Time to metastasis after prostatectomy (TTM) and survival outcomes in patients (pts) with metachronous metastatic hormone-sensitive prostate cancer (mHSPC): A secondary analysis of the SWOG 1216 phase 3 trial.

173 Background: It is well-established that pts with de-novo mHSPC have poorer survival compared to those with metachronous disease. However, the impact of timing of metastatic recurrence after definitive therapy on survival has not been extensively evaluated in pts with mHSPC. Therefore, we assessed the prognostic value of TTM using the SWOG 1216 trial data which randomized pts with mHSPC to androgen deprivation therapy (ADT) with orteronel (ORT) or bicalutamide (bic) (NCT01809691). Methods: Eligibility: Only pts with metachronous mHSPC who underwent prostatectomy were included in the analysis. Metachronous disease was defined as no evidence of metastasis within 90 days of initial prostate cancer diagnosis. TTM was defined from the time of prostatectomy to the time of initial metastatic diagnosis and was analyzed as a continuous variable, then categorized. Multivariable analyses for progression-free survival (PFS) and overall survival (OS) were performed using a Cox proportional hazards model, adjusting for treatment arm, disease burden, Gleason score, performance status, log-transformed PSA, and age. Results: Of the 1279 study participants, 301 underwent prostatectomy and had metachronous mHSPC, of whom 161 were in the experimental arm and 140 in the control arm. In the overall cohort, a longer TTM was not associated with improved PFS (HR 1.0, P=0.3) and OS (HR 1.0, P=0.14). Similarly, after stratification of TTM using 1, 2, 3, and 4 year-thresholds, there was no association with PFS and OS. Results remained comparable in the subgroups of pts receiving ADT + bic and ADT + ORT separately (Table). Conclusions: The timing of metastatic disease after prostatectomy in pts with metachronous mHSPC did not appear to be related to survival and should not be used as a prognostic factor nor to predict treatment outcomes. ADT + ORT ADT Overall HR (P-value) PFS OS PFS OS PFS OS TTM Continuous 1.0 (0.8) 1.0 (0.8) 1.0 (0.3) 1.0 (0.1) 1.0 (0.3) 1.0 ( 0.1) TTM <1 vs ≥1 1.1 (0.8) 1.4 (0.5) 0.9 (0.9) 1.7 (0.2) 1.1 (0.8) 1.6 (0.1) TTM <2 vs ≥2 1.1 (0.7) 1.6 (0.3) 1.1 (0.6) 1.9 (0.1) 1.2 (0.3) 1.8 (0.04) TTM <3 vs ≥3 1.1 (0.7) 1.4 (0.4) 1.5 (0.1) 1.7 (0.1) 1.4 (0.08) 1.6 (0.09) TTM <4 vs ≥4 0.9 (0.8) 0.9 (0.9) 1.7 (0.03) 1.4 (0.4) 1.5 (0.05) 1.3 (0.4)