A \ A Clinical Pathway for Rectal Cancer

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1 A \ 2017 A Clinical Pathway for Rectal Cancer

2 Table of Contents List of Experts Consulted... 3 Clinical Pathway Overview... 5 Standards of Care of the Clinical Pathway... 8 Diagnosis... 9 Pre-operative Staging Neoadjuvant Therapy Surgical Therapy Pathologic Assessment Adjuvant Therapy Key Metrics for Monitoring Quality of the Clinical Pathway P age Disclaimer: This pathway is intended to be used for informational purposes only, is subject to independent medical judgment in consultation with the patient to direct care, and is not a substitute for clinical practice guidelines.

3 List of Experts Consulted The following individuals are acknowledged for contributing their clinical expertise with respect to their medical specialty to the development of this Clinical Pathway for Rectal Cancer in Alberta. They have reviewed the content of the Clinical Pathway for Rectal Cancer in Alberta and confirm that it depicts evidence-based clinical practice and, where evidence is conflicting or missing, expert opinion. Dr. W. Grant Brunet, MD, FRCPC Radiologist, Foothills Medical Centre Clinical Assistant Professor, Department of Radiology, University of Calgary Calgary, Alberta Dr. Corinne Doll, MD, FRCPC Radiation Oncologist, Tom Baker Cancer Centre Associate Professor, Radiation Oncology, Department of Oncology, University of Calgary Calgary, Alberta Dr. X. Sean Gui, MD, FRCPC Pathologist, Foothills Medical Centre Clinical Associate Professor, Department of Pathology & Laboratory Medicine, University of Calgary Calgary, Alberta Dr. W. Donald Buie, MD, FRCSC Colorectal Surgeon, Foothills Medical Centre Clinical Assistant Professor of Surgery, Department of Surgery, University of Calgary Calgary, Alberta Dr. Jay Easaw, MD, FRCPC Medical Oncologist, Tom Baker Cancer Centre, Associate Professor, Medical Oncology, Department of Oncology, University of Calgary Calgary, Alberta Dr. Ronald Hennig, MD, FRCPC Radiologist, Diagnostic Imaging, Cross Cancer Institute Clinical Professor of Radiology & Diagnostic Imaging, Oncologic Imaging, Department of Oncology, University of Alberta Edmonton, Alberta Dr. Neil Chua, MD, FRCPC Medical Oncologist, Cross Cancer Institute Associate Clinical Professor, Medical Oncology, Department of Oncology, University of Alberta Edmonton, Alberta Dr. Vincent Falck, MD, MBChB, FRCPath, FRCPC Pathologist, Foothills Medical Centre Clinical Associate Professor, Department of Pathology & Laboratory Medicine, University of Calgary Calgary, Alberta Dr. Kurian Joseph, MD, FRCSC Radiation Oncologist, Cross Cancer Institute Associate Professor, Radiation Oncology, Department of Oncology, University of Calgary Edmonton, Alberta 3 P age Disclaimer: This pathway is intended to be used for informational purposes only, is subject to independent medical judgment in consultation with the patient to direct care, and is not a substitute for clinical practice guidelines.

4 Dr. Marc Kerba, MD, FRCPC Radiation Oncologist, Cross Cancer Institute Associate Professor, Radiation Oncology, Department of Oncology, University of Calgary Edmonton, Alberta Dr. Ross McLean, MD, FRCSC Pathologist, Royal Alexandra Hospital Assistant Clinical Professor, Department of Laboratory Medicine & Pathology, University of Alberta Edmonton, Alberta Dr. Haili Wang, MD, MSc, FRCSC Colorectal Surgeon, University of Alberta Hospital Assistant Professor of Surgery, Department of Surgery, University of Alberta Edmonton, Alberta Dr. Robert MacEwan, MD, FRCPC Radiologist & Facility Clinical Department Site Chief, Diagnostic Imaging, Cross Cancer Institute Assistant Clinical Professor of Radiology & Diagnostic Imaging, Oncologic Imaging, Department of Oncology, University of Alberta Edmonton, Alberta Dr. Andrew Scarfe, MD, FRCPC Medical Oncologist, Cross Cancer Institute Associate Professor, Medical Oncology, Department of Oncology University of Alberta Edmonton, Alberta Dr. Anthony MacLean, MD, FRCSC Colorectal Surgeon, Foothills Medical Centre Clinical Assistant Professor of Surgery, University of Calgary Calgary, Alberta Dr. Patricia Tang, MD, FRCPC Medical Oncologist, Cross Cancer Institute Assistant Professor, Medical Oncology, Department of Oncology University of Calgary Edmonton, Alberta 4 P age Disclaimer: This pathway is intended to be used for informational purposes only, is subject to independent medical judgment in consultation with the patient to direct care, and is not a substitute for clinical practice guidelines.

