Real-World PSA Response and Safety Outcomes of 177Lu-PSMA-617 in Heavily Pretreated Metastatic Castration-Resistant Prostate Cancer: A Single-Center Retrospective Validation Study

Background/Objectives: 177Lu-PSMA-617 is an established standard-of-care treatment for eligible patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC). Treatment schedules and follow-up in routine practice may differ from clinical trial protocols. Post-approval evaluation is needed to determine whether trial-reported prostate-specific antigen (PSA) responses and adverse events are also observed outside trials. We assessed outcomes in heavily pretreated patients receiving 177Lu-PSMA-617. Methods: This retrospective study included 13 patients treated outside clinical trials at Severance Hospital, with follow-up through 30 June 2026. PSA50 and PSA90 denoted unconfirmed reductions of at least 50% and 90% from pretreatment baseline. Study-defined progression-free survival (PFS) included radiographic progression, a PSA increase of at least 50% from baseline considered disease progression, or death. Results: Median age was 69 years. All patients had received androgen-deprivation therapy, an androgen receptor pathway inhibitor, and docetaxel. Median baseline PSA was 88.79 ng/mL, and the median number of cycles was four. PSA50 and PSA90 occurred in six (46.2%) and three (23.1%) patients, respectively. Eight patients had a PFS event; median study-defined PFS was 5.9 months (95% confidence interval (CI), 1.4 months to not estimable). Two patients required activity reduction for cytopenias. Dry mouth was recorded in five patients (38.5%). Conclusions: PSA responses in this cohort support the applicability of trial findings to routine care. Documented adverse events included recognized toxicities. The PSA-inclusive PFS endpoint differs from trial radiographic PFS. Small sample size, concomitant treatment, and retrospective ascertainment limit interpretation. Larger cohorts with standardized follow-up are needed to assess response durability.