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Rectum

1. Screening

Reviewed 05 Sept 2012

For the ‘average-risk’ population

  • Average risk individuals are those with no additional personal or familial risk factors for colorectal cancer, other than age greater than 50 years.
  • Several randomized studies have shown significant reduction in mortality from colorectal cancer in persons over 50 years of age who were screened by fecal occult blood testing (FOBT).
  • Other accepted modalities include fecal immunochemical testing (FIT), flexible sigmoidoscopy (with or without FOBT) and colonoscopy.
  • Modalities such as computed tomography colonography, and fecal DNA, are not consistently accepted as screening tools at this time.
  • Patient preference and resource availability should guide selection of a single screening method, but the best evidence recommends that FOBT of asymptomatic individuals between age 50 and 75 be performed every one or two years.
  • Positive tests on FOBT, FIT and flexible sigmoidoscopy should be followed by evaluation of the entire colon with colonoscopy.
  • If available, screening should be conducted within an organized program incorporating quality assurance and equitable access rather than opportunistic screening.
  • Recommendations for routine screening in British Columbia have been developed and approved by MSP (see BCGuidelines.ca - Gastrointestinal System).
  • Additional information regarding the provincial colorectal cancer screening initiative is available on the BCCA Colon Screening Program website.

Inflammatory Bowel Disease

  • Risk of colorectal cancer in IBD depends on IBD-related factors such as disease extent, disease duration, dysplasia, concomitant primary sclerosing cholangitis, and non-IBD factors including family history of colorectal cancer.
  • Specific recommendations regarding frequency and type of screening is generally as per the treating gastroenterologist.

Hereditary/Genetic Syndromes

  • Approximately 10% of patients with colorectal cancer display a hereditary pattern.
  • Persons with one or more first-degree relatives diagnosed with colon or rectal cancer should consider screening at age 40 with colonoscopy.
  • Hereditary nonpolyposis colorectal cancer (HNPCC or Lynch syndrome) accounts for 1-3% of all colorectal cancers, and displays an autosomal dominant pattern of inheritance. Due to germline mutations of the mismatch repair genes, the resulting microsatellite instability is clinically manifested by a lifetime risk of colorectal cancer between 40-90%, earlier presentation of colorectal cancer (compared to sporadic), and increased risk for extra-colonic malignancy. Individuals satisfying the Bethesda criteria (see BCCA Hereditary Cancer Program (HCP)) should be tested for HNPCC and if confirmed, be enrolled in a surveillance program of colonoscopy beginning at 20-25 years of age among mutation carriers, and then every 1-2 years. Extra-colonic cancer screening is also recommended.
  • Familial adenomatous polyposis (FAP, including Gardner Syndrome) is responsible for 1% of colorectal cancer presentations, and is secondary to mutations of the adenomatous polyposis coli (APC) gene. Inherited in an autosomal dominant pattern, individuals develop 100-1000 adenomatous colonic polyps by the second to third decade of life, with a 90% risk of progressing to colorectal cancer. Diagnosis is established by genetic testing. Individuals at risk (carriers or indeterminate relatives) are recommended to have yearly flexible sigmoidoscopy beginning at puberty. Once polyposis is identified, colectomy should be performed, as the risk then rises to 100%. If there is rectal sparing, a subtotal colectomy with ileorectal anastomosis can be performed. If not, a total proctocolectomy with ileal pouch-anal anastomosis or end ileostomy should be performed. Gastric and duodenal polyps and ampullary cancer are at increased risk of development, and should be screened for with esophagogastroduodenoscopy and biopsy.
  • Relatives of individuals with genetically confirmed mutations should also be tested.
  • Please refer to the BCCA Hereditary Cancer Program (HCP) for description and indications for referral to HCP regarding:
    • Hereditary Colorectal Cancer
    • Familial Adenomatous Po​lyposis and other polyposis syndromes


2. Diagnostic and Staging Work-Up

​Reviewed 16 October 2012

  • ​​In the absence of bowel obstruction at presentation, a complete colonoscopy to the cecum with adequate bowel preparation should be performed to identify and biopsy any suspicious intraluminal masses and to exclude any synchronous neoplastic polyps or cancers.
  • Preoperative determination of tumour height is essential in determining whether neoadjuvant radiation (with or without chemotherapy) is required. In general, tumours located in the upper rectum above peritoneal reflection (usually > 12 cm from the anal verge) may not benefit from preoperative radiation, although more advanced tumours may be radiated after multidisciplinary evaluation by the radiation oncologist, surgeon, and other treating physicians. Measurement of tumour distance from the anal verge in cm should be documented. Measurements, in decreasing order of reliability are: rigid sigmoidoscopy, flexible sigmoidoscopy/colonoscopy, endorectal ultrasound (which can often overestimate height), digital rectal examination (for low lying tumours), and pelvic imaging with CT or MRI. Tumours should be assessed on digital rectal examination as palpable or not and if palpable, mobile or fixed.
  • Accurate preoperative tumour staging is essential to guide preoperative therapy. Patients with stage I tumours (T1/2, N0) do not benefit from pelvic irradiation and should proceed directly to surgery. A digital rectal examination, one of endorectal ultrasound, endoscopic ultrasound or pelvic MRI (with rectal cancer protocol) are recommended to accurately assess the clinical stage and determine the extent of pelvic disease (e.g. depth of invasion, lymph node involvement, involvement of adjacent structures and proximity to mesorectum).
  • Preoperative serum carcinoembryonic antigen (CEA) tumour marker is recommended to guide subsequent follow-up.
  • Preoperative CT scan of the chest, abdomen and pelvis is recommended to exclude distant metastases and to provide a baseline for surveillance.
  • PET scans are not recommended for staging purposes.
  • In patients with unresectable disease, core biopsy of accessible primary or metastatic lesions (e.g. liver metastasis) is recommended. Consider that predictive biomarker studies for newer targeted agents require a sufficient amount of tissue; fine needle aspirates are deemed to be insufficient in this setting.
  • Although the role of this technique is still under study, computed tomography colonography (CTC) may be an option for patients unable to undergo a conventional colonoscopy. CTC, also known as Virtual Colonoscopy, is a total colonic imaging tool utilizing a specialized multislice CT scanner. This relatively brief procedure does require bowel preparation and insufflation of carbon dioxide gas. The examination occurs during a single breath hold of 10 seconds or less. Although CTG is minimally invasive and has low radiation exposure, the availability of the procedure is limited. As well, the test does not permit concomitant biopsy or polyp removal.

