Prostate cancer: Interventions aimed at improving morbidity, mortality

Abstract

In recent months, FDA approved Xtandi (enzalutamide—Astellas, Medivation), a new agent for metastatic castration-resistant prostate cancer, and expanded the approval of Zytiga (abiraterone—Janssen), an existing agent for the same patient population. In addition, recently published trials have shown the clinical activity of Cometriq (cabozantinib— Exelixis) for patients with advanced prostate cancer and bone metastases, as well as the benefits of aspirin therapy in reducing the risk of prostate cancer mortality in men treated with prostatectomy or radiotherapy.These topics will be reviewed in this article, in addition to an update on last year’s prostate-specific antigen (PSA) cancer screening controversy.Recent FDA approvals offer new hopeEnzalutamideIn August 2012, FDA announced the approval of enzalutamide to treat men with metastatic, castration-resistant prostate cancer who have previously received docetaxel. The agency approved this new therapy 3 months early under its priority review program. Enzalutamide, an androgen receptor signaling inhibitor, is an oral therapy taken as four 40-mg capsules (160 mg) once daily.■Enzalutamide and abiraterone offer new hope to men with metastatic, castration-resistant prostate cancer.■Different organizations have released conflicting PSA screening recommendations.FDA’s approval was based on data from 1,199 patients with metastatic, castration-resistant prostate cancer who had received prior treatment with docetaxel. Patients were randomized 2:1 to enzalutamide 160 mg/d (n = 800)or placebo (n = 399). Results from the trial, published in the September 27, 2012, issue of the New England Journal of Medicine, showed that median overall survival for patients receiving enzalutamide was 18.4 months, compared with 13.6 months for patients who received placebo (P < 0.001). This corresponded to a 37% reduction in the risk of death for patients treated with active drug.The superiority of enzalutamide to placebo was also shown with respect to secondary endpoints including the proportion of patients with a 50% or more reduction in prostate-specific antigen (PSA) level (54% vs. 2%, P < 0.001), soft-tissue response rate (29% vs. 4%, P < 0.001), quality-of-life response rate (43% vs. 18%, P < 0.001), radiographic progression-free survival (8.3 months vs. 2.9 months; P < 0.001), and time to first skeletal-related event (16.7 months vs. 13.3 months, P < 0.001). Fatigue, diarrhea, and hot flashes occurred more frequently in the enzalu- tamide group than with placebo, and seizures were reported in five patients (0.6%) receiving enzalutamide.AbirateroneIn December 2012, FDA announced its approval of abiraterone for use in men with metastatic, castration-resistant prostate cancer prior to receiving chemotherapy. The drug was initially approved in 2011 for use in men whose prostate cancer progressed after treatment with docetaxel. This new indication was granted under the agency’s priority review program.Approval was based on a doubleblind study involving 1,088 men with late-stage, castration-resistant prostate cancer who had not previously received chemotherapy. Patients were randomized to abiraterone 1,000 mg plus prednisone 5 mg twice daily or placebo plus prednisone. Results from the trial, published online in December 2012 in the New England Journal of Medicine, showed that radiographic progression-free survival was 16.5 months with abiraterone, compared with 8.3 months with prednisone alone (P < 0.001). In addition, over a median follow-up period of 22.2 months, overall survival was improved with abiraterone (median not reached vs. 27.2 mo for prednisone alone, P = 0.01). In terms of safety, Grade 3 or 4 mineralocorticoid-related adverse events and abnormalities on liver-function testing were more common with abiraterone.Management of bone metastasisCabozantinib is a tyrosine kinase inhibitor that recently received FDA approval for the management of progressive, metastatic medullary thyroid cancer (see story on page 34). It has also been studied in patients with advanced prostate cancer with promising results. According to a November 2012 study published online in the Journal of Clinical Oncology, cabozantinib has clinical activity in men with castration-resistant prostate cancer, including reduction of soft tissue lesions, improvement in progression-free survival, resolution of bone scans, and reductions in bone turnover markers, pain, and narcotic use.In this Phase II trial, men with castration-resistant prostate cancer were treated with cabozantinib 100 mg/d, and those with stable disease at 12 weeks were then randomly assigned to cabozantinib or placebo. The randomization phase of the trial was halted early based on the observed activity with cabozantinib after 12 weeks of therapy. After 12 weeks, approximately72% of men had regression in skin lesions and 68% of evaluable patients had improvements on their bone scan. For those who entered the randomization phase before it was terminated (n = 31), treatment