Undetectable prostate-specific antigen after short-course androgen deprivation therapy for biochemically recurrent patients correlates with metastasis-free survival and prostate cancer-specific survival

作者：Lim Daniel M; Gulati Roman; Aleshin Guendel Serge; Gawne Agnes; Wingate Jonathan T; Cheng Heather H; Etzioni Ruth; Yu Evan Y

来源：Prostate, 2018, 78(14): 1077-1083.

DOI：10.1002/pros.23666

• endpoint
• landmark
• surrogate

BackgroundOptimal utilization of novel therapies for advanced prostate cancer is challenging without a validated surrogate efficacy endpoint. Ongoing trials are using durable undetectable prostate-specific antigen (PSA) levels as a marker of efficacy. The clinical relevance of prolonged undetectable PSA after a short course of androgen deprivation therapy (ADT) is uncertain.
MethodsThe University of Washington Caisis database was queried for radical prostatectomy patients who received 6-12 months of ADT after biochemical recurrence (BCR), defined as PSA 0.2ng/mL and no radiographically detectable metastasis. Proportions of men with undetectable PSA 12 and 24 months after ending ADT were compared to a hypothesized 5% rate using exact binomial tests. Associations with patient and tumor characteristics were examined using logistic regression, and associations with risk of subsequent metastasis and death were evaluated by log-rank tests.
ResultsAfter ineligibility exclusions, 23/93 (25%; 95%CI 16-35%; P<0.001) and 14/93 (15%; 95%CI 9-24%; P<0.001) had undetectable PSA 12 and 24 months after ending ADT, respectively. Detectable PSA at 12 months was associated with increased risk of metastasis (P=0.006), prostate cancer-specific death (P=0.028), and death from any cause (P=0.065). Being 1 year older at diagnosis was associated with a 14% (95%CI 5-24%; P=0.006) decrease in the odds of having a detectable PSA after controlling for PSA at diagnosis, PSA doubling time, grade group, and time from initial therapy to BCR.
ConclusionsThis single-institution retrospective analysis shows that it is not uncommon to have undetectable PSA 12 or 24 months after a short course of ADT. No baseline prognostic characteristic other than age was associated with a durable (12 month) undetectable PSA. Because a durable undetectable PSA was associated with lower risks of metastasis and prostate cancer-specific death, it may be a reasonable clinical trial endpoint.

• 出版日期2018-10-1