Impact of 18F-DCFPyL-PSMA PET/CT on Radiotherapy Planning and Treatment Intensification in Occult Biochemical Recurrence of Prostate Cancer After Radical Prostatectomy

Biochemical recurrence (BCR) after radical prostatectomy (RP) frequently occurs despite negative conventional imaging, making salvage treatment decisions challenging. We evaluated the impact of 18F-DCFPyL-PSMA PET/CT on disease detection and radiotherapy planning in patients with occult BCR. Methods: We conducted a prospective single-center observational study including 85 patients with BCR after RP, negative or inconclusive conventional imaging, and PSA levels between 0.2 and 1.0 ng/mL or persistent PSA after previous local treatment. Detection rates (DRs) were evaluated according to PSA level, PSA doubling time (PSA-DT), and International Society of Urological Pathology (ISUP) grade. Changes in radiotherapy planning and treatment intensification were assessed by comparing intended management before and after PSMA PET/CT. Results: PSMA PET/CT detected recurrent disease in 53% of patients. DRs increased significantly with PSA level, reaching 31.3% for PSA 0.2–0.5 ng/mL, 60.0% for PSA 0.5–0.9 ng/mL, and 77.8% for PSA 1.0 ng/mL (p < 0.001). Detection was also associated with shorter PSA-DT and higher ISUP grade. Pelvic lymph nodes (LNs) represented the predominant site of recurrence, accounting for 48 of 79 detected lesions. Treatment strategy changed in 97.8% of patients with positive scans, while radiotherapy planning was modified in 84.4%. PSMA PET/CT enabled expansion of target volumes, focal dose escalation, metastasis-directed stereotactic body radiotherapy (SBRT), systemic treatment intensification, and in selected patients with negative findings, treatment de-escalation to active surveillance. Following PSMA-guided treatment adaptation, the median PSA level at 24 months was 0.08 ng/mL, with early biochemical responses (BRs) observed during follow-up. Conclusions: 18F-DCFPyL-PSMA PET/CT provides clinically meaningful information beyond disease detection by substantially modifying radiotherapy planning and treatment selection in patients with occult BCR after RP. These findings support the integration of molecular imaging into salvage treatment planning to enable more personalized, biology-driven radiotherapy strategies.