3. Primary Surgical Therapy

Revised 16 October 2012

Please see the Colorectal Cancer Care​ Map for Physicians (below) developed by the BCCA Surgical Oncology Network and the accompanying text which is included in 8. Appendix.

  • Neoadjuvant (preoperative) radiation therapy (with or without chemotherapy) for patients with clinical stage II or III rectal cancer is the preferred option as preoperative chemoradiation is less toxic and more effective than post-operative therapy. Referral for a Radiation/Medical Oncology consultation at the time of diagnosis is recommended.
  • For patients with localized disease, the surgical standard of care is transabdominal resection with negative proximal, distal, and circumferential margins.
    • For upper rectal tumours, a 5cm proximal and distal resection margin is standard (anterior resection), with en bloc lymphadenectomy (achieved by resecting the mesorectum to the distal rectal margin) and removal of all clinically suspicious lymph nodes outside the field of resection. Primary anastomosis is performed.
    • For mid and lower rectal tumours, a total mesorectal excision (TME) with intact mesorectal envelope is performed, along with removal of all clinically suspicious lymph nodes. Primary anastomosis may be performed if a minimum 1-2 cm distal margin can be achieved (low anterior resection). Diverting loop ileostomy is recommended for low anastomoses, though is left to the discretion of the surgeon.
    • For low rectal tumours where a 1-2 cm distal margin cannot be achieved, and abdominoperineal resection with permanent end colostomy is required
    • Involved adjacent structures should be partially or completely resected where necessary to achieve a negative circumferential resection margin.
  • Local, transanal resection may be considered in select circumstances where certain disease criteria are met or the patient is not a candidate for or refuses transabdominal resection (see below).
  • Malignancy found during pathologic examination of an endoscopic polypectomy specimen can be considered definitive therapy only if the polyp can be completely assessed (removed in one piece), the tumour is well- or moderately-differentiated, there is no lymphovascular or perineural invasion, and the deep margin to malignant cells is greater than 3mm.
  • In patients with obstructing or near-obstructing rectal cancer, a diverting loop colostomy may be performed to allow neoadjuvant radiation prior to definitive resection.
  • For those with metastatic disease, resection of asymptomatic primary tumours is not routinely recommended, although retrospective evidence is conflicting with some studies demonstrating an improved survival associated with resection of the primary tumor. Palliative resection of the primary tumour, palliative (chemo)radiation or creation of a defunctioning loop colostomy may be done in patients with obstructive, hemorrhagic, or otherwise symptomatic rectal cancers. For selected patients with single organ metastases (stage M1a), resection of metastatic disease may be curative. Referral to the BCCA for multi-disciplinary review is recommended.

 

4. Pathology

​Revised 05 Sept 2012

(per College of American Pathologists 2012)

Specimen: specify

  • Type
  • Procedure
  • Length

Tumour: specify

  • Site
  • Size
  • Macroscopic tumour perforation
  • Macroscopic intactness of the mesorectum
  • Histologic type
  • Histologic grade
  • Microscopic tumour depth of invasion
  • Margins: proximal, distal, circumferential
  • Treatment effect (if neoadjuvant therapy given)
  • Lymph nodes: number examined (minimum 12 recommended), number involved
  • Lymphovascular invasion
  • Perineural invasion
  • Tumour deposits (discontinuous extramural extension)
  • Type of polyp in which invasive carcinoma arose
  • pTNM per AJCC 7th Edition

Additional pathologic findings of interest:

Histologic features suggestive of Microsatellite Instability

  • Intratumoural lymphocyte response
  • Peritumoural lymphocyte response
  • Tumour subtype: mucinous, medullary, high histologic grade

Immunohistochemistry studies for Mismatch Repair Proteins

  • MLH1
  • MSH2
  • MSH6
  • PMS2

Mutational analysis

  • KRAS
  • BRAF

5. Staging

​Revised 16 October 2012


Please refer to the American Joint Committee on Cancer (AJCC) staging guidelines or download the BCCA Staging Diagram and Classification Criteria (TNM) . 

6. Treatment Options by Stage

Revised 16 October 2012 

The tumor stage may be clinical (c) or pathological (p). A “yp” stage refers to tumors treated with pre-operative chemo-, radiation-, or chemo-radiation therapy which has the potential effect of “downstaging” a tumor that was previously classified as a higher clinical stage. In general, adjuvant therapy decisions are based on clinical stage with stage 0/I rectal tumors treated with surgery alone and stage II/III tumors treated with surgery, pre-operative radiation/chemoradiation and post-operative chemotherapy. Studies are underway to identify patients that may not require tri-modality therapy.

