Version July 2025
INTRODUCTION —
Colorectal cancer (CRC) is a common disease. In the United States, over 154,000 new cases of colon and rectal cancer are diagnosed annually [1]. CRC can be diagnosed after the onset of symptoms or through screening asymptomatic individuals.
The clinical presentation, diagnosis, and staging of CRC will be reviewed here. The epidemiology and risk factors, screening and surveillance strategies, pathology and prognostic determinants, and treatment of colon and rectal cancer are discussed separately:
●(See "Epidemiology and risk factors for colorectal cancer".)
●(See "Surveillance and management of dysplasia in patients with inflammatory bowel disease" and "Screening for colorectal cancer: Strategies in patients at average risk".)
●(See "Tests for screening for colorectal cancer".)
●(See "Surveillance and management of dysplasia in patients with inflammatory bowel disease" and "Screening for colorectal cancer: Strategies in patients at average risk".)
●(See "Pathology and prognostic determinants of colorectal cancer".)
●(See "Overview of the management of primary colon cancer".)
●(See "Surgical resection of primary colon cancer".)
●(See "Adjuvant therapy for resected stage III (node-positive) colon cancer".)
●(See "Adjuvant therapy for resected stage II colon cancer".)
●(See "Adjuvant therapy for resected colon cancer in older adult patients".)
●(See "Surgical treatment of rectal cancer".)
●(See "Neoadjuvant therapy for rectal adenocarcinoma".)
●(See "Adjuvant therapy for resected rectal adenocarcinoma not treated with neoadjuvant therapy".)
CLINICAL PRESENTATION —
Patients with CRC may present in several ways:
●Asymptomatic individuals who undergo routine screening for CRC or as an incidental finding from an imaging study done for another purpose (see "Screening for colorectal cancer: Strategies in patients at average risk" and "Tests for screening for colorectal cancer")
●Suspicious symptoms and/or signs
●Emergency admission with intestinal obstruction, perforation, or rarely, an acute gastrointestinal bleed
Asymptomatic individuals — There are often no symptoms in most patients with early-stage colon cancer, with many diagnosed during screening. Further details on screening individuals for CRC, including available screening tests, are discussed separately. (See "Screening for colorectal cancer: Strategies in patients at average risk" and "Screening for colorectal cancer in patients with a family history of colorectal cancer or advanced polyp" and "Tests for screening for colorectal cancer".)
Symptomatic individuals — Most CRCs (between 70 to 90 percent) are diagnosed after the onset of symptoms [2,3]. Symptoms of CRC are typically due to growth of the tumor into the lumen or adjacent structures, and as a result, symptomatic presentation usually reflects relatively advanced CRC.
Symptoms from the local tumor — Typical symptoms/signs associated with CRC include hematochezia or melena, abdominal pain, otherwise unexplained iron deficiency anemia, and/or a change in bowel habits [2,4-11]. Less common presenting symptoms include abdominal distension, and/or nausea and vomiting, which may be indicators of obstruction.
In a retrospective cohort of over 29,000 patients referred by their general practitioners to an outpatient colorectal surgery clinic over a 22-year period, presenting symptoms in the 1626 patients who were eventually diagnosed with CRC included [12]:
●Change in bowel habits (74 percent)
●Rectal bleeding in combination with change in bowel habits, which was the most common symptom combination (51 percent of all cancers and 71 percent of those presenting with rectal bleeding) – (See "Approach to acute lower gastrointestinal bleeding in adults".)
●Rectal mass (25 percent) or abdominal mass (13 percent)
●Iron deficiency anemia (10 percent)
●Abdominal pain as a single symptom (4 percent)
Symptoms in early onset colorectal cancer — There is a global epidemiologic trend towards early onset CRC, or the diagnosis of CRC in people under the age of 50 years. Further details on the incidence and risk factors of early onset CRC are discussed separately. (See "Epidemiology and risk factors for colorectal cancer", section on 'Early onset colorectal cancer'.)
In a systematic review and meta-analysis, the most common presenting symptoms in patients with early onset CRC included [13]:
●Hematochezia (45 percent)
●Abdominal pain (40 percent)
●Change in bowel habits (27 percent)
●Weight loss (17 percent)
●Loss of appetite (15 percent)
●Constipation (14 percent)
●Abdominal distension (14 percent)
●Diarrhea (12 percent)
●Anemia (11 percent)
●Other symptoms included tenesmus, obstruction, perforation, fatigue, nausea or vomiting, abdominal mass, and rectal pain
Symptoms based on tumor location — Among symptomatic patients, clinical manifestations also differ depending on tumor location:
●A change in bowel habits is a more common presenting symptom for left-sided than right-sided CRCs. Fecal contents are liquid in the proximal colon and the lumen caliber is larger, and CRCs are therefore less likely to be associated with obstructive symptoms, including colicky pain.
●Hematochezia is more often caused by rectosigmoid than right-sided colon cancer.
●Iron deficiency anemia from unrecognized blood loss is more common with right-sided CRCs [14]. Cecal and ascending colon tumors have a fourfold higher mean daily blood loss (approximately 9 mL/day) than tumors at other colonic sites [15]. (See "Determining the cause of iron deficiency in adolescents and adults", section on 'Evaluation for the cause'.)
●Abdominal pain can occur with tumors arising at all sites; it can be caused by a partial obstruction, peritoneal dissemination, or intestinal perforation leading to generalized peritonitis.
●Rectal cancer can cause tenesmus, rectal pain, and diminished caliber of stools.
