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PD6-03 METFORMIN USE PREDICTS AN OVERALL SURVIVAL ADVANTAGE IN DIABETIC VETERANS WITH PROSTATE CANCER
THE JOURNAL OF UROLOGYâ
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Vol. 193, No. 4S, Supplement, Friday, May 15, 2015
PD6-02 Prostate Cancer: Epidemiology & Natural History II Podium 6 Friday, May 15, 2015
3:30 PM-5:30 PM
PD6-01 ASPIRIN, NSAID AND RISK OF HIGH-GRADE PROSTATE CANCER: RESULTS FROM THE REDUCE STUDY Adriana C. Vidal*, Lauren E. Howard, Durham, NC; Daniel M. Moreira, Rochester, MN; Ramiro Castro-Santamaria, King of Prussia, PA; Gerald L. Andriole, St. Louis, MO; Stephen J. Freedland, Durham, NC INTRODUCTION AND OBJECTIVES: A recent meta-analysis showed aspirin was associated with a reduced risk of total prostate cancer (PC) however the effect of non-aspirin NSAID on PC appeared to vary by geographic region. In North America non-aspirin NSAID were null to protective while studies from Europe found either null or positive associations between PC and any NSAID use. However, as anti-inflammatory medications can alter PSA levels, which is the chief driver of PC detection, whether these findings reflect reduced detection of PC or truly a biological link with lower PC risk is unknown. We tested the association between aspirin and non-aspirin NSAID on PC diagnosis among men with an elevated PSA and negative pre-study biopsy in the REDUCE study where all men received biopsies at 2- and 4-years regardless of PSA levels. METHODS: The REDUCE study tested dutasteride for PC risk reduction in men with a PSA of 2.5-10.0 ng/mL and a negative biopsy. Study participants included 6,390 men who underwent at least one onstudy biopsy. The associations between aspirin users, NSAID users or both users, and risk of total and low-grade (Gleason <7) or high-grade (Gleason 7) PC vs. no PC were examined using multinomial logistic regression as well as stratified analysis by geographic region (Europe vs. North America) and treatment arm. RESULTS: Overall, 3,169 men (50%) were non-users, 1,368 (21%) used aspirin, 1,176 (18%) used NSAID, and 677 (11%) used both. In multivariable analyses, aspirin was associated with reduced risk of total PC (OR¼0.81, p¼0.015). Use of NSAID or both was not associated with total, low- or high-grade PC, though all ORs were <1 (all p0.08). Therefore, we created a dichotomous variable of aspirin and/or NSAID user vs. not. When this was done, on multivariable analysis, the use of aspirin and/or NSAID was significantly associated with decreased total (OR¼0.87, p¼0.030) and high-grade PC (OR¼0.83, p¼0.040), but not with low-grade PC risk (OR¼0.90, p¼0.15). When analyses were stratified by geographic region the association between intake of aspirin, NSAID, both, or either (i.e. the dichotomous variable of any aspirin and/or NSAID) and reduced risk of PC was similar in Europe and North America (p-interaction>0.41). Results were similar in placebo and dutasteride treated men. CONCLUSIONS: Among men in the REDUCE study use of aspirin and/or NSAID was associated with decreased risk of total PC and high-grade PC. These data provide further support to the hypothesis that anti-inflammatory drugs may help reduce the risk of PC. Prospective trials to test this hypothesis are warranted. Source of Funding: NIH 1-R01-CA131235-01A1, 1K24CA160653, GlaxoSmithKline (GSK)
5-ALPHA REDUCTASE INHIBITOR USE AND PROSTATE CANCER SURVIVAL IN THE FINNISH PROSTATE CANCER SCREENING TRIAL Teemu Murtola*, Elina Karppa, Tampere, Finland; Kimmo Taari, Helsinki, Finland; Teuvo Tammela, Anssi Auvinen, Tampere, Finland INTRODUCTION AND OBJECTIVES: Increased proportion of high-grade tumors (Gleason score 8 or greater) in users of 5alphareductase inhibitors (5-ARIs) has led to concerns about safety of the drug group. We studied whether 5-ARI use affects disease-specific survival in men with prostate cancer. METHODS: The source population consisted of 6,537 prostate cancer cases diagnosed in the Finnish Prostate Cancer Screening Trial and linked to the national prescription database for information on medication