5115 Background: Salvage radiotherapy (SRT) after radical prostatectomy (RP) has traditionally been delivered as uniform dose distribution of the prostate bed without lesion visualization. We prospectively implemented an image-guided salvage strategy integrating high-resolution multiparametric MRI (mpMRI) and lesion-directed dose escalation. Here we report long-term oncologic outcomes of this pioneering approach. Methods: This prospective, single-arm clinical study was registered in the UMIN database in 2013. Patients with biochemical recurrence (BCR, PSA ≥0.2 ng/mL) after RP and no evidence of distant metastasis were enrolled. All patients underwent 3 Tesla mpMRI with an endorectal coil prior to SRT. When a focal recurrent lesion was identified, intensity-modulated radiotherapy (IMRT) with simultaneous integrated boost (SIB) was delivered (70 Gy to the MRI-defined lesion and 66 Gy to the prostate bed in 33 fractions). Patients without visible lesions received prostate-bed irradiation alone. Treatment failure after SRT was defined as PSA > 0.2 ng/mL. Long-term clinical outcomes were analyzed. Results: A total of 40 patients completed protocol treatment. mpMRI identified focal recurrence sites in 11 patients (27.5%), all of whom received lesion-directed SIB-IMRT. After a median follow-up of 10.6 years, treatment failure occurred in 13 patients (32.5%). Among patients treated with SIB-IMRT, 4 of 11 developed BCR, whereas among 29 patients without mpMRI-detectable recurrence at the time of SRT, 9 developed BCR. There was no statistically significant difference in BCR rates between the two groups. Importantly, no patient developed radiologically evident local recurrence within the irradiated prostate bed, including those treated with SIB in their disease course. All but one patient with treatment failure received subsequent systemic salvage therapy. Distant metastases developed in 3 patients, and 1 patient died from prostate cancer. One patient without SIB experienced grade 3 perforation of the sigmoid colon. During follow-up after SRT, secondary malignancies were diagnosed in 10 patients. Conclusions: In this prospective study with long-term follow-up, mpMRI-guided SRT achieved excellent durable local control. Although second BCR occurred in a subset of patients, the absence of in-field local failures regardless of mpMRI detectability at the time of SRT supports the biological and clinical validity of lesion-directed salvage intensification. Our findings underscore individualized SIB approach and highlight the need for future studies to refine patient selection and treatment intensification strategies in salvage settings, including androgen deprivation therapy and/or elective pelvic nodal irradiation. Clinical trial information: UMIN000009823.
Shiraishi et al. (2026) studied this question.