with cabozantinib significantly improved progression-free survival compared with placebo (23.9 weeks vs. 5.9 weeks, P < 0.001). The investigators also reported that 67% of evaluable patients had an improvement in bone pain and 56% had a decrease in their narcotic use.Since the randomization phase of this Phase II trial was halted early, leaving only a small sample size, additional trials are needed to determine the true effects of cabozantinib on bone metastases. The Phase III trials COMET-1 and −2 (Cabozantinib MET Inhibition Castration-Resistant Prostate Cancer Efficacy Trial) are currently under way to evaluate the effects of cabozantinib on morbidity and mortality in men with advanced disease who have bone metastases.An aspirin a day to keep prostate cancer away?Researchers conducted a trial published in the October 1, 2012, issue of the Journal of Clinical Oncology suggesting that anticoagulation therapy, particularly aspirin, was associated with a reduced risk of prostate cancer-specific mortality in men treated with radical prostatectomy or radiotherapy.Data from several epidemiologic and prospective studies have suggested that anticoagulant therapies may reduce the incidence of prostate cancer development and that aspirin in particular may have a chemoprotective effect on prostate cancer. Based on these data, the researchers analyzed registry data for 5,955 men in the Cancer of the Prostate Strategic Urologic Research Endeavor to determine if aspirin could improve outcomes in those undergoing treatment for prostate cancer (i.e., radical prostatectomy or radiotherapy). Of the 5,955 men, 2,175 were receiving treatment with anticoagulants such as warfarin (21%), clopidogrel (14%), enoxaparin (27%), and/or aspirin (84%); 20% of patients received combination therapy.The investigators reported that after a median follow-up of 70 months, the risk of prostate cancer-specific mortality was lower among those in the anticoagulant group compared with other patients (3% vs. 8% at 10 y; P < 0.01). The risks of disease recurrence and bone metastasis were also significantly lower in the anticoagulant group.After analyzing data by type of anticoagulant medication, the researchers found evidence that the prostate cancer-specific mortality reduction was primarily associated with aspirin use. Multivariable analysis indicated that aspirin use was independently associated with a lower risk of prostate cancer-specific mortality (adjusted hazard ratio 0.43 [95% CI 0.21-0.87], P = 0.02). These results need to be further validated in a well-designed, prospective trial, but for now, it may be beneficial to recommend daily aspirin for men with prostate cancer.PSA screening: The battle continuesIn May 2012, the United States Preventive Services Task Force (USPSTF) recommended against routine screening for prostate cancer for most men. The task force stated, “There is moderate certainty that the benefits of PSA-based screening for prostate cancer do not outweigh the harms.” USPSTF noted that routine PSA screening could lead to false positives, which in turn could mean overdiagnosis and overtreatment. In addition, it discussed specific harms, including negative psychological effects such as persistent worry and treatment-related adverse effects such as urinary incontinence and erectile dysfunction.In July 2012, however, a panel of experts from the American Society for Clinical Oncology recommended that men with more than 10 years of life to live discuss with their doctors the risks and benefits of screening and whether they should get their PSA levels tested. They agreed with USPSTF that general PSA screening for prostate cancer should be discouraged for men with a life expectancy of 10 years or less because the harms outweigh the potential benefits.In response to these recommendations, the American Cancer Society and the American Urological Association agreed that men should discuss their options with their doctors before undergoing screening. In response to the USP- STF guidelines, the American Urologi- cal Association advised that “men who are in good health and have a 10–15 year life expectancy should have the choice to be tested and not be discouraged from doing so.” The association added, “It is inappropriate and irresponsible to issue a blanket statement against PSA testing, particularly for at-risk populations, such as African American men.”According to an analysis published in the December 1, 2012, issue of Cancer, eliminating PSA testing for prostate cancer would likely result in more men being diagnosed with metastatic prostate cancer at the time of diagnosis. Researchers analyzed the effect of screening on stage of disease at initial diagnosis by reviewing data from the Surveillance, Epidemiology, and End- Results cancer registry for 1983 to 2008. They compared data from the pre-PSA era (1983–1985) to the current era of widespread PSA use (2006–2008), adjusting findings for age, race, and geographic variations.The investigators noted that approximately 8,000 cases of prostate cancer with metastases at initial presentation occurred