Prostate-Specific Membrane Antigen PET Response Associates with Metastasis-Free Survival Following Stereotactic Ablative Radiation Therapy in Oligometastatic Castration-Sensitive Prostate Cancer

Abstract

<h3>Purpose/Objective(s)</h3> Emerging data suggest metastasis-directed therapy (MDT) improves outcomes in patients with oligometastatic castration-sensitive prostate cancer (omCSPC). Prostate-specific membrane antigen positron emission tomography (PSMA-PET/CT) can detect occult metastatic disease and has been proposed as a biomarker for treatment response. Herein we identify and validate a PSMA-PET biomarker for clinical outcomes following MDT in omCSPC. <h3>Materials/Methods</h3> This was an international multi-institutional retrospective study of two independent cohorts of omCSPC, defined as ≤3 lesions, treated with metastasis-directed stereotactic ablative radiation therapy (SABR). Patients underwent PSMA-PET/CT prior to and 3-6 months after treatment. Pre- and post-SABR PSMA-PET/CT standardized uptake value (SUV) was measured for all lesions and PSMA response defined discretely using a cutpoint of ≥ 30% decrease in SUV_max. PSMA-PET response was correlated with lesion local control (LLC), and metastasis-free survival (MFS), defined per ICECaP working group by a new metastasis on conventional imaging alone (not including pelvic lymph node metastases) or death. <h3>Results</h3> A total of 131 patients (discovery n=35, validation n=96) with 261 treated metastases were included in the analysis, with median follow-up of 29 months (IQR 18.5-41.3). Following SABR, 78.4% of lesions experienced a partial or complete PSMA response. Multivariable analysis demonstrated SUV response significantly associated with improved LLC (HR=0.10, 95%CI 0.04-0.26; p<0.01). Patients with PSMA response in all lesions experienced significantly better MFS (HR=0.37, 95%CI 0.21-0.65; p<0.01) compared to their counterparts, and this maintained significance within both the discovery (p=0.02) and validation (p<0.01) cohorts. <h3>Conclusion</h3> Following SABR, PSMA-PET response is a robust and externally validated radiographic biomarker for MFS in omCSPC. This approach holds promise for guiding clinical management of omCSPC and should be validated as an early response indicator biomarker in localized and other advanced states of prostate cancer.