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

Purpose 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) and overall survival (OS) in patients receiving Lu-177-PSMA as first to seventh mCRPC therapy 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 models were applied; multivariable models are additionally adjusted for ECOG status and line of Lu-177-PSMA therapy (1–2 L vs. 3 L vs. 4–7 L). 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. No significant differences were observed in PFS (12.1 vs. 13.0 months) or OS (14.9 vs. 18.3 months) between synchronous and metachronous patients (both p > = 0.09), or in PFS (12.9 vs. 11.8 months) and OS (21.4 vs. 15.1 months) between GS 6–7 and GS 8–10 (both p > = 0.3). M-stage-stratified analyses showed an OS difference (17.9 vs. 17.7 vs. 9.0 months for M1a vs. M1b vs. M1c, p = 0.01), but not for PFS (11.9 vs. 9.5 vs. 8.2 months, p = 0.08). After multivariable adjustment including ECOG status and treatment line, initial timing of metastasis, GS, and M-stage were not independently associated with PFS or OS. However, later treatment line was independently associated with worse OS (3 L vs. 1–2 L: HR 2.40, 95% CI 1.14–5.04, p = 0.021; 4–7 L vs. 1–2 L: HR 4.01, 95% CI 1.83–8.80, p < 0.001) as well as worse ECOG status (1–2 vs. 0: HR 2,60, 95% CI 1.38-4,91, p = 0.003). Conclusion In this real-world cohort of mCRPC patients treated with Lu-177-PSMA, initial timing of metastatic disease, Gleason score, and M-stage were not independently associated with PFS or OS after multivariable adjustment including ECOG status and treatment line. These observational findings should not be interpreted as evidence of equivalent treatment efficacy across subgroups.