Despite recent therapeutic advances, there is a continuing need for novel prostate cancer treatment strategies. Some men with mCRPC may present at some point with oligometastases, a state between loco-regional and widespread metastatic disease with metastases being limited both in number and location. This oligometastatic state exists de novo, can be induced by effective systemic therapies, or may present under the picture of oligoprogression. The latter is a situation where ≤ 3-5 metastatic tumor sites progress, while all other metastases are controlled by ongoing systemic therapy. The typical practice would be to change systemic therapy at this point. SABR is an emerging treatment option for oligometastatic or oligoprogressive malignancies. Used for this indication SABR may improve survival and delay the need to change systemic therapy. However, some patients may derive limited benefit only because of early and widespread metastatic progression following SABR. While there are no validated biomarkers to predict these two scenarios to date, circulating tumor DNA (ctDNA) is a minimally invasive and highly informative biomarker platform for identifying molecular changes associated with treatment outcome.
In the absence of published evidence on the use of SABR for oligoprogressive mCRPC in men undergoing abiraterone therapy, we are conducting a phase I study to determine the incidence of acute and late toxicities (primary endpoint) associated with delivering SABR to all oligoprogressive metastatic sites in 30 men with mCRPC on abiraterone. We also aim to collect preliminary efficacy data of such an approach as secondary endpoints (eg time to biochemical, radiological and/or symptomatic progression following SABR). Using conventional imaging, eligible mCRPC candidates will be identified based on ≤ 5 SABR amenable progressive metastatic lesions (≤ 3 in any one organ system) while all other metastases remain stable or are responding to abiraterone therapy. Before SABR, we will collect ctDNA to perform gene copy number and mutational analyses of prostate cancer relevant genes as a means to predict sustained responses to SABR.
Clinical trial identification
Legal entity responsible for the study
Sunnybrook Research Institute, Toronto, ON, Canada
Janssen Inc., Canada
U. Emmenegger: Research support for this study and paid advisory board meetings of the manufacturer of abiraterone. All other authors have declared no conflicts of interest.