Stage 0 

Cancer is limited to mucosa without invasion of the lamina propria

  • Local, transanalexcision ​or endoscopic polypectomy with clear margins.
  • Transabdominal resection (Anterior Resection, Low Anterior Resection, Abdomino Perineal Resection) for larger lesions not amenable to local excision.

Stage I: T1-2, N0, M0

  • Transabdominal resection (AR, LAR, APR) with no requirement for neoadjuvant or adjuvant radiation therapy remains standard of care.
  • In patients whose medical comorbidities preclude formal transabdominal resection or who refuse major surgery despite counseling, local, transanal excision may be considered on a case by case basis. It is recommended that treatment with local excision only (for example Transanal Endoscopic Microsurgery) be offered in experienced centers only and should consider clinical as well as pathologic criteria (T1 lesion, well or moderate differentiation, size less than 3 cm, and absence of lymphovascular or perineural invasion, node-negative on preoperative imaging, and ability to achieve negative deep margin of at least 3mm). Postoperative radiation therapy is generally considered after local excision has been carried out.

Stage II: T3, N0, M0

  • Referral to Radiation/Medical Oncology for neoadjuvant (preoperative) radiation therapy (with or without chemotherapy) is recommended.
  • For non-fixed tumours in the upper two-thirds of the rectum: neoadjuvant short-course radiation therapy (2500cGy in five fractions) to be followed by LAR or APR within approximately ten days of the first day of radiation. (T3N0 tumours in the upper third of the rectum that have predicted clear radial margins may not benefit from radiation).
  • For any fixed rectal tumours, rectal tumours approaching the mesorectal margin, and for tumours in the distal third of rectum: neoadjuvant long-course radiation therapy (4500cGy in 25 fractions with a possible boost of 540 cGy in 3 fractions) with concurrent chemotherapy to be followed by LAR or APR six to ten weeks following the completion of neoadjuvant therapy.
  • Adjuvant capecitabine is given for 6 months following short-course radiation therapy (GIRCAP) or for 4 months following long-course chemoradiation therapy (GIRCRT).
  • Adjuvant chemotherapy should start as close to four weeks post-op as possible.
  • Patients treated with upfront resection and with pathologic Stage II rectal cancer should be referred to BCCA medical oncology and radiation oncology for postoperative adjuvant chemotherapy and radiation treatment (GIRCRT).
  • See Stage III adjuvant chemotherapy recommendations for patients with ypN+ disease
  • Consider treatment in a clinical trial, if available.

Stage III or T4NX: T4 or Tany, N+1,M0

  • Referral to Radiation/Medical Oncology for neoadjuvant (preoperative) radiation therapy (with or without chemotherapy) is recommended.
  • For mobile, non-fixed tumours in the upper two-thirds of the rectum: neoadjuvant short-course radiation therapy (2500cGy in five fractions of the first day of radiation) to be followed by LAR or APR within approximately ten days of the first day of radiation. Long-course chemoradiotherapy may also be used.
  • For any fixed rectal tumours, rectal tumours or lymph nodes approaching the mesorectal margin, and for tumours in the distal third of rectum: neoadjuvant long-course radiation therapy (4500cGy in 25 fractions with a possible boost of 540 cGy in 3 fractions) with or without concurrent chemotherapy to be followed by LAR or APR six to ten weeks following the completion of neoadjuvant therapy.
      • Adjuvant chemotherapy is given for 6 months following short-course radiation therapy or for 4 months following long-course chemoradiation therapy. Standard of care options include capecitabine or modified FOLFOX6. Current evidence does not specify optimal post-operative systemic therapy. There is some evidence that patients who achieve good downstaging (T0-2, N0) benefit from adjuvant 5-FU based therapy. Capecitabine is recommended for patients with ypT0-2N0 disease.
      • mFOLFOX6 is considered for patients with ypTanyN+ disease as these patients are known to be at high risk of distant relapse.
      • Patients presenting with advanced clinical stage (bulky T or N stage, T4 or N2) who achieve good downstaging may be considered for either capecitabine or FOLFOX.
      • Please refer to current treatment protocols for indications, dosing and eligibility criteria.
  • Adjuvant chemotherapy should start as close to four weeks post-op as possible.
  • Patients treated with upfront resection and with pathologic Stage III rectal cancer should be referred to BCCA medical oncology and radiation oncology for postoperative adjuvant chemotherapy and radiation treatment (GIRCRT).
  • Consider treatment in a clinical trial, if available.

Stage IV: any T, any N, M1

  • In spite of the presence of metastases, excision of the primary tumour may provide the best form of local palliation. In appropriate circumstances, operation may be facilitated by preoperative chemotherapy and radiation.
  • Locoregional/organ specific directed therapy may be considered for patients with isolated liver or lung metastasis. Referral to the BCCA for multi-disciplinary assessment is recommended.
  • Palliative radiation therapy or stereotactic body radiation therapy (SBRT) in selected patients; referral of SBRT patients to the BCCA for multi-disciplinary assessment is recommended.
  • Palliative chemotherapy has been shown to significantly improve survival in patients with unresectable metastatic colorectal cancer achieving an estimated median overall survival of 24 to 28 months as compared to 6 to 12 months with supportive care alone. Currently approved chemotherapeutic agents for metastatic colon cancer include: capecitabine, 5-fluorouracil (5-FU), irinotecan and oxaliplatin.
      • The most commonly used regimens are:
        • oxaliplatin with 5-FU (FOLFOX) or capecitabine (CAPOX)
        • irinotecan with 5-FU (FOLFIRI) or capecitabine (CAPIRI)
        • capecitabine monotherapy
      • The choice and sequence of chemotherapy is determined by disease-related factors, patient factors and patient preferences as assessed by the medical oncologist.
  • Currently approved targeted therapies include: bevacizumab, cetuximab, and panitumumab.
    • Bevacizumab is recommended for use in combination with first-line FOLFIRI chemotherapy (FOLFOX may be considered in selected circumstances). It may also be considered for use in combination with second-line doublet chemotherapy for those patients who did not receive it in first-line.
    • Cetuximab or panitumumab is indicated in patients with previously treated metastatic colorectal cancer with wild-type K-ras gene (i.e. tumour K-ras gene is not mutated).
  • Please refer to current treatment protocols for indications, dosing and eligibility criteria.
  • Consider treatment on a clinical trial, if available.
  • Symptom management, best supportive care, and involvement of palliative care services as indicated by patient’s clinical status.

