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Appendix - Colorectal Cancer Care Map for Physicians

Revised May 2018

This care map in section 6.3 was developed by the Colorectal Surgical Tumour Group of the BC Cancer 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 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 Check” program in BC, currently in pilot study)

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 BC Cancer 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 BC Cancer, 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 BC Cancer 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 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 BC Cancer 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 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 BC Cancer.

The follow-up provided to patients 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 BC Cancer 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 year for 3 years. Chest x-ray every year for 3 years is recommended for patients with rectal primaries.

SOURCE: Appendix - Colorectal Cancer Care Map for Physicians ( )
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