Combining Prostate Cancer Radiotherapy with Therapies Targeting the Androgen Receptor Axis

Background Prostate cancer (PCa) is the most common non-dermatologic cancer and the 3rd leading cause of male cancer mortality in Canada. In patients with high-risk localized or recurrent pca, management typically includes the combination of long-term androgen deprivation therapy (ADT) and radiotherapy (RT). New androgen-receptor-axis targeted therapies (ARATS), which await validation, offer an option to intensify therapy. Methods In this narrative review, we report the relevant history that has supported combining ADT with RT. The literature in PubMed was searched for studies involving PCa and novel ARATS (abiraterone acetate, enzalutamide, apalutamide, darolutamide) published between 1995 and 2019. Literature discussing clinical trials in which those modalities were combined was extracted and synthesized into a combined molecular and clinical discussion. Potential treatment intensification mechanisms and rationales are explored. Results Early results from three phase I/II trials demonstrated that concurrent abiraterone acetate, ADT, and RT is safe, improves the extent of chemical castration, and is associated with limited treatment failures. A single in vitro study implies synergy for radiosensitization beyond that facilitated by conventional adt. Studies investigating the combination of other arats with rt are under way, including multiple phase iii trials, but short-term results are not yet available.