 


6a. Liver Limited Metastatic Colorectal

Updated 10 April 2013

Note – non liver organ confined or oligo-metastatic (eg. Lung) disease should be reviewed in a multi-disciplinary setting.

Diagnostic and Staging Work-up

  • Diagnostic and staging work-up is similar to the rectal and colon guidelines. When liver lesions are determined on the staging work-up, the following imaging work-up is recommended.
  • Accurate staging is needed to determine the suitability of the patient for potential resection as well to determine the systemic management.
  • Preoperative serum carcinoembryonic antigen (CEA) tumour marker is recommended to guide subsequent follow-up.
  • Staging should incorporate contrast enhanced CT Chest/Abdomen/Pelvis preferably.
  • PET/CT should be considered for surgical operable disease to rule out extrahepatic disease.
  • If CT scan shows unresectable extrahepatic disease – should not proceed with PET/CT.
  • Contrast enhanced MRI with Primavist for equivocal lesions less than 1 cm should be performed to characterize malignant lesions.
  • Staging work-up should be performed prior to the start of systemic therapy.
  • Imaging should be performed within 6-8 weeks of a surgical decision ideally.


Surgical Therapy

  • In patients who have a symptomatic primary, it is reasonable to consider primary resection to alleviate the symptoms. This should be discussed with a Medical Oncologist and if possible reviewed in a multidisciplinary setting.
  • At the time of diagnosis of operable metastatic disease – a referral to a HPB surgeon should be considered.
  • If the choice of chemotherapy is influenced by the resectability of the lesion – then the surgical consult should be performed prior to treatment.
  • The sequence of surgery should be discussed in a multidisciplinary role depending on extent of disease, symptoms and response to therapy.
  • The minimal requirements for consideration of liver resections are:
    • Two adjacent hepatic segments 
      (excluding caudate lobe) 
      free of tumor
    • Biliary drainage
    • Arterial inflow
    • Non-thrombosed portal vein
    • 20% or more liver functional reserve
  • Upfront liver resection followed by post-operative chemotherapy vs. peri-operative chemotherapy with liver resection are both reasonable options to consider (see Systemic therapy).
  • Adjunctive conversion procedures such as portal vein embolization (PVE) may be performed in the setting of complex resection or those resections that may require a disproportional percentage of the liver to be resected however should be reviewed and performed on a case by case basis, subject to multidisciplinary review involving medical oncology, surgical oncology and radiology.

Systemic Therapy

  • Patients diagnosed with metastatic disease should be referred to a medical oncologist.
  • For resectable liver limited mCRC, systemic therapy should be considered in either a peri-operative or post-operative setting.
  • Initially unresectable patients should still be considered for local regional strategies if there is a reasonable response and should be reviewed in a multidisciplinary setting.
  • Patients should be assessed by HPB surgeon early in their course of chemotherapy or prior to commencement of chemotherapy.
  • There is no single optimal choice of chemotherapy for peri-operative/post-operative treatment.
  • 5FU/Oxaliplatin or 5FU/Irinotecan or 5FU based chemotherapy can be considered.
  • Steatohepatitis caused by irinotecan can interfere with surgery and therefore should be discussed with the surgeon if used – therefore, it is preferable to consider oxaliplatin based treatment.
  • Irinotecan is NOT a contraindication for surgery and can be considered if the patient is felt to be oxaliplatin resistant or ineligible.
  • Bevacizumab and EGFR monoclonal antibody therapy are still considered investigational in the setting of upfront resectable liver metastases.
  • In borderline patients who are being considered for conversion – biologic therapy in combination with chemotherapy are an option to consider depending on the approval of the GI systemic therapy group.
  • If bevacizumab is used – it should be discontinued at least 4-6 weeks prior to surgery due to wound healing concerns with this medication.
  • Chemotherapy should be discontinued at least 4 weeks prior to surgery.
  • Patients should be reviewed by their medical oncologist after surgery and depending on patient fitness and comorbitiies, chemotherapy should be consider 4-6 weeks after surgery to complete a total of 12 cycles of treatment (or 6 months).

Role of other local regional strategies:

Local Ablation Therapy

  • Patients who are eligible for surgery should be considered for a surgical resection.
  • If there are less than 3 target lesions and each lesion measures less than 3 cm, ablation can be considered in patients who are not optimal surgical candidates.

Stereotactic Body Radiotherapy (SBRT)

  • Reserved for liver metastases that are not eligible for surgical resection or RFA.
  • Patients who have had a cancer recurrence after either surgery or RFA and are medically or surgically ineligible or those that refuse surgery
  • Eligible patients are those with tumors not to exceed 6 cm in diameter, with no more than 3 liver tumors, and Child’s Pugh Grade A (or very early CP Grade B) function.

