Evaluation of time to metastasis (TTM) from prostatectomy and survival in patients (pts) with metachronous metastatic hormone-sensitive prostate cancer (mHSPC) receiving androgen deprivation therapy (ADT) intensification: A real-world study.

100 Background: Metachronous mHSPC is associated with improved outcomes compared to synchronous (de novo) mHSPC. However, there are limited data on the effect of TTM after radical prostatectomy in patients with metachronous mHSPC treated with systemic therapies. Our objective was to explore the association of TTM after prostatectomy with survival outcomes in a real-world population. Methods: In this IRB-approved retrospective study, eligibility criteria were: pts with metachronous mHSPC who underwent radical prostatectomy and were treated with ADT plus androgen receptor pathway inhibitor (ARPI). Metachronous disease was defined as the absence of metastatic disease 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. Progression-free survival (PFS) was defined from the start of therapy for mHSPC to disease progression or death from any cause. Overall survival (OS) was defined from treatment initiation for mHSPC to death from any reason or censored at the last follow-up. Multivariable analyses for PFS and OS were performed using a Cox proportional hazards model, adjusting for disease volume (per CHAARTED criteria), Gleason score, log-transformed PSA, and age. Results: Overall, 186 pts with metachronous mHSPC who previously underwent prostatectomy were eligible and included. Pts with a Gleason score of ≥ 8 comprised 44% of the cohort and those with age ≥ 65 comprised 68% of the cohort. A high volume of disease was present in 34% of the pts. Overall, median TTM was 46 months. On univariate analysis, a longer TTM was not associated with improved PFS (HR 1.0, 95% CI 1.0-1.1, P=0.3) or OS (HR 1.0, 95% CI 1.0-1.1, P=0.8), and results were consistent on multivariate analysis. No PFS or OS benefit was observed in pts achieving a TTM ≥1, 2, 3, and 4 years respectively, versus those who do not (Table). Conclusions: A prolonged TTM is not associated with survival outcomes after onset of metachronous mHSPC in pts treated with ADT + ARPI. OS and PFS in the mHSPC setting appear to be independent of timing of metastatic disease post prostatectomy in this pt population. Univariate Multivariate HR (P-value) PFS OS PFS OS TTM Continuous 1.0 (0.3) 1.0 (0.8) 1.0 (0.5) 1.0 (0.4) TTM <1 vs ≥1 0.9 (0.7) 0.8 (0.6) 0.7 (0.5) 0.7(0.5) TTM <2 vs ≥2 0.9 (0.8) 0.9(0.7) 0.6 (0.3) 0.6 (0.3) TTM <3 vs ≥3 0.9 (0.5) 0.8 (0.6) 0.6 (0.2) 0.6 (0.2) TTM <4 vs ≥4 0.9 (0.7) 1.1 (0.7) 0.9 (0.7) 0.9 (0.7)