For further information about this report, please contact the authors through the PEBC via: Phone: 905-527-4322 ext. 42822 Fax: 905 526-6775 E-mail: ccopgi@mcmaster.ca
For information about the PEBC and the most current version of all reports, please visit the CCO Web site at / or contact the PEBC office at: Phone: 905-527-4322 ext. 42822 Fax: 905 526-6775 E-mail: ccopgi@mcmaster.ca 

# GUIDELINE OBJECTIVE
To provide the optimal strategy to assess patients diagnosed with rectal cancer prior to treatment. This includes: 1. Investigations  to assess for distant metastases and synchronous lesions in patients with rectal cancer 2. Imaging  for local staging of rectal cancer 3. The optimal MRI protocol to locally stage rectal cancer 4. The optimal MRI criteria to locally stage rectal cancer 5. The optimal MRI criteria to select patients for neoadjuvant therapy 6. The role of multidisciplinary cancer conferences (MCCs) 7. The role of restaging MRI after neoadjuvant therapy

# TARGET POPULATION
Newly diagnosed patients with rectal cancer 1 undergoing elective treatment comprise the target population.

# INTENDED USERS
This guideline is intended for radiologists, surgeons, radiation oncologists, medical oncologists, and pathologists. This guideline coincides with the introduction of colorectal cancer Diagnostic Assessment Programs in Ontario. Diagnostic Assessment Programs provide coordination of care using a clinical navigator, fast tracking of diagnostic tests and a multidisciplinary team approach. They are an Ontario-wide strategic priority designed to improve patient access and outcomes, and are outlined in Ontario Cancer Plan 2005and Ontario Cancer Plan 2011-2014.

# RECOMMENDATIONS AND KEY EVIDENCE/JUSTIFICATION

# RECOMMENDATION 1
- Staging for all rectal cancer patients should include:
-CT of the abdomen and pelvis -CT of the chest or chest X-ray. - Complete colonic examination by colonoscopy should be performed preoperatively, if possible. - Serum carcinoembryonic antigen (CEA) should be assessed preoperatively.

# Qualifying Statements
- While CT chest is preferred, chest x-ray may be used as an alternative method of chest imaging. The choice of CT of the chest or chest X-ray should be consistent with the modality used for postoperative surveillance. If CT of the chest is used for postoperative surveillance, then CT of the chest should be done at the same time as staging CT of the abdomen and pelvis. If chest X-ray is used for postoperative surveillance, then CT of the chest is recommended only if abnormalities requiring further investigation were found on chest X-ray. - When CT of the chest is performed in combination with CT of the abdomen and pelvis, intravenous contrast is recommended. However, when CT of the chest is the sole investigation, intravenous contrast is potentially helpful but not required. - If the use of intravenous contrast is contraindicated, abdominal MRI or ultrasound may be used to supplement CT to further assess for liver metastasis. - Colonoscopy is preferred but CT colonography can be used to complete the assessment when the colonoscopy is incomplete. If not completed preoperatively, a complete colonoscopy should be performed postoperatively. - This recommendation applies to patients undergoing elective treatment only (i.e., does not include patients with obstruction or perforation).

# Key Evidence/Justification
This recommendation was adapted from the NICE 2011, NZGG 2011, SIGN 2011 and PEBC 2006 guidelines, which were based on consensus, as there were no high-quality studies to support this recommendation (2)(3)(4)(5). While NICE 2011 and SIGN 2011 have recommended CT of the chest, NZGG 2011 and PEBC 2006 have recommended chest X-ray. The main advantages of CT of the chest discussed by the Guideline Development Group include: (i) the early detection of pulmonary nodules that may lead to a change in management (i.e., first-line chemotherapy, metastasectomy) (6) and (ii) a baseline CT of the chest for comparison if CT of the chest is used for postoperative surveillance. The main disadvantage of CT of the chest discussed by the Guideline Development Group included the high sensitivity and low specificity of CT to detect indeterminate pulmonary nodules and lack of consensus as to how these nodules should be managed (7). The cost of performing a CT of the chest was discussed by the Guideline Development Group and was considered to be neither an advantage nor disadvantage, as the added cost and time required to conduct a CT of the chest in conjunction with a CT of the abdomen/pelvis is minimal. Although there is limited evidence, the Guideline Development Group has made the recommendation to endorse CT of the chest for pulmonary staging. The main reasons for this were the increased risks of pulmonary metastases alone with rectal cancer compared to colon cancer (8,9) and the ability to have a baseline CT chest for comparison during the surveillance period.
Serum CEA was recommended preoperatively only by the NZGG 2011 and postoperatively by NZGG 2011, NICE 2011 and SIGN 2011 (2)(3)(4). The evidence for these recommendations were based on four meta-analyses that show intensive follow-up programs that include CEA testing lead to significantly improved overall survival and detection of asymptomatic recurrences compared to a less intensive follow-up. The advantages of preoperative CEA testing discussed by the Guideline Development Group include: (i) the recommendation and evidence for CEA testing for postoperative surveillance and (ii) limited value of postoperative CEA testing if no preoperative CEA is available for comparison. The Guideline Development Group did not identify or discuss any disadvantages to use of preoperative CEA testing. Therefore, a recommendation to perform preoperative CEA was made and is consistent with the colorectal cancer Diagnostic Assessment Programs in Ontario.

