asked men in this study about their use of other commonly used drugs like statins and NSAIDs; and we measured the PSA on all of these men every 6 months for 5 years," said Dr. Stratton, who chairs the Scientific Review Committee and leads the Prostate Cancer Prevention Team at the University of Arizona Cancer Center, Tucson. "We used statistical models to see if there were relationships between drug use and PSA changes over time."

Men in the study had a PSA greater than 4 ng/mL and/or a suspicious digital rectal examination and/or a PSA velocity (PSAV) of greater than 0.75 ng/mL/year, but with a negative prostate biopsy. During the course of the trial, 73 of the study participants were diagnosed with prostate cancer.

After Dr. Stratton and his associates adjusted for variables including selenium use, age, race, body mass index, and pack-years of smoking, they found that the use of aspirin, NSAIDs, or statins did not demonstrate significant associations with PSA (P = .79, .68, and .79, respectively) or PSAV (P = .23, .43, and .84, respectively). Stratification between men who developed prostate cancer during the course of the study and those with repeated negative prostate biopsies did not alter the results.

"The study wasn’t long enough, nor was it designed to detect a cancer prevention effect of these drugs, but we can say with pretty good confidence that the drug use did not impact the PSA test – a problem called ‘detection bias’ – given that we saw no differences between men taking the drugs and those who did not," Dr. Stratton said. "This is important, because if the drug interfered with the PSA test – regardless of the impact on cancer – it could reduce the usefulness of the PSA test in men taking these drugs."

He acknowledged certain limitations of the study, including the fact that it was a secondary analysis using data from a clinical trial designed for another purpose. "Also, the data on medication use were based on self-reporting by the patients rather than an examination of their medical records or more stringent methods of data collection," he said.

Dr. Stratton said he had no relevant financial conflicts to disclose.

dbrunk@frontlinemedcom.com

SAN DIEGO – About 30% of nodules detected by CT screening fit the criteria for an indeterminate pulmonary nodule. Very few of those nodules represent cancer, and the question is, what do you recommend for those patients in terms of follow-up?

"We’re encountering more and more patients with lung nodules in the clinic, and with the advance of screening, it will become even more of a problem. The numbers are tremendous," Dr. Pierre P. Massion stated at the Joint Conference on the Molecular Origins of Lung Cancer, sponsored by the American Association for Cancer Research and the International Association for the Study of Lung Cancer.

Dr. Massion, the Ingram Professor of Cancer Research at Vanderbilt-Ingram Cancer Center in Nashville, Tenn., said it’s important to differentiate – early, accurately, and noninvasively – benign lesions from cancer. "There is a race for early diagnosis, because surgery is the best chance for cure ... but we also need to decrease the number of thoracotomies performed for benign disease."

Data from eight large trials of lung cancer screening examined the relationship between lesion size and the probability of lung cancer (Chest 2007;132[3 Suppl]:94S-107S). The probability of cancer was 0-1% for lesions less than 5 mm in diameter; 6%-28% for those 5-10 mm, 33%-60% for those 11-20 mm, and 64%-82% for those 21-30 mm.

"The bigger the nodule, the greater the probability of cancer. In fact, however, the number of large nodules is very small," Dr. Massion said. "The indeterminate ones are between 5 and 15 mm in diameter, and these are the ones we struggle with how best to handle." The probability of cancer from indeterminate pulmonary nodules ranges from 6% to 60%, which is a large range.

The shape of the nodule provides additional information, Dr. Massion said. Triangular shape abutting a fissure and central calcification are generally indicators of benign disease and typically do not require follow-up. Alternatively, solid, noncalcified spiculated nodules have a high likelihood of being cancer. Part solid nodules are "very worrisome," he said. "These are most likely to contain malignancy. Nonsolid lesions, also called ground-glass opacities, are troublesome and difficult to assess. They represent about a 20% probability of disease."

The rate of growth of small nodules over time "is probably one of the best imaging markers, [but] for small nodules such as those 5 mm in diameter, the volumetric analysis has a large coefficient of variance," he said.

Prediction models are important to the evaluation of lung nodules, yet even with existing tools "we’re wrong about 30% of the time," he said. The best three prediction models come from studies of patients at the Mayo Clinic (Arch. Intern. Med. 1997;157:849-55) and the Veterans Affairs department (Chest 2007;131:383-88), and from patients enrolled in the PLCO (Prostate, Lung, Colorectal, and Ovarian) Cancer Screening Trial (N. Engl. J. Med. 2013;368:728-36). These prediction models are now recommended for use on nodules greater than 8 mm in diameter in the ACCP 2013 guidelines for evaluation of lung nodules (Chest 2013;143[5 Suppl]:e93S-120S).

