Role of the status of the mesorectal fascia in the selection of patients with rectal cancer for preoperative radiation therapy: a retrospective cohort study
============================================================================================================================================================

* Marko Simunovic
* Vanja Grubac
* Kevin Zbuk
* Raimond Wong
* Angela Coates

## Abstract

**Background:** Patients with rectal cancer in whom the mesorectal fascia is threatened by tumour are more likely than all patients with stage II/III disease to benefit from preoperative radiotherapy (RT). The objective of this study was to assess whether the status of the mesorectal fascia versus a stage II/III designation can best inform the use of preoperative RT in patients undergoing major rectal cancer resection.

**Methods:** We reviewed the charts of consecutive patients with primary rectal cancer treated by a single surgeon at McMaster University, Hamilton, Ontario, between March 2006 and December 2012. The status of the mesorectal fascia was assessed by digital rectal examination, pelvic computed tomography and, when needed, pelvic magnetic resonance imaging (MRI). Patients whose mesorectal fascia was threatened or involved by tumour received preoperative RT. The study outcomes were rates of positive circumferential radial margin (CRM) and local tumour recurrence.

**Results:** A total of 153 patients were included, of whom 76 (49.7%) received preoperative RT because of concerns of a compromised mesorectal fascia. The median length of follow-up was 4.5 years. The number of CRM-positive cases in the RT and no-RT groups was 16 (22%) and 1 (1%), respectively (*p* < 0.01), and the number of cases of local tumour recurrence was 5 (7%) and 2 (3%), respectively (*p* = 0.2). Rates were similar when only patients with stage II/III tumours were included. Overall, 26 patients (17.0%) received MRI.

**Conclusion:** The status of the mesorectal fascia, not tumour stage, may best identify patients for preoperative RT.

Total mesorectal excision techniques adopted worldwide in the last 20 years have improved outcomes for patients undergoing rectal cancer surgery. Certain jurisdictions have seen postoperative local recurrence rates decrease from more than 20% to 10%.1,2 Units that perform fastidious total mesorectal excision have reported local recurrence rates as low as 5%.3 Dutch and UK Medical Research Council (MRC) trials that incorporated total mesorectal excision techniques while testing the role of preoperative radiotherapy (RT) showed reductions in local recurrence of 5% and no improvement in patient survival.4,5 Of relevance, despite the inclusion solely of patients with resectable disease and the intent to provide optimal total mesorectal excision techniques, only about 50% of pathology specimens in both trials could be classified as complete.6,7 Thus, the utility of preoperative RT in settings where optimal total mesorectal excision is consistently delivered still requires evaluation. Such evaluation would not be needed if preoperative RT did not confer on patients the risks of important adverse effects such as poor sexual and bowel function, bowel obstruction and hip fracture.8–12 Even in the era of total mesorectal excision, most North American guidelines recommend the use of preoperative or postoperative long-course chemoradiotherapy for patients with stage II or III disease.13 Many European centres use preoperative short-course RT (delivered over 1 wk) in such patients.4,5 Most jurisdictions also now recommend the use of pelvic magnetic resonance imaging (MRI) to locally stage rectal tumours, despite evidence showing that pelvic MRI assigns an incorrect T or N category in about 30% of patients.14 Limited evidence suggests that both MRI and computed tomography (CT) can adequately evaluate the status of the mesorectal fascia. 15,16 In an attempt to influence current approaches to preoperative RT in rectal cancer, investigators have published case series in which recommendations for preoperative RT are driven largely by the status of the mesorectal fascia versus a TNM stage II or III designation, and most investigators have determined the status of the mesorectal fascia using MRI.17–20

The objective of this study was to further assess whether the status of the mesorectal fascia versus a stage II or III designation can best inform the use of preoperative RT in patients undergoing major rectal cancer resection.

## Methods

### Design

This was a nonmatched cohort study involving retrospective review of the charts of consecutive patients who had undergone rectal cancer surgery with and without preoperative radiation.

