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Colorectal Cancer: Prevention, Diagnosis, and Therapeutic Options
Ali Ahmad, MD | October 6, 2022
| Contributor Information
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Colonoscopy images of malignant colorectal cancer lesions at different sites. Images courtesy of Radu V, Ion D, Serban MB, Ciurea M. J Med Life. 2010;3(3):314-9. [Open access.] PMID: 20945823, PMCID: PMC3019005.
Colorectal Cancer: Prevention, Diagnosis, and Therapeutic Options
Ali Ahmad, MD | October 6, 2022 | Contributor Information
Colorectal cancers are malignant tumors that originate in the colon (large bowel) or rectum.[1] In the United States and worldwide, these are among the most common cancer types.[2,3] Colorectal cancer predominantly occurs in older people—the median age at diagnosis is 66 years[3]—but its incidence is increasing in young adults.[4] Men are affected slightly more commonly than women, as are Black individuals compared with those of other races/ethnicities.[3]
Malignancies in the colon and rectum share many common features, but their prognosis and treatment options can vary significantly.[1,5,6,7]
Image courtesy of Wikimedia Commons/Nephron.
Colorectal Cancer: Prevention, Diagnosis, and Therapeutic Options
Ali Ahmad, MD | October 6, 2022 | Contributor Information
Image shows a colorectal adenocarcinoma under high magnification (hematoxylin and eosin stain [H&E]).
Adenocarcinomas comprise the vast majority (95%) of colorectal malignancies.[1] Colonic adenomas are considered precursor lesions, with about 5% eventually developing into adenocarcinomas,[9] usually over 10-20 years.[10] Rare colorectal cancers include carcinoid tumors, gastrointestinal (GI) stromal tumors (GISTs), lymphomas, and sarcomas.[1]
Image courtesy of Samir via English language Wikipedia.
Colorectal Cancer: Prevention, Diagnosis, and Therapeutic Options
Ali Ahmad, MD | October 6, 2022 | Contributor Information
Colonoscopic image shows multiple adenomatous polyps in a patient with familial adenomatous polyposis (FAP).
An estimated 75% of patients with colorectal cancer have sporadic disease; the remaining 25% have a family history of the disease.[11] Genetic, environmental, and lifestyle factors increase the risk of malignancy,[1,6-8,10,11] as follows:
Hereditary conditions and family history: FAP, hereditary nonpolyposis colon cancer (HNPCC; Lynch syndrome), Turcot syndrome, hyperplastic polyposis syndrome, Peutz-Jeghers syndrome, MUTYH-associated polyposis
Personal history: Older age; inflammatory bowel disease (IBD; ulcerative colitis, Crohn disease); colorectal polyps/cancer; ovarian, endometrial, or breast cancer; type 2 diabetes mellitus
Lifestyle factors: High dietary intake of red or processed meat or alcohol, physical inactivity, being overweight/obese, tobacco use
Race/ethnicity: Black or Ashkenazi Jewish
Image courtesy of Blausen Medical Communications, Inc, via Wikimedia Commons.
Colorectal Cancer: Prevention, Diagnosis, and Therapeutic Options
Ali Ahmad, MD | October 6, 2022 | Contributor Information
Presentation
In its early stage, colorectal cancer is usually asymptomatic.[1,12] As the disease progresses, a change in bowel habits (80%) and bleeding (60%) often occur. Other signs/symptoms may include the following[1,6,12,13]:
Rectal cramping
Hematochezia, dark stool
Abdominal discomfort, cramping, pain, or bloating
Malaise, anorexia, and/or unexplained weight loss
Pelvic pain at later stages of the disease
Image courtesy of Cancer Research UK via Wikimedia Commons.
Colorectal Cancer: Prevention, Diagnosis, and Therapeutic Options
Ali Ahmad, MD | October 6, 2022 | Contributor Information
Signs/symptoms of colorectal cancer may also vary by the location of the lesions.[13] The most commonly affected sites are the rectum (38%), sigmoid colon (20%), and descending colon (10%), followed by the cecum and hepatic flexure (8% each), transverse colon (6%), rectosigmoid junction (7%), ascending colon (3%), and splenic flexure (2%).[13]
Left-sided malignancies generally feature abdominal pain and a change in bowel habits (60% each), the presence of a mass (40%), bleeding and obstruction (20% each), weight loss (15%), and vomiting (10%).[13]
Common features of right-sided lesions are vague abdominal pain (80%) and the presence of a mass (70%), followed by weight loss (50%), change in bowel habits with diarrhea (40%), vomiting (30%), rectal bleeding (20%), and obstruction (5%).[13]
Colorectal Cancer: Prevention, Diagnosis, and Therapeutic Options
Ali Ahmad, MD | October 6, 2022 | Contributor Information
Staging
The American Joint Committee on Cancer (AJCC) tumor, node, and metastasis (TNM) classification has become the international standard for staging of colorectal cancer.[14] The TNM system is based on the anatomic extent of the malignancy. Cancers of the colon and rectum share the same staging system because the TNM categories are associated with similar survival outcomes for both diseases.[15,16]
Tumor extent:
T1 disease has penetrated into the submucosa.