use. Cox proportional hazards regression was used to estimate hazard ratios and 95% confidence intervals for prostate cancerspecific deaths. For comparison, we also evaluated survival among alpha-blocker users. RESULTS: During the median follow-up of 7.5 years after diagnosis the risk of prostate cancer death did not differ between 5-ARI users and non-users (multivariable adjusted HR 1.11, 95% CI 0.811.50). Alpha-blocker usage was associated with increased risk of prostate cancer death during the first years of usage (HR 1.35, 95% CI 1.13-1.62). No consistent mortality trends by cumulative use were observed for either drug group. Limitation is that we had no information on the lower urinary tract symptoms among the participants and thus could not evaluate their association with prostate cancer deaths. CONCLUSIONS: 5-ARI usage does not affect prostate cancer mortality when used in management of benign prostatic hyperplasia. The previously reported increased proportion of high-grade tumors among 5-ARI users may be due to more accurate diagnostics. Increased risk associated with alpha-blocker usage is a novel finding and should prompt further exploration on the prognostic role of lower urinary tract symptoms. Source of Funding: Finnish Cultural Foundation, Finnish Surgical Society, Finnish Medical Association, Maud Kuistila Memorial Fund, and competitive research funding of the Pirkanmaa Hospital District
PD6-03 METFORMIN USE PREDICTS AN OVERALL SURVIVAL ADVANTAGE IN DIABETIC VETERANS WITH PROSTATE CANCER Daniel Reznicek*, Elena Klyushnenkova, Richard Alexander, Baltimore, MD INTRODUCTION AND OBJECTIVES: Prostate cancer is the most common male malignant tumor in the United States and much research has focused on identifying drugs that may impact disease progression and survival. Several studies have shown improved survival in diabetic men using metformin; however, these studies did not evaluate if the effect was due to better diabetic control. This study evaluates the association of metformin, diabetic control, and all-cause mortality among diabetic veterans with prostate cancer at the Baltimore Veterans Administration (VA). METHODS: Using a retrospective cohort design, all men with a positive prostate biopsy and prior diabetic diagnosis at the Baltimore VA from 2002 to 2010 were evaluated. The effect of anti-diabetic medication exposure on all-cause mortality was examined using KaplanMeyer’s survival analysis and multivariable Cox proportional hazard (PH) models. RESULTS: A total of 1,155 men were diagnosed with prostate cancer by transrectal ultrasound biopsies. Of those, 208 had a prior diagnosis of diabetes with no prior history of prostate cancer. During a median follow up period of 5.5 years, 74 men (36%) died. Survival analysis demonstrated that metformin use was associated with a
THE JOURNAL OF UROLOGYâ
Vol. 193, No. 4S, Supplement, Friday, May 15, 2015
significant increase in median time-to-death (p<0.001, log rank test, Figure 1). In the PH model, metformin use resulted in a mortality hazard ratio of 0.39 compared to non-users controlling for age, stage at diagnosis and treatment modality (95% CI 0.24, 0.65, p<0.001). In contrast, the effects of insulin, glyburide, glipizide and statins were not significant. Hemoglobin A1C level at prostate cancer diagnosis, Charlson comorbidity index, and Gleason score also did not show statistically significant effects in the PH model in the presence of other covariates. CONCLUSIONS: Metformin use was associated with a significant survival advantage for diabetic veterans with prostate cancer.
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the cumulative hazard of death from prostate cancer was 0.3% (95% CI 0.1-1.2) and 0.3% (95% CI 0.1-1.2) and death from any cause was 7.0% (95% CI 4.6-9.6) and 27.2% (95% CI 15.4-46.9) (Figure). CONCLUSIONS: AS appears to be a safe management strategy for carefully selected men with favorable-risk prostate cancer. For those with an extended life expectancy (>15 years), surveillance may be safest in the setting of very low risk disease.
Source of Funding: None.
