Stereotactic Radiotherapy to Oligoprogressive Lesions Detected With 68Ga-PSMA-PET/CT in Castration-Resistant Prostate Cancer Patients

Abstract

Few studies have investigated the feasibility of MDT in metastatic castration-resistant prostate cancer (CRPC) patients with heterogeneous patient populations with different treatment strategies and various imaging modalities other than gallium prostate-specific membrane antigen-positron emission tomography (68Ga-PSMA-PET/CT) for detecting oligoprogressive lesions. We assessed the outcomes of stereotactic body radiotherapy (SBRT) to treat oligoprogressive castration-resistant prostate cancer (CRPC) patients with ≤5 lesions using 68Ga-PSMA-PET/CT.The clinical data of 67 CRPC patients with 133 lesions treated with 68Ga-PSMA-PET/CT-based SBRT were retrospectively analyzed. All of the patients had oligoprogressive disease during androgen-deprivation therapy (ADT). The inclusion criteria were as follows: a histologic diagnosis of PC on primary tumor biopsy, less than or equal to 5 bone and/or lymph node metastases detected with 68Ga-PSMA-PET/CT during ADT, being castration-resistant according to the European Association of Urology guidelines, a controlled primary tumor, SBRT fraction doses of at least 6 Gy per fraction and a biologically effective dose (BED) of at least 90 Gy using α⁄β of 3 Gy. The prognostic factors for overall- (OS) and progression-free survival (PFS) and the predictive factors for switching to next-line systemic treatment (NEST) and NEST-free survival (NEST-FS) were analyzed.With a median follow-up of 17.5 months, the 2-year overall survival (OS) and PFS rates were 86.9% and 34.4%, respectively. Most of the patients had GS 9 or 10 tumors and locally advanced disease. The most frequent oligoprogressive site was bone only (64.2%), and more than half of the patients (53.7%) had a single metastasis. The median number of metastases was 1 (range, 1-5). In the case of bone metastasis, the most adopted methods were single-dose 16 Gy and 18 Gy, and the most adopted prescription for nodal metastasis was 30-35 Gy delivered in 5 fractions. The PSA response after SBRT was observed in 49 patients (73.1%). Progression was observed in 37 patients (55.2%) at a median of 11.0 months following SBRT. Forty-five patients (67.2%) remained on ADT after SBRT, and 22 patients (32.8%) had a NEST change at a median of 16.4 months after MDT. Patients with a NEST change had higher post-SBRT PSA values and fewer PSA nadirs after MDT than their counterparts. In multivariate analysis, higher pre-SBRT PSA values were the only significant predictor for worse OS and NEST-FS, and no significant factor was found for PFS. No serious acute or late toxicities were observed.This study demonstrated the feasibility of MDT using SBRT to treat oligoprogressive lesions by 68Ga-PSMA-PET/CT in CRPC patients is efficient and well-tolerated, prolonging the effectiveness of ADT by delaying NEST.