in the United States in 2008, compared with an estimated 25,000 metastatic cases expected in the absence of PSA screening, according to their mathematical model. They concluded that in general, the massive screening and PSA awareness efforts in the 1990s and early 2000s resulted in substantial shifts toward earlier-state disease and fewer cases of metastases at diagnosis.Experts on opposing sides will likely continue to differ over whether or not patients should have a PSA test well into the future.Future targetsProstate cancer researchers have been fairly active, with several new drug approvals and numerous studies evaluating the efficacy and safety of existing therapies. Ongoing research in this area is also focusing on more specific targets, such as blocking the activity of the EZH2 protein, which may be an effective intervention for those with castration-resistant prostate cancer. In recent months, FDA approved Xtandi (enzalutamide—Astellas, Medivation), a new agent for metastatic castration-resistant prostate cancer, and expanded the approval of Zytiga (abiraterone—Janssen), an existing agent for the same patient population. In addition, recently published trials have shown the clinical activity of Cometriq (cabozantinib— Exelixis) for patients with advanced prostate cancer and bone metastases, as well as the benefits of aspirin therapy in reducing the risk of prostate cancer mortality in men treated with prostatectomy or radiotherapy. These topics will be reviewed in this article, in addition to an update on last year’s prostate-specific antigen (PSA) cancer screening controversy. Recent FDA approvals offer new hopeEnzalutamideIn August 2012, FDA announced the approval of enzalutamide to treat men with metastatic, castration-resistant prostate cancer who have previously received docetaxel. The agency approved this new therapy 3 months early under its priority review program. Enzalutamide, an androgen receptor signaling inhibitor, is an oral therapy taken as four 40-mg capsules (160 mg) once daily.■Enzalutamide and abiraterone offer new hope to men with metastatic, castration-resistant prostate cancer.■Different organizations have released conflicting PSA screening recommendations.FDA’s approval was based on data from 1,199 patients with metastatic, castration-resistant prostate cancer who had received prior treatment with docetaxel. Patients were randomized 2:1 to enzalutamide 160 mg/d (n = 800)or placebo (n = 399). Results from the trial, published in the September 27, 2012, issue of the New England Journal of Medicine, showed that median overall survival for patients receiving enzalutamide was 18.4 months, compared with 13.6 months for patients who received placebo (P < 0.001). This corresponded to a 37% reduction in the risk of death for patients treated with active drug.The superiority of enzalutamide to placebo was also shown with respect to secondary endpoints including the proportion of patients with a 50% or more reduction in prostate-specific antigen (PSA) level (54% vs. 2%, P < 0.001), soft-tissue response rate (29% vs. 4%, P < 0.001), quality-of-life response rate (43% vs. 18%, P < 0.001), radiographic progression-free survival (8.3 months vs. 2.9 months; P < 0.001), and time to first skeletal-related event (16.7 months vs. 13.3 months, P < 0.001). Fatigue, diarrhea, and hot flashes occurred more frequently in the enzalu- tamide group than with placebo, and seizures were reported in five patients (0.6%) receiving enzalutamide.AbirateroneIn December 2012, FDA announced its approval of abiraterone for use in men with metastatic, castration-resistant prostate cancer prior to receiving chemotherapy. The drug was initially approved in 2011 for use in men whose prostate cancer progressed after treatment with docetaxel. This new indication was granted under the agency’s priority review program.Approval was based on a doubleblind study involving 1,088 men with late-stage, castration-resistant prostate cancer who had not previously received chemotherapy. Patients were randomized to abiraterone 1,000 mg plus prednisone 5 mg twice daily or placebo plus prednisone. Results from the trial, published online in December 2012 in the New England Journal of Medicine, showed that radiographic progression-free survival was 16.5 months with abiraterone, compared with 8.3 months with prednisone alone (P < 0.001). In addition, over a median follow-up period of 22.2 months, overall survival was improved with abiraterone (median not reached vs. 27.2 mo for prednisone alone, P = 0.01). In terms of safety, Grade 3 or 4 mineralocorticoid-related adverse events and abnormalities on liver-function testing were more common with abiraterone. EnzalutamideIn August 2012, FDA announced the approval of enzalutamide to treat men with metastatic, castration-resistant prostate cancer who have previously received docetaxel. The agency approved this new therapy 3 months early under its priority review program. Enzalutamide, an androgen receptor signaling inhibitor, is an oral therapy taken as four 40-mg capsules (160 mg) once daily.