●Obstructive symptoms are more common with cancers that encircle the bowel, producing the so-called "apple-core" description as seen most classically on barium enema, which is rarely used (image 1 and image 2).
Metastatic disease — CRC can spread by lymphatic and hematogenous dissemination, as well as by contiguous and transperitoneal routes. The most common metastatic sites are the regional lymph nodes, liver, lungs, and peritoneum. Patients may present with signs or symptoms referable to any of these areas. The presence of right upper quadrant pain, abdominal distension, early satiety, supraclavicular adenopathy, or periumbilical nodules usually signals advanced, often metastatic disease.
Because the venous drainage of the intestinal tract is via the portal system, the first site of hematogenous dissemination is usually the liver, followed by the lungs, bone, and many other sites, including the brain. Although brain metastases are exceedingly uncommon, as patients receive more systemic therapy and remain alive for several years after a diagnosis of metastatic cancer there has been an increase in both bone and brain metastases [16]. Tumors arising in the distal rectum may metastasize initially to the lungs rather than liver because the inferior rectal vein drains into the inferior vena cava rather than into the portal venous system.
Atypical presentations — There are a variety of atypical presentations of CRC. These include the following:
●Local invasion or a contained perforation causing malignant fistula formation into adjacent organs, such as bladder (resulting in pneumaturia) or small bowel. This is most common with cecal or sigmoid carcinomas; in the latter case, the condition can mimic diverticulitis.
●Fever of unknown origin, intra-abdominal, retroperitoneal, abdominal wall or intrahepatic abscesses due to a localized perforated colon cancer [17,18]. Streptococcus bovis bacteremia and Clostridium septicum sepsis are associated with underlying colonic malignancies in approximately 10 to 25 percent of patients [19]. (See "Infections due to Streptococcus bovis/Streptococcus equinus complex (SBSEC; formerly group D streptococci)", section on 'Association with colorectal neoplasia'.)
●Rarely, other bacterial infections may be associated with CRC, such as Fusobacterium nucleatum [20], colibactin-producing Escherichia coli [21,22], and extra-abdominal infections caused by colonic anaerobic organisms (eg, Bacteroides fragilis) [23].
●CRC ultimately proves to be the site of origin of approximately 6 percent of adenocarcinomas of unknown primary sites [24]. (See "Adenocarcinoma of unknown primary site".)
●CRC may be detected based on the discovery of liver metastases that are detected incidentally during studies such as gallbladder or kidney ultrasound, or CT scans for evaluation of other symptoms (eg, dyspnea).
Impact of symptoms on prognosis — The presence of and type of symptoms provide some prognostic importance:
●Patients who are symptomatic at diagnosis typically have more advanced disease and a worse prognosis [2,25]. In one study of 1071 patients with newly diagnosed colon cancer, 217 of whom were diagnosed through screening, the patients not diagnosed through screening were at higher risk for a more invasive tumor (≥T3: relative risk [RR] 1.96), nodal involvement (RR 1.92), and metastatic disease on presentation (RR 3.37). In addition, patients not diagnosed through screening had higher risk of death (RR 3.02) and recurrence (RR 2.19) as well as shorter survival and disease-free intervals [25]. (See "Tests for screening for colorectal cancer".)
●The total number of symptoms may be inversely related to survival for colon but not for rectal cancer [26]. Whether the duration of symptoms influences prognosis is unclear; the available data are mixed [27-29].
●Obstruction and/or perforation, although uncommon, carry a poor prognosis, independent of stage [5,30-33]. Among patients with node-negative colon cancer, obstruction or perforation are poor prognostic factors that may influence the decision to pursue adjuvant chemotherapy. (See "Adjuvant therapy for resected stage II colon cancer", section on 'Clinicopathologic features'.)
●Tumors presenting with rectal bleeding (more commonly those involving the distal colon and rectum and at an earlier stage than proximal tumors) have a better prognosis [34,35]. However, bleeding is not an independent predictor of outcome [31,36].
Other determinants of prognosis, including clinicopathologic and molecular features, are discussed separately. (See "Pathology and prognostic determinants of colorectal cancer".)
DIAGNOSIS —
The diagnosis of a CRC is made by histologic examination of malignant colonic tissue which is usually obtained from a biopsy during lower gastrointestinal tract endoscopy or a surgical specimen. Histopathologically, most cancers arising in the colon and rectum are adenocarcinomas. The histologic diagnosis of CRC is discussed in detail separately. (See "Pathology and prognostic determinants of colorectal cancer", section on 'Histology'.)
The diagnosis of CRC should be suspected in individuals with one or more of the symptoms and signs described above or those who are asymptomatic and discovered during routine CRC screening or as an incidental finding on imaging studies. Once CRC is suspected, the next test should be colonoscopy or computed tomography (CT) colonography. (See "Screening for colorectal cancer: Strategies in patients at average risk" and "Screening for colorectal cancer in patients with a family history of colorectal cancer or advanced polyp" and "Lynch syndrome (hereditary nonpolyposis colorectal cancer): Cancer screening and management" and "Familial adenomatous polyposis: Screening and management of patients and families" and "Juvenile polyposis syndrome".)
