Colorectal Cancer ____________________________________________________________________________
The use of chemotherapy in stage IV, metastatic, or recurrent disease involves the combination of agents. A number of chemotherapy regimens have been evaluated and represent the core of therapy. Newer biologically targeted agents are added to the established chemotherapy regimens to gain the advantage of synergistic drug action, and NCCN guidelines recommend the use of as many chemotherapy drugs as pos- sible to maximize the effect of adjuvant therapies for colon and rectal cancer [229; 243]. Several practice guidelines for the treatment of colon and rectal cancer are available and are updated and revised on a regular basis. The importance of guideline-adherent treatment was underscored by a 2015 study of all patients receiving primary treatment for colorectal cancer in a major academic medi- cal center between 2003 and 2010. The results showed that treatment non-adherent to NCCN guidelines was associated with 3.6 times the risk of death in the first year after diagnosis and an 80% increased risk of death after two to five years. The authors state that while medically justifiable reasons for guideline deviation do occur, the overall impact on patients is a markedly greater risk of death, especially in the first year following diagnosis [244]. TREATMENT OF COLON CANCER, STAGES I–III The standard treatment options for colon cancer are [203]:
peritoneal cavity and tumor progression from lack of lymph- adenectomy [190; 229]. Surgery is curative in 25% to 40% of highly selected patients who develop resectable metastases in the liver and lung. Refinements in surgical technique and preoperative imaging have improved patient selection and resection outcomes [203; 245; 246; 247]. Before surgery, all patients should be given information about the likelihood of having a stoma, why it might be necessary, and how long it might be needed. The psychologic and emo- tional impacts of having a stoma should not be overlooked. Between 16% and 26% of patients with a stoma will experience negative psychologic symptoms immediately postoperatively, including anxiety, depression, and suicidal ideation [229; 248; 249]. Having a stoma also can potentially decrease patients’ quality of life as they experience changes to body image, sexual function, social isolation, stigma, embarrassment, and decreased mood [250]. A trained stoma professional should provide specific information on the care and management of stomas to all patients considering surgery that might result in a stoma [229; 251]. Post-Resection Staging Given that tumor depth, nodal metastasis, and distant metas- tasis strongly predict post-surgical prognosis in colon cancer, staging should be performed following surgical resection using TNM staging, histologic grade of the tumor, and resection completeness [190].
• Stage 0: Surgery • Stage I: Surgery
• Stage II: Surgery, adjuvant chemotherapy • Stage III: Surgery, adjuvant chemotherapy • Stage IV and recurrent: Surgery, chemotherapy, and immunotherapy Surgical Resection Treatment of localized and locally advanced colon cancer primarily involves surgical resection, and roughly 80% of patients with colon cancer exhibit localized disease amenable to resection with curative intent [190]. Aside from palliative resection (e.g., alleviating obstruction), the objective of surgery is curative resection based on clear macroscopic and histologic resection margins. Practice recommendations from the ASCRS were published to optimize surgical care of these patients ( Table 9 ) [190]. The primary treatment for localized resectable colon cancer is colectomy with en bloc removal of all associated regional lymph nodes and involved adjacent structures. The extent of a curative resection for colon cancer depends on the site of the primary lesion and lymphovascular drainage of the cancer site. The length of bowel resected is governed by the blood supply to that segment. In the absence of synchronous pathology, an anatomic colon resection for cancer should achieve at least a 5-cm to 7-cm negative margin on either side of the tumor. Colectomy with local excision is not adequate for curative resection, because it increases risks of tumor spillage into the
Adjuvant Chemotherapy Stage II
The value of adjuvant chemotherapy for stage II colon cancer is controversial. In one study, adjuvant 5-FU-based chemo- therapy was evaluated in patients with high-risk stage II colon cancer following curative resection. Compared with surgery alone, adjuvant 5-FU showed inconsistent benefit; these and other results led to guidelines issued by the American Society of Clinical Oncology (ASCO) stating that evidence does not support the routine use of adjuvant chemotherapy for patients with stage II colon cancer who are not in a high-risk subgroup [252; 253]. The NCCN guideline also states there is no survival advantage by adding oxaliplatin to 5-FU/leucovorin, including in patients 70 years of age or older [229]. The combination of folic acid, 5-FU, and oxaliplatin (FOLFOX) is considered reasonable in high-risk cases, but it is not indicated in good-to-average-risk stage II cancers. Stage III Stage III colon cancer denotes lymph node involvement. Studies have shown that prognosis is related to the number of involved lymph nodes; patients with one to three involved nodes have a significantly better survival than those with four or more involved nodes. Before 2000, 5-FU was the only
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