Even an extremely low but still detectable PSA nadir in men receiving androgen-deprivation therapy (ADT) after radical prostatectomy for prostate cancer (PCa) strongly predicts adverse outcomes, according to a new study from the SEARCH Database Study Team.

In a study of 294 men treated with ADT for an elevated PSA following prostate surgery but without radiographic evidence of metastases, those who achieved a PSA nadir between 0.01 and 0.2 ng/mL had a 5-fold increased risk of progression to castration-resistant PCa (CRPC), a 4-fold increased risk of metastases, and a 5-fold increased risk of PCa-specific mortality (PCSM) compared with men who had undetectable PSA (below 0.01 ng/mL), researchers reported online ahead of print in European Urology.

In an interview with Renal & Urology News, lead investigator Stephen J. Freedland, MD, associate professor of both surgery and pathology at Duke University School of Medicine in Durham, N.C., said the new findings suggest that the goal nadir for men on ADT should be a level below 0.01 ng/mL rather than below 0.2 ng/mL, the level now widely used. Patients who do not achieve a level below 0.01 ng/mL should be counseled about additional options, such as clinical trials and other treatments to ensure castration levels of testosterone levels.

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In the study, the median follow-up after PSA nadir was documented was 49 months. Of the 294 men, 223 (76%) had an undetectable nadir. CRPC developed in 55 patients, metastases developed in 42, and 31 died from PCa.

 “One possible reason why a man may not achieve an undetectable nadir on ADT is inadequate androgen deprivation,” Dr. Freedland and his colleagues wrote. “Perhaps some men in our study had an inadequate dose of ADT, which could result from reduced frequency of administration, patient noncompliance, or other explanations such as obesity wherein the volume of distribution of drug is higher and thus the effective dose is lower.”

The investigators stated that, to their knowledge, no previous study had examined whether men with detectable, but still very low PSA nadir levels are at higher PCSM risk compared with men with undetectable PSA nadirs or whether these very low, but detectable, PSA nadir levels predict metastases in men with non-metastatic disease treated with ADT for biochemical failure.