Colonoscopy — Colonoscopy is the most accurate and versatile diagnostic test for CRC, since it can localize and biopsy lesions throughout the large bowel, detect synchronous neoplasms, and remove polyps. Synchronous CRCs, defined as two or more distinct primary tumors at the same time or diagnosed within six months of an initial CRC, separated by normal bowel, and not due to direct extension or metastasis, occur in 3 to 8 percent of patients [37-40]. The incidence is somewhat lower (approximately 2.5 percent) when patients with Lynch syndrome are excluded; the presence of synchronous cancers should raise the clinical suspicion for Lynch syndrome or MUTYH-associated polyposis [41,42]. (See "Lynch syndrome (hereditary nonpolyposis colorectal cancer): Clinical manifestations and diagnosis", section on 'Colonic manifestations'.)
The preparation for, diagnostic use of, and complications associated with colonoscopy are discussed separately. (See "Overview of colonoscopy in adults".)
When viewed through the endoscope, most colon and rectal cancers are endoluminal masses that arise from the mucosa and protrude into the lumen (figure 1). The masses may be exophytic or polypoid. Bleeding (oozing or frank bleeding) may be seen with lesions that are friable, necrotic, or ulcerated (picture 1A-B).
A minority of neoplastic lesions in the gastrointestinal tract (both in asymptomatic and symptomatic individuals) are nonpolypoid and relatively flat or depressed. In one study, nonpolypoid colorectal neoplasms had a greater association with carcinoma than did polypoid neoplasms [43]. Cancers that arise from nonpolypoid (flat) adenomas may be more difficult to visualize colonoscopically than polypoid lesions, but colonoscopy has superior sensitivity to CT colonography in this situation.
For endoscopically visible lesions, methods for tissue sampling include biopsies and polypectomy. For lesions that are completely removed endoscopically (with polypectomy, endoscopic mucosal resection, or endoscopic submucosal dissection), tattooing is important for subsequent localization if an invasive neoplasm is found, and additional local therapy is needed. Following endoscopic resection, a tattoo is typically placed near or several centimeters distal to the site, with the location being documented in the colonoscopy report. Large, laterally spreading colonic polyps may be safely removed endoscopically, provided they meet endoscopic criteria that predict their noninvasive nature (table 1). (See "Tattooing and other methods for localizing gastrointestinal lesions" and "Endoscopic removal of large colon polyps", section on 'Patient selection'.)
Among asymptomatic patients, colonoscopy miss rates for CRCs in the hands of experienced endoscopists range from 2 to 6 percent, and missed cancers are most frequently on the right side of the colon [44-47].
Data concerning miss rates for CRC among symptomatic patients undergoing colonoscopy are as follows:
●In a systematic review and meta-analysis of 25 diagnostic studies providing data on 9223 patients with a cumulative CRC prevalence of 3.6 percent (414 cancers), the sensitivity of optical colonoscopy for detection of CRC was 94.7 percent (178 of 188, 95% CI 90-97.2) [48]. Thus, the miss rate was 5.3 percent.
●Retrospective studies from Canada [49-51] and the United States [52-54] have used administrative databases to identify patients diagnosed with CRC who had had a colonoscopy performed for any indication 6 to 60 months prior to CRC diagnosis. Interval, missed, or post-colonoscopy CRCs accounted for 6 to 9 percent of all CRCs in their series. Other studies of post-colonoscopy CRC (sometimes called interval cancers) have shown a close inverse relationship between the incidence of these cancers in a colonoscopist's practice and that colonoscopist's adenoma detection rate. (See "Overview of colonoscopy in adults", section on 'Quality indicators'.)
If a malignant obstruction precludes a full colonoscopy preoperatively, the entire residual colon should be examined soon after resection. This can be performed either with a postoperative completion colonoscopy or an intraoperative completion colonoscopy immediately following the tumor resection.
What is the role of flexible sigmoidoscopy? — Flexible sigmoidoscopy alone is generally not an adequate diagnostic study for a patient suspected of having CRC. There is the possibility of a right-sided or proximal colon cancer, including a cecal primary (picture 2), as well as synchronous CRC. Even with an increasing incidence of left-sided and rectal cancers in individuals with early onset CRC, a complete colonoscopy is still needed to evaluate the remainder of the colon for synchronous polyps and cancers. (See "Epidemiology and risk factors for colorectal cancer", section on 'Incidence'.)
Computed tomographic (CT) colonography — CT colonography (also called virtual colonoscopy) provides a computer-simulated endoluminal perspective of a prepared and gas-distended colon. The technique uses conventional helical CT scan images acquired as an uninterrupted volume of data and employs sophisticated postprocessing software to generate images that allow the operator to evaluate the colon. CT colonography requires a bowel preparation that is similar to that needed for optical colonoscopy, since stool can mimic polyps. (See "Computed tomographic (CT) colonography in adults".)
CT colonography has been evaluated in patients with incomplete colonoscopy and as an initial diagnostic test in patients with symptoms suggestive of CRC.
Incomplete colonoscopy — In symptomatic patients, non-completion rates for diagnostic colonoscopy in clinical trials are approximately 10 percent or less [55], although these rates may be higher in clinical practice. Reasons for incompleteness include the inability of the colonoscope to reach the tumor or to visualize the mucosa proximal to the tumor for technical reasons (eg, partially or completely obstructing cancer, tortuous colon, poor preparation) and patient intolerance of the examination. In this setting, CT colonography is useful for the detection of CRC and can provide a radiographic diagnosis, although it can overcall stool as masses in poorly distended or poorly prepared colons; it also lacks the capability for biopsy or removal of polyps [48,56-59].
