Survival outcomes with lutetium-177-PSMA-617 in metastatic castration-resistant prostate cancer patient according to baseline tumor characteristics.

35 Background: To investigate cancer-control outcomes in metastatic castration-resistant prostate cancer (mCRPC) patients receiving Lutetium-177 Prostate-Specific Membrane Antigen-617 (Lu-177-PSMA) radioligand therapy according to initial baseline tumor characteristics. Methods: We relied on the FRAMCAP (FRAnkfurt Metastatic Cancer database of the Prostate) database to assess progression-free survival (PFS) overall survival (OS) in patients receiving Lu-177-PSMA as first to seventh mCRPC line, according to initial time of metastasis (synchronous vs. metachronous), tumor grading (Gleason score GS 6-7 vs. 8-10) and M-stage (M1a vs. M1b vs. M1c) at initial metastatic hormone-sensitive prostate cancer (mHSPC). Kaplan-Meier curve analyses and multivariable Cox regression were applied. Results: Of 344 Lu-177-PSMA mCRPC patients, 198 (58%) had synchronous vs. 146 (42%) metachronous mHSPC, 87 (29%) vs. 107 (62%) GS 6-7 vs. 8-10 and 15 (10%) vs. 121 (81%) vs. 13 (9%) M1a vs. M1b vs. M1c mHSPC disease. Regarding cancer-control outcomes, no significant differences were observed in PFS (12.1 vs. 13.0 months) and OS (14.9 vs. 18.3 months) between synchronous and metachronous patients (both p≥0.1). Further, no differences were found in PFS (12.9 vs. 11.8 months) and OS (21.4 vs. 15.1 months) between GS 6-7 vs. GS 8-10 (both p≥0.3). Finally, in M-stage stratified analyses, M1a and M1b patients harbored more favorable survival outcomes compared to M1c in OS (17.9 vs. 17.7 vs. 9.0 months, p=0.01), but not for PFS (11.9 vs. 9.5 vs. 8.2 months, p=0.08). In multivariable Cox regression models adjusted additionally for ECOG status, neither initial time of metastasis, GS 8-10 nor M-stage were independently associated with worse PFS and OS outcomes. Conclusions: Lu-177-PSMA presents a viable therapeutic option providing favourable cancer-control outcomes in mCRPC patients across all subgroups of initially mHSPC patients, such as timing of metastatic disease, different tumor gradings and M-stage categories.