# RECOMMENDATION 2
- Patients with rectal cancer should undergo MRI pelvis in order to assess T and N categories and the distance to the MRF.

# Qualifying Statements
- For the purpose of this guideline, the distance to the mesorectal fascia (MRF) will be used and represents the potential CRM. The use of the term MRF is more appropriate, because CRM is a pathologic term determined by the extent of surgical resection. - For low rectal cancer, defined as 0-5 cm from the anal verge, if local excision (with transanal excision or transanal endoscopic microsurgery) is being considered, transrectal ultrasonography (TRUS) performed by those with demonstrated expertise is preferred to MRI, in order to more accurately discriminate between T1 and T2 lesions. TRUS should not be used to predict CRM involvement. - For upper rectal cancers, defined as 10-15 cm above the anal verge, in which the mesorectal fascia is not threatened, MRI may not provide significantly more information than CT of the pelvis. - MRI is used for local staging of the rectum and does not adequately assess regional disease at the level of the inferior mesenteric artery or distant disease; CT of the abdomen and pelvis should be used to assess for distant metastases and regional disease including lymph node involvement along the inferior mesenteric artery. - If there are contraindications to MRI, CT of the pelvis and/or TRUS are recommended.

# Key Evidence/Justification
The evidence for this recommendation was based on the NICE 2011, NZGG 2011, SIGN 2011 and PEBC 2006 guidelines (2-5). These guidelines discussed the results of two systematic reviews by Kwok et al 2000 and Bipat et al 2004 that assessed the diagnostic accuracy of MRI, CT and US for T and N category (10,11). These studies showed that ultrasound had the highest sensitivity and specificity for T-category, followed by MRI and CT, respectively. Two additional systematic reviews assessing the diagnostic accuracy of MRI only to assess MRF involvement have shown that MRI has good sensitivity and specificity to predict MRF involvement (12,13). Taken together, these studies suggest that transrectal ultrasound has the best diagnostic accuracy for T-category, in particular T1 and T2 tumours, followed by MRI and CT, and MRI has the best diagnostic accuracy to detect MRF involvement. Therefore, based on these studies, we have recommended MRI as the modality of choice for preoperative staging of rectal cancer. To date, there are only a few, poor-quality studies that have directly compared the diagnostic accuracy of CT and MRI for the prediction of MRF involvement, and therefore, there is currently insufficient evidence to support the use of CT to assess distance to the MRF and MRF involvement. However, many experts would likely consider the added benefit of MRI relative to CT relatively small for the assessment of upper rectal and rectosigmoid tumours in which the mesorectal fasica (i.e., potential CRM) is not threated or involved.
The reviews by Kwok et al 2000, Bipat et al 2004, and Lahaye et al 2005 also show that all modalities have moderate accuracy to detect nodal involvement (10)(11)(12). Therefore, the Guidelines Development Group endorsed the recommendations from the NICE 2011, SIGN 2011 and NZGG 2011 guidelines to use MRI for local staging of rectal cancer.

# RECOMMENDATION 3
- At a minimum, axial, coronal and sagittal T2-weighted images of the pelvis and highresolution T2-weighted sequences perpendicular to the long axis of the rectum at the level of the tumour using phased-array coil are required.

# Qualifying Statements
- A high-resolution MRI meets the specifications outlined by the MERCURY Group Protocol and is shown in Appendix 1. - For low rectal cancer, coronal high-resolution images along the long axis of the anal canal should be considered in addition to or instead of the long axis of the rectum in order to better assess the relationship of the tumour to the sphincter components. - Additional sequences, bowel preparation, anti-peristaltics, luminal distension, and intravenous contrast are believed to be supplemental and are not a mandatory requirement for a high-quality MRI.

# Key Evidence/Justification
A review of the literature for MRI protocols including optimal sequences, bowel preparation, enemas, anti-peristaltic agents, and intravenous contrast was performed. There was only one study that suggested rectal distension may improve the accuracy of T-category assessment while having little effect on MRF or lymph node involvement (14).
Four studies assessed use of gadolinium-enhanced T1 images compared to T2 unenhanced images (10,(15)(16)(17). However, these studies generally found no difference in T or N staging, and therefore, use of gadolinium was not recommended as a mandatory component of the MRI protocol. Two meta-analyses demonstrated that multiple readers resulted in better prediction of T category and MRF involvement than when these criteria were assessed by single readers (13,18). While consensus reading is preferred, due to issues with respect to work load and feasibility, The Guideline Development Group also did not recommend this manoeuvre as a mandatory component of the MRI protocol.
Based on these limited data, the Guideline Development Group endorsed the MRI protocol used by the MERCURY study group, which was a prospective, European, multidisciplinary project that demonstrated the accuracy and feasibility of MRI as a method of assessing rectal cancer. The evidence to support this recommendation can be found in Appendix 1. This is also the MRI protocol endorsed by the Surgical Oncology Program (available here: ) (19). 