### Population, staging tests and follow-up

Patients with primary rectal cancer were accrued by a single surgeon with a clinical focus on complex colorectal cancer surgery and who works at an academic centre in Ontario (population 14 million). The cohort consisted of consecutive patients who presented with primary rectal adenocarcinoma and who were treated with major resection between March 2006 and December 2012. Most patients were referred by outside surgeons, in most cases because of concerns about tumour operability or sphincter preservation. All patients who underwent major surgery for primary rectal cancer during the study period were included; there were no exclusions for variables such as tumour stage or comorbidities. For distant and local staging purposes, all patients underwent physical examination including a digital rectal examination, chest radiography, CT of the abdomen and pelvis, and colonoscopy. Pelvic MRI was ordered if the digital rectal examination or CT did not provide a clear status of the mesorectal fascia (i.e., definitely clear or definitely threatened or involved). Magnetic resonance imaging information was also considered if the test had already been ordered by the referring surgeon. Transrectal ultrasonography for local staging is not used in our centre and is not relevant to the evaluation of the mesorectal fascia. For follow-up, patients were seen shortly after hospital discharge, every 6 months for 2 years and once a year thereafter. Colonoscopy was performed 1 year and 6 years after surgery unless more frequent examination was clinically indicated. The following surveillance tests were performed annually: blood testing including liver function tests and measurement of carcino-embryonic antigen levels, chest radiography, and CT of the abdomen and pelvis. Ultrasonography of the liver was performed 6 and 18 months after surgery. This surveillance scheme follows an Ontario guideline developed during the time of this study.21

### Decision-making for pelvic magnetic resonance imaging and preoperative radiotherapy

Following abdominal and pelvic CT imaging and physical examination including a digital rectal examination, patients could be placed into 1 of 3 categories. The first category was patients with a threatened or involved mesorectal fascia who were recommended to receive preoperative RT. These patients had tumour fixation on digital rectal examination, or a primary lesion or abnormal mesorectal lymph nodes that were near or traversed the mesorectal fascia, as seen on CT. Abnormal lymph nodes were defined by signal heterogeneity or extracapsular extension but not by size. The second category was patients with a nonthreatened mesorectal fascia who were recommended to go directly to surgery. These patients had tumour mobility on digital rectal examination or a generous layer of normal mesorectal fat located between tumour and fascia, as seen on CT. There was subjectivity in identifying “tumour near the mesorectal fascia” or a “generous layer of mesorectum,” although, generally, tumour cells 2 mm or less from the mesorectal fascia were considered “near.” The third category was patients in whom the status of the mesorectal fascia was not obvious; for these patients, pelvic MRI was ordered. Lower tumours were more likely to prompt MRI since CT is typically of little use to assess the mesorectal fascia at the level of the pelvic floor. If MRI did not show a clear mesorectal fascia or surgical margin, preoperative RT would be recommended. Fig. 1 summarizes our approach.

![Fig. 1](http://canjsurg.ca/https://www.canjsurg.ca/content/cjs/61/5/332/F1.medium.gif)

[Fig. 1](http://canjsurg.ca/content/61/5/332/F1)

Fig. 1 
Decision-making for pelvic magnetic resonance imaging (MRI) and preoperative radiotherapy (RT). CT = computed tomography; MRF = mesorectal fascia.

Preoperative RT was delivered as long-course chemoradiotherapy treatment or short-course RT with 25 Gy delivered in 5 equal fractions. Patients who could not tolerate chemotherapy or for whom convenience was a concern (e.g., elderly patients or those who had to travel long distances) received short-course treatment. Randomized trials have shown similar outcomes with short- and long-course RT, although long-course RT is the preferred treatment in Ontario.13,32,23 All patients who received preoperative RT had an interval of at least 6 weeks between treatment and surgery to allow for tumour downsizing.

Ontario guidelines recommend preoperative RT for patients with stage II or III rectal cancer.13 Thus, patients with a nonthreatened mesorectal fascia but obvious T3 tumour extension or a positive mesorectal lymph node were encouraged to speak with a radiation oncologist on the risks (e.g., bowel and sexual dysfunction) and benefits (i.e., decrease in risk of local recurrence) of preoperative RT. After surgery, patients with stage II or III cancer who did not undergo some form of preoperative RT were also encouraged to speak with an oncologist regarding potential adjuvant therapy. Most patients with stage III tumours who did not receive preoperative RT received postoperative chemotherapy.

### Data collection

We retrospectively collected from relevant clinic, hospital, operative and pathology notes the following information: patient characteristics (age, sex and comorbidities), investigations (CT and MRI) and tumour characteristics (distance from anal verge to distal tumour edge, degree of fixation, closest distance from tumour cells to circumferential radial margin [CRM], size, TNM stage [postoperative pathology only], differentiation, and presence of vascular, lymphatic or perineural invasion). Palpable tumours on rectal examination were defined as mobile, tethered or fixed. Treatment factors abstracted included use of chemotherapy, RT, permanent colostomy and hospital length of stay.