PD6-05 Source of Funding: None
PD6-04 A PROSPECTIVE, LONGITUDINAL ACTIVE SURVEILLANCE PROGRAM FOR FAVORABLE-RISK PROSTATE CANCER: LONG TERM OUTCOMES Jeffrey Tosoian*, Mufaddal Mamawala, Jonathan Epstein, Patricia Landis, Sacha Wolf, Bruce Trock, H. Ballentine Carter, Baltimore, MD INTRODUCTION AND OBJECTIVES: Active surveillance (AS) is an alternative to immediate treatment aimed at reducing overtreatment of favorable risk prostate cancer. We sought to describe long term outcomes in men enrolled in a prospective, longitudinal AS program. METHODS: Since 1995, 1298 men with favorable-risk prostate cancer have enrolled in AS at median age 66 years (range 41e92). 926 (71.3%) men had very low risk and 372 (28.7%) had low risk disease. Triggers for intervention were reclassification on biopsy (cancer extent or grade). Primary outcomes were overall (OS), cancer specific (CSS), and metastasis-free survival (MFS); secondary outcomes were freedom from grade reclassification (GR) (Gleason score 7 or above), treatmentfree survival (TFS), and biochemical recurrence (BCR) in those who underwent treatment. Outcomes were evaluated using Kaplan-Meier survival analysis and comparisons were made using the log-rank test. RESULTS: Median follow-up was 5.0 years (range 0.01-18.0) and 174 (13.4%) men were followed for 10 years or more (6,766 person-years of follow-up). At 10 and 15 years from diagnosis, OS was 93.2% and 68.7%, CSS was 99.9% and 99.9%, and MFS was 99.4% and 99.4%, respectively. The 5, 10, and 15 year freedom from GR was 82.3%, 70.2%, and 62.7%, and TFS was 60.5%, 44.1%, and 37.3%, respectively. There was no significant difference between proportions of men with very low risk disease and low risk disease that had GR (17.4%, 19.4%; p¼0.73) or underwent curative intervention (36.0%, 37.1%; p¼0.42). For 138 men treated surgically and 149 treated with radiation, the 5-year freedom from BCR was 88.7% and 91.5%, respectively among those with at least one year of follow-up. There was no difference in BCR when comparing treatment modalities (p¼0.90). There were 2 deaths from prostate cancer; at 10 years and 15 years,
CHANGE IN PREDICTED PROGNOSIS AFTER RADICAL PROSTATECTOMY DURING FOLLOW-UP IN AN ACTIVE SURVEILLANCE COHORT John B. Eifler, Jr.*, Daren Diiorio, Chaochen You, Nashville, TN; Vidhush Yarlagadda, Birmingham, AL; David F. Penson, Joseph A. Smith, Jr., Sam Chang, Nashville, TN; Michael S. Cookson, Oklahoma City, OK; Daniel A. Barocas, Nashville, TN INTRODUCTION AND OBJECTIVES: The objective of active surveillance (AS) for prostate cancer is to delay the morbidities of curative intervention while minimizing the likelihood of developing incurable disease. To determine the curability of AS patients, we calculated the predicted pretreatment probability of biochemical recurrence within 10 years after radical prostatectomy (BCR-RP) at the time of each follow-up biopsy using a commonly available nomogram. METHODS: The study population consisted of men with Gleason 3þ3¼6 prostate cancer who elected AS at our institution between 2004 and 2012. Biopsies were recommended every 12e18 months. Inclusion required at least one follow-up biopsy after diagnosis. At the time of each biopsy, the predicted BCR-RP was calculated using an externally validated preoperative nomogram. Survival analysis was performed to estimate the incidence of a BCR-RP >10% during AS. A separate logistic regression analysis was performed to evaluate clinical factors at the time of biopsy associated with suboptimal BCR-RP. RESULTS: With a median follow-up interval of 21.4 months (range 3 e 89.7 mo) and median number of biopsies of 2 (range 2e7), 213 patients met inclusion criteria and underwent a total of 351 followup biopsies. Overall, the median predicted BCR-RP at the time of follow-up biopsy was 3 (range 0e36). Over the duration of follow-up, the proportion of patients with a likelihood of BCR-RP above 10% increased with each passing year (3.4%, 6.7%, 20.1%, 39.9%, and 63.3%). On multivariable logistic regression analysis, at the time of any follow-up biopsy, age (O.R. 1.06, p ¼ 0.029), log PSA density (O.R. 4.06, p ¼ 0.007), the number of positive cores on previous biopsy (O.R. 1.36, p ¼ 0.013), and interval since the prior biopsy of 2 years (referent < 1 year, O.R. 4.68, p ¼ 0.014) were associated with BCR-RP>10%. CONCLUSIONS: Active surveillance safely maintains curability in the majority of men with Gleason 6 prostate cancer. However, within 5 years of entering surveillance, more than half of men would have a
