Response and tolerability of a single dose of ¹⁷⁷Lu-PSMA-617 in patients with metastatic castration-resistant prostate cancer: a multicenter retrospective analysis

Abstract

Background: Radiolabelled prostate specific membrane antigen (PSMA) ligands represent a true theranostics concept for diagnosis and therapy of relapsed and metastatic prostate cancer patients. The aim of this study was to evaluate response and tolerability of a single dose of ¹⁷⁷Lutetium-PSMA-617 (Lu-PSMA) in a large cohort of patients with metastatic castration resistant prostate cancer (mCRPC). Methods: The data of 82 consecutive patients (median age: 73 years, range: 43-87) with metastatic castration resistant prostate cancer who received a single dose of Lu-PSMA (mean: 5.9±0.5 GBq) were retrospectively analyzed. Data was collected at baseline and 8 weeks after therapy. ⁶⁸Ga-PSMA-11 PET/CT was performed in all patients to verify sufficient PSMA expression. Bone, lymph node, liver and lung metastases were present in 99%, 65%, 17% and 11% of the patients, respectively. Tolerability and response were evaluated using hematologic parameters, renal scintigraphy, clinical data and prostate specific antigen (PSA) value at baseline and 8 weeks after therapy application. Results: A total of six patients died and two patients dropped out not willing to continue therapy and follow-up. Complete dataset of 74 patients were available for analysis. 47 (64%) of the patients showed a PSA-Decline, of these 23 (31%) had a PSA decline > 50%, 35 (47%) had a stable disease with a PSA decline from <50% to an increase <25% and 17 (23%) showed a progressive disease with a PSA increase >25%. There were no significant changes indicative of toxicity in hemoglobin, white blood cells, creatinine and tubular extraction rates. There was a significant but mild decrease of platelets with a median value still within the normal range. Conclusion: This retrospective multicenter analysis suggests that radioligand therapy with Lu-PSMA is safe, well tolerated and shows considerable response in PSA values. Therefore, it offers an additional therapeutic option for patients with mCRPC. This data may justify further prospective randomized studies to evaluate and prove the clinical benefit in survival and quality of life.