BACKGROUND: The optimal timing to start androgen deprivation therapy (ADT) in patients with rising PSA as the only sign of relapse is unknown. ASCO guidelines state "the critical issue is to determine whether there is benefit and how large it is for starting ADT while patients are asymptomatic."
METHODS: We studied 2,022 men in the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE), a national prospective registry, staged < cT3aN0M0, treated with radical prostatectomy (RP) or radiotherapy (RT) and had a PSA relapse (> 0.2 ng/mL [RP] or three rising determinations one month apart [RT]). Exclusion criteria included ADT in the 12 months before inclusion, metastatic disease by CT scan or bone scan, and symptoms. We assigned patients to the "immediate" strategy if they initiated ADT within 3 months (grace period) of PSA relapse and to the "deferred" strategy if they initiated ADT 2 or more years after PSA relapse or when they presented with metastasis, symptoms or a short PSA doubling time. We did not allow a treatment other than ADT for PSA relapse (e.g., rescue RT). We censored patients when they deviated from the assigned strategy and adjusted for this censoring via inverse probability weighting where the weights are a function of time-varying confounders: PSA, Karnofsky, weight loss, and bone pain.
RESULTS: Of the 2,022 patients analyzed, median age was 69 (range 63 to 74) years, 33.8% had a Gleason score >7, 31.8% received radiotherapy as primary treatment, and median time from primary treatment to PSA relapse was 27 (range 14 to 51) months. After relapse, patients were followed a median of 53.2 months. All cause mortality HR for "immediate ADT" vs. “deferred ADT” was 1.06 (95% CI: 0.59 to 1.89), corresponding to a survival difference at 5 years of -5.5% (95% CI: -15.1 % to 4.2%). The prostate-cancer specific mortality HR was 1.48 (95% CI 0.69-3.16), corresponding to a 5-year survival difference of -5.6% (95% CI: -12.5% to 1.3%).
CONCLUSIONS: Our study suggests little or no survival benefit of immediate ADT initiation for immediate ADT initiation compared with deferred ADT initiation (at clinical progression or at least two years after PSA relapse) among prostate cancer patients with PSA-only relapse.
