Colorectal Cancer _ ___________________________________________________________________________
adenocarcinoma (52.2%) than in those with signet-ring cell carcinoma (31.7%). Peritoneal metastases were more common in patients with signet-ring cell carcinoma (51.2%) or mucinous adenocarcinoma (48.2%) than in those with adenocarcinoma (20.1%) [212]. Metastases to distant lymph nodes occurred in more signet-ring cell carcinoma patients (43.9%) than patients with either mucinous adenocarcinoma (22.3%) or adenocarcinoma (19.9%). Abdominal metastases were more frequent with colon cancer, and extra-abdominal metastases more common with rectal cancer [212]. PROGNOSTIC FACTORS FOLLOWING RESECTION OF LIVER METASTASES Approximately one in three patients who undergo resection for colorectal liver metastases become actual five-year survivors. Of those, approximately half survive 10 years and are considered “cured” of colorectal liver metastases [213]. A multivariate analysis of 1,001 patients who underwent potentially curative resection of liver metastases identified five factors as independent predictors of worse outcome [214]: • Tumor size >5 cm • Disease-free interval less than one year • More than one tumor • Primary lymph-node positivity • CEA level >200 ng/mL
PROGNOSTIC FACTORS
PROGNOSTIC FACTORS ASSOCIATED WITH STAGING As discussed, KRAS mutations are present in 40% of colon adenocarcinomas and affect sensitivity to treatment with biologic 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 [206]. dMMR is associated with high-frequency MSI (H-MSI), a predictor 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 [207; 208; 209]. Testing for dMMR with H-MSI may become useful for prognosis and treatment planning in patients with resectable colon cancer [209]. Some research also emphasizes the role of immune regulation in the natural course and prognosis of patients with colorectal cancers [210]. MOLECULAR AND CLINICAL PROGNOSTIC FACTORS There are a variety of molecular/genetic and clinical factors that impact the disease course and prognosis. Molecular prognostic factors include [211]: • 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 [211]: • 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 metastasized 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 [212]. Metastatic disease was more prevalent, and more frequent in multiple sites, in patients with mucinous adenocarcinoma (33.9% and 58.6%, respectively) or signet-ring cell carcinoma (61.2% and 70.7%) than with adenocarcinoma (27.6% and 49.9%) [212]. Liver metastases were more frequent in patients with adenocarcinoma (73.0%) or mucinous
SURVIVAL Prognostic Factors of Survival by TNM Stage
Patient prognosis is most powerfully associated with clinical and histopathologic stage of colorectal cancer at diagnosis as reflected by the TNM classification and staging. The National Cancer Institute SEER database tracks five-year relative survival rates for colon and rectal cancer, based on how far the cancer has spread; it does not group cancers by AJCC TNM stages. Instead, it groups cancers into localized, regional, and distant stages ( Table 8 ) [13]. COLORECTAL CANCER FIVE-YEAR SURVIVAL RATES BY STAGE SEER Stage Five-Year Relative Survival Rate Colon cancer Localized 91% Regional 72% Distant 14% All SEER stages combined 64% Rectal cancer IV 12% Source: [13] Table 8
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