Colorectal cancer is one of the most common diseases today, with about 1.2 million patients diagnosed worldwide each year, while more than 600,000 die directly or indirectly from colorectal cancer. Its incidence varies significantly by region, which is closely linked to the so-called Western lifestyle. The incidence of colorectal cancer is higher in men than in women. In addition, the incidence of colorectal cancer increases with age, for example, the median age of colorectal cancer incidence in developed countries is 70 years.
Although genetic factors are risk factors for colorectal cancer, most colorectal cancers are disseminated and occur as adenoma-tumors over a period of years.
The most current treatments for colorectal cancer are surgery, neoadjuvant radiation therapy (in patients with rectal cancer), and adjuvant chemotherapy (in patients with stage III, IV, or high-risk stage II colon cancer).
In terms of survival, stage I patients have a 5-year survival rate of over 90%, while stage IV patients have a survival rate of only slightly more than 10%. Endoscopic or blood screening has been shown to be effective in reducing colorectal cancer incidence and mortality, but organized screening has still not been initiated in most countries.
1.Epidemiological analysis.
(1), Incidence and mortality rate.
Colorectal cancer is one of the major malignant tumors in humans, and its incidence and mortality rates are in the third and fourth place, respectively. There are 1.2 million newly diagnosed cases and more than 600,000 patients die from colorectal cancer every year. The incidence of colorectal cancer is low in the age group below 50 years, but increases with age. The median age of colorectal cancer incidence in developed countries is 70 years.
The disease is more prevalent in Europe, North America and Oceania, while it is less common in South Asia, Central Asia and Africa. As shown in Figure 1, in 2008, the age-standardized incidence rates per million standard population ranged from 4.3 (Central Africa, men) to 45.7 (Australia and New Zealand, men) and from 3.3 (Central Africa, women) to 33 (Australia and New Zealand, women).Some of the original low-risk countries with age-standardized incidence rates for colorectal cancer in men in 2008, such as Spain, Eastern Europe, and Several countries in East Asia were found to have a strong association between their rapidly increasing domestic incidence rates and the so-called Western lifestyle. In contrast, some developed countries, including the United States, are showing a steady decline in the incidence of colorectal cancer with the widespread use of colorectal screening and colorectal polypectomy.
In 2008, age-standardized mortality rates per million standard population ranged from 3.5 (Central Africa, men) to 20.1 (Central and Eastern Europe, men) and 2.7 (Central Africa, women) to 12.2 (Central and Eastern Europe, women).
Since the 1980s, colorectal cancer mortality is declining in some developed countries due to early detection and treatment. However, colorectal cancer mortality is still increasing in areas with poor access to health care, such as rural areas in Central and South America and China.
Prognosis of age-standardized mortality trends for colorectal cancer in men in selected countries between 1955 and 2010.
Colorectal cancer survival rates have improved in many countries over the past few decades. In particular, in some high-income countries, such as the United States, Australia, Canada and some European countries, the 5-year survival rate for colorectal cancer has reached more than 65%. However, in contrast, in some low-income countries this value is less than 50%.
The expected survival for colorectal cancer decreases with increasing age at presentation. And for younger people, survival rates are higher for women than for men.
The stage of disease in colorectal cancer is the most important prognostic factor. For example, between 2001 and 2007, the 5-year survival rates of colorectal cancer patients with different stages in the United States were 90.1% (stage I), 69.2% (stages II and III) and 11.7% (stage IV), respectively.
(2), Risk factors and prevention.
(3), Risk factors and prevention.
Unlike lung cancer, there is more than one risk factor for most colorectal cancers. In addition to age and gender, there are many risk factors worth noting, such as family history of colorectal cancer, inflammatory bowel disease, smoking, excessive alcohol consumption, consumption of large amounts of red processed meat (mainly processed four-legged animal meat), obesity, and diabetes. Among these risk factors, family history of colorectal cancer and inflammatory bowel disease are most strongly associated with colorectal cancer. Although other risk factors can be theoretically avoided, they are more common in real life and play an extremely important role in the history of colorectal cancer development.
New evidence suggests that infection with Helicobacter pylori, Clostridium spp. bacteria, and a number of other potentially infectious agents may be associated with the development of colorectal cancer.
Prevention methods for colorectal cancer include physical activity, use of hormone replacement therapy, taking aspirin, and use of endoscopy to remove precancerous lesions (adenomas). In addition, some studies have shown that including a diet rich in fruits, vegetables, grains and fish has a preventive effect on colorectal cancer. For people with hyperlipidemia, the use of statins is also beneficial in reducing the probability of colorectal cancer.
