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PD19-06 ALCOHOL INTAKE INCREASES HIGH-GRADE PROSTATE CANCER RISK AMONG MEN TAKING DUTASTERIDE IN THE REDUCE TRIAL
THE JOURNAL OF UROLOGYâ
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CONCLUSIONS: These data indicated that androgen is the main factor controlling the production of PSA and low serum PSA levels in mice with prostate cancer xenografts is related to low serum testosterone levels. We propose applying combined tests of PSA and T in prostate cancer diagnosis and monitoring the progression to avoid false negative results. For men with low levels of both T and PSA, further examination should be applied including retesting PSA levels after normalizing T levels. Source of Funding: none
PD19-06 ALCOHOL INTAKE INCREASES HIGH-GRADE PROSTATE CANCER RISK AMONG MEN TAKING DUTASTERIDE IN THE REDUCE TRIAL Jay Fowke, Nashville, TN; Lauren Howard*, Durham, NC; Gerald Andriole, St. Louis, MO; Stephen Freedland, Durham, NC INTRODUCTION AND OBJECTIVES: Although most studies found no association between alcohol intake and prostate cancer (PC) risk, an analysis of the Prostate Cancer Prevention Trial (PCPT) found high alcohol intake significantly increased PC risk, but only among men randomized to the 5a-reductase inhibitor (5-ARI) finasteride study arm. Thus, we sought to confirm the PCPT analysis to determine if alcohol use affects PC risk among men taking the 5-ARI dutasteride. METHODS: REDUCE was a randomized trial to compare PC risk after administration of dutasteride (0.5 mg/day) vs. placebo. Participants had a baseline PSA between 2.5-10.0 ng/ml and a recent negative prostate biopsy. Alcohol intake was determined by baseline questionnaire, and participants underwent a prostate biopsy to determine PC status at 2 and 4 years, regardless of PSA levels. Logistic regression was used to examine the association between alcohol intake and PC risk vs. no PC. Multinomial logistic regression was used examine the associations between alcohol intake and low-grade (Gleason <7) vs. no PC or high-grade (Gleason >7) PC vs. no PC. Results were adjusted for age, race, BMI, geographic region, family history of PC, diabetes, smoking status, PSA, TRUS prostate volume, and stratified by treatment arm. RESULTS: Of 6,374 men in the analysis, 998 (16%) low-grade and 435 (7%) high-grade PC cases were detected. Approximately 25% of participants reported no alcohol consumption, 49% were moderate drinkers (1-6 drinks/week) and 26% heavy drinkers (>7 drinks/week). Heavy drinkers were younger, more likely to be white, smokers, European, had lower BMI, and were less likely to be diabetic (all p<0.01). On multivariable analysis, alcohol intake was not associated with lowgrade, high-grade, or overall PC risk in the placebo arm, and was not associated with low-grade PC among men taking dutasteride. In contrast, heavy drinkers in the dutasteride arm were 30% more likely to be diagnosed with PC (p¼0.047), and 86% more likely to be diagnosed with high-grade PC (p¼0.01). Among alcohol abstainers, dutasteride was significantly associated with reduced risk of high-grade PC (OR¼0.59, p¼0.02). However, dutasteride was not associated with reduced high-grade PC risk among heavy drinkers (OR¼0.99, p¼0.95). CONCLUSIONS: Alcohol consumption negated the overall protective association between dutasteride and high-grade prostate cancer. Physicians may wish to advise patients to eliminate alcohol when taking 5ARIs if they are concerned about prostate cancer. Source of Funding: GlaxoSmithKline
PD19-07 PROSTATE BIOPSY TRENDS IN RELATION TO U.S. PREVENTATIVE TASK FORCE RECOMMENDATIONS AGAINST ROUTINE PSA-BASED SCREENING: A TIME-SERIES ANALYSIS Bimal Bhindi*, Muhammad Mamdani, Girish S. Kulkarni, Antonio Finelli, Robert J. Hamilton, John Trachtenberg, Alexandre R. Zlotta, Ants Toi, Toronto, Canada; Andrew Evans, Theodorus van der Kwast, Please choose an option below; Neil E. Fleshner, Toronto, Canada INTRODUCTION AND OBJECTIVES: In May 2012, the U.S. Preventative Task Force (USPTF) released recommendations against