T2 disease extends from the submucosa into the muscularis propria.
T3 disease penetrates up to but not beyond the serosa.
T4 disease extends beyond the serosa (visceral peritoneum) (T4a) or has directly invaded or is attached to nearby structures or organs.
Stages:
Stage I - T1 and T2 disease, without lymph node involvement or metastasis
Stage II - T3 and T4 disease, without lymph node involvement or metastasis
Stage III - T1-T4 disease with variations of lymph node involvement but no distant metastasis
Stage IV - Any variation with distant metastasis
Endoscopic view of a tumor on the cecum in a patient with FAP and colon cancer. Image courtesy of Mastalier B, Tihon C, Ghita B, et al. J Med Life. 2012;5(3):348-53. [Open access.] PMID: 23144667, PMCID: PMC3493968.
Colorectal Cancer: Prevention, Diagnosis, and Therapeutic Options
Ali Ahmad, MD | October 6, 2022 | Contributor Information
Screening
In the US, routine screening has played a major role in reducing the incidence and mortality of colorectal cancer in the last decade, primarily owing to early detection and removal of precancerous lesions.[9] Commonly recommended screening tests and screening intervals include the following[17-19]:
Computed tomography (CT) colonography (virtual colonoscopy) every 5 years
Previously, guidelines recommended screening in average-risk individuals age 50-75 years; however, the increasing incidence of colorectal cancer in young adults has led to lowering of the age for starting screening to 45 years.[17-19] For example, the 2021 update of colorectal cancer screening guidelines of the US Preventive Services Task Force (USPSTF) maintained its grade A recommendation of screening in all adults from age 50 years until age 75 years, but added a grade B recommendation for screening in adults age 45 to 49 years. In adults aged 76 to 85 years, the USPSTF recommends individualizing the decision to screen, taking into account the patient's overall health and prior screening history.[17] Guidelines generally recommend against screening after age 85 years.[17-19]
Gross specimen from an open colectomy containing invasive colorectal carcinoma and two adenomatous polyps. Image courtesy of Wikimedia Commons/Emmanuelm.
Colorectal Cancer: Prevention, Diagnosis, and Therapeutic Options
Ali Ahmad, MD | October 6, 2022 | Contributor Information
Risk assessment for screening
The American Cancer Society advises that the risk of colorectal cancer is increased in individuals with any of the following[1]:
Strong family history or personal history of colorectal cancer or adenomatous polyps
Personal history of inflammatory bowel disease (ulcerative colitis or Crohn disease)
Known family history of a hereditary colorectal cancer syndrome (eg, FAP, HNPCC)
Personal history of radiation to the abdomen or pelvic area to treat a prior cancer
Different organizations (eg, US Multi-Society Task Force on Colorectal Cancer, National Comprehensive Cancer Network [NCCN]) provide recommendations for screening of patients at elevated risk, depending on the risk factor.[18,20] Screening and surveillance in those with a hereditary colorectal cancer syndrome are determined on an individual basis, but they typically involve genetic testing (if not previously done), beginning screening at an earlier age, and more frequent evaluation with flexible sigmoidoscopy or colonoscopy and/or other studies.[18,21]
Image of a lymph node with colorectal carcinoma (H&E stain) courtesy of Wikimedia Commons/Nephron.
Colorectal Cancer: Prevention, Diagnosis, and Therapeutic Options
Ali Ahmad, MD | October 6, 2022 | Contributor Information
Workup
In patients with suspected colorectal cancer on the basis of clinical findings (including digital rectal examination) or screening results, perform rectal examination with flexible sigmoidoscopy or colonoscopy, and biopsy any suspicious lesions.[1,4,8,12,13]
Laboratory studies
Routine laboratory studies include the following[1,4,5,7,15,16]:
Complete blood count
Chemistry panel
Liver function tests
Carcinoembryonic antigen (CEA) levels
It is recommended that patients with newly diagnosed colorectal cancer undergo genetic testing and/or microsatellite instability testing.[1,7,15,16]
Images courtesy of Elyassi AR, Lin-Hurtubise K, Gagliano R. Cases J. 2009;2(1):131. [Open access.] PMID: 19200375, PMCID: PMC2644681.