■Enzalutamide and abiraterone offer new hope to men with metastatic, castration-resistant prostate cancer.■Different organizations have released conflicting PSA screening recommendations.FDA’s approval was based on data from 1,199 patients with metastatic, castration-resistant prostate cancer who had received prior treatment with docetaxel. Patients were randomized 2:1 to enzalutamide 160 mg/d (n = 800)or placebo (n = 399). Results from the trial, published in the September 27, 2012, issue of the New England Journal of Medicine, showed that median overall survival for patients receiving enzalutamide was 18.4 months, compared with 13.6 months for patients who received placebo (P < 0.001). This corresponded to a 37% reduction in the risk of death for patients treated with active drug.The superiority of enzalutamide to placebo was also shown with respect to secondary endpoints including the proportion of patients with a 50% or more reduction in prostate-specific antigen (PSA) level (54% vs. 2%, P < 0.001), soft-tissue response rate (29% vs. 4%, P < 0.001), quality-of-life response rate (43% vs. 18%, P < 0.001), radiographic progression-free survival (8.3 months vs. 2.9 months; P < 0.001), and time to first skeletal-related event (16.7 months vs. 13.3 months, P < 0.001). Fatigue, diarrhea, and hot flashes occurred more frequently in the enzalu- tamide group than with placebo, and seizures were reported in five patients (0.6%) receiving enzalutamide. In August 2012, FDA announced the approval of enzalutamide to treat men with metastatic, castration-resistant prostate cancer who have previously received docetaxel. The agency approved this new therapy 3 months early under its priority review program. Enzalutamide, an androgen receptor signaling inhibitor, is an oral therapy taken as four 40-mg capsules (160 mg) once daily. ■Enzalutamide and abiraterone offer new hope to men with metastatic, castration-resistant prostate cancer.■Different organizations have released conflicting PSA screening recommendations. ■Enzalutamide and abiraterone offer new hope to men with metastatic, castration-resistant prostate cancer.■Different organizations have released conflicting PSA screening recommendations. ■Enzalutamide and abiraterone offer new hope to men with metastatic, castration-resistant prostate cancer.■Different organizations have released conflicting PSA screening recommendations. FDA’s approval was based on data from 1,199 patients with metastatic, castration-resistant prostate cancer who had received prior treatment with docetaxel. Patients were randomized 2:1 to enzalutamide 160 mg/d (n = 800) or placebo (n = 399). Results from the trial, published in the September 27, 2012, issue of the New England Journal of Medicine, showed that median overall survival for patients receiving enzalutamide was 18.4 months, compared with 13.6 months for patients who received placebo (P < 0.001). This corresponded to a 37% reduction in the risk of death for patients treated with active drug. The superiority of enzalutamide to placebo was also shown with respect to secondary endpoints including the proportion of patients with a 50% or more reduction in prostate-specific antigen (PSA) level (54% vs. 2%, P < 0.001), soft-tissue response rate (29% vs. 4%, P < 0.001), quality-of-life response rate (43% vs. 18%, P < 0.001), radiographic progression-free survival (8.3 months vs. 2.9 months; P < 0.001), and time to first skeletal-related event (16.7 months vs. 13.3 months, P < 0.001). Fatigue, diarrhea, and hot flashes occurred more frequently in the enzalu- tamide group than with placebo, and seizures were reported in five patients (0.6%) receiving enzalutamide. AbirateroneIn December 2012, FDA announced its approval of abiraterone for use in men with metastatic, castration-resistant prostate cancer prior to receiving chemotherapy. The drug was initially approved in 2011 for use in men whose prostate cancer progressed after treatment with docetaxel. This new indication was granted under the agency’s priority review program.Approval was based on a doubleblind study involving 1,088 men with late-stage, castration-resistant prostate cancer who had not previously received chemotherapy. Patients were randomized to abiraterone 1,000 mg plus prednisone 5 mg twice daily or placebo plus prednisone. Results from the trial, published online in December 2012 in the New England Journal of Medicine, showed that radiographic progression-free survival was 16.5 months with abiraterone, compared with 8.3 months with prednisone alone (P < 0.001). In addition, over a median follow-up period of 22.2 months, overall survival was improved with abiraterone (median not reached vs. 27.2 mo for prednisone alone, P = 0.01). In terms of safety, Grade 3 or 4 mineralocorticoid-related adverse events and abnormalities on liver-function testing were more common with abiraterone. In December 2012, FDA announced its approval of abiraterone for use in men with metastatic, castration-resistant prostate cancer prior to receiving chemotherapy. The drug was initially approved in 2011 for use