### Groups and outcomes

We defined study groups by whether patients did or did not receive preoperative RT. The primary outcomes were rate of positive CRM (tumours cells ≤ 1 mm from the CRM) and local tumour recurrence. To determine rates of CRM positivity, we defined the numerator as patients with tumour cells 1 mm or less from the cut edge of the surgical specimen, or a pathology report identifying a positive CRM but with no CRM distance provided; the denominator included patients with CRM distance reported plus patients deemed CRM-positive without a measurement reported. We have used this approach for evaluation of CRM positivity elsewhere.24 Tumour cells could be from the main tumour, from a positive lymph node, from a discontinuous tumour focus, or from cells in a vascular, lymphatic or neural structure. Local recurrence was defined as recurrent disease anywhere in the pelvis. Local recurrence was confirmed by biopsy. It was also decided a priori that any pelvic mass with associated symptoms of pain or pressure would be classified as a local recurrence.

### Statistical analysis

We used the χ2 and Fisher exact tests for categorical variables, and the Mann–Whitney and Student *t* tests for continuous variables to assess differences between the subcohorts with regard to patient, tumour, treatment and outcome measures. We assessed the odds of local recurrence using a logistic model while controlling for patient (age, sex and comorbidity), tumour (TNM stage, tumour fixation) and treatment (use of radiation, type of surgery) variables. All statistical analyses were carried out with SPSS version 20.0 (IBM Corp.). We considered *p* < 0.05 statistically significant. There were no external funding sources for this work. The study received ethics approval from the Hamilton Health Sciences Research Ethics Board.

## Results

We reviewed the charts of 153 patients, of whom 76 (49.7%) received preoperative RT. No patient with likely stage II or III disease and a clear mesorectal fascia elected to receive preoperative RT. One patient in the no-RT group with a clear mesorectal fascia but stage III disease elected to receive postoperative chemoradiotherapy. The median length of follow-up was 4.5 (range 0–10.5) years for the RT group and 6.0 (range 0–10.8) years for the no-RT group (5.3 yr overall). There were no significant differences in median age, sex or comorbidities between the 2 groups (Table 1). All patients underwent staging CT. Twenty-six patients (17.0%) underwent staging MRI; the use of MRI was significantly greater in the RT group than in the non-RT group (19 [25%] v. 7 [9%], *p* < 0.01).

View this table:
[Table 1](http://canjsurg.ca/content/61/5/332/T1)

Table 1 
Patient and tumour characteristics

There were differences between the 2 groups in rates of tumour fixation (*p* < 0.001): of the 59 patients with a palpable tumour in the no-RT group, none had a fixed tumour, and 4 (7%) had tethered tumours. In the RT group, palpable tumours were fixed or tethered in 53 (79%) of 67 patients. Patients were more likely to have a higher postoperative TNM stage in the RT group than in the non-RT group (*p* < 0.01). Pathology stage differences were likely even greater since tumour downsizing could have occurred only among patients who had preoperative RT. Five patients (7%) in the RT group had a complete pathologic response. Of note, of the patients who did not receive preoperative RT, 40 (52%) had stage II or III tumours, and 8 (10%) had stage IV tumours.

The CRM distance was reported for 141 patients (92.2%). The rate of CRM positivity in the RT and no-RT groups was 16/73 (22%) and 1/72 (1%), respectively (*p* < 0.001) (Table 2). Among patients with stage II or III disease, the corresponding rates were 9/44 (20%) and 1/40 (2%) (*p* = 0.01). There were 5 local recurrences (7%) among the patients who received preoperative RT and 2 (3%) among those who did not (*p* = 0.2). Among patients with stage II and III disease, the corresponding values were 3/44 (7%) and 2/40 (5%) (*p* = 0.7). Nearly half (34 [45%]) of the patients who received preoperative RT also received a permanent colostomy, compared to 7 patients (9%) in the no-RT group (*p* < 0.001). The anastomotic leak rate, wound infection rate and median length of stay were similar between the 2 groups. When we controlled for patient and tumour variables, the odds of local recurrence with preoperative RT versus no preoperative RT was similar (odds ratio 0.26, 95% confidence interval 0.04–1.57). The small number of local recurrences likely undermines the clinical usefulness of this finding.