Colorectal Cancer: Prevention, Diagnosis, and Therapeutic Options
Ali Ahmad, MD | October 6, 2022 | Contributor Information
Imaging studies
Imaging studies that may facilitate staging and treatment planning include the following[1,7,15,16]:
Chest radiography
Double-contrast barium enema
Chest, abdominal, and/or pelvic CT scanning
Abdominal and/or pelvic magnetic resonance imaging (MRI)
Endorectal ultrasonography
Positron emission tomography (PET) scan
These CT scans show the front (left) and axial views (right) of a large right-sided, ill-defined soft-tissue mass involving the ascending colon. The patient had adenocarcinoma of the cecum.
Image courtesy of Zhang Z, Wang J, Huang J, Yu X. World J Surg Oncol. 2014;12:82. [Open access.] PMID: 24708697, PMCID: PMC3992153.
Colorectal Cancer: Prevention, Diagnosis, and Therapeutic Options
Ali Ahmad, MD | October 6, 2022 | Contributor Information
This enhanced pelvic MRI shows a low rectal tumor.
Image courtesy of Wikimedia Commons/Hg6996.
Colorectal Cancer: Prevention, Diagnosis, and Therapeutic Options
Ali Ahmad, MD | October 6, 2022 | Contributor Information
PET is emerging as a very useful modality for staging and assessment of colorectal cancers.[8] Combined PET/CT allows for the detection of metastatic lesions. Note that some histologic types (eg, mucinous signet-ring cell variants) may not be well visualized on a PET scan.[8]
This PET/CT scan of a staging evaluation of colon cancer reveals the primary tumor in addition to several metastatic lesions.
Images courtesy of Radu V, Ion D, Serban MB, Ciurea M. J Med Life. 2010;3(3):314-9. [Open access.] PMID: 20945823, PMCID: PMC3019005.
Colorectal Cancer: Prevention, Diagnosis, and Therapeutic Options
Ali Ahmad, MD | October 6, 2022 | Contributor Information
Treatment: Colon Cancer
The top left image is a barium enema. The remaining photographs show intraoperative aspects of invasive colon cancer at two sites.
Surgical resection
Primary management of localized colon cancer involves surgical resection of the primary tumor and regional lymph nodes.[1,6,15] Surgical options for resectable disease include the following[1,15]:
Polypectomy and local excision (small T1 lesions only)
Partial or total colectomy
Image courtesy of Wikimedia Commons/Anpol42.
Colorectal Cancer: Prevention, Diagnosis, and Therapeutic Options
Ali Ahmad, MD | October 6, 2022 | Contributor Information
The photograph shows an intraoperative laparoscopic view of a malignant tumor of the sigmoid colon.
Chemotherapy: colon cancer
In patients with advanced or metastatic colon cancer, the NCCN guidelines indicate that neoadjuvant chemotherapy may be considered.[15]
The potential value of adjuvant chemotherapy for patients with stage II colon cancer remains a matter of debate.[1,6]
Common chemotherapy regimens include, but are not limited to, the following[1,6,15]:
Oxaliplatin/leucovorin/5-fluorouracil (5-FU)(FOLFOX) or FOLFOX plus bevacizumab or panitumumab or cetuximab
Oxaliplatin/capecitabine (CapeOX) or CapeOX plus bevacizumab
Irinotecan/leucovorin/5-FU (FOLFIRI) or FOLFIRI plus bevacizumab, cetuximab, panitumumab, ziv-aflibercept, or ramucirumab
Image courtesy of Ali Ahmad, MD.
Colorectal Cancer: Prevention, Diagnosis, and Therapeutic Options
Ali Ahmad, MD | October 6, 2022 | Contributor Information
Treatment: Rectal Cancer
The management of rectal cancer is complex, in part due to the increased risk of local recurrence and a more poor prognosis overall, and it involves a multidisciplinary team of cancer specialists.[5] Key considerations include the intent of surgery (curative or palliative); possible functional outcome; and preservation of anal continence, genitourinary function, and sexual function.[4,5]
Differences in therapeutic options for neoplasms of the colon and rectum include surgical technique, the use of radiation therapy, and the method of chemotherapy administration.[5]
The gross abdominal perineal specimen shown was resected for rectal adenocarcinoma. The tumor involves the sphincter muscles (arrows).
Image courtesy of Ali Ahmad, MD.
Colorectal Cancer: Prevention, Diagnosis, and Therapeutic Options
Ali Ahmad, MD | October 6, 2022 | Contributor Information
Surgical resection: rectal cancer
The primary treatment for patients with rectal cancer is surgical resection of the primary tumor and regional lymph nodes.[1,5,16] The operative approach varies on the basis of the tumor location and extent, as well as the presence or absence of high-risk features (ie, positive margins, lymphovascular invasion, perineural invasion, poorly differentiated histology).[5,16]
Types of surgical resection include the following[1,5,16]:
Polypectomy and local excision for select T1 disease
Transanal local excision and transanal endoscopic microsurgery (TEM) for select clinically staged T1 N0 rectal cancers (shown)
Total mesorectal excision via low-anterior resection
Total mesorectal excision via abdominoperineal resection for patients who are not candidates for sphincter preservation (permanent end-colostomy)
The image is an intraoperative photograph of a perineal approach during abdominal perineal resection for rectal cancer.
