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Colorectal Cancer

Colorectal cancer

Colorectal Cancer:

Colonic / rectal cancer is one of the commonest cancers seen all over the world. The incidence is on the rise in India. It is one of the few malignancies where long term survival is possible even in advanced stage of detection. Hence it is very important for all the patients with this disease to understand various aspects of this disease.

What is the cause of colorectal cancer?

There is no specific cause for colorectal cancer except for de novo genetic changes leading to cancer, polyposis syndromes (cancerous change in a benign polyp) that are again associated with mutation and inflammatory bowel disease (malignant change in chronically inflamed lining of the large intestine). Polyposis syndromes are due to genetic mutations which are inherited or sporadic. Hence multiple family members of various generations are seen affected. Continuous inflammation in IBD / UC leads to cellular changes / overgrowth and finally cancer. Colorectal cancer can be due to genetic changes that lead to cancer in multiple organs like large intestine, uterus. Breast, stomach, pancreas etcetera (Lynch syndrome) and is a familial occurrence / hereditary. Important to note that all genetic changes are not inherited, actually majority are de novo (in that patient). Hence majority of the colorectal cancers are sporadic / isolated in occurrence. Few are part of polyposis syndromes, Lynch syndrome or following inflammation.

High fat diet, diet rich in red meat, excess alcohol, diabetes, smoking, obesity / high BMI, inflammation are few associations.

Who is at a higher risk of developing a colorectal cancer?

Individuals with personal or family history of polyps, inflammatory bowel disease or colorectal cancer are at higher risk of developing a colorectal cancer. Person with age >50 years and no such history is at an average risk. The decision to screen and the screening protocol depends on whether one is average risk or high risk.

What are the symptoms of colorectal cancer?

Common symptoms are fresh blood in stools, abdominal pain, bloating, weight loss, constipation, diarrhea (spurious). However patient may be completely asymptomatic and the disease will be detected as an incidental pick up during health check-up. It may be detected during work up for anemia or can manifest as acute intestinal obstruction. It is also detected while screening patients with known backgrounds for high risk of colon cancer like ulcerative colitis, familial polyposis syndromes (e.g. FAP), hereditary conditions predisposing to multiple cancers like Lynch syndrome.

Patients with polyposis syndrome & Lynch syndrome can develop cancers at younger age ; in their thirties and forties. Family members of these patients may also have this problem or are at high risk to develop cancer. Patients with inherited polyposis syndrome have involvement of other organ systems too, depending on genes involved. This includes brain tumors, thyroid cancer, gastric / duodenal polyps, liver tumors etcetera. Occasionally patients without known family history can also have these mutations (sporadic mutation) and may or may not pass it to the next generation.

What are the investigations done to detect colorectal cancer?

Stool test for blood, sigmoidoscopy, colonoscopy, virtual colonoscopy (CT colonography), CT scan of abdomen and pelvis are some of the tests done during detection / initial diagnosis of colorectal cancer.

Is screening for colorectal cancer routinely advised?

Screening for colorectal cancer is advised only after age of 50 years if the person does not have any family or personal history of cancer or high risk factors.

Patients with family / personal history of cancer or polyposis should get investigated from younger age. In specific cases of polyposis syndromes, screening endoscopy sometimes starts at age of 18 years or 25 years. Patients with family history of cancer should undergo screening from age 40 years or earlier when necessary depending on age of onset in the family.

What is the aim of screening?

Screening is supposed to pick up disease before it is cancerous or is at early stage thus offering curative treatment and ensuring long survival; also avoiding the issues associated with treatment at advanced stage later. Screening may prevent a cancer by picking disease before it has become cancerous.

What are the modalities of screening for colorectal cancer?

Stool test for blood, colonoscopy, virtual colonoscopy (CT colonography) are some of the tests for screening of colorectal cancer. MRI scan is NOT a screening tool for colorectal cancer. The DNA based stool or blood tests are yet to establish their regular role / protocol in screening even though they are commercially available in selected places.

Which one is better?

