Promising Therapeutic Activity of 177 Lu-PSMA-617 in Synchronous High-Volume Metastatic Hormone-Sensitive Prostate Cancer : A Pilot Experience.

PURPOSE:177 Lu-PSMA-617 has been shown to improve survival outcomes in patients with end-stage metastatic castration-resistant prostate cancer. However, data in earlier lines remain limited. In this study, we intended to evaluate the efficacy and safety of 177 Lu-PSMA-617 in patients with synchronous high-volume metastatic hormone-sensitive prostate cancer (mHSPC). PATIENTS AND METHODS:Hormone-sensitive prostate cancer patients with synchronous high-volume metastases (defined as ≥4 skeletal metastases with ≥1 extra-axial site or any visceral metastasis) showing high PSMA expression on 68 Ga-PSMA-11 PET/CT and ineligible/unwilling for conventional chemohormonal treatment options were selected. Approximately, ~5.55-7.4 GBq of 177 Lu-PSMA-617 was administered intravenously at 8-12 weeks intervals, up to 6 cycles. All patients underwent concomitant androgen deprivation therapy/orchiectomy. The outcome measures included the proportion of patients achieving an undetectable serum prostate-specific antigen (PSA) (ie, ≤0.2 ng/mL) at any time point after therapy, best PSA response rate, objective radiographic response rate, radiographic progression-free survival, overall survival, and adverse events. RESULTS:Ten patients with high-volume mHSPC received a median cumulative activity of 32.4 GBq (range, 7.4-44.4) of 177 Lu-PSMA-617 over 1-6 cycles. Five patients (50%) achieved an undetectable PSA with 9 patients (90%) showing a ≥50% decline in PSA from baseline. Nine patients underwent radiological follow-up, of which 7 (77.8%) had an objective response. The median radiographic progression-free survival was 24 months (95% confidence interval, 18-30), whereas the median overall survival was not reached. None of the patients had any grade 3/4 adverse event. CONCLUSIONS:177 Lu-PSMA-617 seems to be a promising efficacious and safe treatment option for patients with synchronous high-volume mHSPC.