Embolic therapy

  • Radioembolization – ongoing data is pending with respect to this therapy and at present is not a funded option.
  • Chemoembolization is an evolving therapy and not formally recommended.

Follow-up

  • There are no standard guidelines for follow-up. The reason for follow-up is to detect liver limited recurrence that may be amenable for future local regional treatment.
  • A contrast enhanced CT scan of the Chest/Abdo/pelvis should be performed within 3 months of the procedure.
  • No standard guidelines currently exist for surveillance in Stage IV NED and are as determined by the treating oncologist. However, at the treating physician’s discretion, follow up per BCCA colorectal surveillance guidelines for stage II & III can be considered. This schedule can also be modifed at the treating physician’s disc​retion.
  • Follow-up and Surveillance of Colon Cancer Patients Treated with Curative Intent
  • Follow-up imaging – CT scan of the Chest/abdo/pelvis (contrast enhanced) should be considered every 3-6 months for the first 3 years and then annually for a further 2 years.
  • A CEA can be considered every 3 months for the first 3 years then every 6 months for 2 further years.
  • Colonoscopy should be performed as per adjuvant guidelines.

7. Follow-up and Surveillance of Rectal Cancer Patients Treated with Curative Intent

Revised 1 February 2014

Following completion of definitive surgery and chemotherapy, patients are typically advised to undergo a surveillance program for a period of up to 5 years, except colonoscopy, which should continu​e while the patient is a candidate for treatment should a metachronous or recurrent cancer be found. This is typically managed under the direction of their primary care provider.

Stage 0-I:

  • If complete colonoscopy was not performed at time of initial cancer diagnosis, it should be completed within 6 months to rule out metachronous lesions. Otherwise, repeat colonoscopy is recommended in one year, and if normal, in three years, and if normal every five years thereafter.
  • For patients with specific genetic syndromes, the American Gastroenterological Association guidelines should be followed.
  • No evidence of improved survival with routine imaging or blood work.

Stage II-III:

  • History and physical examination every three to six months for the first three years and then every six months for two additional years. Rectal examination at least annually. 
  • If the patient is a potential candidate for hepatic or pulmonary metastatectomy:

  1. Carcinoembryonic antigen (CEA) tumour marker level should be checked at each follow-up visit 
  2. If CEA is elevated, repeat test within 28 days 
  3. Abdominal and pelvic imaging (CT preferred or ultrasound if CT contraindicated or not available) should be done once a year during the 5 years of follow-up
  • If complete colonoscopy was not performed at time of initial cancer diagnosis, it should be completed within 6 months to rule out metachronous lesions. Otherwise, repeat colonoscopy is recommended in one year, and if normal, in three years, and if normal every five years thereafter. 
  • If the patient is not a candidate for metastatectomy, CEA and routine imaging studies are not recommended as there is little to no utility in diagnosing an early metastatic recurrence in an asymptomatic patient. 
  • If the patient is found to have an elevated CEA and/or signs and symptoms of recurrent colon cancer, imaging of the thorax, abdomen and pelvis should be done and a re-referral to the primary oncologist is indicated. 
  • Other imaging and routine blood work are not recommended in follow-up, but may be appropriate in a patient with symptoms suggestive of recurrence.

Stage IV treated with curative-intent metastatectomy (Stage IV NED)

  • No standard guidelines currently exist for surveillance in Stage IV NED and are as determined by the treating oncologist.
  • May follow the recommendations as per Stage II-III.

8. Appendix - Colorectal Cancer Care Map for Physicians

​Revised 05 Sept 2012

This care map in section 6.3 was developed by the Colorectal Surgical Tumour Group of the BC Cancer Agency Surgical Oncology Network. Its intention is to outline the typical approach to the investigation and management of the colon and rectal cancer, highlighting the role of the surgeon in the process. The care map is not intended as a substitute for the advice, expertise or professional judgment of a physician trained in the management of colorectal cancer, nor is it intended to be the only approach to the management of colon and rectal cancer.

This colorectal cancer care map reflects the steps that a typical patient follows in the diagnosis and treatment of colorectal cancer in BC. Of course, certain nuances of the disease and patients with atypical symptoms or complex disease may determine the need for additional or different steps in the process of care. This care map is intended for surgeons, family doctors, medical and radiation oncologists, gastroenterologists, as well as other physicians, practitioners, and administrators, and highlights the surgeon’s role in the treatment of patients with colorectal cancer. It also may help to identify and overcome potential barriers to expeditious care.

The main steps outlined in the maps follow the patients from the suspicion of colorectal cancer to diagnosis through to treatment. A summary of post-treatment surveillance guidelines endorsed by the BC Cancer Agency Gastrointestinal Tumour Group is also included for reference.

Suspicion of Colorectal Cancer to Diagnosis

Patient’s Initial Presentation

A typical first step in the process is patient presentation to a family doctor with signs and/or symptoms consistent with colon or rectal cancer. These symptoms may include (but are not limited to) rectal bleeding or mass, abdominal pain, and altered bowel habit (constipation, diarrhea). Alternatively, asymptomatic patients with positive screening tests (fecal occult blood, fecal immunochemical test, contrast enema with “apple core” or other lesion, cancer found on screening colonoscopy) may be the point of entry. Screening may be based on family history or population-level programs (e.g., “Colon Screening Program" in BC). 