View this table:
[Table 2](http://canjsurg.ca/content/61/5/332/T2)

Table 2 
Outcomes

Of note, none of the 7 patients with local recurrence had a positive CRM (Table 3). The 5 patients in the RT group with a local recurrence all presented with a fixed tumour, and all were treated with long-course chemoradiation. The 2 cases of local recurrence in the no-RT group are of particular interest. In 1 case, the tumour was tethered to the pelvic sidewalls and prostate, but preoperative RT was precluded by the use of radical RT for prostate cancer 3 years earlier. In the second case, the tumour was mobile, and the presence of 4 of 18 positive lymph nodes led to full-dose adjuvant chemotherapy. Symptomatic local recurrence developed in the left pelvic sidewall, and the patient underwent pelvic chemoradiation, additional full-dose chemotherapy and resective surgery of an isolated positive lymph node. The patient was disease free 3 years after surgery for recurrence and 6 years after the original rectal surgery.

View this table:
[Table 3](http://canjsurg.ca/content/61/5/332/T3)

Table 3 
Summary characteristics of patients with local recurrence

## Discussion

Guidelines from many jurisdictions related to rectal cancer surgery recommend the use of preoperative RT for patients with stage II or III tumours and the use of pelvic MRI for local staging.13,25 Our results suggest an opportunity to modify these norms. A total of 52% of patients who did not receive preoperative RT had stage II or III tumours. However, in this group, only 1 patient had a positive CRM, and only 2 patients experienced a local recurrence. One of the patients with local recurrence likely would have received preoperative RT owing to tumour tethering but could not because of recent pelvic RT for prostate cancer. The second patient had a recurrence in a pelvic sidewall lymph node and was free of disease 3 years after therapy for the recurrence and 6 years after the original surgery. The rate of CRM positivity among the patients who received preoperative RT was understandably high (22%). Only patients with a compromised or involved mesorectal fascia on preoperative assessment were recommended to receive RT. As well, only 26 patients overall (17%) received pelvic MRI. Our findings suggest that pelvic CT and digital rectal examination, with the as-needed use of pelvic MRI, can identify patients with a compromised mesorectal fascia who will likely most benefit from preoperative RT. Similarly, patients with a non-compromised mesorectal fascia and thus a much lower risk of negative outcomes can also be identified and can avoid the risks of preoperative RT, even in the presence of stage II or III disease.

In the era of total mesorectal excision, the benefits of RT are confined to a decreased risk of local recurrence; there are no survival benefits. However, the use of RT is associated with major adverse effects including sexual impotence (1 in 6 women, 1 in 11 men) and debilitating bowel function (1 in 8 patients).8–12 It is possible that such risks can be mitigated or removed with the use of newer conformal RT approaches, but we are unaware of evidence to support this position. In Ontario and other jurisdictions, the use of preoperative RT is recommended for all patients with stage II or III rectal cancer.13 However, in the era of total mesorectal excision, we suggest that the risk–benefit ratio for preoperative RT should be considered differently for patients with and without a clear mesorectal fascia. We suspect that our results are generalizable to many other surgeons and surgical units, and we encourage surgeons to correlate their own rates of CRM positivity and local recurrence with preoperative mesorectal fascia status.

Our results add to a growing number of case series reports suggesting that the status of the mesorectal fascia versus a stage II or III tumour designation can largely inform the use of preoperative RT in patients with rectal cancer.17–20 Strassburg and colleagues17 used digital rectal examination and MRI to identify patients at low risk who could avoid preoperative RT: those with nonfixed tumours located higher than 6 cm from the anal verge and no evidence of tumour within 1 mm of the mesorectal fascia. This approach was extended to numerous other German centres and is being currently evaluated.20 In the Magnetic Resonance Imaging and Rectal Cancer European Equivalence (MERCURY) Study, MRI was used alone to identify low-risk tumours: no evidence of tumour within 1 mm of the mesorectal fascia, no extramural vascular invasion and a maximum extent of tumour beyond the bowel wall of 5 mm.19

In the MERCURY Study, nodal status (i.e., positive or negative) did not influence the use of preoperative RT.19 There would be little impetus for clinicians to modify indications for preoperative RT away from the current stage II or III paradigm practised in many jurisdictions, including Ontario, if pre- or postoperative RT did not expose patients with rectal cancer to possible adverse effects.8–12

