Single most important prognostic factor for colorectal carcinoma is (AIIMS Nov 2012)
|A||Tumor size and characteristic|
|C||Lymph node status|
(Ref: Chapter 4 of Colon & Rectal Cancer: A Comprehensive Guide for Patients & Families by Lorraine Johnston.)
a. The most important factor contributing to long-term survival…is the stage, or spread, of cancer found at the time of surgery
b. Stage, or more correctly, pathologic stage, is determined after surgery gives access to colon, rectum, liver, and lymph node tissue that can be biopsied, and direct visual or assisted imaging assessment of other abdominal organs.
c. The existence of just one lesion predicts a good outcome.
d. Many other measures of tumor burden or tumor behavior have been sought and studied as means to predict outcome, but as of now, none is as important as the pathologic stage.
Individual prognostic factors are
Site of disease
a. Peritoneal carcinomatosis, the implanting of numerous tumors on the inside lining of the abdomen and the pelvis, is considered a bad sign if many large tumors are found at surgery and cannot be completely removed.
b. The portion of the intestine in which the tumor develops is thought to contribute to outcome: tumors arising in the appendix have better outcome than those arising in other parts of the colon;2 right-side disease (excepting that in the appendix) may, in some patients, have a worse prognosis than left-side disease. Left-side disease expressed the desirable p53 gene more often.
c. In females, the spread of large secondary tumors to the ovary is correlated to worse prognosis.
d. Bone marrow involvement confers a worse prognosis.
e. Tumors that adhere to adjacent structures are thought to be more likely to recur.
f. If the spine is involved, the preoperative neurological status and the number of vertebrae affected correlates to a worsening prognosis.
Tumor aggressiveness (tumor grade)
a. Histologic grade and the number of tumor cells actively dividing (percentage of S phase content) are thought to contribute to recurrence of disease.
b. Mucinous adenocarcinoma has been shown to be a poor risk factor.
c. Signet-ring cell carcinomas appear to have a worse prognosis than ordinary colon adenocarcinoma.
d. Antigen CD17-1A is detectable with monoclonal antibodies when colorectal cancer is present. This antigen, also the target of treatment involving a monoclonal antibody that is now in clinical trials, can be used to highlight cancer cells in imaging studies using a scintigraphic agent connected to a monoclonal antibody that attaches to this antigen.
e. Variants of CD44, an antigen on the surface of white blood cells, are higher in patients with active colorectal cancer. Variants 8 and 10 are higher in all patients; variant 6 is higher in primary tumors, but not in liver metastases.
f. SLX (sialyl Lewis X antigen) rises with tumor activity.
g. Lower levels of alfa-catenin are linked to poorly differentiated tumors with a higher potential to spread, and a worse prognosis.
h. Lower levels of P-selectin correlate to lower tumor growth and fewer metastases.
i. Increased levels of the ICAM-1 antigen in blood are linked to higher stages of colorectal cancer. Blood levels of ICAM-1 were higher in patients with liver metastases.
j. Levels of ELAM-1 were higher in those with lung metastases.
k. Tumors that do not express the MRP1/CD9 antigen have a significantly higher frequency of blood-vessel penetration of the tumor, and of liver metastasis.
a. Damage to one of the cell-death genes, p53, which resides on chromosome 17, appears to affect negatively the outcome of many cancers, including colorectal cancer, but at least one study has found that it does not affect prognosis in colorectal cancer.
b. Absence of DCC, the "deleted in colon cancer" gene protein, appears to have a negative effect on survival.
c. Extra copies of chromosomes 7, 13, or 20 have been correlated with a worse prognosis for colorectal cancer survivors.
d. Loss of one copy of chromosome 11 is correlated with a lower incidence of spread of colorectal cancer to lymph nodes.
e. Losses of chromosomes 8 or 18, or of the long arm of chromosome 18 (18q), have been correlated with a worse prognosis for colorectal cancer.
f. Loss of genes at positions (loci) 32 or 36 on the short arm of chromosome 1 (indicated as 1p32, 1p36) are linked to a worse prognosis for colorectal cancer survivors.
Byproducts of tumor metabolism
a. P-glycoprotein (P-gp) which is expressed by tumors that have become resistant to many chemotherapy drugs (multiple drug resistance or MDR) is correlated to a higher risk of recurrence in those staged at Dukes B2.
b. Cytokeratin-producing cells that are found in the bone marrow when no signs of metastases exist upon physical examination have been linked to higher risk of recurrence of disease in the liver and in the lungs.
c. One form of the growth factor VEGF, type 3, increases when liver metastases are present. VEGF type 3 is found in the presence of new blood vessels in growth; tumor growth is accompanied by the growth of new blood vessels to feed the tumor.