CT colonography should be restricted to patients who are able to pass flatus and capable of tolerating the oral preparation. For clinically obstructed patients, a gastrointestinal protocol abdominal CT scan is a good alternative to CT colonography.
Initial diagnostic test — Systematic reviews of screening studies conducted in asymptomatic patients suggest that both CT colonography and colonoscopy have similar diagnostic yield for detecting CRC and large polyps. Comparison of the benefits and costs of the two procedures depends on other factors, one of the most important of which is the need for additional investigation after CT colonography and the exposure to radiation, which is particularly important where recurrent scanning over time may be contemplated such as in screening. (See "Radiation-related risks of imaging".)
Abnormal results with CT colonography should be followed up by colonoscopy for excision and tissue diagnosis, or for smaller lesions, additional surveillance with CT colonography. There is controversy as to the threshold size of a polyp that would indicate the need for (interventional) colonoscopy and polypectomy. CT colonography also has the ability to detect extracolonic lesions, which might explain symptoms and provide information as to the tumor stage, but also could generate anxiety and cost for unnecessary investigation and may have a low yield of clinically important pathology [60]. (See "Tests for screening for colorectal cancer", section on 'Computed tomography colonography'.)
The performance of diagnostic CT colonography as compared with colonoscopy in patients with symptoms suggestive of CRC has been addressed in the following studies:
●A systematic review and meta-analysis included 49 studies (11,551 patients) in which patients underwent CT colonography for the diagnosis of colorectal polyps and cancer with subsequent colonoscopy for verification of the findings; 43 studies (6668 patients) examined a symptomatic or disease-enriched population [48]. There were 394 cancers in the symptomatic population (prevalence 6 percent) and a total of 414 cancers in the entire cohort. CT colonography detected 96.1 percent of the histologically proven cancers (95% CI 93.9-97.7 percent). In a subset of 25 studies (9223 patients) in which the sensitivity of colonoscopy could be assessed independently (ie, when the colonoscopy was performed without knowledge of the prior CT colonography result, an analysis which included predominantly data from asymptomatic individuals), the sensitivity of colonoscopy was 94.7 percent (178 of 188 cancers, 95% CI 90.4-97.2 percent).
●The diagnostic performance of CT colonography was directly compared with colonoscopy in the SIGGAR (Special Interest Group in Gastrointestinal and Abdominal Radiology) trial in which 1610 patients with symptoms suggestive of CRC were randomly assigned to colonoscopy (n = 1072) or CT colonography (n = 538) [55]. The primary endpoint was the rate of additional colonic investigation after the primary procedure for detection of CRC or large (>10 mm) polyps. Detection rates for CRC and large polyps were 11 percent for both procedures. CT colonography missed 1 of 29 CRCs and colonoscopy missed none of 55. However, patients undergoing CT colonography were more than three times more likely to get additional colonic investigations (30 versus 8 percent). Only one-third of the patients who underwent additional investigations were found to have CRC or a large polyp.
At least one previously unknown extracolonic finding was reported in 60 percent of the 475 patients who had CT colonography and no diagnosis of CRC. Most were judged to be clinically unimportant. Among the 48 patients who were investigated further for extracolonic findings, only approximately one-third received a diagnosis that explained at least one of their presenting symptoms and only nine patients were found to have an extracolonic malignancy.
Overall, CT colonography had superior patient acceptability compared with colonoscopy in the short term (immediately after the test) but the benefits of colonoscopy (being more satisfied with how results were received and less likely to require follow-up colonic investigations) became apparent after longer-term follow-up (three months) [61].
The available data suggest that CT colonography provides a similarly sensitive, less invasive alternative to colonoscopy in patients presenting with symptoms suggestive of CRC. CT colonography may be particularly valuable in patients with an obstructing CRC with the ability to tolerate a bowel preparation. In one study, performing a CT colonography led to a change in the surgical plan because of the presence of synchronous tumors in 1.4 percent of cases [62]. However, given that colonoscopy permits removal/biopsy of the lesion and any synchronous cancers or polyps that are seen during the same procedure, in our view, colonoscopy remains the gold standard for investigation of symptoms suggestive of CRC. CT colonography is preferred over barium enema where access to colonoscopy is limited.
PILLCAM 2 — A colon capsule for CRC screening has been approved by the European Medicines Agency in Europe and by the US Food and Drug Administration. In the United States, it is approved for use in patients who have had an incomplete colonoscopy. While its role in screening for CRC is still uncertain, it could be an option in a patient with an incomplete colonoscopy who lacks obstruction.
Laboratory tests — Although CRC is often associated with iron deficiency anemia, its absence does not reliably exclude the disease. There is no diagnostic role for other routine laboratory test, including liver function tests, which lack sensitivity for detection of liver metastases.
Tumor markers — Neither serum carcinoembryonic antigen (CEA) nor any other marker, including carbohydrate antigen 19-9 (CA 19-9), should be used as a screening or diagnostic test for CRC. A variety of serum markers have been associated with CRC, particularly CEA. However, all these markers, including CEA, have a low diagnostic ability to detect primary CRC due to significant overlap with benign disease and low sensitivity for early-stage disease [63-65]. A meta-analysis concluded that the pooled sensitivity of CEA for diagnosis of CRC was only 46 percent (95% CI 0.45-0.47) [66]. No other conventional tumor marker had a higher diagnostic sensitivity, including CA 19-9 (pooled sensitivity 0.30, 95% CI 0.28-0.32).