Investigations

The family doctor initiates the diagnostic process by referring to a surgeon (or gastroenterologist), who will direct further investigations and workup. Alternatively, the referral is occasionally made to the BC Cancer Agency if there is a high index of suspicion. The timeline for investigation will depend upon the degree of clinical suspicion for colorectal cancer. The diagnostic workup will include a colonoscopy and biopsy, conducted by a surgeon or gastroenterologist. Complete colonoscopy to the cecum with adequate preparation is required. If an obstructing tumour is found such that endoscopic evaluation of the entire colon is not possible, a completion colonoscopy should generally be performed within 3 to 6 months following resection to rule out synchronous neoplasms. Following pathology confirmation of colorectal cancer as biopsied endoscopically, a metastatic workup is undertaken. The submucosa distal to the tumour is often inked or tattooed endoscopically to facilitate intraoperative identification, particularly for small tumours.

For rectal cancers, accurate measurement of tumour height endoscopically or clinically is critical in judging whether the patient should receive neoadjuvant radiation (with or without chemotherapy). In decreasing order of preference, height can be measured by rigid sigmoidoscopy, flexible endoscopy, endorectal ultrasound (ERUS), digital rectal examination, and cross-sectional imaging (CT or MRI). Clinical fixity for low lesions may also help the decision for neoadjuvant therapy.

Diagnosis to Initiation of Treatment

Preoperative Imaging & Metastatic Workup

Staging investigations are promptly initiated following tissue confirmation of colorectal cancer. Although frequently directed by the surgeon, preoperative imaging can also be organized by the family physician, gastroenterologist, and/or oncologist to expedite the process. Ideally preoperative imaging should be performed within 2 weeks of definitive diagnosis. Serum carcinoembryonic antigen (CEA) is drawn during staging investigations.

Standard imaging consists of CT scan of the abdomen and pelvis and a chest X-ray. Some guidelines recommend CT of the chest rather than X-ray. Evidence that CT is better than chest X-ray is equivocal at this time. If CT is not readily available or the patient cannot receive intravenous contrast (due to allergy or renal impairment, for example), an ultrasound of the abdomen can assess for liver metastases. Other imaging studies are guided by symptoms or indeterminate lesions found on initial imaging and may include abdominal ultrasound, MRI, bone scan, spinal X-rays and CT of other regions, but none of these are considered routine in the absence of compelling symptoms. A PET-CT scan to rule out occult disease may be useful if resection of liver or lung metastases is being considered, as occult disease not identified by other modalities may preclude curative resection. However, PET-CT scan is not routinely recommended as a matter of course for all patients diagnosed with colorectal cancer.

Most patients with rectal cancer are referred to the BC Cancer Agency, usually by the surgeon after consultation and imaging. Additional imaging is indicated to obtain local T and N stage and to demonstrate relationship of the cancer to nearby pelvic organs. MRI is particularly useful for demonstrating the radial distance from the cancer to the mesorectal fascia, allowing prediction of the radial surgical margin. ERUS is beneficial to assess local invasion, including demonstrating the fat plane between the anterior wall of the rectum and the posterior aspect of vagina or prostate/seminal vesicles or involvement of the anal sphincters. ERUS is also particularly helpful in distinguishing T1 from T2 lesions in the case of superficial cancers being considered for local excision by the transanal route (see below regarding local excision). Interpretation of ERUS and MRI for rectal cancer is operator dependent and it is recommended that an experienced radiologist be involved. Patients with early rectal cancers (T1/2, N0) which do not require neoadjuvant therapy and will therefore proceed directly to surgery may not be referred to the BCCA at the surgeon’s discretion.

Multidisciplinary preoperative consultation is recommended for more complex patients including rectal cancer location less than 12 cm from the anus and colorectal cancer that might require en bloc multi-organ resection or resection of liver or lung metastases. Such a panel may include various surgeons (general surgeons, colorectal surgery subspecialists, surgical oncologists, hepatobiliary surgeons, urologists, gynecologic oncologists, and thoracic surgeons), radiation oncologists, medical oncologists, pathologists, and radiologists.

Decision for Curative versus Palliative Treatment

Curative resection is possible when the primary lesion is surgically resectable with clear proximal, distal, and radial margins. Limited distant metastases to the liver and lungs can also be resected with curative intent. Colon cancer and stage I rectal cancer (T1/2, N0) generally proceed directly to surgery. For all other rectal cancers, preoperative (neo-adjuvant) radiation or chemoradiation is indicated. Adjuvant (postoperative) chemotherapy is offered when all gross disease has been resected but the risk of recurrence is high as indicated by metastases in regional lymph nodes in the surgical specimen of the resected primary tumour (stage III) or the presence of high risk features such as lymphovascular or perineural invasion even without lymph node involvement (high risk stage II – see below).

If investigations suggest that curative resection is not possible, referral to a BC Cancer Agency medical oncologist (and radiation oncologist, for rectal cancers) is made if not already initiated earlier. In some cases chemotherapy (and possibly radiation) may be given in an effort to downstage the tumour, following which the patient is re-staged to assess if surgical extirpation for cure is made possible. If the tumour is not thought to be curable even with downstaging preceding surgery, a multidisciplinary discussion is held during which goals of care are determined. The patient may then be offered a number of palliative therapy options.

Surgery

Surgery for colon cancer involves removing a segment of colon with at least 5 cm proximal and distal margins of grossly normal-appearing colon, with en bloc regional lymphadenectomy, usually followed by primary anastomosis (e.g., right hemicolectomy, left hemicolectomy, sigmoid colectomy, anterior resection). Adequate lymphadenectomy (12 or more lymph nodes) is ensured by wide resection of the mesentery and high ligation of the vessels leading to the tumour, ensuring that grossly positive lymph nodes are included en bloc with the resection specimen. Clinically positive lymph nodes outside the intended field of resection should be removed if possible (or biopsied).