Colonoscopy is the best screening method / gold standard but is expensive than others, invasive in nature, requires bowel preparation, has risk of complication, operator dependent and may not be easily available everywhere. Sigmoidoscopy (endoscopy limited to examination of only the distal colon) is useful for disease of distal colon but not helpful in picking disease in the proximal part. Hence inferior to a complete colonoscopy. CT based virtual colonoscopy is a good alternative for patients unwilling or unfit to undergo a colonoscopy. Positive findings will necessitate a colonoscopy. Results depend on how carefully it is performed and reported. Risk of radiation exposure is low. Stool test for blood is the most easily available and cheapest but not the most sensitive. May need to be done on more than one sample. Any positive results for stool blood test need to be followed up by a colonoscopy.

Any screening test apart from colonoscopy, when positive has to be followed up with a complete colonoscopy.

How frequently is the screening required in average risk person?

Conventional stool test for blood should be done frequently like in annual health check up. FIT, also a stool based test is repeated every 3 years. Colonoscopy is done once in 10 years. CT colonography / virtual colonoscopy is repeated every 5 years. Sigmoidoscopy is repeated every 5-10years. A combination of tests like FIT & sigmoidoscopy may allow one to avoid a colonoscopy.

Patients with known high risk factors should undergo screening more frequently depending on patient condition, personal & family history & physician discretion.

Patients above 75 years of age are screened based on fitness and expected life expectancy.

When should you suspect a possibility of colonic polyposis syndrome?

If there are multiple polyps (>20) especially at younger age (before forty) with or without involvement of other organs like brain & thyroid, one should rule out a polyposis syndrome. These patients may have more than 100 polyps and have a very high chance of developing cancer at young age. Such a patient is carefully worked up (family history, genetic analysis, features of other organ system – thyroid / brain etcetera) for polyposis syndrome. If established then family members (especially 1st generation) at risk are also counseled and encouraged to undergo work up to rule out polyposis / similar syndrome in them.

What special investigations are required in patients suspected with polyposis syndromes?

Patients with personal and family history / clinical suspicion of polyposis need special genetic studies to assess familial / hereditary problems. This is especially true for younger patients (<40 years of age). These include mutation in APC gene, MUTyH mutation and some uncommon gene mutations (Gene panel for colon cancer, multigene panel).

Patient with polyposis syndromes may require investigations for other organ systems, endoscopy for polyps in stomach & duodenum etcetera

What are the investigations done after detection of colorectal cancer?

Once diagnosed all nonemergency patients need important investigations like colonoscopy & biopsy, CT / MRI scan of chest, abdomen & pelvis, tumor markers (CEA), special tests on biopsy specimen before surgery or tumor specimen after surgery (IHC—MMR/MSI, genetic / mutation studies – RAS/RAF/HER2/NTRK -- if disease is in advanced stage as it helps in deciding on chemotherapy drugs). In very selected cases PET-CT scan is done too.

Patients with personal and family history or clinical suspicion of polyposis with cancer need special genetic studies to assess familial / hereditary problems. This is especially true for younger patients (<40 years of age). Genetic study is also advised if pathology suggests a de novo mutation.

On investigations the tumor could be in the form of a malignant polyp to a small /medium / large sized tumor which may or may not have spread locally or to distant organs. In polyposis cases the number of polyps could be form 10 to hundreds depending on type of mutation. One or many (multicentric) could be malignant at the same time and it is very difficult to pinpoint unless cancer is obvious. The CT / MRI scans show the local & distant staging of the cancer. Based on the clinical staging, patient fitness, age and many other factors the treatment is decided.

What is the importance of stage of cancer and how is it decided?

Stage of cancer suggests whether cancer is localized and curable or is advanced. Stage gives an indication whether patient will need & benefit multidisciplinary treatment like combination of surgery, chemotherapy and radiotherapy. Clinical staging and postoperative pathological staging can be different. Clinical staging is decided by the extent of tumor growth locally, extent of involvement of lymph nodes, spread of disease inside the abdomen and extent to which distant organs like liver, lungs, brain, bone etcetera. Clinical staging is based on imaging findings. Staging guides the treatment, indicates survival & suggests the prognosis.

What is the treatment for benign non-syndromic colorectal polyp?