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Vol. 193, No. 4S, Supplement, Friday, May 15, 2015
PD6-02 Prostate Cancer: Epidemiology & Natural History II Podium 6 Friday, May 15, 2015
3:30 PM-5:30 PM
PD6-01 ASPIRIN, NSAID AND RISK OF HIGH-GRADE PROSTATE CANCER: RESULTS FROM THE REDUCE STUDY Adriana C. Vidal*, Lauren E. Howard, Durham, NC; Daniel M. Moreira, Rochester, MN; Ramiro Castro-Santamaria, King of Prussia, PA; Gerald L. Andriole, St. Louis, MO; Stephen J. Freedland, Durham, NC INTRODUCTION AND OBJECTIVES: A recent meta-analysis showed aspirin was associated with a reduced risk of total prostate cancer (PC) however the effect of non-aspirin NSAID on PC appeared to vary by geographic region. In North America non-aspirin NSAID were null to protective while studies from Europe found either null or positive associations between PC and any NSAID use. However, as anti-inflammatory medications can alter PSA levels, which is the chief driver of PC detection, whether these findings reflect reduced detection of PC or truly a biological link with lower PC risk is unknown. We tested the association between aspirin and non-aspirin NSAID on PC diagnosis among men with an elevated PSA and negative pre-study biopsy in the REDUCE study where all men received biopsies at 2- and 4-years regardless of PSA levels. METHODS: The REDUCE study tested dutasteride for PC risk reduction in men with a PSA of 2.5-10.0 ng/mL and a negative biopsy. Study participants included 6,390 men who underwent at least one onstudy biopsy. The associations between aspirin users, NSAID users or both users, and risk of total and low-grade (Gleason <7) or high-grade (Gleason 7) PC vs. no PC were examined using multinomial logistic regression as well as stratified analysis by geographic region (Europe vs. North America) and treatment arm. RESULTS: Overall, 3,169 men (50%) were non-users, 1,368 (21%) used aspirin, 1,176 (18%) used NSAID, and 677 (11%) used both. In multivariable analyses, aspirin was associated with reduced risk of total PC (OR¼0.81, p¼0.015). Use of NSAID or both was not associated with total, low- or high-grade PC, though all ORs were <1 (all p0.08). Therefore, we created a dichotomous variable of aspirin and/or NSAID user vs. not. When this was done, on multivariable analysis, the use of aspirin and/or NSAID was significantly associated with decreased total (OR¼0.87, p¼0.030) and high-grade PC (OR¼0.83, p¼0.040), but not with low-grade PC risk (OR¼0.90, p¼0.15). When analyses were stratified by geographic region the association between intake of aspirin, NSAID, both, or either (i.e. the dichotomous variable of any aspirin and/or NSAID) and reduced risk of PC was similar in Europe and North America (p-interaction>0.41). Results were similar in placebo and dutasteride treated men. CONCLUSIONS: Among men in the REDUCE study use of aspirin and/or NSAID was associated with decreased risk of total PC and high-grade PC. These data provide further support to the hypothesis that anti-inflammatory drugs may help reduce the risk of PC. Prospective trials to test this hypothesis are warranted. Source of Funding: NIH 1-R01-CA131235-01A1, 1K24CA160653, GlaxoSmithKline (GSK)
5-ALPHA REDUCTASE INHIBITOR USE AND PROSTATE CANCER SURVIVAL IN THE FINNISH PROSTATE CANCER SCREENING TRIAL Teemu Murtola*, Elina Karppa, Tampere, Finland; Kimmo Taari, Helsinki, Finland; Teuvo Tammela, Anssi Auvinen, Tampere, Finland INTRODUCTION AND OBJECTIVES: Increased proportion of high-grade tumors (Gleason score 8 or greater) in users of 5alphareductase inhibitors (5-ARIs) has led to concerns about safety of the drug group. We studied whether 5-ARI use affects disease-specific survival in men with prostate cancer. METHODS: The source population consisted of 6,537 prostate cancer cases diagnosed in the Finnish Prostate Cancer Screening