# Key Evidence/Justification
The Guideline Development Group endorsed the synoptic MRI report, which was based on evidence and multidisciplinary consensus. The evidence and justification to support these MRI criteria are available here  (19).
It is important to note that the overall rationale for the synoptic MRI report was to provide clear definition for each item on the synoptic report and to improve overall consistency and completeness (but not necessarily accuracy) of MRI reports across the province.

# RECOMMENDATION 5
- According to current practice, patients with stage II or III rectal cancer should be offered preoperative therapy using T and N categories to preoperatively stage patients.

# Qualifying Statement
- To date, there is insufficient evidence to change the current selection criteria from T and N categories to distance to the MRF (i.e., potential CRM), extramural depth of invasion (EMD) and/or extramural vascular invasion (EMVI).

# Key Evidence/Justification
Several RCTs have been done showing that preoperative radiation or chemoradiation leads to a decrease in the risk of local recurrence (21)(22)(23)(24). These RCTs assessed T and N category with digital rectal examination and/or TRUS to select patients for neoadjuvant therapy. While there have been no RCTs that have used MRI criteria to select patients for preoperative therapy, more recently, two prospective non-randomized cohort studies used distance to the MRF of less than 1 mm on MRI to select patients for preoperative therapy (25,26). In these studies, patients with distance to the MRF of greater than or equal to 1 mm on MRI, regardless of T and N category, were treated with surgery alone. The results for these patients suggested that the rate of positive CRM was 1.5% (2/134) (25), and local recurrence was 3.3% (4/122) (26). These studies are clinically relevant because they suggest that preoperative radiation or chemoradiation may not be necessary in as many patients when MRI is used to select patient for preoperative therapy. This has significant clinical implication because preoperative radiation has been shown to lead to poorer bowel and sexual function compared to surgery alone (27). While these findings are important, the Guideline Development Group recommended that higher quality evidence is required before a change in the selection criteria can be recommended.

# RECOMMENDATION 6
- All rectal cancer patients in Ontario, independent of their geographic locale, should have their case presented at a multidisciplinary cancer conference (MCC).

# Qualifying Statement
- Alternatively, each case should be reviewed through collaborative discussion(s) and/or multidisciplinary clinic with appropriate clinicians (surgeon, radiation oncologist, radiologist, medical oncologist and pathologist). The goal is to provide clinical correlation, decide on an individualized treatment plan, and provide feedback to the radiologist and other members of the team.

# Key Evidence/Justification
The effect of having an MCC discussion on patient outcomes was weak and conflicting. One study did find fewer positive CRM rates for those patients who were discussed at an MCC, but another study did not (28,29). Three studies investigated the effect of having an MCC on survival and did not find an association (30)(31)(32). Four studies suggested that patients were more likely to receive appropriate therapy if they were reviewed at an MCC (33)(34)(35)(36). The Guideline Development Group chose to recommend that all patients with rectal cancer be discussed at an MCC, which is consistent with CCO's MCC standards document (37).

# RECOMMENDATION 7
- Restaging MRI following preoperative chemoradiation is optional.

# Qualifying Statement
- No recommendation can be made to support or refute the routine use of restaging MRI following neoadjuvant therapy. However, restaging MRI may be appropriate in cases where there is suspected MRF involvement or when complete response would change management, on a per patient basis.

# Key Evidence/Justification
The Guideline Development Group did not recommend routine use of restaging MRI following neoadjuvant therapy due to lack of evidence. In particular, there were no studies assessing the effect of restaging MRI on surgical management or patient outcomes. However, two studies have shown that a lower tumour regression grade score (i.e., TRG 1 and 2) on restaging MRI was an independent and positive predictor of overall and disease-free survival (38,39). In addition, one of these studies showed that MRF involvement on restaging MRI was an independent and positive predictor of local recurrence (38). Two other studies found that tumour reduction volume was a significant predictor of disease-free survival (40,41) and overall survival (41). Due to lack of evidence, the Guideline Development Group does not recommend routine use of restaging MRI. However, the Guideline Development group believed that restaging MRI in select patient populations where observation following a complete response on MRI would be considered a reasonable treatment option (e.g., high-risk surgical patients, patients requiring abdominoperineal resection) or in patients with a potentially threatened CRM to ensure adequate response to chemoradiation prior to surgery. Copyright This report is copyrighted by Cancer Care Ontario; the report and the illustrations herein may not be reproduced without the express written permission of Cancer Care Ontario. Cancer Care Ontario reserves the right at any time, and at its sole discretion, to change or revoke this authorization.

# FUTURE RESEARCH