The approach that we outline to identify patients for preoperative RT is practical and efficient. Digital rectal examination and preoperative CT findings allow for most patients to be classified as having or not having a threatened or involved mesorectal fascia. Pelvic MRI can be used in the minority of patients where such classification is not clear. Magnetic resonance imaging and CT can evaluate the status of the mesorectal fascia with high accuracy, with some evidence that MRI is superior for lower tumours.15,16 An additional issue that we have observed with rectal tumour staging is a propensity to rely on pelvic MRI to assess mesorectal lymph nodes. However, the mesorectal lymph node package extends to the origin of the inferior mesenteric artery, an area not normally assessed by pelvic MRI.26 Abdominopelvic CT can assess this area, and obviously worrisome nodes can influence surgeon planning (e.g., high ligation in a young patient with nonmetastatic disease) or can lead to a request that pelvic MRI cover the inferior mesenteric artery origin.

Three other relevant findings are presented in our paper. First, in our preoperative RT group, only 5 patients (7%) had a complete pathologic response. This likely resulted from reservation of preoperative RT for patients with advanced tumours that compromised the mesorectal fascia. Second, none of the 7 patients with a local tumour recurrence had a positive CRM on pathologic assessment. Of relevance, the MRC CR07 trial investigators observed that a positive CRM did not predict local tumour recurrence when tumour stage, quality of the mesorectal specimen and other factors were included in multivariable analyses.6 Finally, all 5 patients in the RT group who experienced a local recurrence had a fixed tumour on digital rectal examination. For patients with fixed tumours on digital examination at presentation, current reliance on long-course chemoradiation alone may not be adequate to minimize the risk of local recurrence.

### Limitations

Our study has limitations. First, there was some subjectivity in identifying a threatened mesorectal fascia, although, generally, tumour cells 2 mm or less from the mesorectal fascia were considered near. As noted, in most cases, digital rectal examination and CT alone can identify a threatened, involved or clear mesorectal margin, but, in a small number of cases, this assessment does not provide a clear answer, even with the addition of MRI. However, other investigators have used approaches related to those that we outline to determine the mesorectal fascia status and the need for preoperative RT.17–20 Regardless, although the low rates of CRM positivity and local recurrence in our no-RT group provide some validation of our approach, we encourage other investigators to replicate or modify our approach and report their results. Second, our low rate of wound infection was derived retrospectively from hospital chart review. It is likely that hospital notes did not capture evidence of all wound infections and that many infections presented following hospital discharge and were managed by family physicians. However, this would not affect our main outcomes of CRM positivity and local tumour recurrence. Finally, cohort studies are associated with inherent biases that can be dealt with only by using a randomized controlled trial design. However, as with many other surgical changes and innovations, the evolution of standards related to preoperative RT in rectal cancer will likely be catalyzed first by cohort studies and then, it is hoped, studies with more robust designs.

## Conclusion

Observations from the current series suggest that, in rectal cancer, the status of the mesorectal fascia and not tumour stage can best identify patients for preoperative RT and that mesorectal fascia status can usually be determined by pelvic CT and digital rectal examination with the occasional addition of MRI.

## Footnotes

*   **Competing interests:** None declared.

*   **Contributors:** All authors designed the study, acquired and analyzed the data, wrote and reviewed the article, and approved the final version for publication.

*   Accepted December 6, 2017.

## References

1.  Martling AL, Holm T, Rutqvist LE, et al.Effect of a surgical training programme on outcome of rectal cancer in the country of Stokholm. Stockholm Colorectal Cancer Study Group, Basingstoke Bowel Cancer Research Project.Lancet 2000;356:93–6.
    
    [CrossRef](http://canjsurg.ca/lookup/external-ref?access_num=10.1016/S0140-6736(00)02469-7&link_type=DOI) 
    
    [PubMed](http://canjsurg.ca/lookup/external-ref?access_num=10963244&link_type=MED&atom=%2Fcjs%2F61%2F5%2F332.atom) 
    
    [Web of Science](http://canjsurg.ca/lookup/external-ref?access_num=000088036600008&link_type=ISI) 

2.  Kapiteijn E, Marijnen CA, Colenbrander AC, et al.Local recurrence in patients with rectal cancer diagnosed between 1988 and 1992: a population-based study in the west Netherlands.Eur J Surg Oncol 1998;24:528–35.
    