Image courtesy of Valenzuela CD, Moore HG, Huang WC, et al. World J Surg Oncol. 2009;7:94. [Open access.] PMID: 19995443, PMCID: PMC2795749.
Colorectal Cancer: Prevention, Diagnosis, and Therapeutic Options
Ali Ahmad, MD | October 6, 2022 | Contributor Information
Chemotherapy and radiotherapy: rectal cancer
The National Cancer Institute (NCI) indicates that neoadjuvant therapy with radiotherapy for rectal cancer is the standard of care for patients with stages II and III disease, although postoperative chemoradiation treatment is also an option.[5]
For those with clinically staged T3-T4 or node-positive disease (stages II/III), preoperative chemoradiation therapy is also the standard of care.[5]
Preferred combination chemotherapy/radiotherapy regimens include, but are not limited to, the following[16]:
Combined capecitabine/radiotherapy or infusional 5-FU/radiotherapy. Another option is bolus 5-FU/leucovorin/radiotherapy.
FOLFOX or CapeOX or capecitabine, then capecitabine/radiotherapy
Infusional 5-FU/radiotherapy, then FOLFOX or CapeOX, then capecitabine/radiotherapy
Image a is a CT scan with contrast that is suspicious for the presence of a large tumor of the ascending colon (downward-facing arrow). Enlarged pericolic lymph nodes can be seen, suggesting metastases, and a right-sided hydroureteronephrosis is caused by a mid-ureteral tumor (upward-facing arrow). In image b, a colon tumor is visible at the splenic flexure (arrow).
Image courtesy of Ali Ahmad, MD.
Colorectal Cancer: Prevention, Diagnosis, and Therapeutic Options
Ali Ahmad, MD | October 6, 2022 | Contributor Information
Metastatic and Recurrent Disease
The management of metastatic colorectal adenocarcinoma continues to evolve and usually requires a multimodality approach. The most common sites of metastasis from colorectal cancer are the liver, lung, and peritoneum.[22]
Colon cancer has a high incidence of abdominal metastasis, whereas rectal cancer has a high incidence of extra-abdominal metastasis.[22] In addition, histologic subtypes also appear to affect the pattern of metastasis: Colorectal adenocarcinomas predominantly metastasize to the liver, whereas mucinous adenocarcinoma and signet-ring cell carcinoma subtypes more often metastasize to multiple sites and to the peritoneal cavity.[23]
The intraoperative photograph shows peritoneal metastases from mucinous colorectal cancer.
Images courtesy of Engels B, Gevaert T, Everaert H, et al. Radiat Oncol. 2012;7:34. [Open access.] PMID: 22423615, PMCID: PMC3355052.
Colorectal Cancer: Prevention, Diagnosis, and Therapeutic Options
Ali Ahmad, MD | October 6, 2022 | Contributor Information
For patients with locally recurrent and/or liver-only and/or lung-only metastatic colorectal disease, a multidisciplinary approach should be considered. Surgical resection can be considered in select patients as a potentially curative treatment.[5,6]
The radiologic scans display complete metabolic response in a patient with colorectal cancer and a solitary lung metastasis who was treated with intensity-modulated and image-guided radiotherapy (IMRT-IGRT) via helical tomotherapy. Image A: pretreatment PET/CT scan; image B: planning CT with superimposed radiation dose distribution; image C: PET/CT scan 3 months after initiation of radiotherapy, with complete remission; image D: PET/CT scan 6 months after completion of radiotherapy, with no evidence of progressive disease, but an asymptomatic radiation-induced pneumonitis around the irradiated metastasis (white arrow) is present.
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Contributor Information
Author
Ali Ahmad, MD
Surgical Oncologist
University of Kansas School of Medicine
Wichita, Kansas
Disclosure: Ali Ahmad, MD, has received honoraria from Intuitive Surgical, USA for educational lectures and proctoring fellow surgeons.
Editors
Olivia Wong, DO
Section Editor
Medscape Drugs & Diseases
New York, New York
Disclosure: Olivia Wong, DO, has disclosed no relevant financial relationships.
John Heinegg, RN
Section Editor
Medscape Drugs & Diseases
New York, New York
Disclosure: John Heinegg, RN, has disclosed no relevant financial relationships.
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Hugen N, van de Velde CJ, de Wilt JH, Nagtegaal ID. Metastatic pattern in colorectal cancer is strongly influenced by histological subtype. Ann Oncol. 2014 Mar;25(3):651-7. PMID: 24504447
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