Options for obstructing but still resectable cancers include resection with primary anastomosis as above, resection and anastomosis with a diverting loop ileostomy, diversion alone without resection, and colonoscopic stent placement. The last two options require subsequent segmental colectomy once the obstruction is relieved.

The goals of rectal cancer are negative proximal, distal and circumferential resection margins. Careful preoperative clinical examination and review of imaging is imperative in achieving negative margins. For rectal cancer in the upper third of the rectum (>12 cm from the anal verge), resection with a 5 cm distal margin and primary anastomosis is performed (anterior resection), with intact mesorectal envelope. The mesorectal bulk up to the level of the distal rectal margin should be maintained intact to achieve adequate lymphadenectomy. For tumours in the mid and distal rectum, resection of the entire rectum and its mesentery with intact mesorectal envelope (total mesenteric resection, or TME) to the pelvic floor is required, and anastomosis can be performed provided at least a 1-2 cm distal margin can be achieved. A temporary diverting loop ileostomy should be performed for low rectal anastomoses, as the anastomotic leak rate increases as the height of the anastomosis above the anal verge decreases, even in the absence of radiation. For low rectal cancers where a 1 cm distal margin cannot be achieved, the patient should have an abdominoperineal resection with permanent end colostomy. The field of resection for the perineal dissection is defined by the coccyx posteriorly, the ischiorectal fat laterally (outside the sphincter complex), and the transverse perineal muscle/rectovaginal septum/prostate anteriorly. Resection of adjacent structures (uterus, bladder, ureter, prostate, urethra, posterior vaginal wall, pelvic sidewall, presacral fascia, etc.) is indicated when preoperative imaging and clinical examination suggests threatened circumferential resection margins. Areas on the resected specimen where the surgeon is concerned about circumferential margin should be marked with a suture to allow the pathologist to comment on those areas specifically. Resection of lymph nodes beyond the field of resection (e.g., obturator or iliac lymph nodes) is not recommended unless clinically involved.

In all TME resections, it is important not to “cone in” on the mesorectum distally, to ensure all lymph nodes are removed. Although preoperative radiation may result in reduction of the gross tumour size, residual tumour may be present in the muscularis distal to the shrunken mucosal margin. Therefore, the distal resection margin of 1 cm should be based on the location of the pre-radiated gross lesion. In other words, the decision to perform an APR or low anterior resection with anastomosis should be ideally made before radiation, although this recommendation is controversial and not universally endorsed.

Surgical options for obstructing but resectable rectal cancers are similar to those discussed above for colon cancer. Diversion without resection may relieve the obstruction and allow for neoadjuvant radiation. For all rectal resections, great care must be taken to preserve the nervi erigentes and ureters where possible (i.e., not involved by the tumour).

A previous study in BC showed that rectal cancers within 5 cm of the anus had a high rate of positive radial margins, prior to the initiation of educational programs. Therefore, such low rectal cancers should ideally be operated on by surgeons with the necessary expertise and volume to ensure that this positive margin rate is kept as low as possible.

Laparoscopic or laparoscopic-assisted resection of colon cancer is considered technically and oncologically safe when performed by experienced surgeons who can concurrently perform thorough abdominal exploration and when the disease is not locally advanced or perforated. Endoscopic marking (submucosal tattoo) is important for localization of tumours and ensuring adequate margins. Patients may realize benefit in postoperative recovery from minimally invasive surgery. The safety of laparoscopic rectal cancer surgery is currently being studied in several randomized, controlled trials. Open resection of rectal cancer is currently the standard of care until results of these trials become available.

Local, transanal excision of rectal cancer (including T1 lesions) has increased risk of recurrence compared to major resection. However, local excision may be considered for superficial lesions in situations where patients have medical comorbidities that preclude major surgery or where patients refuse major resection having understood the negative oncologic aspects of transanal excision. Local excision for rectal cancer should be discussed on a case-by-case basis. A newer technique for local excision, transanal endoscopic microsurgery (TEM), is now being performed at St. Paul’s Hospital in Vancouver. There is evidence that TEM resection offers better oncologic outcomes than conventional transanal excision, though not as good as radical resection. “Low risk” lesions which may be considered for transanal (including TEM) resection in the context above are T1 lesions, well- or moderately-differentiated, do not have lymphovascular or perineural invasion, have negative margins (at least 3mm), are less than 3cm in size, are mobile (non-fixed), and are node-negative on preoperative imaging.

Postoperative Pathologic Staging

Pathology reporting of the resected cancer should include assessment of proximal, distal, and radial margins, T stage, N stage (with at least 12 nodes being evaluated for accurate staging), lymphovascular invasion, perineural invasion, and grade of differentiation. For rectal cancers, the quality of the TME specimen (intactness of the mesorectal envelope) and relation to the peritoneal reflection should be reported. Lack of complete reporting should prompt a discussion between the surgeon and pathologist.

