Clinical and genomic characterization of secondary rectal cancer after radiotherapy for prostate cancer: single-center case-control study

Patients treated with radiotherapy (RT) for prostate cancer (PC) have increased risk of secondary rectal cancer (SRC). A case-control study at Memorial Sloan Kettering Cancer Center (New York, NY) assessed the tumor molecular profile, clinical characteristics, and oncologic outcomes of SRC after PC and compared them with those of primary rectal cancer (PRC). The study included 64 patients with SRC at least 5 years after RT for PrC and 604 male patients with PRC. SRC patients were significantly older, more often presented with tumors in the distal rectum and anterior rectal wall and had worse survival outcomes compared with PRC patients. Patients with SRC also had significantly lower mutational burden, fewer APC alterations, and higher rates of frameshift deletions and SMAD4 inactivation. The authors conclude that these findings suggest that distinct clinical and genomic features reflect differences in the underlying biologic characteristics of SRC versus PRC.