Vol. 191, No. 4S, Supplement, Monday, May 19, 2014
routine Prostate-Specific-Antigen (PSA) screening for prostate cancer (PC). In the context of a single-payer healthcare system, the objective of our study was to examine how this event has impacted our institutional biopsy rate and cancer detection using a time-series analysis. METHODS: We examined the University Health Network (UHN, Toronto) BioBank database for prostate biopsies done from Oct 2008 to Jun 2013. The BioBank approaches all patients undergoing prostate biopsy at UHN and has a 94.7% consent rate for inclusion. Biopsies for active surveillance or solely targeting MRI-detected lesions were excluded. Low risk PC (LRPC) was defined as no Gleason pattern 4, 3 cores involved or 1/3 of total number of cores involved, and no core with >50% cancer involvement. High grade PC (HGPC) was defined as Gleason 7-10. A time-series analysis using interventional auto-regressive integrated moving average (ARIMA) models with step intervention functions were conducted to examine the effect of the recommendations on number of biopsies performed and cancer detection per month. RESULTS: Within the study period, 3397 biopsies were performed and 1591 (46.8%) PCs were detected (LRPC ¼ 558 (31.3%); HGPC ¼ 909 (26.8%)). The median for biopsies per month decreased from 65.5 (IQR¼58-78) before the USPTF recommendations to 31 (IQR¼24-38) afterward (p¼0.003), while median number of patients undergoing their first-time biopsies decreased from 45 (IQR¼41.5-58.5) to 24 (IQR¼20-32, p¼0.022). The median PSA of men undergoing biopsy did not change significantly after recommendations (p¼0.76). The median number of LRPCs detected per month decreased from 10 (IQR¼8-14) to 5 (IQR¼4-6, p¼0.005), while the median number of HGPCs detected per month also decreased from 17 (IQR¼15.5-21) to 9 (IQR¼8-11, p<0.001). CONCLUSIONS: Since the USPTF recommendations, the number of biopsies (total and first-time biopsies) performed at UHN, based on referrals from our catchment area, has decreased. This is likely due to decreased PSA-screening and referral by general practitioners. Although encouraging that less low risk (often clinically insignificant) PCs are being diagnosed, the magnitude of sudden decrease in detection rate of Gleason 7-10 PCs is concerning. It is unclear to what extent selective screening is taking place. Unfortunately, men with “missed PCs” cannot be directly studied. Long-term population based studies are needed to assess the repercussions. Source of Funding: None
PD19-08 A COMPARISON OF THE DETECTION RATES OF PROSTATE CANCER: REAL-TIME-ELASTOGRAPHY (RTE) VS. MULTIPLE CORE BIOPSIES Oliver Lenherr*, Afshin Fayyazi, Konrad Tschan, Peter Liske, Sven Lahme, Pforzheim, Germany INTRODUCTION AND OBJECTIVES: Ultrasound guided transrectal biopsy of the prostate gland is the primary technique of choice to detect prostate cancer. As a new imaging modality RTE was evaluated to enhance detection rate and thus reduce the number of biopsies. However RTE had only been compared to standard biopsies with 10 samples or less. This study evaluates the significance of RTE in comparison to schematic multiple core biopsies with 21 samples. METHODS: In a prospective study 485 patients with pathological digital rectal examination of the prostate and/or value of PSA 4100ng/ml were randomized into two groups. The volume was measured by transrectal ultrasound. In both groups the total number of biopsies was 21. Group1 (with RTE) included 248 patients. In Group1 dependent on the RTE-examination a maximum of 5 RTE-targeted biopsies were taken followed by additional schematic biopsies to complete 21 samples. In Group2 each of the 237 patients received 21 schematic biopsies. RESULTS: Overall detection rate of prostate cancer was 30.9%. The detection rate in Group1 was 34.3%, in Group2 27.4%. 85 carcinomas were found in Group1 within 248 patients. RTE found 29 of them, which is a detection rate of 11.7% in Group1 compared to 33.8% of the additional biopsies (84 of 85 carcinomas found). There was no
