PURPOSEChemoradiotherapy has replaced radical surgery as the initial treatment of choice for anal canal cancer. The roles of these therapeutic modalities are discussed and recommendations on management of anal canal cancer are made based on currently available evidence. Areas for further studies also are identified.METHODSLiterature on management of anal canal cancer from January 1970 to July 2003 obtained via MEDLINE was reviewed. Reports on anal margin cancers were excluded.RESULTSRandomized, prospective, Phase 3 trials in Europe and the United States showed that chemoradiotherapy with 5-fluorouracil and mitomycin C was superior in local control, colostomy-free rate, progression-free survival, and cancer-specific survival compared with radiation alone. In larger tumors, the addition of mitomycin C to radiotherapy and 5-fluorouracil improves local control, colostomy-free, and disease-free survival but is associated with more acute hematologic toxicity. Chemoradiotherapy, including Cisplatin and 5-fluorouracil, appeared to be equal or superior to surgery as salvage therapy in patients with residual disease six weeks after initial nonsurgical treatment.CONCLUSIONSTo improve treatment outcomes and reduce treatment-related toxicities, further studies are required to elucidate the optimal drug combination and doses, optimal radiation field, total dose, and fraction sizes. Randomized, multicenter trials are needed to define the treatment protocol that provides the highest rate of sphincter preservation with acceptable toxicity. Few studies addressed the treatment of metastatic disease, which remains a major cause of mortality.