    [CrossRef](http://canjsurg.ca/lookup/external-ref?access_num=10.1016/S0748-7983(98)93500-4&link_type=DOI) 
    
    [PubMed](http://canjsurg.ca/lookup/external-ref?access_num=9870729&link_type=MED&atom=%2Fcjs%2F61%2F5%2F332.atom) 
    
    [Web of Science](http://canjsurg.ca/lookup/external-ref?access_num=000077486200013&link_type=ISI) 

3.  Heald RJ, Moran BJ, Ryall RDH, et al.Rectal cancer: the Basingstoke experience of total mesorectal excision, 1978–1997.Arch Surg 1998;133:894–9.
    
    [CrossRef](http://canjsurg.ca/lookup/external-ref?access_num=10.1001/archsurg.133.8.894&link_type=DOI) 
    
    [PubMed](http://canjsurg.ca/lookup/external-ref?access_num=9711965&link_type=MED&atom=%2Fcjs%2F61%2F5%2F332.atom) 
    
    [Web of Science](http://canjsurg.ca/lookup/external-ref?access_num=000075269100028&link_type=ISI) 

4.  Sebag-Montefiore D, Stephens RJ, Steele R, et al.Preoperative radiotherapy versus selective postoperative chemoradiotherapy in patients with rectal cancer (MRC CR07 and NCIC-CTG C016): a multicentre, randomized trial.Lancet 2009;373:811–20.
    
    [CrossRef](http://canjsurg.ca/lookup/external-ref?access_num=10.1016/S0140-6736(09)60484-0&link_type=DOI) 
    
    [PubMed](http://canjsurg.ca/lookup/external-ref?access_num=19269519&link_type=MED&atom=%2Fcjs%2F61%2F5%2F332.atom) 
    
    [Web of Science](http://canjsurg.ca/lookup/external-ref?access_num=000263980900031&link_type=ISI) 

5.  Peeters KCMJ, Marijnen CAM, Nagtegaal ID, et al.The TME trial after a median follow-up of 6 years: increased local control but no survival benefit in irradiated patients with resectable rectal carcinoma.Ann Surg 2007;246:693–701.
    
    [CrossRef](http://canjsurg.ca/lookup/external-ref?access_num=10.1097/01.sla.0000257358.56863.ce&link_type=DOI) 
    
    [PubMed](http://canjsurg.ca/lookup/external-ref?access_num=17968156&link_type=MED&atom=%2Fcjs%2F61%2F5%2F332.atom) 
    
    [Web of Science](http://canjsurg.ca/lookup/external-ref?access_num=000250773400001&link_type=ISI) 

6.  Quirke P, Steele R, Monson J, et al.Effect of the plane of surgery achieved on local recurrence in patients with operable rectal cancer: a prospective study using data from the MRC CR07 and NCIC-CTG CO16 randomised clinical trial.Lancet 2009;373:821–8.
    
    [CrossRef](http://canjsurg.ca/lookup/external-ref?access_num=10.1016/S0140-6736(09)60485-2&link_type=DOI) 
    
    [PubMed](http://canjsurg.ca/lookup/external-ref?access_num=19269520&link_type=MED&atom=%2Fcjs%2F61%2F5%2F332.atom) 
    
    [Web of Science](http://canjsurg.ca/lookup/external-ref?access_num=000263980900032&link_type=ISI) 

7.  Nagtegaal ID, van de Velde CJ, van der Worp E, et al.Macroscopic evaluation of rectal cancer resection specimen: clinical significance of the pathologist in quality control.J Clin Oncol 2002;20:1729–34.
    
    [Abstract/FREE Full Text](http://canjsurg.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6MzoiamNvIjtzOjU6InJlc2lkIjtzOjk6IjIwLzcvMTcyOSI7czo0OiJhdG9tIjtzOjE4OiIvY2pzLzYxLzUvMzMyLmF0b20iO31zOjg6ImZyYWdtZW50IjtzOjA6IiI7fQ==) 

8.  Kollmorgen CE, Meagher AP, Wolff BG, et al.The long-term effect of adjuvant postoperative chemoradiotherapy for rectal carcinoma on bowel function.Ann Surg 1994;220:676–82.
    
    [CrossRef](http://canjsurg.ca/lookup/external-ref?access_num=10.1097/00000658-199411000-00012&link_type=DOI) 
    
    [PubMed](http://canjsurg.ca/lookup/external-ref?access_num=7979617&link_type=MED&atom=%2Fcjs%2F61%2F5%2F332.atom) 
    
    [Web of Science](http://canjsurg.ca/lookup/external-ref?access_num=A1994PR00800012&link_type=ISI) 

9.  Dahlberg M, Glimelius B, Graf W, et al.Preoperative irradiation affects functional results after surgery for rectal cancer: results from a randomized study.Dis Colon Rectum 1998;41:543–9.
    