Finally, some epidemiological studies have shown a negative correlation between vitamin D levels and colorectal cancer incidence in humans. However, the mechanism needs to be further investigated.
The development of colorectal cancer is also closely related to genetics. According to the results of a large twin study, 34.35% of colorectal cancer risk can be attributed to genetic factors. This genetic factor includes familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer (Lynch syndrome) in addition to a family history of colorectal cancer in the traditional sense. Genome-wide association studies, however, have found an increasing number of single nucleotide polymorphisms (SNPs) that are not strongly associated with colorectal cancer. Meta-analyses have shown that SNPs associated with colorectal cancer account for only a small proportion of colorectal cancer risk, and they do not predominate when interacting with known environmental risk factors.
2. Pathological staging.
Colorectal cancer is staged according to the depth of local infiltration (T-stage), lymphatic metastasis (N-stage) and the presence of distal metastasis (M-stage). And the treatment is decided according to the staging. Although TNM staging according to the UICC can guide standardized treatment and assess prognosis as a whole, neither can be achieved specifically for individuals (in the context of NCCN treatment guidelines going hand in hand with individualized treatment, this statement is worth playing with.) . This is especially true for patients with UICC staging of stages II and III.
In fact, a significant number of patients do not benefit from chemotherapy. Therefore, improving informative markers of tumors could help those patients with a high risk of recurrence to benefit from adjuvant therapy.
3. Molecular pathogenesis.
The molecular pathogenesis of colorectal cancer is gene mutation. Several studies in the last two decades have shown that gene mutations are closely related to the prognosis and treatment options of colorectal cancer, and because of this, many targeted therapeutic agents have emerged.
(1) Adenoma-cancer sequence.
Atypical proliferative adenoma is the most common precancerous colorectal lesion, but it often takes more than 10 years to develop into colorectal cancer. more than 70% of adenoma formation is accompanied by APC gene mutation, which seems to predict that APC gene mutation is closely related to the precancerous lesion of colorectal cancer. In addition, adenoma-carcinoma progression is usually accompanied by activation of KRAS genes and suppression of P53 oncogene expression. Mutations in these characteristic genes are often accompanied by changes in chromosome number and structure. (For example, mutations in the APC gene arise from a genetic deletion of 5q21 on chromosome 5, and suppression of p53 gene expression is thought to be a genetic deletion of 17p13.1 on chromosome 17.) However, more than 15% of sporadic colorectal cancers occur through a completely different molecular pathogenesis. For example, serrated lesions, which are typical precancerous lesions of this type often show methylation of the CpG locus and mutations in the BRAF gene. These lesions are inconspicuous and therefore often difficult to identify during colonoscopic screening.
Most colorectal cancers caused by broad-based serous adenomas in the elderly, especially in elderly women, exhibit high-level microsatellite instability (MSI-H).
(2), genetic pattern.
About 3-5% of colorectal cancers come from heredity. Hereditary colorectal cancer is a tumor that is well worth further investigation of molecular mechanisms. Genetically, the tumor is mainly caused by inactivation of expression of important oncogenes and DNA repair genes and mutations of wild-type alleles.
The two most common forms of hereditary colorectal cancer are hereditary non-polyposis colon cancer (Lynch syndrome, estimated allele frequency 1:350 to 1:1700) and familial adenomatous colon polyposis (estimated allele frequency 1:10,000). Both of these colorectal cancers are autosomal inherited diseases.
(3), mismatch repair defects and MSI-H.
Mismatch repair gene-deficient colorectal cancer is characterized by the accumulation of many gene deletions and insertion errors distributed through chromosomal microsatellites. MSI-H tumors present the following characteristics: localization in the proximal colon; patients younger than 50 years of age (genetic type) or older adults (disseminated type); simultaneous occurrence of other tumors; large local lesions and few organ metastases.
The histopathology of MSI-H is characterized by poor or mixed differentiation (hyperdifferentiation) and dense infiltration of tumor-infiltrating lymphocytes. 90% of MSI-H tumors have loss of expression of at least one DNA mismatch repair protein.
Although inactivation of DNA mismatch repair genes appears to accelerate rather than initiate colorectal cancer, the exact timing of DNA mismatch repair initiation in tumor development remains unknown.
