Prior to the 1980s, the primary management of localized anal cancer was surgical resection. Dr. Norman Nigro and colleagues introduced neoadjuvant chemoradiotherapy prior to abdominoperineal resection. Chemoradiotherapy 5-fluorouracil and mitomycin C afforded patients complete pathologic response and obviated the need for upfront surgery. More recent studies have attempted to alter or exclude chemotherapy used in the Nigro regimen to mitigate toxicity, often with worse outcomes. Reductions in acute adverse effects have been associated with marked advancements in radiotherapy delivery using intensity-modulated radiation therapy (IMRT) and image-guidance radiation delivery, resulting in increased tolerance to greater radiation doses. Ongoing trials are attempting to improve IMRT-based treatment of locally advanced disease with efforts to increase personalized treatment. Studies are also examining the role of newer treatment modalities such as proton therapy in treating anal cancer. Here we review the evolution of radiotherapy for anal cancer and describe recent advances. We also elaborate on radiotherapy's role in locally persistent or recurrent anal cancer.
Keywords: 5-fluorouracil; Nigro regimen; RTOG 0529; chemoradiotherapy; intensity-modulated radiation therapy; mitomycin C.