    [CrossRef](http://canjsurg.ca/lookup/external-ref?access_num=10.1007/BF02235256&link_type=DOI) 
    
    [PubMed](http://canjsurg.ca/lookup/external-ref?access_num=9593234&link_type=MED&atom=%2Fcjs%2F61%2F5%2F332.atom) 
    
    [Web of Science](http://canjsurg.ca/lookup/external-ref?access_num=000073594600001&link_type=ISI) 

10. Peeters KC, van de Velde CJ, Leer JW, et al.Late side effects of short-course preoperative radiotherapy combined with total mesorectal excision for rectal cancer: increased bowel dysfunction in irradiated patients — a Dutch colorectal cancer group study.J Clin Oncol 2005;23:6199–206.
    
    [Abstract/FREE Full Text](http://canjsurg.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6MzoiamNvIjtzOjU6InJlc2lkIjtzOjEwOiIyMy8yNS82MTk5IjtzOjQ6ImF0b20iO3M6MTg6Ii9janMvNjEvNS8zMzIuYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9) 

11. Marijnen CAM, van de Velde CJH, Putter H, et al.Impact of short-term preoperative radiotherapy on health-related quality of life and sexual functioning in primary rectal cancer: report of a multicenter randomized trial.J Clin Oncol 2005;23:1847–58.
    
    [Abstract/FREE Full Text](http://canjsurg.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6MzoiamNvIjtzOjU6InJlc2lkIjtzOjk6IjIzLzkvMTg0NyI7czo0OiJhdG9tIjtzOjE4OiIvY2pzLzYxLzUvMzMyLmF0b20iO31zOjg6ImZyYWdtZW50IjtzOjA6IiI7fQ==) 

12. Stephens RJ, Thompson LC, Quirke P, et al.Impact of short-course preoperative radiotherapy for rectal cancer on patients’ quality of life: data from the Medical Research Council CR07/National Cancer Institute of Canada Clinical Trials Group C016 randomized clinical trial.J Clin Oncol 2010;28:4233–9.
    
    [Abstract/FREE Full Text](http://canjsurg.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6MzoiamNvIjtzOjU6InJlc2lkIjtzOjEwOiIyOC8yNy80MjMzIjtzOjQ6ImF0b20iO3M6MTg6Ii9janMvNjEvNS8zMzIuYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9) 

13. Wong RKS, Berry S, Spithoff K, et al.Preoperative or postoperative therapy for stage II or III rectal cancer: an updated practice guideline.Clin Oncol (R Coll Radiol) 2010;22:265–71.
    
    [PubMed](http://canjsurg.ca/lookup/external-ref?access_num=20398849&link_type=MED&atom=%2Fcjs%2F61%2F5%2F332.atom) 

14. Al-Sukhni E, Milot L, Fruitman M, et al.Diagnostic accuracy of MRI for assessment of T category, lymph node metastases, and circumferential resection margin involvement in patients with rectal cancer: a systematic review and meta-analysis.Ann Surg Oncol 2012;19:2212–23.
    
    [CrossRef](http://canjsurg.ca/lookup/external-ref?access_num=10.1245/s10434-011-2210-5&link_type=DOI) 
    
    [PubMed](http://canjsurg.ca/lookup/external-ref?access_num=22271205&link_type=MED&atom=%2Fcjs%2F61%2F5%2F332.atom) 
    
    [Web of Science](http://canjsurg.ca/lookup/external-ref?access_num=000305558000020&link_type=ISI) 

15. Maizlin ZV, Brown JA, So G, et al.Can CT replace MRI in preoperative assessment of the circumferential resection margin in rectal cancer?.Dis Colon Rectum 2010;53:308–14.
    
    [PubMed](http://canjsurg.ca/lookup/external-ref?access_num=20173478&link_type=MED&atom=%2Fcjs%2F61%2F5%2F332.atom) 

16. Taylor A, Slater A, Mapstone N, et al.Staging rectal cancer: MRI compared to MDCT.Abdom Imaging 2007;32:323–7.
    
    [PubMed](http://canjsurg.ca/lookup/external-ref?access_num=16967240&link_type=MED&atom=%2Fcjs%2F61%2F5%2F332.atom) 

17. Strassburg J, Junginger T, Trinh T, et al.Magnetic resonance imaging (MRI)-based indication for neoadjuvant treatment of rectal carcinoma and the surrogate endpoint CRM status.Int J Colorectal Dis 2008;23:1099–107.
    