Isolated small polyp/s (<10 in number) is/are usually removed in toto when possible, sent for histopathological confirmation that there is no cancer / high risk features and then no further treatment is usually necessary especially in average risk individuals (>50 years and without family history of polyposis or colorectal cancer). Yes patient will need surveillance later. This is easily possible for smaller polyps. Benign appearing polyps more than 1 cm in in size should also be removed endoscopically in entirety whenever possible and subjected for pathological examination. Once the benign nature is established then average risk patients are advised a surveillance program (colonoscopy once in in 5 or 10 years). In experienced centers multiple polyps are also removed endoscopically.

Large or difficult benign polyps (after initial biopsy confirmation) need special endoscopic procedure (EMR / ESD ) for removal. These procedure need advanced equipment / set up, skills, experience, back-up support for difficult situations and complications; hence these should be treated only at specialized centers. After final histopathological confirmation of benign nature, again the surveillance instructions are given. If the final histopathology shows evidence of cancer then the polyp is considered a malignant / cancerous polyp and treatment is adjusted accordingly.

What are the possible complications in the endoscopic treatment of polyps?

Simple biopsy or snaring is usually not associated with complications except rare chance of bleeding which is usually controlled easily through endoscope. However special procedures like EMR / ESD done for larger polyps have more risk of bleeding and perforation of intestine.

What is the surveillance / follow up protocol suggested for patients with polyps & IBD?

All patients with benign polyp/s are followed up at regular intervals (3-6 months / 6-12 months / yearly / 3 yearly / 5 yearly / 10 yearly) based on age / risk assessment, associated conditions like acive ulcerative colitis, primary sclerosing cholangitis etcetera.

What is the surveillance / follow up protocol suggested for patients with Lynch syndrome?

Lynch syndrome is a disease where a patient is more prone for cancer of multiple organs like colon, rectum, uterus, ovary, stomach, pancreas, duodenum, prostate, kidney etcetera. Hence surveillance in these patients involves multiple organ systems.

When do you need surgery for a benign polyp?

Some difficult polyps are unsuitable for endoscopic treatment and an upfront surgery is performed by open or laparoscopic or robotic way. Patient may develop a complication like perforation of intestine after endoscopic resection of a difficult polyp necessitating an emergency surgery. If an early malignancy is detected on final histopathology, then patient will need a surgery even after a successful endoscopic resection. Patients diagnosed with polyposis syndromes may need a complete removal of large intestine as they are prone for early malignancy.

What is the treatment of a malignant polyp?

A malignant polyp is a colorectal cancer & is treated on internationally accepted guidelines for colorectal cancer. This includes a pathology review of the biopsy, tumor markers in blood, molecular studies on biopsy specimen, imaging (MRI, EUS) investigations for staging before endoscopic removal (exceptional circumstances – very early cancer, medically unfit patient), local surgical removal or a major colorectal resection based on risk assessment / stage. Endoscopically / local surgically removed malignant polyps again are reviewed in detail with the pathologist and patient may be advised a formal surgery if needed on the risk assessment.

What is the treatment of colorectal cancer & what is the nature of surgery?

The treatment may be an endoscopic removal of malignant polyp as mentioned before, transanal removal of polyp, robotic / laparoscopic / open surgery (colorectal resection) depending on size, location, depth, extent, pathology, stage, availability of expertise, experience, knowledge of the subject and infrastructure . Extent of colorectal resection can range from a small colectomy to a complete proctocolectomy.

Patients in early stage are suitable candidates for upfront surgery and a surgery is accordingly performed. Occasionally the histopathology shows a higher stage / risk factors than expected in which case patient needs postoperative chemotherapy and / or radiotherapy.

Some patients are not suitable for immediate surgery due to local or systemic spread or as a protocol based on stage of disease. These patients need chemotherapy or short course radiotherapy or a long course combination of chemo and radiotherapy as a pre-surgery treatment (neoadjuvant) or as a palliative treatment. When used as pre-surgery this course may take 2-3 months or longer (except short course RT) followed by a restaging / reassessment for surgery. The restaging involves many blood and imaging investigations. If suitable, patient undergoes surgery and it is followed by further course of chemotherapy. Very selected patients are given only short course radiotherapy prior to surgery, which is completed 8-10 days later or after 7-8 weeks. Most patients except those in very early stage will require postoperative chemotherapy for 3-6 months.