4. Molecular markers related to prognosis and treatment.
(1), microsatellite instability.
Except for hereditary colorectal cancer, microsatellite instability detection can provide effective prognostic information and treatment response. According to a systematic evaluation of a pooled 32 studies (total of 7642 colorectal cancer patients), patients with MSI-H had a better prognosis than those with microsatellite stability (MSS) (hazard ratio of 0.65 for overall survival). In addition, MSI patients do not seem to benefit from 5-FU chemotherapy regimens, so irinotecan is their base chemotherapy agent. However, this result is still controversial. These findings have contributed to the ongoing debate on “whether molecular tumor analysis should be performed in colorectal cancer patients receiving adjuvant chemotherapy”.
(2) Immune system cell infiltration.
The MSI-H phenotype is closely associated with an associated high density of tumor-infiltrating lymphocytes. This association may arise from an auto-anti-tumor immune response that may contribute to improved prognosis in MSI-H colorectal cancer. Local immune cell infiltration has been shown to be an effective prognostic factor. Patients with colorectal cancer (regardless of UICC stage) who show dense infiltration of CD45 R0-positive and CD3-positive lymphocytes in the center of the lesion can have a good prognosis. Conversely, low lymphocyte infiltration is an independent factor of poor prognosis.
Therefore, there are current efforts in various countries to develop a novel immunological classification for prognostic staging of colorectal cancer.
(3), KRAS and other gene mutations as prognostic indicators.
The most prominent example of a molecular marker is the KRAS gene test, which has entered routine clinical testing for patients with metastatic colorectal cancer. patients with KRAS mutations in colorectal cancer are poorly treated against EGFR, thereby reducing the effectiveness of monotherapy from 20% to 0%. Further studies are needed to determine the relationship between BRAF mutations and EGFR. This novel classification system based on complex mutation and expression patterns could be used to differentiate patients for individualized treatment planning.
In conclusion, the prognosis of different types of colorectal cancer can be determined by molecular typing identification. patients with MSI-H generally have a better prognosis, while patients with MSS and CpG locus methylation generally have an extremely poor prognosis.
5. Diagnosis and staging.
Colorectal cancer is primarily diagnosed by histological specimens removed by endoscopy. 2-4% of patients with a diagnosis of colorectal cancer are mandated to undergo complete colonoscopy or CT colon imaging to rule out other concurrent tumors. If this is not possible preoperatively with radical resection, colon visualization testing should be performed within six months postoperatively.
For rectal cancer, accurate local staging at diagnosis is mandatory and is an important basis for neoadjuvant therapy. In addition to the exact distance to the anal opening, the extent of tumor invasion is also important. Ultrasound endoscopy, as a non-invasive examination, can distinguish whether the tumor is infiltrated or not, and thus determine the T-stage of rectal cancer. Therefore, ultrasound endoscopy is one of the optional methods for local tumor staging. Of course, the most reliable one is MRI, but due to the influence of radiation during neoadjuvant therapy, the results of either method are not 100% reliable.
For the diagnosis of colorectal cancer, distant metastasis is also an important indicator. Approximately 20% of patients have already developed distant metastases by the time colorectal cancer is diagnosed. The most common location of distant metastasis is the liver. Therefore, all patients with colorectal cancer should have a liver imaging to rule out metastases.
A meta-analysis of prospective studies showed that CT was slightly less sensitive than MRI for ruling out liver metastases, especially for those lesions less than 1 cm in diameter. In contrast, abdominal ultrasound is much less sensitive than the first two. However, the use of ultrasonography can substantially increase the sensitivity to the extent of multilayer spiral CT.
In France, 2.1% of newly diagnosed colorectal cancer patients have lung metastases at the time of diagnosis. The proportion of patients with rectal cancer is approximately three times higher than that of colon cancer. Small studies using lung CT have shown that 9-18% of patients with rectal cancer have pulmonary metastases. Although the clinical effectiveness of detecting lung metastases in patients with colorectal cancer is unknown. However, an x-ray is often recommended for colorectal cancer staging. Considering the incidence of pulmonary metastases, it also makes sense to perform a CT lung test in those patients with locally advanced rectal cancer.
Although colorectal cancer can also metastasize to other sites, such as bone and brain, there is no evidence to support routine examination of these locations. In addition, the data do not support PET-CT screening in the absence of suspected distant metastases. Investigations have shown that while the use of PET-CT (compared to the use of CT screening) is more likely to detect liver metastases and thus gain access to surgery (or reduce to so-called laparoscopic surgery), these have no impact on survival.