    [PubMed](http://canjsurg.ca/lookup/external-ref?access_num=18633624&link_type=MED&atom=%2Fcjs%2F61%2F5%2F332.atom) 

18. Simunovic M, Jacob S, Coates AJ, et al.Outcomes following a limited approach to radiotherapy in rectal cancer.Br J Surg 2011;98:1483–8.
    
    [PubMed](http://canjsurg.ca/lookup/external-ref?access_num=21633949&link_type=MED&atom=%2Fcjs%2F61%2F5%2F332.atom) 

19. Taylor F, Quirke P, Heald R, et al.MERCURY Study GroupPreoperative high-resolution magnetic resonance imaging can identify good prognosis stage I, II, and III rectal cancer best managed by surgery alone: a prospective, multicenter, European study.Ann Surg 2011;253:711–9.
    
    [CrossRef](http://canjsurg.ca/lookup/external-ref?access_num=10.1097/SLA.0b013e31820b8d52&link_type=DOI) 
    
    [PubMed](http://canjsurg.ca/lookup/external-ref?access_num=21475011&link_type=MED&atom=%2Fcjs%2F61%2F5%2F332.atom) 

20. Kreis ME, Ruppert R, Ptok H, et al.Use of preoperative magnetic resonance imaging to select patients with rectal cancer for neoadjuvant chemoradiation — interim analysis of the German OCUM Trial ([NCT01325649](http://canjsurg.ca/lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01325649&atom=%2Fcjs%2F61%2F5%2F332.atom)).J Gastrointest Surg 2016;20:25–32.
    
    

21. (2012) Cross-sectional imaging in colorectal cancer (Cancer Care Ontario, Toronto) [archived 2012 April]. Program in Evidence-based Care recommendations report archived 2012.
    
    

22. Bujko K, Nowacki MP, Nasierowska-Guttmejer A, et al.Long-term results of a randomized trial comparing preoperative short-course radiotherapy with preoperative conventionally fractionated chemoradiation for rectal cancer.Br J Surg 2006;93:1215–23.
    
    [CrossRef](http://canjsurg.ca/lookup/external-ref?access_num=10.1002/bjs.5506&link_type=DOI) 
    
    [PubMed](http://canjsurg.ca/lookup/external-ref?access_num=16983741&link_type=MED&atom=%2Fcjs%2F61%2F5%2F332.atom) 
    
    [Web of Science](http://canjsurg.ca/lookup/external-ref?access_num=000241584900007&link_type=ISI) 

23. Ngan SY, Burmeister B, Fisher RJ, et al.Randomized trial of short-course radiotherapy versus long-course chemoradiation comparing rates of local recurrence in patients with T3 rectal cancer: Trans-Tasman Radiation Oncology Group trial 01.04.J Clin Oncol 2012;30:3827–33.
    
    [Abstract/FREE Full Text](http://canjsurg.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6MzoiamNvIjtzOjU6InJlc2lkIjtzOjEwOiIzMC8zMS8zODI3IjtzOjQ6ImF0b20iO3M6MTg6Ii9janMvNjEvNS8zMzIuYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9) 

24. Keng C, Coates A, Grubac V, et al.The need for consensus and transparency when assessing population-based rates of positive circumferential radial margins in rectal cancer: data from consecutive cases in a large region of Ontario, Canada.Ann Surg Oncol 2016;23:397–402.
    
    

25. Kennedy ED, Vella E, MacDonald DB, et al. (2014) Optimization of preoperative assessment in patients diagnosed with rectal cancer (Cancer Care Ontario, Toronto) Program in Evidence-Based Care Evidence-Based series no. 17–8, Available: [www.cancercare.on.ca/common/pages/UserFile.aspx?fileId=294945](http://www.cancercare.on.ca/common/pages/UserFile.aspx?fileId=294945). accessed 2017 June 1.
    
    

26. Simunovic M, Smith AJ, Heald RJ.Rectal cancer surgery and regional lymph nodes.J Surg Oncol 2009;99:256–9.
    
    [PubMed](http://canjsurg.ca/lookup/external-ref?access_num=19101955&link_type=MED&atom=%2Fcjs%2F61%2F5%2F332.atom)