TY - JOUR
T1 - Detectable prostate-specific antigen nadir during androgen-deprivation therapy predicts adverse prostate cancer-specific outcomes
T2 - Results from the SEARCH database
AU - Keto, Christopher J.
AU - Aronson, William J.
AU - Terris, Martha K.
AU - Presti, Joseph C.
AU - Kane, Christopher J.
AU - Amling, Christopher L.
AU - Freedland, Stephen J.
N1 - Funding Information:
Funding/Support and role of the sponsor: Department of Veterans Affairs, the Department of Defense, Prostate Cancer Research Program (CJK, SJF), NIH R01CA100938 (WJA), NIH Specialized Programs of Research Excellence Grant P50 CA92131–01A1 (WJA), Georgia Cancer Coalition (MKT), and the American Urological Association Foundation/Astellas Rising Star in Urology Award (SJF). Views and opinions of and endorsements by the authors do not reflect those of the US Army or the Department of Defense.
PY - 2014/3
Y1 - 2014/3
N2 - Background: A prostate-specific antigen (PSA) level <0.2 ng/ml 8 mo after starting on androgen-deprivation therapy (ADT) is correlated with better outcomes. However, not all men reach a nadir PSA level within 8 mo. Whether the lowest PSA on ADT - specifically, <0.2 ng/ml - can be used for risk stratification is untested. Objective: We examined the predictive value of small but detectable PSA nadir values on prostate cancer (PCa)-specific outcomes in men treated with early ADT after radical prostatectomy (RP). Design, setting, and participants: We performed a retrospective review of men treated with ADT after RP before metastases from the SEARCH database. We identified 402 men treated with ADT for elevated PSA following RP, of whom 294 men had complete data. Median follow-up after PSA nadir was 49 mo. All men had a PSA nadir <4 ng/ml; 223 men (76%) had an undetectable nadir. Intervention: ADT for an elevated PSA following RP with no radiographic evidence of metastatic disease. Outcome measurements and statistical analysis: PSA nadir on ADT was defined as the lowest PSA value during ADT. Proportional hazards models and the C index were used to test the association and predictive accuracy, respectively, between PSA nadir and PCa-specific outcomes. Results and limitations: Men with a PSA nadir between 0.01 and 0.2 ng/ml had a greater risk of progression to castration-resistant PCa (CRPC) (hazard ratio [HR]: 5.14; p < 0.001), metastases (HR: 3.98; p = 0.006), and PCa-specific mortality (PCSM) (HR: 5.33; p = 0.003) than men with an undetectable nadir. When data were restricted to men followed with ultrasensitive PSA values (sensitivity of 0.01 ng/ml), the C index of PSA nadir alone for predicting CRPC, metastases, and PCSM was 0.88, 0.91, and 0.96, respectively. Conclusions: A PSA nadir on ADT, even at a very low level, strongly predicts progression to CRPC, metastases, and PCSM. Men with a detectable PSA nadir during ADT should be considered for clinical trials.
AB - Background: A prostate-specific antigen (PSA) level <0.2 ng/ml 8 mo after starting on androgen-deprivation therapy (ADT) is correlated with better outcomes. However, not all men reach a nadir PSA level within 8 mo. Whether the lowest PSA on ADT - specifically, <0.2 ng/ml - can be used for risk stratification is untested. Objective: We examined the predictive value of small but detectable PSA nadir values on prostate cancer (PCa)-specific outcomes in men treated with early ADT after radical prostatectomy (RP). Design, setting, and participants: We performed a retrospective review of men treated with ADT after RP before metastases from the SEARCH database. We identified 402 men treated with ADT for elevated PSA following RP, of whom 294 men had complete data. Median follow-up after PSA nadir was 49 mo. All men had a PSA nadir <4 ng/ml; 223 men (76%) had an undetectable nadir. Intervention: ADT for an elevated PSA following RP with no radiographic evidence of metastatic disease. Outcome measurements and statistical analysis: PSA nadir on ADT was defined as the lowest PSA value during ADT. Proportional hazards models and the C index were used to test the association and predictive accuracy, respectively, between PSA nadir and PCa-specific outcomes. Results and limitations: Men with a PSA nadir between 0.01 and 0.2 ng/ml had a greater risk of progression to castration-resistant PCa (CRPC) (hazard ratio [HR]: 5.14; p < 0.001), metastases (HR: 3.98; p = 0.006), and PCa-specific mortality (PCSM) (HR: 5.33; p = 0.003) than men with an undetectable nadir. When data were restricted to men followed with ultrasensitive PSA values (sensitivity of 0.01 ng/ml), the C index of PSA nadir alone for predicting CRPC, metastases, and PCSM was 0.88, 0.91, and 0.96, respectively. Conclusions: A PSA nadir on ADT, even at a very low level, strongly predicts progression to CRPC, metastases, and PCSM. Men with a detectable PSA nadir during ADT should be considered for clinical trials.
KW - Androgen-deprivation therapy
KW - Prostate cancer
KW - Prostate-specific antigen
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U2 - 10.1016/j.eururo.2012.11.052
DO - 10.1016/j.eururo.2012.11.052
M3 - Article
C2 - 23245686
AN - SCOPUS:84895061392
SN - 0302-2838
VL - 65
SP - 620
EP - 627
JO - European urology
JF - European urology
IS - 3
ER -