"We have no models for never-smokers, which is a huge problem in the community at the moment."

Dr. Massion predicted that serum biomarkers might "come to the rescue" for deciding which patients with indeterminate pulmonary nodules might need to go for a biopsy or resection and which can be carefully watched over time.

In a separate study of 62 lung nodules that integrated clinical, imaging, and protein biomarker findings, clinical information alone resulted in about 50% sensitivity for predicting disease, "which is not great," said Dr. Massion, who was the principal investigator (Cancer Epidemiol. Biomarkers Prev. 2012;21:786-92). The addition of CT imaging increased the area under the curve to about 61%. Adding biomarkers in the blood raised the bar to about 69%.

"It’s not a panacea, but we show a trend toward improvement of classification of these nodules, which is where I think this field is going – integrating information from the clinic, imaging, and the discriminatory power of biomarkers."

Dr. Massion said that he had no relevant financial conflicts to disclose.

dbrunk@frontlinemedcom.com

SAN DIEGO – About 30% of nodules detected by CT screening fit the criteria for an indeterminate pulmonary nodule. Very few of those nodules represent cancer, and the question is, what do you recommend for those patients in terms of follow-up?

"We’re encountering more and more patients with lung nodules in the clinic, and with the advance of screening, it will become even more of a problem. The numbers are tremendous," Dr. Pierre P. Massion stated at the Joint Conference on the Molecular Origins of Lung Cancer, sponsored by the American Association for Cancer Research and the International Association for the Study of Lung Cancer.

Dr. Massion, the Ingram Professor of Cancer Research at Vanderbilt-Ingram Cancer Center in Nashville, Tenn., said it’s important to differentiate – early, accurately, and noninvasively – benign lesions from cancer. "There is a race for early diagnosis, because surgery is the best chance for cure ... but we also need to decrease the number of thoracotomies performed for benign disease."

Data from eight large trials of lung cancer screening examined the relationship between lesion size and the probability of lung cancer (Chest 2007;132[3 Suppl]:94S-107S). The probability of cancer was 0-1% for lesions less than 5 mm in diameter; 6%-28% for those 5-10 mm, 33%-60% for those 11-20 mm, and 64%-82% for those 21-30 mm.

"The bigger the nodule, the greater the probability of cancer. In fact, however, the number of large nodules is very small," Dr. Massion said. "The indeterminate ones are between 5 and 15 mm in diameter, and these are the ones we struggle with how best to handle." The probability of cancer from indeterminate pulmonary nodules ranges from 6% to 60%, which is a large range.

The shape of the nodule provides additional information, Dr. Massion said. Triangular shape abutting a fissure and central calcification are generally indicators of benign disease and typically do not require follow-up. Alternatively, solid, noncalcified spiculated nodules have a high likelihood of being cancer. Part solid nodules are "very worrisome," he said. "These are most likely to contain malignancy. Nonsolid lesions, also called ground-glass opacities, are troublesome and difficult to assess. They represent about a 20% probability of disease."

The rate of growth of small nodules over time "is probably one of the best imaging markers, [but] for small nodules such as those 5 mm in diameter, the volumetric analysis has a large coefficient of variance," he said.

Prediction models are important to the evaluation of lung nodules, yet even with existing tools "we’re wrong about 30% of the time," he said. The best three prediction models come from studies of patients at the Mayo Clinic (Arch. Intern. Med. 1997;157:849-55) and the Veterans Affairs department (Chest 2007;131:383-88), and from patients enrolled in the PLCO (Prostate, Lung, Colorectal, and Ovarian) Cancer Screening Trial (N. Engl. J. Med. 2013;368:728-36). These prediction models are now recommended for use on nodules greater than 8 mm in diameter in the ACCP 2013 guidelines for evaluation of lung nodules (Chest 2013;143[5 Suppl]:e93S-120S).

"We have no models for never-smokers, which is a huge problem in the community at the moment."

Dr. Massion predicted that serum biomarkers might "come to the rescue" for deciding which patients with indeterminate pulmonary nodules might need to go for a biopsy or resection and which can be carefully watched over time.

In a separate study of 62 lung nodules that integrated clinical, imaging, and protein biomarker findings, clinical information alone resulted in about 50% sensitivity for predicting disease, "which is not great," said Dr. Massion, who was the principal investigator (Cancer Epidemiol. Biomarkers Prev. 2012;21:786-92). The addition of CT imaging increased the area under the curve to about 61%. Adding biomarkers in the blood raised the bar to about 69%.

