Abstract
Simple SummaryPrior to the 1980s, primary management of localized anal cancer was surgery. Dr. Norman Nigro and colleagues found that neoadjuvant chemoradiotherapy with 5-fluorouracil and mitomycin C afforded complete response, obviating the need for surgery upfront. Advancements in radiotherapy delivery using intensity-modulated radiation therapy (IMRT) and image-guided radiation have resulted in reductions in radiation-associated adverse effects, allowing for the delivery of greater doses of radiation. Ongoing prospective trials are attempting to improve IMRT-based treatment of locally advanced disease with efforts to increase personalized treatment. Trials of newer modalities such as proton therapy are underway. In this review, we present the evolution of radiotherapy for anal cancer and describe recent advances to contextualize ongoing studies and inform future directions in efforts to mitigate treatment toxicities, further personalize treatment, and improve oncologic outcomes.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.
Highlights
abdominoperineal resection (APR) remained an option for patients with persistent or recurrent disease, with a 5-year survival rate up to 92% [20,22,26,27,28,29,30,31,32,33,34,35,36,37,38,39], subsequent studies assessing primary treatment options for localized anal cancer sought to optimize upfront nonsurgical management
Anal cancer-specific mortality relative risk 0.71 (95%CI 0.53–0.95, p = 0.02)
Group (ECOG) Radiation Therapy Oncology Group (RTOG) 87-04/ECOG 1289 trial evaluated the omission of mitomycin C
Summary
Of patients for whom treatment was curative, three-quarters maintained normal anal function [24] Another series of 221 patients treated with external beam radiation to 30 Gy and iridium implant boost to 10–20 Gy resulted in a 5-year overall survival rate of 65%, 90% of whom maintained normal anal function [23]. APR remained an option for patients with persistent or recurrent disease, with a 5-year survival rate up to 92% [20,22,26,27,28,29,30,31,32,33,34,35,36,37,38,39], subsequent studies assessing primary treatment options for localized anal cancer sought to optimize upfront nonsurgical management
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