e548
CONCLUSIONS: These data indicated that androgen is the main factor controlling the production of PSA and low serum PSA levels in mice with prostate cancer xenografts is related to low serum testosterone levels. We propose applying combined tests of PSA and T in prostate cancer diagnosis and monitoring the progression to avoid false negative results. For men with low levels of both T and PSA, further examination should be applied including retesting PSA levels after normalizing T levels. Source of Funding: none
PD19-06 ALCOHOL INTAKE INCREASES HIGH-GRADE PROSTATE CANCER RISK AMONG MEN TAKING DUTASTERIDE IN THE REDUCE TRIAL Jay Fowke, Nashville, TN; Lauren Howard*, Durham, NC; Gerald Andriole, St. Louis, MO; Stephen Freedland, Durham, NC INTRODUCTION AND OBJECTIVES: Although most studies found no association between alcohol intake and prostate cancer (PC) risk, an analysis of the Prostate Cancer Prevention Trial (PCPT) found high alcohol intake significantly increased PC risk, but only among men randomized to the 5a-reductase inhibitor (5-ARI) finasteride study arm. Thus, we sought to confirm the PCPT analysis to determine if alcohol use affects PC risk among men taking the 5-ARI dutasteride. METHODS: REDUCE was a randomized trial to compare PC risk after administration of dutasteride (0.5 mg/day) vs. placebo. Participants had a baseline PSA between 2.5-10.0 ng/ml and a recent negative prostate biopsy. Alcohol intake was determined by baseline questionnaire, and participants underwent a prostate biopsy to determine PC status at 2 and 4 years, regardless of PSA levels. Logistic regression was used to examine the association between alcohol intake and PC risk vs. no PC. Multinomial logistic regression was used examine the associations between alcohol intake and low-grade (Gleason <7) vs. no PC or high-grade (Gleason >7) PC vs. no PC. Results were adjusted for age, race, BMI, geographic region, family history of PC, diabetes, smoking status, PSA, TRUS prostate volume, and stratified by treatment arm. RESULTS: Of 6,374 men in the analysis, 998 (16%) low-grade and 435 (7%) high-grade PC cases were detected. Approximately 25% of participants reported no alcohol consumption, 49% were moderate drinkers (1-6 drinks/week) and 26% heavy drinkers (>7 drinks/week). Heavy drinkers were younger, more likely to be white, smokers, European, had lower BMI, and were less likely to be diabetic (all p<0.01). On multivariable analysis, alcohol intake was not associated with lowgrade, high-grade, or overall PC risk in the placebo arm, and was not associated with low-grade PC among men taking dutasteride. In contrast, heavy drinkers in the dutasteride arm were 30% more likely to be diagnosed with PC (p¼0.047), and 86% more likely to be diagnosed with high-grade PC (p¼0.01). Among alcohol abstainers, dutasteride was significantly associated with reduced risk of high-grade PC (OR¼0.59, p¼0.02). However, dutasteride was not associated with reduced high-grade PC risk among heavy drinkers (OR¼0.99, p¼0.95). CONCLUSIONS: Alcohol consumption negated the overall protective association between dutasteride and high-grade prostate cancer. Physicians may wish to advise patients to eliminate alcohol when taking 5ARIs if they are concerned about prostate cancer. Source of Funding: GlaxoSmithKline
PD19-07 PROSTATE BIOPSY TRENDS IN RELATION TO U.S. PREVENTATIVE TASK FORCE RECOMMENDATIONS AGAINST ROUTINE PSA-BASED SCREENING: A TIME-SERIES ANALYSIS Bimal Bhindi*, Muhammad Mamdani, Girish S. Kulkarni, Antonio Finelli, Robert J. Hamilton, John Trachtenberg, Alexandre R. Zlotta, Ants Toi, Toronto, Canada; Andrew Evans, Theodorus van der Kwast, Please choose an option below; Neil E. Fleshner, Toronto, Canada INTRODUCTION AND OBJECTIVES: In May 2012, the U.S. Preventative Task Force (USPTF) released recommendations against
Vol. 191, No. 4S, Supplement, Monday, May 19, 2014