Those patients that do not respond to initial line of chemotherapy are then shifted to second line therapy. Some patients require expensive special anticancer drugs (monoclonal antibodies). This is often seen in patients with widespread / metastatic disease. In patients with locally advanced disease sometimes a major resectional procedure involving multiple organs like bowel, urinary bladder, uterus & vagina, part of sacral bone is needed which has significant risk of complications (anastomotic leak, bleeding, infections, need to live with a stoma, urinary and sexual dysfunction) and risk to life.

Patients with spread to liver & / or lung often benefit from surgery (liver &/or lung resection) & / or ablative therapy (Radiofrequency ablation) if the disease is suitable for surgical treatment / ablation / combination. Sometimes this surgery is done simultaneously with the surgery for the primary tumor. However often this has to be done in multiple stages.

What is the treatment for polyposis syndrome with or without colonic cancer?

Patients diagnosed at young age with huge number of polyps are at high risk of developing colorectal cancer at young age. Hence these patients are advised to undergo a prophylactic surgery even if they are asymptomatic (picked up in screening when known family history present). This surgery involves complete removal of colon and rectum at risk of developing polyps followed by joining of small intestine with anal canal. Few patients are at risk of requiring a temporary or permanent stoma (end ileostomy – bringing the end of small intestine to the surface). Few patients have their rectum relatively spared of polyps and opt for a surgery where rectum is preserved and entire colon is removed. Small intestine is then joined to rectum. These patients require diligent frequent screening of the remaining rectum. A second surgery to remove this remnant rectum may also be necessary.

If a colorectal cancer patient is detected with polyposis at the time of investigations, the surgery is like any polyposis patient i.e. a complete removal of colon and rectum is advised and performed preferably unless again rectum is spared in which case small intestine is joined to rectum. The option of sparing rectum is not available when cancer involves the rectum itself. All cancer surgery principles (mentioned later) are followed when cancer is diagnosed.

What is the treatment for colorectal cancer in IBD patient?

Patients with colorectal cancer and IBD are advised a complete removal of colon and rectum and joining of small intestine to the anal canal. Occasionally patient may need a permanent stoma after surgery. In some patients rectum may be left behind, however such patients need good monitoring later.

What is the treatment of patients with liver metastasis?

Patients with colorectal cancer liver metastasis are a special group. If the disease is very limited in liver at the time of 1st diagnosis, an upfront surgery / ablation can be done separately or along with the surgery for primary tumor. However this is possible in very few cases.

Most patients with liver metastasis (whether diagnosed initially or at a later stage) will require chemotherapy as the initial treatment and depending on the response a surgery / ablation may be considered at a later stage. The surgery includes various types of liver resections from minor to major to extensive liver resection. Sometimes percutaneous vascular interventions are needed before surgery to enlarge the portion of liver that will remain with the patient after the surgery. In such cases surgery is performed in stages. In very rare cases liver transplantation may be considered. Patient will require chemotherapy after liver resection too. Occasionally internal radiation therapy may also be used, via percutaneous intervention. All this makes the treatment extremely expensive.

What is the treatment of patient with lung metastasis?

Principles of treatment are similar to liver metastasis due to colorectal cancer i.e. surgery or ablation wherever possible. Otherwise chemotherapy is the mainstay of treatment. Occasionally radiation therapy can be used.

What is the treatment if the disease has spread in abdomen / peritoneum?

Few patients are suitable candidates for surgery even when there is peritoneal disease, which can be surgically removed. Some of these patients present with intestinal obstruction and may need bowel resection with or without a stoma. This is followed by chemotherapy. However extremely spread peritoneal metastasis with ascites is often a terminal disease and family should be convinced that one should accept the fate.

What is the role of specialized GI Pathologist?

Pathology specimen needs assessment from a skilled gastrointestinal pathologist just the way the endoscopy / surgery is done by specialized gastrointestinal surgeon. Hence a second opinion & further tests may be asked on biopsy / surgery specimen.