in men whose prostate cancer progressed after treatment with docetaxel. This new indication was granted under the agency’s priority review program. Approval was based on a doubleblind study involving 1,088 men with late-stage, castration-resistant prostate cancer who had not previously received chemotherapy. Patients were randomized to abiraterone 1,000 mg plus prednisone 5 mg twice daily or placebo plus prednisone. Results from the trial, published online in December 2012 in the New England Journal of Medicine, showed that radiographic progression-free survival was 16.5 months with abiraterone, compared with 8.3 months with prednisone alone (P < 0.001). In addition, over a median follow-up period of 22.2 months, overall survival was improved with abiraterone (median not reached vs. 27.2 mo for prednisone alone, P = 0.01). In terms of safety, Grade 3 or 4 mineralocorticoid-related adverse events and abnormalities on liver-function testing were more common with abiraterone. Management of bone metastasisCabozantinib is a tyrosine kinase inhibitor that recently received FDA approval for the management of progressive, metastatic medullary thyroid cancer (see story on page 34). It has also been studied in patients with advanced prostate cancer with promising results. According to a November 2012 study published online in the Journal of Clinical Oncology, cabozantinib has clinical activity in men with castration-resistant prostate cancer, including reduction of soft tissue lesions, improvement in progression-free survival, resolution of bone scans, and reductions in bone turnover markers, pain, and narcotic use.In this Phase II trial, men with castration-resistant prostate cancer were treated with cabozantinib 100 mg/d, and those with stable disease at 12 weeks were then randomly assigned to cabozantinib or placebo. The randomization phase of the trial was halted early based on the observed activity with cabozantinib after 12 weeks of therapy. After 12 weeks, approximately72% of men had regression in skin lesions and 68% of evaluable patients had improvements on their bone scan. For those who entered the randomization phase before it was terminated (n = 31), treatment with cabozantinib significantly improved progression-free survival compared with placebo (23.9 weeks vs. 5.9 weeks, P < 0.001). The investigators also reported that 67% of evaluable patients had an improvement in bone pain and 56% had a decrease in their narcotic use.Since the randomization phase of this Phase II trial was halted early, leaving only a small sample size, additional trials are needed to determine the true effects of cabozantinib on bone metastases. The Phase III trials COMET-1 and −2 (Cabozantinib MET Inhibition Castration-Resistant Prostate Cancer Efficacy Trial) are currently under way to evaluate the effects of cabozantinib on morbidity and mortality in men with advanced disease who have bone metastases. Cabozantinib is a tyrosine kinase inhibitor that recently received FDA approval for the management of progressive, metastatic medullary thyroid cancer (see story on page 34). It has also been studied in patients with advanced prostate cancer with promising results. According to a November 2012 study published online in the Journal of Clinical Oncology, cabozantinib has clinical activity in men with castration-resistant prostate cancer, including reduction of soft tissue lesions, improvement in progression-free survival, resolution of bone scans, and reductions in bone turnover markers, pain, and narcotic use. In this Phase II trial, men with castration-resistant prostate cancer were treated with cabozantinib 100 mg/d, and those with stable disease at 12 weeks were then randomly assigned to cabozantinib or placebo. The randomization phase of the trial was halted early based on the observed activity with cabozantinib after 12 weeks of therapy. After 12 weeks, approximately 72% of men had regression in skin lesions and 68% of evaluable patients had improvements on their bone scan. For those who entered the randomization phase before it was terminated (n = 31), treatment with cabozantinib significantly improved progression-free survival compared with placebo (23.9 weeks vs. 5.9 weeks, P < 0.001). The investigators also reported that 67% of evaluable patients had an improvement in bone pain and 56% had a decrease in their narcotic use. Since the randomization phase of this Phase II trial was halted early, leaving only a small sample size, additional trials are needed to determine the true effects of cabozantinib on bone metastases. The Phase III trials COMET-1 and −2 (Cabozantinib MET Inhibition Castration-Resistant Prostate Cancer Efficacy Trial) are currently under way to evaluate the effects of cabozantinib on morbidity and mortality in men with advanced disease who have bone metastases. An aspirin a day to keep prostate cancer away?Researchers conducted a trial published in the October 1, 2012, issue of the Journal of Clinical Oncology suggesting that anticoagulation therapy, particularly aspirin, was associated with a reduced risk of prostate