Furthermore, specificity of CEA is also limited. In the previously mentioned meta-analysis, the specificity of CEA for diagnosis of CRC was 89 percent (95% CI 0.88-0.92). Non-cancer-related causes of an elevated CEA include gastritis, peptic ulcer disease, diverticulitis, liver disease, chronic obstructive pulmonary disease, diabetes, and any acute or chronic inflammatory state. In addition, CEA levels are significantly higher in cigarette smokers than in non-smokers [67,68].
However, CEA levels do have value in the prognosis and follow-up of patients with diagnosed CRC:
●Serum levels of CEA have prognostic utility in patients with newly diagnosed CRC. Patients with preoperative serum CEA >5 ng/mL have a worse prognosis, stage for stage, than those with lower levels, although at least some data suggest that elevated preoperative CEA that normalizes after resection is not an indicator of poor prognosis [69]. (See "Pathology and prognostic determinants of colorectal cancer", section on 'Preoperative serum CEA'.)
●Elevated preoperative CEA levels that do not normalize following surgical resection may imply the presence of persistent disease and the need for further evaluation. (See "Post-treatment surveillance for colorectal cancer", section on 'Carcinoembryonic antigen'.)
Furthermore, serial assay of postoperative CEA levels should be performed for five years for patients with stage II and III disease if they may be a potential candidate for surgery or chemotherapy if metastatic disease is discovered. A rising CEA level after surgical resection implies recurrent disease and should prompt follow-up radiologic imaging. (See "Post-treatment surveillance for colorectal cancer".)
Other stool- and blood-based tests — Other tests that are used for the diagnosis of CRC, such as stool-based tests (such as fecal immunohistochemical test [FIT] for blood, guaiac-based fecal occult blood test [gFOBT], multitarget stool deoxyribonucleic acid [DNA] tests, and multitarget stool ribonucleic acid [RNA] tests), blood-based tests (such as cell-free DNA, circulating tumor DNA, and multicancer detection [MCD] tests) are discussed separately. (See "Tests for screening for colorectal cancer", section on 'Stool-based tests' and "Tests for screening for colorectal cancer", section on 'Blood tests' and "Overview of preventive care in adults", section on 'Multi-cancer detection tests'.)
DIFFERENTIAL DIAGNOSIS —
The signs and symptoms associated with CRC are nonspecific, and the differential diagnosis, particularly among patients presenting with abdominal pain and rectal bleeding, is broad. (See "Causes of abdominal pain in adults" and "Etiology of lower gastrointestinal bleeding in adults" and "Evaluation of occult gastrointestinal bleeding" and "Approach to acute lower gastrointestinal bleeding in adults".)
Many conditions cause signs or symptoms that are similar to colorectal adenocarcinomas including other malignancies as well as benign lesions such as hemorrhoids, diverticulitis, infection, or inflammatory bowel disease.
The differential diagnosis of a colonic mass as seen on radiographic or endoscopic studies includes a number of benign and malignant disorders, the differentiation of which generally requires biopsy and histologic evaluation (table 2). In particular, rare malignancies other than adenocarcinomas that are primary to the large bowel include Kaposi sarcoma (KS), gastrointestinal stromal tumors, lymphomas, carcinoid (well-differentiated neuroendocrine) tumors, and metastases from other primary cancers. (See "Pathology and prognostic determinants of colorectal cancer", section on 'Histology'.)
●Kaposi sarcoma – Disseminated KS can involve the colon, particularly in patients with acquired immunodeficiency syndrome (AIDS), manifested as characteristic violaceous macules or nodules [70]. (See "AIDS-related Kaposi sarcoma: Clinical manifestations and diagnosis", section on 'Gastrointestinal tract'.)
●Lymphoma – Primary non-Hodgkin lymphoma of the large bowel most commonly arises in the cecum, right colon, or rectum and usually presents at an advanced stage in adults. Colonic lymphoma typically appears as a large solitary mass, although multiple polypoid lesions or diffuse involvement can occur [71]. (See "Clinical presentation and diagnosis of primary gastrointestinal lymphomas".)
●Neuroendocrine tumors – Colonic neuroendocrine tumors are found most commonly in the appendix, rectum, and cecum, and they tend to develop at a younger age than adenocarcinomas of the colon. Appendiceal and rectal neuroendocrine tumors, most of which are less than 2 cm, appear as submucosal nodules and tend to be indolent. By contrast, primary colonic neuroendocrine tumors can present as large apple-core lesions, which can be clinically aggressive and may metastasize. (See "Clinical characteristics of well-differentiated neuroendocrine tumors arising in the gastrointestinal and genitourinary tracts".)
●Gastrointestinal stromal tumors – Gastrointestinal stromal tumors develop in the wall of the gastrointestinal tract from interstitial cells of Cajal. Other mural tumors that derive from smooth muscle include a spectrum of histologic characteristics that range from slow growing with low mitotic activity (classified as leiomyomas) to faster growing tumors with very high mitotic activity (designated as leiomyosarcomas). (See "Clinical presentation, diagnosis, and prognosis of gastrointestinal stromal tumors" and "Local treatment for gastrointestinal stromal tumors, leiomyomas, and leiomyosarcomas of the gastrointestinal tract".)
●Metastases from primary cancers other than CRC – Metastases from primary cancers other than CRC, most often ovarian cancer, can mimic a primary large bowel malignancy. (See "Epithelial carcinoma of the ovary, fallopian tube, and peritoneum: Clinical features and diagnosis", section on 'Differential diagnosis'.)
