Prognostic impact of residual cancer burden (RCB) on long-term outcomes after neoadjuvant (neo) androgen receptor pathway inhibitor (ARPI) and radical prostatectomy (RP) for high-risk localized prostate cancer (HRLPC): A pooled analysis of phase 2 trials.

5099 Background: 6 months (mths) of neo-ARPI prior to RP for HRLPC has shown promising results in a series of phase 2 trials, with 15-20% of patients experiencing pathologic complete response (pCR) or minimal residual disease (≤5mm residual tumor, MRD). However, longer-term outcomes and the prognostic impact of residual cancer burden (RCB) at RP has not been evaluated. Methods: Data from patients (pts) treated on 5 neoadjuvant trials evaluating 6mths of neo-ARPI (abiraterone abi, enzalutamide enza, abi+enza, abi+apalutamide) and androgen deprivation therapy (ADT) at our institution between 2006 to 2018 were pooled. All pts had central pathology review performed to evaluate pCR/MRD and RCB on the RP specimen. RCB was quantified as the calculated tumor volume adjusted for tumor cellularity. Metastasis-free survival (MFS) was defined as the time from RP to development of metastasis outside of the pelvis on CT, bone scan or MRI, or death from any cause, or censored at the date of last follow-up. Utilizing the Contal The median RCB was 0.05cm 3 (IQR 0.00-0.32). During a median follow-up of 5yrs, 45 pts (21%) developed metastases and 11 (5%) died; 5-yr MFS rate was 81% (95% CI 74-86). On multivariate analysis, a higher RCB was associated with poorer MFS (HR 1.26 1.03-1.54), along with cT3-4 disease (HR 3.86 1.59-9.41). RCB index categories were defined as RCB-0 (no residual disease i.e. pCR; n=23), RCB-1 (80%. The depth of pathologic response was prognostic for MFS, with a 100% 5-yr MFS in patients achieving pCR. RCB could be used to guide intensified adjuvant strategies in pts with residual disease at RP after neo-ARPI. Expert pathology review of pts treated in this manner is crucial.