Timing of Surgery and Neoadjuvant/Adjuvant Treatment

Neoadjuvant radiation is generally given for rectal cancers in the mid (5-10 cm above anal verge) or distal (0-5 cm above anal verge) rectum. Neoadjuvant short course radiation (without chemotherapy) is given for mobile rectal cancers over a 5-day course (2500 cGy total) and is followed by surgery within 10 days of the start of radiation. Neoadjuvant long course chemoradiation is given for 5 weeks (5040 cGy total) followed by surgery 6 to 8 weeks after completion of chemoradiation. Neoadjuvant long course chemoradiation is indicated for clinically fixed tumours or tumours where the radial margin is predicted to be positive with surgery alone (whether from the tumour itself or from lymph nodes positioned close to the mesorectal fascia), or for tumours in the lower third of the rectum. Long course chemoradiation for the purpose of sphincter preservation (avoidance of permanent colostomy) is controversial.

Adjuvant chemotherapy is most commonly indicated for node positive (stage III) or high risk stage II disease and should be ideally be started within 8 weeks of surgery for maximum benefit (within 4 weeks is preferable). As such, early referral to the BC Cancer Agency is highly encouraged. The definition of “high-risk” in stage II cancers is controversial, but generally accepted criteria include pathologic evidence of lymphovascular or perineural invasion, poor differentiation, T4 lesions, obstruction, perforation, and inadequate lymphadenectomy (less than 12 nodes examined). The role of molecular assay including microsatellite instability is evolving, but generally patients with MSI-High tumours can avoid undergoing chemotherapy. The exact chemotherapy regimen, length of therapy (typically 6 months), or route of administration (oral or intravenous) is recommended after consultation with the medical oncologist, and is directed as per the Colorectal Cancer Treatment Guidelines of the BC Cancer Agency GI Tumour Group.

Post-Treatment Surveillance

Following neoadjuvant treatment, surgery, and adjuvant therapy where indicated, the patient is recommended to undergo periodic surveillance for recurrence or metastasis for 5 years. Surveillance may be conducted by the patient’s surgeon, family physician, oncologist, gastroenterologist, or combination thereof. While a comprehensive discussion of surveillance is beyond the scope of this document, the following guidelines are published and endorsed by the BC Cancer Agency.

The follow-up provided to p​atients treated for colorectal cancer varies a great deal. The following suggestions are intended to encourage standardised follow-up, while maximizing benefits without wasteful use of resources. These recommendations apply to Stage II and III colorectal cancer patients who have undergone surgery with curative intent, whether or not they have also received adjuvant chemotherapy and/or radiation therapy. Most (but not all) recurrences from colorectal carcinoma occur within the first 2 to 3 years after primary therapy.

Purpose of Follow-up

1. To ensure that problems due to surgery or to therapy are identified and managed.

2. To identify, at an early stage, evidence of disease recurrence which may be amenable to salvage by a secondary surgical procedure with curative intent.

3. In patients with rectal carcinoma, to monitor for the possible development of recurrent disease in the pelvis or perineal scar after an abdominoperineal resection (APR), in order to manage this complication before it reaches an advanced stage.

4. To detect and offer palliative therapy to patients with symptomatic recurrence. Most of these patients will present to the physician with symptoms, rather than being detected on routine follow-up.

5. To detect the development of neoplastic colonic polyps, or second primary colonic or rectal neoplasms, which occur with increased frequency in patients with a prior history of colorectal cancer.

6. To assess the results of therapy (outcome analysis).

Follow-up Responsibilities

Follow-up during the period of active adjuvant therapy (radiation and/or chemotherapy) will be conducted by the physician coordinating the adjuvant therapy (at BCCA or the Community Oncology Program). Thereafter, unless there are special concerns, follow-up is usually performed by the patient's family physician and, as appropriate, gastroenterologist or surgeon.

Specific Follow-up Recommendations

The recommended intervals for follow-up are every three months for three years, then every six months for two further years.

1. Each followup visit should include a careful history to elicit gastrointestinal and constitutional symptomatology, including nutritional status, and physical examination with particular attention to the left supraclavicular fossa, the abdomen, liver and careful rectal evaluation (or perineal inspection and palpation in those patients who have had an APR.)

2. Routine laboratory investigations in the absence of symptoms are generally not useful. A possible exception is for the tumour marker, carcinoembryonic antigen (CEA). There is some evidence to suggest that CEA monitoring may increase the detection of patients with resectable metastases. Accordingly, if the patient's general medical status would permit consideration of resection of a solitary metastasis (usually hepatic or pulmonary), CEA should be checked at each visit. If the CEA is elevated, investigations (e.g. thoracic, abdominal imaging) should be performed to look for recurrence. This is important as a proportion of patients will relapse in a solitary site, and a proportion of these may be cured by resection. Five years following initial resection, if there is no evidence of recurrence, CEA testing should be discontinued

3. Colonoscopy should be performed either prior to surgery or within the first 12 months post surgery and then repeated at intervals of three to six years, to look for another primary colorectal malignancy or pre-malignant changes. For patients with specific genetic syndromes, the American Gastroenterological Association guidelines should be followed. Additionally, in those patients who have undergone anterior resection for Stage II (Duke's B) or III (Duke's C) rectosigmoid adenocarcinomas and who have not had radiation therapy, frequent flexible sigmoidoscopy is recommended to look for anastomotic recurrence. In persons in whom colonoscopy is not advisable or available, flexible sigmoidoscopy combined with double contrast barium enema is an alternative approach. Colonoscopy, however, is the preferred investigation, as it offers the advantage of greater accuracy and the ability to remove and/or biopsy suspicious or pre-malignant lesions.

4. The use of routine imaging may detect early metastases that would be amenable to potentially curative surgery in patients who could tolerate such a procedure. Liver imaging every 6 months for 3 years and then annually for 2 years is recommended for these patients. Chest x-ray every 6 - 12 months for 5 years is recommended for patients with rectal primaries.

SOURCE: Rectum ( )
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