Outcome of 177Lu-PSMA-617 Radioligand Therapy in Chemo-Refractory Patients with Metastatic Castration-Resistant Early-Onset Prostate Cancer

Nicolai Mader; Daniel Groener; Nikolaos Tselis; Séverine Banek; James Nagarajah; Frank Grünwald; Amir Sabet

doi:10.3390/cancers13164193

Outcome of ¹⁷⁷Lu-PSMA-617 Radioligand Therapy in Chemo-Refractory Patients with Metastatic Castration-Resistant Early-Onset Prostate Cancer

Cancers (Basel). 2021 Aug 20;13(16):4193. doi: 10.3390/cancers13164193.

Authors

Nicolai Mader¹, Daniel Groener¹, Nikolaos Tselis², Séverine Banek³, James Nagarajah⁴, Frank Grünwald¹, Amir Sabet¹

Affiliations

¹ Department of Nuclear Medicine, University Hospital Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
² Department of Radiation Oncology, University Hospital Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
³ Department of Urology, University Hospital Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
⁴ Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 GA Nijmegen, The Netherlands.

Abstract

The aim of this retrospective study was to assess the outcome of patients with metastasized castration-resistant early-onset prostate cancer refractory to chemotherapy receiving radioligand therapy with ¹⁷⁷Lutetium-PSMA-617 (LuPSMA-RLT). Twenty-five patients of ≤55 years of age at prostate cancer diagnosis, treated with a median of four (IQR 2-6) cycles (mean of 7.7 ± 1.4 GBq per cycle) every 6-8 weeks, were analyzed. Survival outcome was calculated based on the Kaplan-Meier method. The median progression-free survival (PFS) was 3.8 months (95% CI 2.3-5.3), and overall survival (OS) was 8.5 months (95% CI 6.2-10.8). An initial PSA reduction (≥ 50%) was observed in 9/25 (36%) of patients without being significantly associated with OS (p = 0.601). PSA response (PSA decline ≥50% at 12 weeks) was observed in 12/25 (48%) of patients and significantly associated with longer OS (16.0 months, 95% CI 7.4-24.6 vs. 4.0 months, 95% CI 1.1-6.9, p = 0.002). Imaging-based response using ⁶⁸Ga-PSMA-11-PET/CT after two to three cycles was seen in 11/25 (44%). Additionally, responders had a significantly longer median PFS (8.7 months, 95% CI 1.3-16.1 vs. 1.9 months, 95% CI 1.7-2.2, p < 0.001) and OS (16.0 months, 95% CI 7.6-24.4 vs. 4.0 months, 95% CI 0.9-7.1; p = 0.002). Intra- or post-therapeutic toxicity was graded according to the CTCAE v5.0 criteria. Newly developing grade ≥ 3 anemia, leukopenia, and thrombocytopenia occurred in three (12%), one (4%), and three (12%) patients, respectively. One patient showed renal toxicity (grade ≥ 3) during follow-up. Pain palliation (>2 level VAS decline) was achieved in 9/14 (64%) and performance status improvement (ECOG level decline ≥ 1) in 8/17 (47%) of patients. Compared to previous reports, radioligand therapy with ¹⁷⁷Lu-PSMA-617 in metastasized castration-resistant early-onset prostate cancer patients refractory to chemotherapy yields similar response rates with a comparable safety profile, but is associated with shorter survival.

Keywords: 177Lu-PSMA-617; PSMA; early-onset prostate cancer; metastatic castration-resistant prostate cancer; younger.