"It’s not a panacea, but we show a trend toward improvement of classification of these nodules, which is where I think this field is going – integrating information from the clinic, imaging, and the discriminatory power of biomarkers."

Dr. Massion said that he had no relevant financial conflicts to disclose.

dbrunk@frontlinemedcom.com

SAN DIEGO – About 30% of nodules detected by CT screening fit the criteria for an indeterminate pulmonary nodule. Very few of those nodules represent cancer, and the question is, what do you recommend for those patients in terms of follow-up?

"We’re encountering more and more patients with lung nodules in the clinic, and with the advance of screening, it will become even more of a problem. The numbers are tremendous," Dr. Pierre P. Massion stated at the Joint Conference on the Molecular Origins of Lung Cancer, sponsored by the American Association for Cancer Research and the International Association for the Study of Lung Cancer.

Dr. Massion, the Ingram Professor of Cancer Research at Vanderbilt-Ingram Cancer Center in Nashville, Tenn., said it’s important to differentiate – early, accurately, and noninvasively – benign lesions from cancer. "There is a race for early diagnosis, because surgery is the best chance for cure ... but we also need to decrease the number of thoracotomies performed for benign disease."

Data from eight large trials of lung cancer screening examined the relationship between lesion size and the probability of lung cancer (Chest 2007;132[3 Suppl]:94S-107S). The probability of cancer was 0-1% for lesions less than 5 mm in diameter; 6%-28% for those 5-10 mm, 33%-60% for those 11-20 mm, and 64%-82% for those 21-30 mm.

"The bigger the nodule, the greater the probability of cancer. In fact, however, the number of large nodules is very small," Dr. Massion said. "The indeterminate ones are between 5 and 15 mm in diameter, and these are the ones we struggle with how best to handle." The probability of cancer from indeterminate pulmonary nodules ranges from 6% to 60%, which is a large range.

The shape of the nodule provides additional information, Dr. Massion said. Triangular shape abutting a fissure and central calcification are generally indicators of benign disease and typically do not require follow-up. Alternatively, solid, noncalcified spiculated nodules have a high likelihood of being cancer. Part solid nodules are "very worrisome," he said. "These are most likely to contain malignancy. Nonsolid lesions, also called ground-glass opacities, are troublesome and difficult to assess. They represent about a 20% probability of disease."

The rate of growth of small nodules over time "is probably one of the best imaging markers, [but] for small nodules such as those 5 mm in diameter, the volumetric analysis has a large coefficient of variance," he said.

Prediction models are important to the evaluation of lung nodules, yet even with existing tools "we’re wrong about 30% of the time," he said. The best three prediction models come from studies of patients at the Mayo Clinic (Arch. Intern. Med. 1997;157:849-55) and the Veterans Affairs department (Chest 2007;131:383-88), and from patients enrolled in the PLCO (Prostate, Lung, Colorectal, and Ovarian) Cancer Screening Trial (N. Engl. J. Med. 2013;368:728-36). These prediction models are now recommended for use on nodules greater than 8 mm in diameter in the ACCP 2013 guidelines for evaluation of lung nodules (Chest 2013;143[5 Suppl]:e93S-120S).

"We have no models for never-smokers, which is a huge problem in the community at the moment."

Dr. Massion predicted that serum biomarkers might "come to the rescue" for deciding which patients with indeterminate pulmonary nodules might need to go for a biopsy or resection and which can be carefully watched over time.

In a separate study of 62 lung nodules that integrated clinical, imaging, and protein biomarker findings, clinical information alone resulted in about 50% sensitivity for predicting disease, "which is not great," said Dr. Massion, who was the principal investigator (Cancer Epidemiol. Biomarkers Prev. 2012;21:786-92). The addition of CT imaging increased the area under the curve to about 61%. Adding biomarkers in the blood raised the bar to about 69%.

"It’s not a panacea, but we show a trend toward improvement of classification of these nodules, which is where I think this field is going – integrating information from the clinic, imaging, and the discriminatory power of biomarkers."

Dr. Massion said that he had no relevant financial conflicts to disclose.

dbrunk@frontlinemedcom.com

In an interview at the Joint Conference on the Molecular Origins of Lung Cancer, Dr. Roy Herbst, chief of medical oncology at the Yale Cancer Center in New Haven, Conn., offers his perspectives on new developments in lung cancer screening and treatment, and he discusses the promise that genetically targeted approaches and immunotherapy may offer.

