A secondary rectal cancer in the field of prior prostate radiation is bad, and not just because it’s tricky to deliver further radiation. This case-control study suggests, not only are these tumors likely to be distal–making any absence of upfront radiation more unfortunate–but they also have unique genetic signatures. Targeted sequencing of 31 secondary rectal cancers compared with matched controls revealed lower mutational burden, lower frequency of APC alterations, and higher rates of SMAD4 inactivation, all genomic features typical of more aggressive tumors. | Omer, JAMA Netw Open 2025
