Real-world outcomes of 177Lu-PSMA-I&T in metastatic castration-resistant prostate cancer: the KuPSMALu trial in Eastern Finland.

BACKGROUND AND PURPOSE: Radioligand therapy targeting prostate-specific membrane antigen (PSMA) with lutetium-177 PSMA (¹⁷⁷Lu-PSMA) compounds has emerged as an effective treatment for metastatic castration-resistant prostate cancer (mCRPC). The KuPSMALu trial evaluated the real-world efficacy and safety of in-house produced ¹⁷⁷Lu-PSMA imaging & therapy (I&T) for mCRPC patients in a public healthcare setting and assessed whether selection based on ¹⁸F-PSMA-PET and contrast-enhanced CT - without FDG-PET - provides favourable oncological outcomes.

PATIENTS/MATERIAL AND

METHODS

This prospective, single-centre observational study included 40 patients with PSMA-positive mCRPC who had progressed after chemotherapy and at least one androgen receptor pathway inhibitor. Patients received 3-6 cycles of ¹⁷⁷Lu-PSMA-I&T at 6-8-week intervals. Imaging, blood-based markers and patient-reported outcomes were collected longitudinally. Dosimetry, adverse events (AEs) and quality-of-life metrics were systematically assessed.

RESULTS

The median overall survival (mOS) was 16.0 months. ECOG 0-1 patients had significantly longer mOS than ECOG 2 patients (20.0 vs. 4.7 months, p < 0.01). A PSA decrease ≥ 50% was observed in 40% of patients and correlated with improved mOS (23.7 vs. 9.1 months, p < 0.01). PSA doubling time (dt) > 4 months predicted superior survival (23.8 vs. 12.6 months, p = 0.040). Grade ≥ 3 AEs occurred in only 12.3% of patients.

INTERPRETATION: In-house ¹⁷⁷Lu-PSMA-I&T production combined with pragmatic imaging-based patient selection provides a safe, cost-effective therapy for mCRPC in public healthcare. PSA kinetics, particularly PSA dt, are strong predictors of therapeutic benefit. The findings align with VISION and TheraP trials and highlight the feasibility of integrating radioligand therapy into routine clinical care.