cancer-specific mortality in men treated with radical prostatectomy or radiotherapy.Data from several epidemiologic and prospective studies have suggested that anticoagulant therapies may reduce the incidence of prostate cancer development and that aspirin in particular may have a chemoprotective effect on prostate cancer. Based on these data, the researchers analyzed registry data for 5,955 men in the Cancer of the Prostate Strategic Urologic Research Endeavor to determine if aspirin could improve outcomes in those undergoing treatment for prostate cancer (i.e., radical prostatectomy or radiotherapy). Of the 5,955 men, 2,175 were receiving treatment with anticoagulants such as warfarin (21%), clopidogrel (14%), enoxaparin (27%), and/or aspirin (84%); 20% of patients received combination therapy.The investigators reported that after a median follow-up of 70 months, the risk of prostate cancer-specific mortality was lower among those in the anticoagulant group compared with other patients (3% vs. 8% at 10 y; P < 0.01). The risks of disease recurrence and bone metastasis were also significantly lower in the anticoagulant group.After analyzing data by type of anticoagulant medication, the researchers found evidence that the prostate cancer-specific mortality reduction was primarily associated with aspirin use. Multivariable analysis indicated that aspirin use was independently associated with a lower risk of prostate cancer-specific mortality (adjusted hazard ratio 0.43 [95% CI 0.21-0.87], P = 0.02). These results need to be further validated in a well-designed, prospective trial, but for now, it may be beneficial to recommend daily aspirin for men with prostate cancer. Researchers conducted a trial published in the October 1, 2012, issue of the Journal of Clinical Oncology suggesting that anticoagulation therapy, particularly aspirin, was associated with a reduced risk of prostate cancer-specific mortality in men treated with radical prostatectomy or radiotherapy. Data from several epidemiologic and prospective studies have suggested that anticoagulant therapies may reduce the incidence of prostate cancer development and that aspirin in particular may have a chemoprotective effect on prostate cancer. Based on these data, the researchers analyzed registry data for 5,955 men in the Cancer of the Prostate Strategic Urologic Research Endeavor to determine if aspirin could improve outcomes in those undergoing treatment for prostate cancer (i.e., radical prostatectomy or radiotherapy). Of the 5,955 men, 2,175 were receiving treatment with anticoagulants such as warfarin (21%), clopidogrel (14%), enoxaparin (27%), and/or aspirin (84%); 20% of patients received combination therapy. The investigators reported that after a median follow-up of 70 months, the risk of prostate cancer-specific mortality was lower among those in the anticoagulant group compared with other patients (3% vs. 8% at 10 y; P < 0.01). The risks of disease recurrence and bone metastasis were also significantly lower in the anticoagulant group. After analyzing data by type of anticoagulant medication, the researchers found evidence that the prostate cancer-specific mortality reduction was primarily associated with aspirin use. Multivariable analysis indicated that aspirin use was independently associated with a lower risk of prostate cancer-specific mortality (adjusted hazard ratio 0.43 [95% CI 0.21-0.87], P = 0.02). These results need to be further validated in a well-designed, prospective trial, but for now, it may be beneficial to recommend daily aspirin for men with prostate cancer. PSA screening: The battle continuesIn May 2012, the United States Preventive Services Task Force (USPSTF) recommended against routine screening for prostate cancer for most men. The task force stated, “There is moderate certainty that the benefits of PSA-based screening for prostate cancer do not outweigh the harms.” USPSTF noted that routine PSA screening could lead to false positives, which in turn could mean overdiagnosis and overtreatment. In addition, it discussed specific harms, including negative psychological effects such as persistent worry and treatment-related adverse effects such as urinary incontinence and erectile dysfunction.In July 2012, however, a panel of experts from the American Society for Clinical Oncology recommended that men with more than 10 years of life to live discuss with their doctors the risks and benefits of screening and whether they should get their PSA levels tested. They agreed with USPSTF that general PSA screening for prostate cancer should be discouraged for men with a life expectancy of 10 years or less because the harms outweigh the potential benefits.In response to these recommendations, the American Cancer Society and the American Urological Association agreed that men should discuss their options with their doctors before undergoing screening. In response to the USP- STF guidelines, the American Urologi- cal Association advised that “men who are in good health and have a 10–15 year life expectancy should have the choice to be tested