___________________________________________________________________________ Colorectal Cancer
teric artery. Pelvic CT and/or transrectal ultrasonography are recommended with contraindications to MRI. All patients with rectal cancer should have preoperative radiologic staging with contrast-enhanced CT to assess for metastatic disease [190; 202]. Histologic Assessment Histologic confirmation of colon cancer is ideal, and for rectal cancer, it is essential [174]. Research has demonstrated an association between the number of lymph nodes examined in colon and rectal cancer surgery and oncologic outcomes [203]. In patients with colon or rectal cancer, the American Joint Committee on Cancer (AJCC) and National Cancer Institute jointly recommend examination of a minimum of 12 lymph nodes to rule out regional lymphatic node involvement [204]. The TNM Classification System The AJCC has developed the TNM classification system, and this approach is the universal standard in clinical cancer care [204]. The AJCC TNM classification system is identical for colon and rectal cancer. The 2023 update to the AJCC system uses the pathologic stage (also called the surgical stage), as this is likely to be more accurate than the clinical stage, which takes into account the results of the physical exam, biopsies, and imaging tests done prior to surgery ( Table 6 ) [204; 205]. The system was initially developed as a prognostic tool. While numerous studies have evaluated other clinical, pathologic, and molecular parameters for validity in outcome prediction, none have been validated in multi-institutional prospective trials, and the TNM system remains the only prognostic tool validated in multi-institutional prospective studies. With TNM [205]: • T describes the extent of primary tumor growth into the intestinal wall or adjacent areas. This grade reflects the extent of tumor spread in the colon and rectum wall, from the inner to the outermost layers. • N describes the extent of primary tumor spread to nearby (regional) lymph nodes. • M indicates whether the tumor has metastasized to other organs (most commonly, the liver or lungs). When the T, N, and M categories have been determined (usually after surgery), the information is combined for stage grouping, with stage I the least advanced and stage IV the most advanced ( Table 7 ) [189; 190]. In rectal cancer, AJCC staging does not apply to the following malignant histologies [206]: • Sarcoma • Lymphoma • Carcinoid tumors • Melanoma
PROGNOSTIC FACTORS
PROGNOSTIC FACTORS ASSOCIATED WITH STAGING
As discussed, KRAS mutations are present in 40% of colon adenocarcinomas and affect sensitivity to treatment with bio- logic agents directed against EGFR. The FDA has approved a qualitative real-time polymerase chain reaction assay, the therascreen KRAS RGQ PCR Kit, for detection of specific mutations in the KRAS oncogene [207]. dMMR is associated with high-frequency MSI (H-MSI), a pre- dictor of better clinical outcomes for resectable colon cancer based on analysis of several large trials. In addition, patients with stage II dMMR (H-MSI) do not appear to benefit from 5-FU-based adjuvant therapy. Among patients with stage III disease, the predictive impact of dMMR status for adjuvant chemotherapy remains controversial [208; 209; 210]. Testing for dMMR with H-MSI has become an integral part of the routine diagnostic workup for colorectal cancer and has gained interest as a biomarker for patients with advanced cancer to determine their eligibility for immune checkpoint inhibitors [211; 212]. Some research also emphasizes the role of immune regulation in the natural course and prognosis of patients with colorectal cancers [213]. Amino acid metabolism is a verified part of the progression of cancer and is an area of interest for its potential role in colorectal cancer [214; 215]. MOLECULAR AND CLINICAL PROGNOSTIC FACTORS There are a variety of molecular/genetic and clinical factors that impact the disease course and prognosis. Molecular prog- nostic factors include [216]: • p53 • Loss of heterozygosity for 18q • Mutations of deleted in colon cancer ( DCC ) gene • EGFR gene amplification Specific clinical features associated with worse prognosis are [216]: • Bowel obstruction at diagnosis • Ulcerative growth pattern • Perforation • Elevated preoperative CEA level
HISTOLOGIC SUBTYPES AS PREDICTORS OF METASTASES
A study of autopsy results from 1,675 patients with metasta- sized colorectal cancer and from 88 patients with synchronous metastases observed that histologic subtype and localization of the primary colorectal cancer tumor strongly influenced metastatic pattern [217]. Metastatic disease was more preva- lent, and more frequent in multiple sites, in patients with
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