Trial and linked to the national prescription database for information on medication use. Cox proportional hazards regression was used to estimate hazard ratios and 95% confidence intervals for prostate cancerspecific deaths. For comparison, we also evaluated survival among alpha-blocker users. RESULTS: During the median follow-up of 7.5 years after diagnosis the risk of prostate cancer death did not differ between 5-ARI users and non-users (multivariable adjusted HR 1.11, 95% CI 0.811.50). Alpha-blocker usage was associated with increased risk of prostate cancer death during the first years of usage (HR 1.35, 95% CI 1.13-1.62). No consistent mortality trends by cumulative use were observed for either drug group. Limitation is that we had no information on the lower urinary tract symptoms among the participants and thus could not evaluate their association with prostate cancer deaths. CONCLUSIONS: 5-ARI usage does not affect prostate cancer mortality when used in management of benign prostatic hyperplasia. The previously reported increased proportion of high-grade tumors among 5-ARI users may be due to more accurate diagnostics. Increased risk associated with alpha-blocker usage is a novel finding and should prompt further exploration on the prognostic role of lower urinary tract symptoms. Source of Funding: Finnish Cultural Foundation, Finnish Surgical Society, Finnish Medical Association, Maud Kuistila Memorial Fund, and competitive research funding of the Pirkanmaa Hospital District
PD6-03 METFORMIN USE PREDICTS AN OVERALL SURVIVAL ADVANTAGE IN DIABETIC VETERANS WITH PROSTATE CANCER Daniel Reznicek*, Elena Klyushnenkova, Richard Alexander, Baltimore, MD INTRODUCTION AND OBJECTIVES: Prostate cancer is the most common male malignant tumor in the United States and much research has focused on identifying drugs that may impact disease progression and survival. Several studies have shown improved survival in diabetic men using metformin; however, these studies did not evaluate if the effect was due to better diabetic control. This study evaluates the association of metformin, diabetic control, and all-cause mortality among diabetic veterans with prostate cancer at the Baltimore Veterans Administration (VA). METHODS: Using a retrospective cohort design, all men with a positive prostate biopsy and prior diabetic diagnosis at the Baltimore VA from 2002 to 2010 were evaluated. The effect of anti-diabetic medication exposure on all-cause mortality was examined using KaplanMeyer’s survival analysis and multivariable Cox proportional hazard (PH) models. RESULTS: A total of 1,155 men were diagnosed with prostate cancer by transrectal ultrasound biopsies. Of those, 208 had a prior diagnosis of diabetes with no prior history of prostate cancer. During a median follow up period of 5.5 years, 74 men (36%) died. Survival analysis demonstrated that metformin use was associated with a
THE JOURNAL OF UROLOGYâ
Vol. 193, No. 4S, Supplement, Friday, May 15, 2015
significant increase in median time-to-death (p<0.001, log rank test, Figure 1). In the PH model, metformin use resulted in a mortality hazard ratio of 0.39 compared to non-users controlling for age, stage at diagnosis and treatment modality (95% CI 0.24, 0.65, p<0.001). In contrast, the effects of insulin, glyburide, glipizide and statins were not significant. Hemoglobin A1C level at prostate cancer diagnosis, Charlson comorbidity index, and Gleason score also did not show statistically significant effects in the PH model in the presence of other covariates. CONCLUSIONS: Metformin use was associated with a significant survival advantage for diabetic veterans with prostate cancer.
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the cumulative hazard of death from prostate cancer was 0.3% (95% CI 0.1-1.2) and 0.3% (95% CI 0.1-1.2) and death from any cause was 7.0% (95% CI 4.6-9.6) and 27.2% (95% CI 15.4-46.9) (Figure). CONCLUSIONS: AS appears to be a safe management strategy for carefully selected men with favorable-risk prostate cancer. For those with an extended life expectancy (>15 years), surveillance may be safest in the setting of very low risk disease.
Source of Funding: None.