STAGING —
Once the diagnosis of CRC is established, the local and distant extent of disease is determined to provide a framework for discussing therapy and prognosis. A review of the biopsy specimen is important prior to making a decision about the need for clinical staging studies and surgical resection, especially for a cancerous polyp. Polyps with an area of invasive malignancy that have been completely removed and lack associated adverse histologic features (positive margin, poor differentiation, lymphovascular invasion) have a low risk of lymphatic and distant metastases; in such patients, polypectomy alone may be adequate. This is more easily determined if the polyp is pedunculated. (See "Overview of colon polyps".)
TNM staging system — The Tumor, Node, Metastasis (TNM) staging system of the combined American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) is the preferred staging system for CRC. Use of the Astler-Coller modification of the Duke's classification is discouraged. However, the AJCC TNM staging classification is not used in all countries.
The eighth edition TNM staging classification contains few changes compared with the earlier 2010 seventh edition (table 3) [72]. The M1c stage has been introduced to reflect peritoneal carcinomatosis as a poor prognostic factor, and nodal micrometastases (tumor clusters >0.2 mm in diameter) are scored as positive given the results of a meta-analysis demonstrating a poor prognosis in these patients [73] (see "Pathology and prognostic determinants of colorectal cancer", section on 'Nodal micrometastases'). In addition, the definition of tumor deposits as they apply to regional nodal status is clarified.
The following clinical factors are important to evaluate when making decisions about treatment but are not incorporated into the formal staging criteria:
●Preoperative serum carcinoembryonic antigen (CEA) levels. (See 'Tumor markers' above.)
●Tumor regression score, which reflects the pathologic response to preoperative radiation therapy, chemoradiation, or systemic therapy (table 4) and the status of the circumferential resection margin for rectal cancers. (See "Pathology and prognostic determinants of colorectal cancer", section on 'Circumferential (radial) margin' and "Neoadjuvant therapy for rectal adenocarcinoma", section on 'Prognosis and extent of tumor regression'.)
●Lymphovascular and perineural invasion. (See "Pathology and prognostic determinants of colorectal cancer", section on 'Lymphovascular invasion' and "Pathology and prognostic determinants of colorectal cancer", section on 'Perineural invasion'.)
●Microsatellite instability, which reflects deficiency of mismatch repair enzymes and is both a good prognostic factor and predictive of a lack of response to fluoropyrimidine therapy. It also identifies patients who might be responsive to immune checkpoint inhibitors in the setting of locoregionally advanced or metastatic disease. (See "Pathology and prognostic determinants of colorectal cancer", section on 'Mismatch repair deficiency' and "Initial systemic therapy for metastatic colorectal cancer", section on 'DNA mismatch repair deficient/microsatellite unstable tumors' and "Overview of the management of primary colon cancer", section on 'Neoadjuvant therapy' and "Adjuvant therapy for resected stage III (node-positive) colon cancer", section on 'Patients with deficient mismatch repair'.)
●Tumor border and tumor budding. (See "Pathology and prognostic determinants of colorectal cancer", section on 'Tumor border and tumor budding'.)
Radiographic imaging, endoscopic (including biopsy), and intraoperative findings can be used to assign a clinical stage, while assessment of the pathologic stage (termed pT, pN, pM) requires histologic examination of the resection specimen. Preoperative radiation therapy and systemic therapy (which are often used to treat locally advanced rectal cancer) can significantly alter clinical staging; as a result, posttherapy pathologic staging is designated with a yp prefix (ie, ypT, ypN). (See "Pathology and prognostic determinants of colorectal cancer", section on 'Posttherapy staging for rectal cancer'.)
Clinical staging evaluation — Preoperative clinical staging is best accomplished by physical examination and contrast-enhanced CT scan of the chest, abdomen, and pelvis to assess for distant metastatic disease.
Although frequently obtained preoperatively, liver enzymes may be normal in the setting of small hepatic metastases and are not a reliable marker for exclusion of liver involvement (picture 3). The single most common liver test abnormality associated with liver metastases is an elevation in the serum alkaline phosphatase level [74].
For patients with colon cancer who undergo resection of the primary tumor, pathologic assessment of the surgical specimen is used to define the pathologic tumor (T) and nodal (N) stage. Further details are discussed separately. (See "Pathology and prognostic determinants of colorectal cancer".)
Computed tomography scan — In the United States and elsewhere, the standard practice at most institutions is that all patients with stage II, III, or IV CRC undergo a contrast-enhanced CT of the chest, abdomen, and pelvis, either prior to or following resection, an approach endorsed by the National Comprehensive Cancer Network [75]. In general, it is preferable to obtain these scans prior to, rather than after surgery, as the scan results will occasionally change surgical planning.
Abdomen and pelvis — In patients with newly diagnosed CRC, a preoperative contrast-enhanced CT of the abdomen and pelvis can demonstrate regional tumor extension, regional lymphatic and distant metastases, and tumor-related complications (eg, obstruction, perforation, fistula formation) [76,77]. The sensitivity of CT for detecting distant metastasis is higher (75 to 87 percent) than for detecting nodal involvement (45 to 73 percent) or the depth of transmural invasion (approximately 50 percent) [76,78-83]. The sensitivity of CT for detection of malignant lymph nodes is higher for rectal than for colon cancers; perirectal adenopathy is presumed to be malignant since benign adenopathy is typically not seen in this area in the absence of demonstrable inflammatory process (eg, proctitis, fistula, perirectal abscess) [84]. However, pelvic magnetic resonance imaging (MRI) provides a better assessment of clinical tumor and nodal stage as well as proximity of the tumor to the circumferential resection margin, and is the gold standard for rectal cancer staging. This subject is discussed separately. (See "Pretreatment locoregional staging evaluation for rectal cancer".)
