TY - JOUR A1 - Mader, Nicolai A1 - Gröner, Daniel A1 - Tselis, Nikolaos A1 - Banek, Séverine A1 - Nagarajah, James A1 - Grünwald, Frank A1 - Sabet, Amir T1 - Outcome of 177Lu-PSMA-617 radioligand therapy in chemo-refractory patients with metastatic castration-resistant early-onset prostate cancer T2 - Cancers N2 - 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. KW - PSMA KW - 177Lu-PSMA-617 KW - early-onset prostate cancer KW - metastatic castration-resistant prostate cancer KW - younger Y1 - 2021 UR - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/62628 UR - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-626282 SN - 2072-6694 VL - 13 IS - 16, art. 4193 SP - 1 EP - 11 PB - MDPI CY - Basel ER -