Salvage radiotherapy with PSMA-directed focal boost: A precision approach for recurrent prostate cancer

Background: With the advent of novel therapies and advanced imaging modalities, prostate cancer patients are living longer, but biochemical recurrence has become increasingly common. Prostate-specific membrane antigen (PSMA) PET imaging demonstrates high sensitivity in detecting recurrence at low PSA levels, surpassing conventional imaging. While salvage radiotherapy traditionally targets the prostate fossa, PSMA PET enables focal dose escalation to PSMA-avid lesions. This study evaluated whether PSMA PET–guided salvage radiotherapy improves disease control compared with androgen deprivation therapy (ADT) alone, while maintaining an acceptable toxicity profile. Methods: Patients with suspected recurrent prostate cancer underwent PSMA PET, with eligibility defined as a PSMA score >3. Salvage treatment consisted of high-dose radiotherapy to the prostate fossa with focal boost to PSMA-avid lesions (with or without ADT) or ADT alone. The primary endpoint was failure-free survival. Secondary endpoints included treatment-related toxicities. Results: Fifty-six patients were included (mean age, 70.3 years). The mean initial PSA was 25.2 ng/mL, and the mean PSA prior to PSMA PET was 2.47 ng/mL. Patients who had previously undergone radical prostatectomy demonstrated significantly longer FFS compared with those initially treated with radiotherapy (41.2 vs. 31.5 months, p = 0.045), although baseline PSA was higher in the radiotherapy group. Salvage radiotherapy yielded significantly longer FFS than ADT alone (42.1 vs. 23.4 months, p < 0.001). Acute grade 1–2 gastrointestinal or genitourinary toxicities occurred in 23 patients (46.9%), late grade 1–2 events in 16 patients (32.7%), and grade 3 hematuria requiring intervention in 4 patients (8.2%). Conclusion: PSMA PET–guided salvage radiotherapy is an effective and personalized strategy for patients with biochemically recurrent prostate cancer. Compared with ADT alone, it provides superior failure-free survival with manageable toxicity, supporting its role as a standard component of salvage management.