Stereotactic Ablative Radiation Therapy for Abiraterone-Resistant, Oligoprogressive Metastatic Prostate Cancer

Overview

There is increasing worldwide interest in exploring stereotactic ablative body radiotherapy (SABR) for treating metastases in men with prostate cancer, including for the treatment of oligoprogressive metastases. The latter applies to a situation whereby patients with widespread metastases undergoing systemic therapy present with a solitary or a few metastatic tumors that progress, while all other metastases are stable or responding. The usual practice would be to change systemic therapy at this point, but another approach is to locally ablate the "rogue" metastases and continue the same systemic therapy. SABR used in this scenario may delay the need to switch to another line of systemic therapy and improve progression-free survival while patients stay on the same systemic therapy.

There is increasing worldwide interest in exploring the use of SABR for metastatic, treatment-naive prostate cancer, eg for delaying the need to start androgen deprivation therapy (ADT), and ultimately to improve patient outcome. Another potential use of SABR for metastatic prostate cancer is in the setting of oligoprogression. In patients undergoing systemic therapy, oligoprogression describes the clinical situation where a solitary or a few metastatic tumors progress, while all other metastases are stable or responding. The usual practice would be to change systemic therapy at this point, but another approach is to locally ablate the "rogue" metastases and continue the same systemic therapy. There is limited clinical evidence for such an approach, eg in renal cell and non-small cell lung cancer. While there is a lack of published evidence of such an approach in metastatic castration-resistant prostate cancer (mCPRC), SABR for oligoprogressive mCRPC in men undergoing abiraterone therapy may delay the need to switch to another line of systemic therapy, such as chemotherapy, and thereby to improve progression-free survival while patients stay on the same systemic therapy. mCRPC is a unique solid tumor to study the oligoprogressive setting for several reasons. First, there still remains a limited number of proven systemic agents in the CRPC setting. Second, serum prostate specific antigen (PSA) is an excellent biomarker of prostate cancer activity, which is easy to collect and analyze to monitor treatment response and disease progression. Third, because of the low α/β value of prostate cancer, hypofractionated SABR may be a very effective and convenient way to eradicate areas of known disease. The primary objective of this phase I study is to determine the incidence of acute and late toxicities associated with delivering SABR to all progressive metastatic sites in patients with metastatic CRPC who present with oligoprogression while on abiraterone. We also aim to obtain preliminary efficacy data of this novel approach. Patients will remain on abiraterone after SABR to measure the added progression-free survival.