Colorectal Cancer _ ___________________________________________________________________________
patients with any KRAS or NRAS mutation should not be treated with cetuximab or panitumumab, as these mutations strongly predict resistance to EGFR inhibitor agents. In contrast, non-mutational KRAS , termed wild-type KRAS , responds to targeted therapy [111; 201; 217; 222; 228; 229]. GENERAL APPROACH TO TREATMENT Overall, there is a substantial overlap between treatment approaches for colon and rectal cancer, especially in stage IV and metastasized cancer. Treatment approaches for stage I–III cancer (earlier stage) differs the most. In this section, treatment of earlier-stage colon and rectal cancer are discussed separately, and discussion of metastatic colon and rectal cancer is combined. For both cancers, the foundation of care is surgical resection for patients with local or locally advanced tumor, and chemotherapy for stage IV, metastatic, and recurrent tumor. Unlike rectal cancer, radiotherapy has limited use in colon cancer. The timing of chemotherapy and/or radiotherapy is sequenced in relation to surgery as follows: • Neoadjuvant chemotherapy and/or radiation therapy: Delivered before surgery, to downsize the tumor. Most often used in rectal cancer. • Adjuvant chemotherapy and/or radiation therapy: Delivered following surgery with the intent to destroy remaining local or micro-metastasized malignant cells and colonies. • Palliative chemotherapy or radiotherapy: Delivered to downsize or eradicate colorectal cancer tumors that have metastasized to other organs. The objective is to relieve symptoms and pain, instead of cure or prolonging survival. • Liver metastases: The liver is the most common site of metastatic colon and rectal cancer. Treatment of hepatic metastases of primary colorectal cancer can involve surgery with neoadjuvant or adjuvant chemotherapy, local ablation, or intra-arterial chemotherapy. 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 possible to maximize the effect of adjuvant therapies for colon and rectal cancer [220; 230].
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 medical 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 [231]. TREATMENT OF COLON CANCER, STAGES I–III The standard treatment options for colon cancer are [201]: • Stage 0: Surgery • Stage I: Surgery • Stage II: Surgery • 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 [188]. 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 ) [188]. 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 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 peritoneal cavity and tumor progression from lack of lymphadenectomy [188; 220].
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