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

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.

Safety and Efficacy of 177Lutetium-PSMA-617 Radioligand Therapy Shortly after Failing 223Radium-Dichloride

“…The significance of initial PSA response (≥50% after 4 weeks) to 177 Lu-PSMA-617 as a positive predictor of outcome remains controversial. A few studies in heterogeneous patient cohorts showed a longer OS in patients with early PSA response [13,21,25], whereas other studies reported no significantly longer survival in early responders [23,26]. In a study by Leibowitz et al on 24 elderly patients at >75 years of age, 14 of whom previously treated with 223 Ra, a PSA decline of ≥ 50% was associated with a significantly longer OS (10.9 vs. 3.1 months, p = 0.0006) [13].…”

Aptamers as Theragnostic Tools in Prostate Cancer

“…Actually, 177 Lutetium-PSMA-617 has been approved in PCa therapy by the FDA. Although this radioligand therapy has been shown to be safe in patients resistant to chemotherapy, the median progression-free survival is still limited (3.8 months) [ 106 ]. Therefore, therapy with aptamers is an advantageous tool since it would allow the design of molecules capable of specifically recognizing various types of tumor populations to achieve an effective pharmacological treatment.…”