6. Evaluation and treatment.
(1), Role of the multidisciplinary team.
As with other tumors, colorectal cancer should be evaluated by a multidisciplinary team. The multidisciplinary team should include surgeons, oncologists, gastroenterologists, radiologists, pathologists, and radiation therapists. A hepatobiliary or thoracic surgeon is also necessary for certain cases of distant metastases.
Those patients with colorectal cancer with distant metastases and those with rectal cancer requiring neoadjuvant therapy prior to local resection need to be evaluated prior to initiating treatment. For those patients with colorectal cancer without signs of distant metastases, post-surgical evaluation for adjuvant therapy is also sufficient.
In conclusion, evaluation by a multidisciplinary team can reduce over-resection in patients with rectal cancer and increase the rate of adjuvant treatment in patients with colon cancer and surgery in patients with stage IV disease. One study showed that Denmark (where all hospitals have multidisciplinary teams) increased the use of MRI in patients and reduced perioperative mortality, but had no effect on survival.
(2), Surgery.
The standard surgical procedure for the treatment of rectal cancer is total rectal mesenteric resection, which is the removal of the rectum and perirectal mesentery. Complete resection of the rectal mesentery is important because it achieves complete clearance of the perirectal lymph nodes. Several studies have been performed to demonstrate the importance of clear lateral margins (so-called circumferential margins). A clear circumferential margin is usually defined as a distance between the tumor and the margin greater than 1 mm, which increases the patient’s risk of local recurrence and distal metastasis if the distance is less than or equal to 1 mm. If the tumor is found to have spread beyond the rectal mesenteric fascia during surgery, then the resection will also need to be expanded.
In colon cancer surgery, the lesion with corresponding lymph nodes will also be removed and cleared. The extent of surgery is determined by the location of the tumor and the blood vessels supplying it. This rectal mesenteric resection for rectal cancer is similar. Some experts propose performing a complete mesenteric resection in colon cancer surgery, which would result in more of the colonic mesentery and lymph nodes being cleared. However, the risks and benefits of doing so need to be confirmed by further studies.
Open surgery used to be the only option for patients with colorectal cancer. However, laparoscopic resection has caught up to develop as an alternative option. Several meta-analyses have shown that laparoscopic surgery for radical rectal cancer achieves long-term outcomes consistent with open surgery and requires fewer patients to have blood transfusions (3.4% versus 12.2%); faster recovery of bowel function (days to first bowel movement 3.3 versus 4.6 days); and shorter hospital stays (9.1 versus 11.7 days). Of course, laparoscopic resection takes longer (208 minutes: 167 minutes) and is more costly to perform. Some evidence also recommends the use of robotics for rectal cancer resection, but further data are needed to support this.
(3), neoadjuvant therapy.
Since the availability of total rectal mesenteric resection, there has been a substantial decrease in local recurrence rates after surgery for rectal cancer. van Gijn and his colleagues have demonstrated that neoadjuvant radiotherapy followed by total rectal mesenteric resection and neoadjuvant therapy in patients with colorectal cancer reduces the local recurrence rate of tumors (5%:11% overall, 9%:19% in stage III), demonstrating the importance of neoadjuvant therapy.
The question now is who to treat and how to treat them. stage I patients do not need to receive any additional treatment other than surgery because their local recurrence rate is very low (about 3%) and the benefit of performing neoadjuvant therapy is very small. stage III patients can benefit from neoadjuvant therapy, while it is unclear whether stage II patients benefit. It is now generally accepted that patients with stage T4 and advanced T3 (tumor infiltration of the rectal mesenteric fascia) may benefit from neoadjuvant therapy. However, the industry remains skeptical about the benefit of neoadjuvant chemotherapy in patients with T3 tumors more than 1 mm from the rectal mesenteric fascia (regardless of N-stage status). There is a current OCUM trial to demonstrate this.
Compared to timed radiotherapy, neoadjuvant therapy is superior to adjuvant therapy in that it reduces both local recurrence rates and toxicities. However, the question is which is more effective: short course radiotherapy (5*5Gy) or long course radiotherapy (50.4Gy) combined with chemotherapy. In the United States and some European countries, long-course radiotherapy is preferred, while some other European countries (such as Sweden, Norway, the Netherlands, etc.) mainly use short-course radiotherapy.