and not be discouraged from doing so.” The association added, “It is inappropriate and irresponsible to issue a blanket statement against PSA testing, particularly for at-risk populations, such as African American men.”According to an analysis published in the December 1, 2012, issue of Cancer, eliminating PSA testing for prostate cancer would likely result in more men being diagnosed with metastatic prostate cancer at the time of diagnosis. Researchers analyzed the effect of screening on stage of disease at initial diagnosis by reviewing data from the Surveillance, Epidemiology, and End- Results cancer registry for 1983 to 2008. They compared data from the pre-PSA era (1983–1985) to the current era of widespread PSA use (2006–2008), adjusting findings for age, race, and geographic variations.The investigators noted that approximately 8,000 cases of prostate cancer with metastases at initial presentation occurred in the United States in 2008, compared with an estimated 25,000 metastatic cases expected in the absence of PSA screening, according to their mathematical model. They concluded that in general, the massive screening and PSA awareness efforts in the 1990s and early 2000s resulted in substantial shifts toward earlier-state disease and fewer cases of metastases at diagnosis.Experts on opposing sides will likely continue to differ over whether or not patients should have a PSA test well into the future. In May 2012, the United States Preventive Services Task Force (USPSTF) recommended against routine screening for prostate cancer for most men. The task force stated, “There is moderate certainty that the benefits of PSA-based screening for prostate cancer do not outweigh the harms.” USPSTF noted that routine PSA screening could lead to false positives, which in turn could mean overdiagnosis and overtreatment. In addition, it discussed specific harms, including negative psychological effects such as persistent worry and treatment-related adverse effects such as urinary incontinence and erectile dysfunction. In July 2012, however, a panel of experts from the American Society for Clinical Oncology recommended that men with more than 10 years of life to live discuss with their doctors the risks and benefits of screening and whether they should get their PSA levels tested. They agreed with USPSTF that general PSA screening for prostate cancer should be discouraged for men with a life expectancy of 10 years or less because the harms outweigh the potential benefits. In response to these recommendations, the American Cancer Society and the American Urological Association agreed that men should discuss their options with their doctors before undergoing screening. In response to the USP- STF guidelines, the American Urologi- cal Association advised that “men who are in good health and have a 10–15 year life expectancy should have the choice to be tested and not be discouraged from doing so.” The association added, “It is inappropriate and irresponsible to issue a blanket statement against PSA testing, particularly for at-risk populations, such as African American men.” According to an analysis published in the December 1, 2012, issue of Cancer, eliminating PSA testing for prostate cancer would likely result in more men being diagnosed with metastatic prostate cancer at the time of diagnosis. Researchers analyzed the effect of screening on stage of disease at initial diagnosis by reviewing data from the Surveillance, Epidemiology, and End- Results cancer registry for 1983 to 2008. They compared data from the pre-PSA era (1983–1985) to the current era of widespread PSA use (2006–2008), adjusting findings for age, race, and geographic variations. The investigators noted that approximately 8,000 cases of prostate cancer with metastases at initial presentation occurred in the United States in 2008, compared with an estimated 25,000 metastatic cases expected in the absence of PSA screening, according to their mathematical model. They concluded that in general, the massive screening and PSA awareness efforts in the 1990s and early 2000s resulted in substantial shifts toward earlier-state disease and fewer cases of metastases at diagnosis. Experts on opposing sides will likely continue to differ over whether or not patients should have a PSA test well into the future. Future targetsProstate cancer researchers have been fairly active, with several new drug approvals and numerous studies evaluating the efficacy and safety of existing therapies. Ongoing research in this area is also focusing on more specific targets, such as blocking the activity of the EZH2 protein, which may be an effective intervention for those with castration-resistant prostate cancer. Prostate cancer researchers have been fairly active, with several new drug approvals and numerous studies evaluating the efficacy and safety of existing therapies. Ongoing research in this area is also focusing on more specific targets, such as blocking the activity of the EZH2 protein, which may be an effective intervention for those with castration-resistant prostate cancer.