In an interview at the Joint Conference on the Molecular Origins of Lung Cancer, Dr. Roy Herbst, chief of medical oncology at the Yale Cancer Center in New Haven, Conn., offers his perspectives on new developments in lung cancer screening and treatment, and he discusses the promise that genetically targeted approaches and immunotherapy may offer.

In an interview at the Joint Conference on the Molecular Origins of Lung Cancer, Dr. Roy Herbst, chief of medical oncology at the Yale Cancer Center in New Haven, Conn., offers his perspectives on new developments in lung cancer screening and treatment, and he discusses the promise that genetically targeted approaches and immunotherapy may offer.

SAN DIEGO – Online stem cell clinics pose a threat to the advancement of regenerative medicine, according to a team of Irish researchers.

"It is imperative that the scientific community is made aware of the threat to stem cell therapy posed by unregulated online clinics," researchers led by Dr. Ruairi Connolly wrote in a poster presented at the World Stem Cell Summit.

"These clinics are harnessing the Internet to attract a wide range of patients suffering from a diverse catalogue of conditions to therapies that are described in an attractive manner. A concerted effort from scientists, researchers, doctors, advocacy groups, and governments alike is required to rapidly address the existing legislative deficiencies to prevent these clinics from offering clinically unproven treatments to vulnerable patients."

Dr. Connolly, of National University of Ireland, Galway, and his associates conducted a web search using five terms: stem cell clinic, stem cell therapy, stem cell treatment center, stem cell cure, and stem cell treatment. Websites were included if they involved stem cells to treat human diseases. Of the 1,091 candidate websites, 68 met the inclusion criteria. The top five countries of origin housing online stem cell clinics were the United States (27), China (12), India (12), Thailand (11), and Mexico (9).

The majority of websites (88%) invited patients to contact them through online comment boxes. "In many instances patients are prompted to initiate contact by the promise of further information following such communication," the researchers wrote. In addition, 29% of clinics had an internationally recognized accreditation, but 65% of these were laboratory-related accreditations and were not pertinent to the clinical applications themselves. About one-third of clinics (34%) mention the number of patients they have treated while 25% provide outcome data and have patented their therapies.

The top 10 indications for stem cell therapy were multiple sclerosis, anti-aging, Parkinson’s disease, stroke, spinal cord injury, cerebral palsy, autism, amyotrophic lateral sclerosis, Alzheimer’s disease, and arthritis.

The top five types of stem cells reportedly used by the clinics were adult autologous (82%), umbilical (19%), adult-allogenic (12%), fetal (10%), and cord blood (9%). More than half of clinics (60%) reported that the stem cells were delivered intravenously.

In the realm of safety, 15% of online clinics state that there is "no risk" involved with stem cell therapy, and 88% claim treatment effectiveness, with 16% "describing the curative potential of therapy," according to Dr. Connolly and his colleagues. In addition, "9% refer to specific research publications to support their outcomes [and] over 40% of sites did not specify the number of treatments required, duration of procedure, or therapeutic course. Almost one-quarter of sites reference contraindications to treatment, with 41% of sites mentioning follow-up patient care."

"It remains beyond doubt that enhanced regulation would benefit vulnerable patients and also [would] protect the unquestionable, immense potential of stem cells as a therapy for human beings," the researchers concluded. "Stem cell therapy is only in its infancy and needs to [be] regulated and monitored adequately today so that it can change the lives of patients tomorrow."

The researchers stated that they had no conflicts of interest.

dbrunk@frontlinemedcom.com

SAN DIEGO – Online stem cell clinics pose a threat to the advancement of regenerative medicine, according to a team of Irish researchers.

"It is imperative that the scientific community is made aware of the threat to stem cell therapy posed by unregulated online clinics," researchers led by Dr. Ruairi Connolly wrote in a poster presented at the World Stem Cell Summit.

"These clinics are harnessing the Internet to attract a wide range of patients suffering from a diverse catalogue of conditions to therapies that are described in an attractive manner. A concerted effort from scientists, researchers, doctors, advocacy groups, and governments alike is required to rapidly address the existing legislative deficiencies to prevent these clinics from offering clinically unproven treatments to vulnerable patients."

Dr. Connolly, of National University of Ireland, Galway, and his associates conducted a web search using five terms: stem cell clinic, stem cell therapy, stem cell treatment center, stem cell cure, and stem cell treatment. Websites were included if they involved stem cells to treat human diseases. Of the 1,091 candidate websites, 68 met the inclusion criteria. The top five countries of origin housing online stem cell clinics were the United States (27), China (12), India (12), Thailand (11), and Mexico (9).