Short-course radiotherapy is usually used in conjunction with surgery, and there is rarely a delay. Therefore, short-course radiotherapy does not significantly reduce the tumor. For patients with T4 or T3 tumors infiltrating the rectal mesenteric fascia who want to reduce the tumor, long-course radiotherapy combined with chemotherapy is the preferred regimen. In a randomized trial, long-course radiotherapy achieved a significantly lower rate of circumferential margins than short-course radiotherapy (4%:13%).
The ideal treatment option for patients with stage T3 tumors is currently unknown. The results of the first randomized trial comparing short-course radiotherapy with long-course radiotherapy combined with chemotherapy for stage T3 rectal cancer showed that the local recurrence rate was lower with long-course radiotherapy combined with chemotherapy than with short-course radiotherapy, especially for patients with lesions in the distal rectum, but the difference was not statistically significant. Other data similarly suggest that long-course radiotherapy combined with chemotherapy appears to be the preferred treatment for patients with stage T3 lesions in the distal rectum. However, in stage T3 patients with lesions in the proximal rectum, short-course radiotherapy is more effective if the tumor does not infiltrate the rectal mesenteric fascia. Most of these studies have used fluorouracil in combination with radiotherapy, but in fact capecitabine is also a good option.
Currently, many institutions are studying the timing of chemotherapy in combination with short-course radiotherapy and the benefit of delayed surgery. Most studies have found no evidence that the use of radiotherapy changes distal metastasis rates and overall survival.
Data on the role of neoadjuvant therapy in the management of advanced colon cancer remain inadequate. A study including 150 patients treated with radiation at locally advanced stages showed that preoperative chemotherapy is feasible. The toxicity and perioperative complications of preoperative chemotherapy were acceptable, while the patients had a significant increase in R0 resection rate (p=0.002). However, more data from randomized trials are needed to draw this conclusion.
(4), adjuvant therapy.
Patients with stage III colon cancer have a 15%-50% risk of recurrence. Therefore, adjuvant chemotherapy is recommended for all patients with stage III colon cancer after radical surgery if there is no significant contraindication. Fluorouracil-containing chemotherapy regimens can reduce the recurrence rate by 17% and increase the overall survival rate by 13%-15%. In addition, capecitabine as an oral agent for fluorouracil is comparable to intravenous agents.
To improve disease-free survival and overall survival, several large prospective studies are trying oxaliplatin with fluorouracil or capecitabine. By adding oxaliplatin can increase 5-year disease-free survival by 6.2%-7.5% and overall survival by 2.7%-4.2% in patients with stage III colon cancer.
However, sub-studies of this study showed that oxaliplatin was beneficial only in patients younger than 65 or 70 years of age. Additional studies have shown that the addition of bevacizumab or cetuximab to an oxaliplatin-containing regimen had no effect on disease-free survival. In addition, the use of irinotecan in combination with fluorouracil has shown no benefit and increased drug toxicity.
Both disease-free survival and overall survival are better in stage II colon cancer than in stage III colon cancer, and the benefit of adjuvant chemotherapy on survival does not appear to be as great. Therefore, adjuvant chemotherapy is usually recommended for stage II patients with concomitant high risk factors for recurrence (e.g., stage T4, presence of perforation, previous bowel obstruction during surgery, fewer than 12 lymph nodes cleared, etc.). In the Quasar trial, chemotherapy with a fluorouracil-containing regimen after radical resection in stage II patients reduced all-cause mortality (relative risk of 0.82). In other words, assuming a 5-year mortality rate of 20% for these patients without chemotherapy, chemotherapy with a fluorouracil-containing regimen would increase it by 3.6%.
(5) and treatment after the development of distant metastases.
Research on the treatment of colorectal cancer with distant metastases is actually beyond the scope of this article. In general, for those resectable liver or lung metastases, surgical resection is recommended as a priority. And for unresectable metastases, palliative chemotherapy should be given. Chemotherapeutic approaches for colorectal cancer have made great strides, including drugs that inhibit the action of vascular endothelial cells (bevacizumab and aflibercept), monoclonal antibodies that inhibit epidermal growth factor (cetuximab and panitumumab), and protein kinase inhibitors (regofenib). Of these, cetuximab and panitumumab are generally used as part of combination therapy for patients with a mutation-free (wild-type) RAS.
With advances in combination chemotherapy regimens, some studies have shown that the median survival of patients who develop distant metastases has exceeded 20 months. Some patients with liver metastases diagnosed as unresectable become amenable to surgical resection after chemotherapy, and about 30% of them have a disease-free survival of up to 5 years. The regimen and intensity of chemotherapy depends mainly on the patient’s age, comorbidities, and the degree of tumor progression.
