PSMA-Directed Biologically-Guided Radiation Therapy of Castration-Sensitive Oligometastatic Prostate Cancer Patients

Abstract

Local ablative treatment to oligometastatic (OM) patients can result in long term disease-free survival in cancer patients. The importance of consolidating all tumors in prostate cancer in the modern era is unknown. Stereotactic ablative radiation (SABR) is highly focused, high-dose radiation, but further dose escalation is still limited by target motion, localization uncertainties and difficultly irradiating multiple metastases simultaneously. Biology-guided radiotherapy (BgRT) is currently being developed to utilize PET emission data to guide radiotherapy delivery in real-time and to multiple targets. With this modality, the PET signals act as a biological fiducial that inherently tracks target motion and treatment setup uncertainties. Prostate membrane specific antigen (PSMA) is a cell surface protein that is overexpressed preferentially in prostate cancer and radiolabeled-ligands have been used for unprecedented molecular imaging in prostate cancer. Here we report on a pilot study examining PSMA-directed BgRT using a cohort from our Phase II randomized trial of SABR to men with recurrent low volume (1-3 metastases) metastatic hormone sensitive prostate cancer (HSPC) who have been imaged with PSMA PET-CT. Patients are randomized 2:1 to SABR:observation with minimization to balance assignment by primary intervention, prior hormonal therapy, and PSA doubling time. All men treated with SABR were imaged with PSMA PET-CT at day 1 prior to SABR and day 180 from randomization. Four patients from this trial were used for a proof-of-concept study to compare conventionally planned SABR treatments versus BgRT treatments generated from a prototype treatment planning system (TPS). BgRT treatment plan prescriptions were duplicated from the conventional SABR treatment plans and the dose constraints for organs-at-risk (OARs) followed AAPM TG101 guidelines. No additional dose shaping structures were used for the BgRT plans. All patients had one metastatic site (n= 2 node & n= 2 bone) with an average PTV of 5.1 cc (range = 1.8-9.5 cc). All four BgRT plans met pre-specified planning objectives and were qualitatively acceptable even without the use of optimization structures. The BgRT plans displayed better PTV coverage, V95=96.9±2% versus V95=95.6%±1 for conventional SABR planning, were more heterogeneous [average Dmax of the prescription dose was 149% (range = 137-164%) for BgRT versus 123% (112-131%) for the conventional SABR] and gave more dose on average [Dmean 123% (range = 117-127%) for BgRT versus 112% (range = 109-116%) for conventional SABR] but had similar and in many cases better avoidance of OARs. This is a pilot BgRT planning study from the first randomized Phase II study evaluating the safety and efficacy of SABR in OM HSPC who have been imaged with PSMA PET-CT. Our study suggests comparable treatment plans between conventional and BgRT planned SABR and demonstrates the feasibility of PSMA-directed BgRT-guided SABR for OM HSPC.