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The NCCN Guidelines for Rectal Cancer are now more closely aligned with those for colon cancer. A new MRI-based definition of the rectum has been included and the use of MRI in staging has been elevated in importance. There is a new emphasis on neoadjuvant therapy, especially the concurrent use of chemotherapy and radiotherapy. One of the biggest changes is more acceptance of an observational approach—“watch and wait, nonoperative management”—for select patients experiencing a complete clinical response with no evidence of residual disease after neoadjuvant therapy.

A plethora of advancements in the management of locally advanced rectal cancer continue to be developed. Treatment strategies have primarily focused on modifying the current standard paradigm of rectal cancer management—including the complete omission of surgery or radiotherapy, or instead using immunotherapy as first-line treatment in eligible patients. Recommendations for optimal therapeutic strategies, based on a patient’s clinical stage, have been outlined in the NCCN Guidelines for Rectal Cancer.

Excellent long-term outcomes and manageable toxicity are being achieved with contemporary treatment strategies for rectal cancer. Short-course radiotherapy is now an acceptable standard. Total neoadjuvant therapy (TNT), which incorporates induction or consolidation chemotherapy, has improved the delivery of treatment regiments. TNT is now a standard of care, although the sequencing of radiation and chemotherapy in TNT, appropriate amount of chemotherapy in TNT, and addition of irinotecan to the regimen are still being debated. Nonoperative management of rectal cancer appears to be a safe option for select patients, but it is not yet an NCCN recommendation. In addition, the omission of radiation is being evaluated as a treatment option in some cases.

Few treatment advances have been observed in recent years for the treatment of advanced colorectal cancer (CRC). The goal remains to find approaches beyond FOLFOX and bevacizumab that will prolong remission. Immunotherapy for patients with microsatellite instability–high tumors represents progress, but this is a very small subset and approximately 30% of patients will not experience response. In locally advanced CRC, good long-term outcomes and manageable toxicity are being achieved with contemporary treatment strategies. Total neoadjuvant therapy, which incorporates induction or consolidation chemotherapy, has improved the treatment of patients with rectal cancer and is now a standard of care, although optimal sequencing is still being debated. Nonoperative management is an emerging option for sphincter preservation, and ongoing studies are evaluating the omission of radiation in select patients.

Radiation therapy (RT) is established as the primary treatment of squamous cell carcinoma of the anus. Multiple randomized trials have shown that combined modality therapy with RT, 5-fluorouracil, and mitomycin-C results in high rates of local control, disease-free survival, and sphincter preservation. However, treatment-related toxicity using conventional radiation approaches remains high and may compromise therapeutic efficacy because of prolonged treatment breaks and inability to deliver adequate radiation dose. Recent developments, including the use of PET for staging, radiation planning, and response assessment, and advanced RT planning using intensity-modulated radiation therapy (IMRT), may decrease acute and late treatment-related toxicity, provide high-dose target conformality, and permit safe radiation dose escalation. This article reviews the basic principles of IMRT and highlights current literature on these recent advances and the application of new RT techniques.

Although tumor biology and genomics of colon and rectal cancer are no different, patients with locally advanced rectal cancer (LARC) require neoadjuvant fluoropyrimidine-based chemoradiation and total mesorectal excision. In addition to known clinical risk factors, improved algorithms integrating molecular tools are needed to stratify patients with LARC to improve treatment outcomes and reduce acute and long-term toxicities. Simply combining newer systemic or targeted agents with standard treatment in all patients yielded little success but added toxicities. This article reviews the historical data, current standards of care, and ongoing research efforts regarding biomarkers, molecular imaging, and personalized genomic information.

These NCCN Clinical Practice Guidelines in Oncology provide recommendations for the management of rectal cancer, beginning with the clinical presentation of the patient to the primary care physician or gastroenterologist through diagnosis, pathologic staging, neoadjuvant treatment, surgical management, adjuvant treatment, surveillance, management of recurrent and metastatic disease, and survivorship. This discussion focuses on localized disease. The NCCN Rectal Cancer Panel believes that a multidisciplinary approach, including representation from gastroenterology, medical oncology, surgical oncology, radiation oncology, and radiology, is necessary for treating patients with rectal cancer.