7.Prevention.
(1), primary prevention.
Reducing the risk factors of tumor and increasing the preventive measures of tumor are both primary prevention. Among them, risk factors include smoking, alcohol consumption, obesity and some common chronic diseases.
Although some randomized trials have shown that certain drugs (such as aspirin and hormone replacement therapy) have chemopreventive effects in colorectal cancer, their side effects make them unavailable for preventive treatment in people with high risk of colorectal cancer. An observational study suggests that vitamin D is a promising candidate for chemoprevention of colorectal cancer. However, more randomized trials are needed to confirm the specific effects.
(2), Secondary prevention.
Most colorectal cancers are slow to develop and can be surgically cured by early detection. Therefore, the secondary prevention view of colorectal cancer is early detection and early resection. A meta-analysis of randomized trials showed that annual screening for fecal occult blood reduced colorectal cancer mortality by 16%.
Some observational studies have found that colonoscopy is associated with a greater reduction in colorectal cancer incidence and mortality, but randomized trials of this research have only recently begun, and definitive conclusions will not be available until the mid-1920s.
The fecal occult blood test using traditional chemistry has been shown to reduce mortality from colorectal cancer. However, this method has high specificity and poor sensitivity, especially when screening for colorectal adenomas. Over the past 30 years, immunochemical detection of human hemoglobin in stool has gradually replaced the traditional chemical method. It has gained more acceptance for its high sensitivity in screening for both colorectal cancer and colorectal adenoma. In addition, immunochemical methods can be automated and standardized for quantitative measurement thus making the test more standard and simple; and its specificity in detecting human hemoglobin can effectively avoid interference in food, so patients do not need to restrict their diet when undergoing immunochemical testing for fecal occult blood.
Several model studies have evaluated the effectiveness and benefits of colorectal cancer screening. Typically, annual or biennial fecal occult blood screening and sigmoidoscopy (or fiberoptic colonoscopy every 10 years) screening is required for those over 50 years of age. Studies have shown that each screening tool is effective and cost-efficient. However, the most cost-effective screening program needs to be tailored to local conditions (e.g., colorectal cancer incidence, treatment techniques, etc.).
Current major research efforts are focused on non-invasive blood or stool screening. Examples include blood-based DNA methylation, protein markers, and fecal DNA testing. Although these options are advancing at a rapid pace, so far they have not been competitive in terms of diagnostic performance and cost-effectiveness when compared to conventional methods. A large number of studies are also exploring alternative imaging techniques. Such as CT and capsule endoscopic screening. But so far, they are not competitive in terms of cost-effectiveness. Moreover, there are radiation limitations in using CT for initial screening. Nevertheless, CT colon imaging remains the method of choice when colonoscopy is not available (e.g., intestinal strictures).
Based on the available evidence, the guidelines recommend colorectal cancer screening beginning at age 50 years with annual or biennial screening for fecal occult blood and sigmoidoscopy (or fiberoptic colonoscopy every 10 years). Patients with positive fecal occult blood must undergo colonoscopy. Adenomas, serrated adenomas, large hyperplastic polyps (greater than 1 cm), mixed polyps, and hyperplastic polyps located in the proximal colon must be surgically removed if found by colonoscopy.
If there are additional risk factors, such as a first-degree relative diagnosed with colorectal cancer, screening needs to start earlier (e.g., beginning at age 40 or 10 years earlier at the age of onset of the youngest immediate family member). For high-risk families (with a family history of adenomatous polyposis, hereditary nonpolyp colon cancer, or inflammatory bowel disease), the guidelines recommend a more specialized and rigorous prevention program in early life.
Experts agree that screening programs should be organized and include personal invitation, testing, and quality assurance. However, the vast majority of countries do not yet have the capacity to implement them.
(3), Tertiary prevention.
Randomized studies on tertiary prevention are very sparse. Nonetheless, there is some evidence that exercise interventions may enhance the quality of life of colorectal cancer patients. New evidence suggests that smoking may contribute to disease progression and reduce overall survival. Therefore, smoking cessation is necessary for colorectal cancer patients.
There are also data suggesting that aspirin may improve the prognosis of specific subgroups of colorectal cancers. More clinical trials and epidemiological studies are needed to refine the tertiary prevention of colorectal cancer.