The majority of websites (88%) invited patients to contact them through online comment boxes. "In many instances patients are prompted to initiate contact by the promise of further information following such communication," the researchers wrote. In addition, 29% of clinics had an internationally recognized accreditation, but 65% of these were laboratory-related accreditations and were not pertinent to the clinical applications themselves. About one-third of clinics (34%) mention the number of patients they have treated while 25% provide outcome data and have patented their therapies.

The top 10 indications for stem cell therapy were multiple sclerosis, anti-aging, Parkinson’s disease, stroke, spinal cord injury, cerebral palsy, autism, amyotrophic lateral sclerosis, Alzheimer’s disease, and arthritis.

The top five types of stem cells reportedly used by the clinics were adult autologous (82%), umbilical (19%), adult-allogenic (12%), fetal (10%), and cord blood (9%). More than half of clinics (60%) reported that the stem cells were delivered intravenously.

In the realm of safety, 15% of online clinics state that there is "no risk" involved with stem cell therapy, and 88% claim treatment effectiveness, with 16% "describing the curative potential of therapy," according to Dr. Connolly and his colleagues. In addition, "9% refer to specific research publications to support their outcomes [and] over 40% of sites did not specify the number of treatments required, duration of procedure, or therapeutic course. Almost one-quarter of sites reference contraindications to treatment, with 41% of sites mentioning follow-up patient care."

"It remains beyond doubt that enhanced regulation would benefit vulnerable patients and also [would] protect the unquestionable, immense potential of stem cells as a therapy for human beings," the researchers concluded. "Stem cell therapy is only in its infancy and needs to [be] regulated and monitored adequately today so that it can change the lives of patients tomorrow."

The researchers stated that they had no conflicts of interest.

dbrunk@frontlinemedcom.com

SAN DIEGO – Online stem cell clinics pose a threat to the advancement of regenerative medicine, according to a team of Irish researchers.

"It is imperative that the scientific community is made aware of the threat to stem cell therapy posed by unregulated online clinics," researchers led by Dr. Ruairi Connolly wrote in a poster presented at the World Stem Cell Summit.

"These clinics are harnessing the Internet to attract a wide range of patients suffering from a diverse catalogue of conditions to therapies that are described in an attractive manner. A concerted effort from scientists, researchers, doctors, advocacy groups, and governments alike is required to rapidly address the existing legislative deficiencies to prevent these clinics from offering clinically unproven treatments to vulnerable patients."

Dr. Connolly, of National University of Ireland, Galway, and his associates conducted a web search using five terms: stem cell clinic, stem cell therapy, stem cell treatment center, stem cell cure, and stem cell treatment. Websites were included if they involved stem cells to treat human diseases. Of the 1,091 candidate websites, 68 met the inclusion criteria. The top five countries of origin housing online stem cell clinics were the United States (27), China (12), India (12), Thailand (11), and Mexico (9).

The majority of websites (88%) invited patients to contact them through online comment boxes. "In many instances patients are prompted to initiate contact by the promise of further information following such communication," the researchers wrote. In addition, 29% of clinics had an internationally recognized accreditation, but 65% of these were laboratory-related accreditations and were not pertinent to the clinical applications themselves. About one-third of clinics (34%) mention the number of patients they have treated while 25% provide outcome data and have patented their therapies.

The top 10 indications for stem cell therapy were multiple sclerosis, anti-aging, Parkinson’s disease, stroke, spinal cord injury, cerebral palsy, autism, amyotrophic lateral sclerosis, Alzheimer’s disease, and arthritis.

The top five types of stem cells reportedly used by the clinics were adult autologous (82%), umbilical (19%), adult-allogenic (12%), fetal (10%), and cord blood (9%). More than half of clinics (60%) reported that the stem cells were delivered intravenously.

In the realm of safety, 15% of online clinics state that there is "no risk" involved with stem cell therapy, and 88% claim treatment effectiveness, with 16% "describing the curative potential of therapy," according to Dr. Connolly and his colleagues. In addition, "9% refer to specific research publications to support their outcomes [and] over 40% of sites did not specify the number of treatments required, duration of procedure, or therapeutic course. Almost one-quarter of sites reference contraindications to treatment, with 41% of sites mentioning follow-up patient care."

"It remains beyond doubt that enhanced regulation would benefit vulnerable patients and also [would] protect the unquestionable, immense potential of stem cells as a therapy for human beings," the researchers concluded. "Stem cell therapy is only in its infancy and needs to [be] regulated and monitored adequately today so that it can change the lives of patients tomorrow."

The researchers stated that they had no conflicts of interest.

dbrunk@frontlinemedcom.com