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. Baseline clinical/molecular characteristics and PSMA PET parameters were analyzed and association with PSA30 and PSA50 response was evaluated. Results: 97 pts were included. Median age was 73.4 (55.9, 90.2). At baseline PSMA PET: 78 pts had PSMA + disease in bone, 61 lymph nodes, 9 lungs, 5 liver, and 1 brain. 33 pts had 1 prior ARPI, 64 pts had ≥2 prior ARPI. 13 pts had no prior taxane regimen, 42 had 1 prior taxane, 31 had 2 prior taxanes and 11 had ≥3 taxane regimens. 17 pts had prior PARP inhibitor. With a median follow-up of 6.5 months (1.38-14.54) from starting Lu177 therapy, 56 (57.7%) pts achieved a PSA30 response, and 49 (50.5%) pts achieved a PSA50 response. 59 (60.8%) pts achieved any confirmed PSA response. Grade≥3 toxicity occurred in 9 pts. Differential PSA response by subgroups is listed in the Table. Conclusions: There is a trend with higher PSA30 and PSA50 response to Lu177 with higher SUVmean, higher SUVmax, and less prior taxane exposure.