What are the complications of colonic / rectal surgery (resection)?

Colon /rectal resection surgery is a major surgery. It involves removal of a portion of large intestine followed by joining the two ends. This may involve some blood loss needing blood transfusion; although it is avoided whenever possible.. The most important complication of this surgery is nonhealing of the anastomosis (joining the intestines). This leads to a leak and infection. This requires an emergency colostomy / ileostomy (protective surgical measure) to allow the intestines to heal without further damage and control infection. However if not done in time, it can become life threatening.

Apart from this other complications include bleeding from the suture line, infections, postoperative intestinal obstruction, urinary & sexual dysfunction etcetera.

What is the role of RT in colorectal cancer?

Radiation therapy has a very important role to play in the treatment of rectal cancer. It is given preferably in the preoperative period when felt necessary based on clinical stage of the disease. It is usually combined with chemotherapy and goes on for 5 weeks. Surgery is performed 4-6 weeks after course is completed. Sometimes only a short course of radiotherapy is given over 5 days without any accompanying chemotherapy. Surgery is performed 7-10 days later. Sometimes radiotherapy is given postoperatively provided it was not given in the preoperative period and the need to give is felt on postoperative final staging. Occasionally RT is given as palliative treatment for pain when disease is advanced or recurrence after surgery.

Radiotherapy is rarely used in the treatment of colonic cancer. There are few indications in case of advanced cancer.

Radiation therapy has many technical advances in the form of image guidance, intensity modulation, protection of surrounding organs etcetera. To get the best of these advantages and minimize the side effects, it is important to be at centers with good setup and expertise.

What is the role of chemotherapy in colorectal cancer?

Chemotherapy has a very important role in treatment of both colon and rectal cancer. Chemotherapy in the preoperative period (neoadjuvant) is especially required for rectal cancer and tumors that have already spread to distant organs like liver and lung. Chemotherapy in the postoperative period (Adjuvant) is given based on pre & postoperative staging and is required in most of the patients except those who are in very early stage of disease.

Multidisciplinary cancer care involves aggressive chemotherapy in the postoperative period or to downstage the disease (inoperable & / or unresectable disease to operable & resectable disease – neoadjuvant treatment) before any surgery. A chemoport (surgery) is inserted for delivering the chemotherapy to avoid problems of venous access. In neoadjuvant setting, chemotherapy is followed by a curative surgery where possible. Surgery is again followed by multiple cycles & lines (1st line, 2nd line etcetera) of chemotherapy. It is especially useful in young &/or fit patients with aggressive cancer disease. These patients can withstand the demanding nature of this treatment regime and may have better survival. A typical neoadjuvant chemotherapy (often with radiotherapy for rectal cancer) goes on for 3 months and then patient is reassessed for a possible surgery. Post-surgery chemotherapy is restarted as early as possible (4-5 weeks) and goes on for further 3-4 months.

Chemotherapy is also used in palliative setting for inoperable advanced disease

What decides the survival of a patient with colorectal cancer?

Stage of disease (extent of tumor spread), patient’s general condition / fitness / performance score, tumor biology (aggressiveness), genetic status are some of the most important factors that decide the survival.

What is the follow up required for operated patient?

Patients are followed up at interval of 3 months in 1st year with blood investigations & imaging. Endoscopy is repeated at the end of 3-6 or 12 months depending upon the status of preop endoscopy. Intensive follow up is done in 1st 2 years and is reduced later.

What are the treatment options if there is recurrence of cancer?

Recurrent cancer treatment depends upon the site of recurrence. Treatment in liver or lungs are treated as previously discussed with a combination of chemotherapy, surgery, & ablation. Selectively radiotherapy is also used.

For recurrence at local site (intestine / pelvis), a combination of chemotherapy, surgery and selectively radiotherapy is used. If surgery is possible a major resectional procedure involving multiple organs like bowel, urinary bladder, uterus & vagina, part of sacral bone is needed which has significant risk of complications (anastomotic leak, bleeding, infections, need to live with a stoma, urinary and sexual dysfunction) and risk to life.

Many more questions can come to the mind of a patient or relatives depending on the situation and the treating doctor would be in the best position to answer them.

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