Rectal Cancer after Prostate Radiation: A Complex and Controversial Disease

Simple Summary Radiation therapy is commonly used in the treatment of prostate cancer, but it is a carcinogen itself. Long-term survivors of prostate cancer who were treated with pelvic radiotherapy have been reported to be at increased risk for developing rectal cancer compared to those treated with surgery. The treatment of radiation-associated rectal cancer is challenging, and the evidence behind this disease is limited and often contradictory. Here, we review the available literature and discuss the unique considerations of treating patients with rectal cancer after prostate radiotherapy. A small proportion of rectal adenocarcinomas develop in patients many years after the treatment of a previous cancer using pelvic radiation, and the incidence of these rectal cancers depends on the length of follow-up from the end of radiotherapy. The risk of radiation-associated rectal cancer (RARC) is higher in patients treated with prostate external beam radiotherapy than it is in patients treated with brachytherapy. The molecular features of RARC have not been fully investigated, and survival is lower compared to non-irradiated rectal cancer patients. Ultimately, it is unclear whether the worse outcomes are related to differences in patient characteristics, treatment-related factors, or tumor biology. Radiation is widely used in the management of rectal adenocarcinoma; however, pelvic re-irradiation of RARC is challenging and carries a higher risk of treatment complications. Although RARC can develop in patients treated for a variety of malignancies, it is most common in patients treated for prostate cancer. This study will review the incidence, molecular characteristics, clinical course, and treatment outcomes of rectal adenocarcinoma in patients previously treated with radiation for prostate cancer. For clarity, we will distinguish between rectal cancer not associated with prostate cancer (RCNAPC), rectal cancer in non-irradiated prostate cancer patients (RCNRPC), and rectal cancer in irradiated prostate cancer patients (RCRPC). RARC represents a unique but understudied subset of rectal cancer, and thus requires a more comprehensive investigation in order to improve its treatment and prognosis.