Colorectal Cancer ____________________________________________________________________________
For stage II/III colon cancer, the NCCN asserts that adju- vant bevacizumab, cetuximab, panitumumab, or irinotecan should not be used outside of clinical trials [229]. In stage III colon cancer, FOLFOX is superior to 5-FU/leucovorin, and capecitabine/oxaliplatin (CAPEOX) is superior to bolus 5-FU/ leucovorin. FLOX is an alternative to FOLFOX or CAPEOX, but FOLFOX or CAPEOX are preferred [229]. Adjuvant Radiation Therapy Unlike in rectal cancer, the role of adjuvant radiation therapy is poorly defined in colon cancer treatment. Radiation therapy has no current adjuvant role following curative resection but may have a potential role in patients with residual disease [229]. If used, radiation fields should include the tumor bed, as defined by preoperative radioimaging or surgical clips. Radiation should be given in doses of 45–50 Gy in 25 to 28 fractions; the dose in the small bowel should be no greater than 45 Gy [229]. Neoadjuvant chemoradiotherapy that includes 5-FU should be delivered concurrently to aid resectability. Conformal external beam radiation is preferred; intensity- modulated radiation therapy should be limited to unique clinical situations. Intraoperative radiation therapy should be considered in T4 or recurrent cancer [229]. TREATMENT OF RECTAL CANCER, STAGES 0–III The standard treatment options for rectal cancer are [206]: • Stage 0: Polypectomy or surgery • Stage I: Surgery with or without chemoradiation therapy • Stage II and III: Surgery, neoadjuvant chemoradiotherapy, short-course neoadjuvant radiotherapy, adjuvant chemoradiotherapy, immunotherapy • Stage IV, metastatic, and recurrent: Surgery with or without chemotherapy or radiotherapy, chemotherapy, and targeted therapy Approximately 30% of colorectal malignancies are attribut- able to rectal carcinoma. Although surgical resection is the only curative option for rectal cancer, complete resection is rendered technically difficult by the lack of serosa covering the rectum and proximity of the rectum to the bony pelvis and other pelvic organs. Local tumor invasion is promoted by this extra-colorectal proximity to other organs, which, along with surgical difficulty, contributes to high local recurrence rates [189; 206]. Compared with colon cancer, the increased risk of local recur- rence and poorer overall prognosis in rectal cancer has led to differences in the management of localized or locally advanced disease, including greater emphasis on multimodal treatment to minimize morbidity, decrease recurrence risk, and prolong survival [255]. Other differences in rectal cancer treatment
include surgical techniques, use of radiation therapy, and chemotherapy protocol. In stage II or III rectal cancer, neo- adjuvant therapy is now favored over adjuvant therapy based on evidence of improved local control and increased rates of sphincter preservation [243; 256; 257; 258]. An important consideration is the impact of rectal cancer surgery on the structure and function of adjacent sensitive tissues, and the therapeutic issues related to the maintenance or restoration of normal anal sphincter, genitourinary, and sexual function [255; 259; 260]. Practice recommendations for the surgical treatment of localized rectal cancer have been published by the ASCRS ( Table 10 ) [189]. Treatment of rectal cancer is determined by clinical disease stage and the risk of local recurrence. Low-risk, early-stage disease is generally treated with primary surgical therapy, while locally advanced or high-risk disease requires multimodality therapy that includes neoadjuvant radiation or chemoradiation [189]. The risk of local recurrence is estimated using MRI imag- ing before surgical intervention. Risk level is defined as low, moderate, or high based on the following criteria [189; 251]:
Low Risk • Clinical stage T1, T2 or T3a, AND • No lymph node involvement
Moderate Risk • T3b or greater, in which the potential surgical margin is not threatened, OR • Any suspicious lymph node not threatening surgical resection margins, OR • The presence of extramural vascular invasion High Risk • A threatened (<1 mm) or breached resection margin, OR • Low tumors encroaching onto the intersphincteric plane or with levator involvement Primary Surgical Therapy Rectal cancer surgery involves surgical resection of the primary tumor. Surgical approach is guided by tumor location, disease stage, and presence of high-risk features (e.g., positive margins, lymphovascular invasion, perineural invasion, poorly differenti- ated histology) [206]. Polypectomy alone may be sufficient when polyps with inva- sive cancer can be completely resected with clear margins and show favorable histologic features, generally select T1 cancers [206; 261]. Approaches with minimal morbidity and mortality include transanal excision and transanal endoscopic microsur- gery. Local excision is appropriate in selected T1 tumors, with mesorectal excision preferred for all other T1–T2/N0 tumors.
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