Background: Lu177-PSMA-617 (Lu177) therapy is effective in a subgroup of patients with metastatic castration resistant prostate cancer (mCRPC). We evaluated PSA responses in subgroups of pts with mCRPC. Methods: Pts with mCRPC who progressed after androgen receptor pathway inhibitor (ARPI) and taxane chemotherapy (or who have refused chemotherapy) were treated with Lu177. Pts with ≥6 weeks follow-up after start of Lu177 therapy were included. Baseline clinical/molecular characteristics and PSMA PET parameters were analyzed and association with PSA30 response was evaluated. Results: 45 pts were included. Median age 71.7 (range, 58-90). At baseline PSMA PET: 37 pts had PSMA + disease in bone, 28 lymph nodes, 5 lungs, 4 liver, and 1 brain. 14 pts had 1 prior ARPI, 31 pts had ≥2 prior ARPI. 5 pts had no prior taxane regimen, 18 had 1 prior taxane, 14 had 2 prior taxanes and 8 had ≥3 taxane regimens. 10 pts had prior PARP inhibitor. With a median follow-up of 2.8 months (1.4-6.1) from starting Lu177 therapy, 21 (46.7%) pts achieved a PSA30 response, and 18 (40.0%) pts achieved a PSA50 response. 24 (53.3%) pts achieved any confirmed PSA response. Grade≥3 toxicity occurred in 3 pts. Conclusions: There is a trend with higher PSA30 and PSA50 response to Lu177 with higher SUVmean, less prior taxane exposure, and in pts with homologous recombination repair mutations (HRR).