Evolving Concepts toward Individualized Treatment of Squamous Cell Carcinoma of the Anus

Treatment of squamous cell carcinoma of the anus has evolved over the last 5 decades from radical surgery to combined chemoradiation therapy. Radiation treatment techniques have dramatically improved with the development of more powerful computers, algorithms and treatment machines. The clinical impact of the modern radiation treatment techniques, such as intensity-modulated radiotherapy and volumetric modulated arc therapy, is discussed. The standard-of-care regimen still is concurrent Mitomycin C, 5-fluorouracil and high-dose radiation, as was conceived 45 years ago. Variants of this schedule are discussed in this chapter. International guidelines have been generated and implemented. Whereas concurrent chemoradiation therapy is the treatment of choice for locally advanced tumors, early tumors are probably adequately controlled with either reduced dose chemoradiation therapy or radiation therapy alone. Prognostic factors, such as high-risk human papillomavirus, epidermal growth factor receptor and immune response, will be highlighted. The role of surgery in primary care is limited to local excision of T1N0 tumors ≤ 1 cm of the anal margin. Salvage radical surgery is limited to locoregional recurrent, non-metastasized and resectable tumors after chemoradiation therapy. In addition, new treatment modalities, such as targeted therapy and immunotherapy, will be discussed. Current research aims at refining prognostic subgroups to further individualize treatment strategy, implementing quality assurance protocols in international trials and investigating the molecular profile of squamous cell carcinoma of the anus, in order to identify new treatment avenues. This will hopefully change the landscape of anal cancer treatment in the future.