CT scan is not a reliable diagnostic test for low-volume tumor on peritoneal surfaces [85]. The sensitivity of CT for detecting peritoneal implants depends on the location and size of the implants. In one study, the sensitivity of CT for nodules <0.5 cm was 11 percent and it was only 37 percent for implants 0.5 to 5 cm [86].
The finding of liver metastases on preoperative studies may not necessarily alter the surgical approach to the primary tumor, particularly in patients who are symptomatic from their primary tumor (eg, bleeding, impending obstruction). In patients with four or fewer hepatic lesions, resection may be curative, with five-year relapse-free survival rates of 24 to 38 percent. Although most surgeons advocate resection of the primary tumor and synchronous hepatic metastases at two different operations, some approach both sites at the same time. (See "Potentially resectable colorectal cancer liver metastases: Integration of surgery and chemotherapy".)
Chest — The clinical benefit of routine clinical staging with a contrast-enhanced chest CT is also controversial. At least in theory, imaging of the chest might be of more value for rectal cancer since venous drainage of the lower rectum is through the hemorrhoidal veins to the vena cava, bypassing the liver, and lung metastases might be more common [87].
The major issue is the frequent finding of indeterminate lesions (10 to 30 percent), which add to the clinical complexity (ie, should further preoperative diagnostic workup be undertaken) but are seldom malignant (7 to 20 percent). A systematic review of 12 studies including 5873 patients undergoing staging for a newly diagnosed CRC [88] found that 732 (9 percent) had indeterminate pulmonary nodules on preoperative chest CT. Of these, 80 (11 percent) turned out to be colorectal metastases at follow-up. Generally, the presence of regional nodal metastases at the time of resection, multiple numbers of indeterminate pulmonary nodules, size ≥5 mm, rectal as compared with colon cancer, parenchymal versus subpleural location of the nodule, and distant metastases elsewhere were significantly associated with malignancy, while calcification was associated with a benign etiology. Overall, the risk of malignancy for most patients with indeterminate pulmonary nodules (approximately 1 percent) seems sufficiently low that further preoperative diagnostic workup is unnecessary.
Liver magnetic resonance imaging — Contrast-enhanced MRI of the liver can identify more hepatic lesions than are visualized by CT and is particularly valuable in patients with background fatty liver changes [89]. A meta-analysis concluded that MRI is the preferred first-line imaging study for evaluating CRC liver metastases in patients who have not previously undergone therapy [90]. However, contemporary CT scanners and the use of triple-phase imaging during contrast administration has improved sensitivity of CT for detection of liver metastases. In practice, liver MRI is generally reserved for patients who have suspicious but not definitive findings on CT scan, particularly if better definition of hepatic disease burden is needed in order to make decisions about potential hepatic resection. (See "Potentially resectable colorectal cancer liver metastases: Integration of surgery and chemotherapy".)
Positron emission tomography scans — Positron emission tomography (PET) scans with or without integrated CT (PET/CT) do not appear to add significant information to CT scans for routine preoperative staging of CRC [91-93]. The established role of PET scanning in patients with CRC as an adjunct to other imaging modalities is described in the following settings:
●Localizing site(s) of disease recurrence in patients who have a rising serum CEA level and nondiagnostic conventional imaging evaluation following primary treatment. In this setting, PET scanning can potentially localize occult disease, permitting the selection of patients who may benefit from exploratory laparotomy [94-97]. (See "Post-treatment surveillance for colorectal cancer".)
In an illustrative series, 105 such patients underwent PET scanning and subsequent abdominopelvic CT scans [94]. Compared with CT and other conventional diagnostic studies, PET scanning had a higher sensitivity (87 versus 66 percent) and specificity (68 versus 59 percent) for the detection of clinically relevant tumor. In a second report, PET scan findings led to a potentially curative resection in 14 of 50 patients (28 percent) with elevated serum CEA levels and a completely normal or equivocal conventional diagnostic workup [95].
●Evaluation of patients who are thought to be present or future candidates for resection of isolated CRC liver metastases. The routine use of PET prior to attempted resection reduces the number of nontherapeutic laparotomies, but the impact on long-term outcomes is uncertain. As an example, in one randomized trial, routine preoperative evaluation of potentially resectable CRC liver metastases with PET-CT resulted in a change in surgical management in 8 percent of patients, but there was no effect on recurrence rates or long-term survival [98].
An important point is that recent chemotherapy may alter the sensitivity of PET for the detection of colorectal liver metastases, an effect thought related to decreased cellular metabolic activity of the tumor. However, generally, the benefit of a PET scan is to detect extrahepatic metastases in patients who are candidates for liver resection, and in this situation, it is appropriate to obtain a PET prior to initiation of chemotherapy. This subject is addressed in detail separately. (See "Hepatic resection for colorectal cancer liver metastasis", section on 'Positron emission tomography' and "Potentially resectable colorectal cancer liver metastases: Integration of surgery and chemotherapy", section on 'Pretreatment considerations'.)
Locoregional staging for rectal cancer — In patients with rectal cancer, an accurate determination of tumor location within the rectum and disease extent is necessary prior to treatment in order to select the optimal treatment approach. (See "Neoadjuvant therapy for rectal adenocarcinoma".)
