We've arrived at our final primary site in the lower GI tract: anal cancer. In many ways, this disease is the ultimate success story for radiation oncology. It is one of the few solid tumors where we have moved from a paradigm of radical, mutilating surgery to a non-operative, organ-preserving standard of care, with definitive chemoradiation as the backbone. Today, we'll trace the history of this remarkable shift. We’ll start with the fundamentals of anatomy and staging that make anal cancer unique. Then we'll cover the revolutionary Nigro protocol that started it all, and finally, dive deep into the pivotal trials that fine-tuned this approach, answering the key questions of which chemotherapy drugs to use and for how long.