PD6-05 Source of Funding: None
PD6-04 A PROSPECTIVE, LONGITUDINAL ACTIVE SURVEILLANCE PROGRAM FOR FAVORABLE-RISK PROSTATE CANCER: LONG TERM OUTCOMES Jeffrey Tosoian*, Mufaddal Mamawala, Jonathan Epstein, Patricia Landis, Sacha Wolf, Bruce Trock, H. Ballentine Carter, Baltimore, MD INTRODUCTION AND OBJECTIVES: Active surveillance (AS) is an alternative to immediate treatment aimed at reducing overtreatment of favorable risk prostate cancer. We sought to describe long term outcomes in men enrolled in a prospective, longitudinal AS program. METHODS: Since 1995, 1298 men with favorable-risk prostate cancer have enrolled in AS at median age 66 years (range 41e92). 926 (71.3%) men had very low risk and 372 (28.7%) had low risk disease. Triggers for intervention were reclassification on biopsy (cancer extent or grade). Primary outcomes were overall (OS), cancer specific (CSS), and metastasis-free survival (MFS); secondary outcomes were freedom from grade reclassification (GR) (Gleason score 7 or above), treatmentfree survival (TFS), and biochemical recurrence (BCR) in those who underwent treatment. Outcomes were evaluated using Kaplan-Meier survival analysis and comparisons were made using the log-rank test. RESULTS: Median follow-up was 5.0 years (range 0.01-18.0) and 174 (13.4%) men were followed for 10 years or more (6,766 person-years of follow-up). At 10 and 15 years from diagnosis, OS was 93.2% and 68.7%, CSS was 99.9% and 99.9%, and MFS was 99.4% and 99.4%, respectively. The 5, 10, and 15 year freedom from GR was 82.3%, 70.2%, and 62.7%, and TFS was 60.5%, 44.1%, and 37.3%, respectively. There was no significant difference between proportions of men with very low risk disease and low risk disease that had GR (17.4%, 19.4%; p¼0.73) or underwent curative intervention (36.0%, 37.1%; p¼0.42). For 138 men treated surgically and 149 treated with radiation, the 5-year freedom from BCR was 88.7% and 91.5%, respectively among those with at least one year of follow-up. There was no difference in BCR when comparing treatment modalities (p¼0.90). There were 2 deaths from prostate cancer; at 10 years and 15 years,
CHANGE IN PREDICTED PROGNOSIS AFTER RADICAL PROSTATECTOMY DURING FOLLOW-UP IN AN ACTIVE SURVEILLANCE COHORT John B. Eifler, Jr.*, Daren Diiorio, Chaochen You, Nashville, TN; Vidhush Yarlagadda, Birmingham, AL; David F. Penson, Joseph A. Smith, Jr., Sam Chang, Nashville, TN; Michael S. Cookson, Oklahoma City, OK; Daniel A. Barocas, Nashville, TN INTRODUCTION AND OBJECTIVES: The objective of active surveillance (AS) for prostate cancer is to delay the morbidities of curative intervention while minimizing the likelihood of developing incurable disease. To determine the curability of AS patients, we calculated the predicted pretreatment probability of biochemical recurrence within 10 years after radical prostatectomy (BCR-RP) at the time of each follow-up biopsy using a commonly available nomogram. METHODS: The study population consisted of men with Gleason 3þ3¼6 prostate cancer who elected AS at our institution between 2004 and 2012. Biopsies were recommended every 12e18 months. Inclusion required at least one follow-up biopsy after diagnosis. At the time of each biopsy, the predicted BCR-RP was calculated using an externally validated preoperative nomogram. Survival analysis was performed to estimate the incidence of a BCR-RP >10% during AS. A separate logistic regression analysis was performed to evaluate clinical factors at the time of biopsy associated with suboptimal BCR-RP. RESULTS: With a median follow-up interval of 21.4 months (range 3 e 89.7 mo) and median number of biopsies of 2 (range 2e7), 213 patients met inclusion criteria and underwent a total of 351 followup biopsies. Overall, the median predicted BCR-RP at the time of follow-up biopsy was 3 (range 0e36). Over the duration of follow-up, the proportion of patients with a likelihood of BCR-RP above 10% increased with each passing year (3.4%, 6.7%, 20.1%, 39.9%, and 63.3%). On multivariable logistic regression analysis, at the time of any follow-up biopsy, age (O.R. 1.06, p ¼ 0.029), log PSA density (O.R. 4.06, p ¼ 0.007), the number of positive cores on previous biopsy (O.R. 1.36, p ¼ 0.013), and interval since the prior biopsy of 2 years (referent < 1 year, O.R. 4.68, p ¼ 0.014) were associated with BCR-RP>10%. CONCLUSIONS: Active surveillance safely maintains curability in the majority of men with Gleason 6 prostate cancer. However, within 5 years of entering surveillance, more than half of men would have a