Colorectal Cancer

An Overview and Update
by Kenny Koo MD, FRCS (Edin), FACS

Cancer of the large intestine is the fourth most common malignancy in the United States, with approximately 130,000 new cases diagnosed annually. However, colorectal cancer has become the second leading cause of all cancer-related deaths in recent years after lung cancer, surpassing prostate cancer in the male and breast cancer in the female. Approximately 57,000 patients suffering from colorectal cancer will die each year. If diagnosed early, however, the disease is curable with surgical and adjuvant therapy. Furthermore, because of the recent understanding that cancers of the colon and rectum do not arise de novo but go through a series of molecular and cellular events that macroscopically present as adenomatous polyp (the adenoma to carcinoma sequence), it is believed that colorectal cancers may be preventable by elimination of these polyps before cancerous changes occur.

Epidemiology

In the United States, the incidence of colon cancer, but not rectal cancer rose substantially in the second half of 20th century, more so among men than women. Within a study period of 1975 to 1994, the rates of cancer of the proximal colon were higher than those of the distal colon and rectum (1). This challenges the belief that most cancers are within reach by flexible sigmoidoscopy in screening with previous data suggesting that at least 75% of the colon cancers occurred in the distal colon.

Etiology

The most important etiology factor to date related to colon cancer is genetic predisposition. Genetic alteration such as mutation of the K-ras protooncogene and APC (adenomatous polyposis coli) tumor suppressor gene has been demonstrated to lead to polyps and cancer formation in the large intestine.

Dietary factors also play important roles in the development of colorectal cancer with fat intake a causative and fiber intake a protective role.

Diagnosis

Symptoms of colorectal cancer can be non-specific. They vary from intermittent pain, bleeding in the form of melena in right-sided cancers, gross blood with distal lesions and change of bowel habits.

The diagnosis of colorectal cancer is increasingly based on evaluation of a positive fecal occult blood test result as screening. Although only 10% to 15% of patients tested positive have colorectal cancer (2), several prospective, randomized clinical trials concluded that these patients have earlier stage diseases on diagnosis and a 15 to 21% decrease in mortality (3).Digital examination, flexible sigmoidoscopy, barium enema, and colonoscopy with histopathological confirmation with biopsies usually reach a final diagnosis of colorectal cancer.

Treatment

With the availability of colonoscopy, endoscopic polypectomy has become the standard treatment of cancer harboring in a neoplastic polyp provided that the cancer has not invaded into the muscularis mucosae. For all invasive cancers, the treatment will be surgical resection with or without adjuvant therapies depending on the site and stages of the disease.

Radiation therapy in general has been limited to rectal cancers for local tumor control.

Adjuvant Chemotherapy has demonstrated in clinical trials to improve survival in patients with stage II and III colon cancers and the National Institute of Health has recommended adjuvant chemotherapy as standard treatment in these subgroups of patients (4).

Adjuvant Immunotherapy is in its developmental stage and early results with nonspecific immunostimulatory agent (BCG) and tumor specific monoclonal antibody (Edrecolomab) initially look promising. Unfortunately, subsequent larger studies cannot verify the early benefits (5). Confirmatory trials need to be performed before these and other forms of immunotherapies can be considered as standard.

Prognosis

The prognosis of patients having colorectal cancer is dependent on the staging of the disease which in turn is dependent on the depth of the tumor penetrat on into the bowel wall, the involvement of regional lymph nodes and the presence of distant metastases. The overall survival rate of patients with colorectal cancer is about 35%. The best outcome is associated with Stage I disease, with more than 90% of patients surviving at 5 years. This figure drops to 60% to 80% for Stage II, 30% to 50% for patients with lymph node metastasis (Stage III), and less than 5% when distant metastasis are present (Stage IV). This survival data indicates that early diagnosis is the key to successful treatment and prolonged disease free survival.

Whidbey Island Statistics

In reviewing the statistics for colorectal cancer on Whidbey Island for the five year period between 1997 to 2001 there were 115 cases of colon cancer. The site of cancer in six of these patients was not specified. Of the 109 patients with the site of the cancers documented, 54% occurred in the proximal colon, which includes the cecum, ascending colon, hepatic flexure, transverse colon and splenic flexure. None of these are within reach of the flexible sigmoidoscope. The rest of the cancers occurred 26% in the descending and sigmoid colon and 20% in the rectum. The incidence of colon cancer in both the male and the female is almost equal. During the same period of time, 35% of the 109 patients presented with localized disease according to the SEER Staging system. 41% of the patients have regional stage defined as tumor extending beyond the limits of the colon or rectum directly into the surrounding tissue, organs, or regional lymph nodes, and 18% were of distant stage with metastasis to other areas of the body at diagnosis. Our data is very close to the landmark study (Troisi, et al.) from more than 220,000 cases diagnosed between 1975 and 1994 in the U.S. Surveillance, Epidemiology, and End Results program (1).

The 5 year relative survival rates of the same group of patient followed up through August 2002 according to the SEER Staging system was 83% for local disease, 76% for regional disease and 16% for patient with distant metastasis. It showed no significant statistical difference compared to the national statistic for patients diagnosed to have colorectal cancer in a comparable period of time of 5 years from 1993 to 1997. The relative survival rates of these patients by site were 52% for proximal colon cancers, 75% for distal cancers, and 68% for rectal cancers respectively. No conclusion can be drawn from this data due to the small size of the patient population and the short follow-up. It is believed that due to the paucity and late presentation of symptoms in patients with right sided cancer, they usually have more advanced disease at diagnosis and therefore poorer prognosis. Multivariate analysis however did not identify sites of the cancer in the colon as an independent prognostic factor.

In summary, it appears that colon cancers occurred more frequently in the right colon than in the left. In order to ensure that cancers in every segment of the colon will not be missed, a complete examination of the whole length of the colon with Barium enema or colonoscopy appears the logical choice. As the prognosis of the disease is dependent almost entirely on the stage of the cancer, screening of the colon with fecal occult blood test, barium enema, and colonoscopy is essential for catching colon cancers at an earlier presymptomatic stage of the disease that will improve survival. Furthermore, because virtually all colorectal cancers arise from adenomas, it is theoretically possible to prevent colon cancer by the early detection and removal of adenomas. It has been demonstrated in the National Polyp Study, that patients who underwent colonoscopy and subsequent removal of benign polyps showed a 90% decrease in colorectal cancer in comparison with a general population registry (6). The importance of colorectal screening, therefore, cannot be overemphasized.