Digital rectal examination, rigid sigmoidoscopy, transrectal ultrasound, transrectal endoscopic ultrasound, and pelvic MRI can all assist in determining the need for radical resection versus local excision, and whether the patient is a candidate for preoperative therapy. This subject is discussed separately. (See "Pretreatment locoregional staging evaluation for rectal cancer".)
SOCIETY GUIDELINE LINKS —
Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Colorectal cancer".)
INFORMATION FOR PATIENTS —
UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topic (see "Patient education: Colon and rectal cancer (The Basics)")
●Beyond the Basics topics (see "Patient education: Colon and rectal cancer (Beyond the Basics)" and "Patient education: Treatment of metastatic colorectal cancer (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Clinical presentation – Patients with colorectal cancer (CRC) may present in several ways (see 'Clinical presentation' above):
•Asymptomatic individuals who undergo routine screening for CRC or as an incidental finding on an imaging study done for another purpose (see 'Asymptomatic individuals' above)
•Suspicious symptoms and/or signs
•Emergency admission with intestinal obstruction, peritonitis, or rarely, an acute gastrointestinal bleed
●Symptoms from the local tumor – Most patients with CRCs, including those with early onset CRC, are diagnosed after the onset of symptoms, most commonly rectal bleeding, abdominal pain, otherwise unexplained iron deficiency anemia, and/or a change in bowel habits. (See 'Symptoms from the local tumor' above and 'Symptoms in early onset colorectal cancer' above.)
●Symptoms based on tumor location – A change in bowel habits is a more common presenting symptom for left-sided as compared with right-sided cancers. Hematochezia is more likely with rectal than colon cancers, and occult colonic bleeding is more common with cecal and ascending colon cancers. (See 'Symptoms based on tumor location' above.)
●Metastatic disease – The most common sites for metastatic disease are the regional lymph nodes, liver, lungs, and peritoneum. (See 'Metastatic disease' above.)
●Atypical presentations – Atypical presentations of CRC include malignant fistula formation, fever of unknown origin, sepsis from Streptococcus bovis and Clostridium septicum, and adenocarcinoma of unknown primary. (See 'Atypical presentations' above.)
●Diagnosis – The diagnosis of CRC should be suspected in individuals with one or more of the symptoms and signs described above or those who are asymptomatic and discovered through routine CRC screening or as an incidental finding on imaging studies. Once CRC is suspected, the next test should be colonoscopy or CT colonography. (See 'Diagnosis' above.)
•Tissue diagnosis – Most CRCs are endoluminal adenocarcinomas that arise from the mucosa. The diagnosis is made by histologic examination of malignant colonic tissue, which is usually obtained from a biopsy during lower gastrointestinal tract endoscopy or a surgical specimen. (See 'Diagnosis' above.)
•Colonoscopy – Colonoscopy is the most versatile diagnostic test for CRC. (See 'Colonoscopy' above.)
•CT colonography – CT colonography provides a similarly sensitive, less invasive alternative to colonoscopy in patients presenting with symptoms suggestive of CRC. However, colonoscopy is preferred as it permits removal/biopsy of the lesion and any synchronous cancers or polyps that are seen during the same procedure. (See 'Initial diagnostic test' above.)
For patients in whom, for technical reasons, the tumor cannot be reached by colonoscopy (eg, partially obstructing cancer, tortuous colon, poor preparation) or because of patient intolerance, CT colonography can provide a radiographic diagnosis, but without the capability for biopsy or removal of polyps. (See 'Computed tomographic (CT) colonography' above.)
CT colonography is preferred over barium enema where access to colonoscopy is limited.
•Serum tumor markers – Serum tumor markers should not be used to screen for or diagnose CRC. However, serum carcinoembryonic antigen (CEA) levels should be obtained preoperatively and postoperatively in patients with demonstrated CRC to aid surgical treatment planning and assessment of prognosis. (See 'Tumor markers' above.)
●Staging evaluation
•Once the diagnosis is established, the local and distant extent of disease spread is determined to provide a framework for discussing therapy and prognosis. Preoperative clinical staging is best accomplished by physical examination and contrast-enhanced CT scan of the chest, abdomen, and pelvis to assess for distant metastatic disease. (See 'Clinical staging evaluation' above.)
Positron emission tomography (PET) scans do not appear to add significant information to CT scans for routine preoperative staging of a newly diagnosed CRC except for the evaluation of patients who are thought to be candidates for resection of isolated CRC liver metastases. (See 'Positron emission tomography scans' above.)
•For patients with colon cancer who undergo resection of the primary tumor, pathologic assessment of the surgical specimen is used to define the pathologic tumor (T) and nodal (N) stage. (See "Pathology and prognostic determinants of colorectal cancer".)
•For patients with rectal cancer, additional procedures (digital rectal examination, rigid sigmoidoscopy, transrectal endoscopic ultrasound, and/or MRI) are indicated for locoregional staging and to select the optimal management approach. (See 'Locoregional staging for rectal cancer' above.)
●Staging system – The Tumor, Node, Metastasis (TNM) staging system of the combined American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) is the preferred staging system for CRC (table 3), although it is not used in all countries.
ACKNOWLEDGMENTS —
The UpToDate editorial staff acknowledges Johanna Bendell, MD, who contributed to an earlier version of this topic review.
The UpToDate editorial staff acknowledges Dennis J Ahnen, MD, now deceased, who contributed to an earlier version of this topic review.
