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Eur Urol. 2014 Mar;65(3):620-7. doi: 10.1016/j.eururo.2012.11.052. Epub 2012 Dec 6.

Detectable prostate-specific antigen Nadir during androgen-deprivation therapy predicts adverse prostate cancer-specific outcomes: results from the SEARCH database.

Author information

1
Duke University School of Medicine, Durham, NC, USA; Veterans Affairs Medical Center, Durham, NC, USA.
2
University of California at Los Angeles Medical Center, Los Angeles, CA, USA; Veterans Affairs Medical Center, Greater Los Angeles, Los Angeles, CA, USA.
3
Medical College of Georgia, Augusta, GA, USA; Veterans Affairs Medical Center, Augusta, GA, USA.
4
Stanford University Medical Center, Palo Alto, CA, USA; Veterans Affairs Medical Center, Palo Alto, CA, USA.
5
University of California at San Diego, San Diego, CA, USA.
6
Oregon Health and Science University, Portland, OR, USA.
7
Duke University School of Medicine, Durham, NC, USA; Veterans Affairs Medical Center, Durham, NC, USA. Electronic address: steve.freedland@duke.edu.

Abstract

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.

KEYWORDS:

Androgen-deprivation therapy; Prostate cancer; Prostate-specific antigen

PMID:
23245686
PMCID:
PMC3634863
DOI:
10.1016/j.eururo.2012.11.052
[Indexed for MEDLINE]
Free PMC Article

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