routine Prostate-Specific-Antigen (PSA) screening for prostate cancer (PC). In the context of a single-payer healthcare system, the objective of our study was to examine how this event has impacted our institutional biopsy rate and cancer detection using a time-series analysis. METHODS: We examined the University Health Network (UHN, Toronto) BioBank database for prostate biopsies done from Oct 2008 to Jun 2013. The BioBank approaches all patients undergoing prostate biopsy at UHN and has a 94.7% consent rate for inclusion. Biopsies for active surveillance or solely targeting MRI-detected lesions were excluded. Low risk PC (LRPC) was defined as no Gleason pattern 4, 3 cores involved or 1/3 of total number of cores involved, and no core with >50% cancer involvement. High grade PC (HGPC) was defined as Gleason 7-10. A time-series analysis using interventional auto-regressive integrated moving average (ARIMA) models with step intervention functions were conducted to examine the effect of the recommendations on number of biopsies performed and cancer detection per month. RESULTS: Within the study period, 3397 biopsies were performed and 1591 (46.8%) PCs were detected (LRPC ¼ 558 (31.3%); HGPC ¼ 909 (26.8%)). The median for biopsies per month decreased from 65.5 (IQR¼58-78) before the USPTF recommendations to 31 (IQR¼24-38) afterward (p¼0.003), while median number of patients undergoing their first-time biopsies decreased from 45 (IQR¼41.5-58.5) to 24 (IQR¼20-32, p¼0.022). The median PSA of men undergoing biopsy did not change significantly after recommendations (p¼0.76). The median number of LRPCs detected per month decreased from 10 (IQR¼8-14) to 5 (IQR¼4-6, p¼0.005), while the median number of HGPCs detected per month also decreased from 17 (IQR¼15.5-21) to 9 (IQR¼8-11, p<0.001). CONCLUSIONS: Since the USPTF recommendations, the number of biopsies (total and first-time biopsies) performed at UHN, based on referrals from our catchment area, has decreased. This is likely due to decreased PSA-screening and referral by general practitioners. Although encouraging that less low risk (often clinically insignificant) PCs are being diagnosed, the magnitude of sudden decrease in detection rate of Gleason 7-10 PCs is concerning. It is unclear to what extent selective screening is taking place. Unfortunately, men with “missed PCs” cannot be directly studied. Long-term population based studies are needed to assess the repercussions. Source of Funding: None
PD19-08 A COMPARISON OF THE DETECTION RATES OF PROSTATE CANCER: REAL-TIME-ELASTOGRAPHY (RTE) VS. MULTIPLE CORE BIOPSIES Oliver Lenherr*, Afshin Fayyazi, Konrad Tschan, Peter Liske, Sven Lahme, Pforzheim, Germany INTRODUCTION AND OBJECTIVES: Ultrasound guided transrectal biopsy of the prostate gland is the primary technique of choice to detect prostate cancer. As a new imaging modality RTE was evaluated to enhance detection rate and thus reduce the number of biopsies. However RTE had only been compared to standard biopsies with 10 samples or less. This study evaluates the significance of RTE in comparison to schematic multiple core biopsies with 21 samples. METHODS: In a prospective study 485 patients with pathological digital rectal examination of the prostate and/or value of PSA 4100ng/ml were randomized into two groups. The volume was measured by transrectal ultrasound. In both groups the total number of biopsies was 21. Group1 (with RTE) included 248 patients. In Group1 dependent on the RTE-examination a maximum of 5 RTE-targeted biopsies were taken followed by additional schematic biopsies to complete 21 samples. In Group2 each of the 237 patients received 21 schematic biopsies. RESULTS: Overall detection rate of prostate cancer was 30.9%. The detection rate in Group1 was 34.3%, in Group2 27.4%. 85 carcinomas were found in Group1 within 248 patients. RTE found 29 of them, which is a detection rate of 11.7% in Group1 compared to 33.8% of the additional biopsies (84 of 85 carcinomas found). There was no