5 Clinical Pathway Overview This Clinical Pathway for Rectal Cancer serves to describe the optimal care for rectal cancer patients in Alberta. It outlines the standards of care from diagnosis to treatment (ASCRS 2013), key indicators to continuously monitor quality for each step of the pathway, optimal resources to operationalize the pathway, and a governance model to monitor Continuous Process Improvement (CPI) and to promote sustainability. Multidisciplinary physician groups are developing strategies to implement these standards of care ongoing measurement program based on the defined quality metrics. Local and regional operational and medical leads are being consulted to examine barriers to implementation and sustainability of the clinical pathway. Readers should also refer to AHS Clinical Practice Guidelines (CPG) GI-005 Early Stage Rectal Cancer for consensus of the AHS Gastrointestinal Provincial Tumor Team on comprehensive approaches to diagnosis, staging, treatment and follow-up for rectal cancer, derived from a review of relevant scientific literature. Disclaimer - This pathway is intended to be used for informational / educational purposes only, is subject to independent medical judgment in consultation with the patient to 5 P age Disclaimer: This pathway is intended to be used for informational purposes only, is subject to independent medical judgment in consultation with the patient to direct care, and is not a substitute for clinical practice guidelines.

6 Diagnosis Treatment SUSPICION & DIAGNOSTIC PROCEDURES * PRE-OPERATIVE STAGING DECISION TO TREAT NEOADJUVANT THERAPY SURGICAL THERAPY PATHOLOGIC ASSESSMENT ADVJUVANT THERAPY FOLLOW-UP SCREENING *,5 Standards of Care: Thorough disease history Full physical exam, Proctosigmoidoscopy, DRE Full colonic evaluation Refer to Surgeon for suspicion or positive screening result * Refer to : AHS CPG GI-005 Early Stage Rectal Cancer Refer to a Radiologist for pre-operative clinical staging For curative intent surgery, dedicated high resolution pelvic MRI using the MERCURY protocol (References 2-3) For transanal excision, endorectal ultrasound For assessment of metastatic disease, CT of Chest, Abdomen and Pelvis Refer to a Radiation and Medical Oncologist to determine the appropriateness for neoadjuvant chemoradiation therapy Consider neoadjuvant therapy for clinical T3, clinical T4, and node positive cancers of mid-to-distal rectum Discuss treatment plan with multimodal therapy at MDC Footnotes: Refer to Surgeon for suspicion: 1) Unexplained signs or symptoms (palpable rectal mass, unexplained rectal bleeding, unexplained iron-deficiency anemia) 2) Positive Fecal Immunochemical Test 3) Suspicious Abdominal Imaging Result Refer to : AHS CPG GI-005 Early Stage Rectal Cancer Refer to : AHS CPG GI-005 Early Stage Rectal Cancer Complete TME as part of a low anterior or APR, for tumors of the middle and lower thirds of the rectum Complete tumor, specific mesorectal excision with a margin of at least 5 cm, for tumors of the upper third of the rectum Local excision for carefully selected T1 rectal cancers without high-risk features Refer GI pathology special interest guidelines Tumour is fixed with the tumour containing segment unopened followed by cross sectional slicing when fully fixed (Quirke) Assessment of the quality of ME should be performed on the fresh specimen Pathology report is in synoptic format with all mandatory elements described in the CAP Colorectal checklist Refer to : AHS CPG GI-005 Early Stage Rectal Cancer Refer to a Medical Oncologist to determine the appropriateness for adjuvant chemotherapy Adjuvant chemoradiotherapy for stage II or high-risk stage II patients who have not received neoadjuvant therapy Adjuvant chemotherapy for high-risk stage II and all stage III patients previously treated with neoadjuvant therapy. Refer to : AHS CPG GI-005 Early Stage Rectal Cancer References: 1. Practice Parameters for the Management of Rectal Cancer (Revised). Diseases of the Colon & Rectum 2013; 56:5. 2. MERCURY study - Annals of Surgery 2011; 253(4): Five year follow-up results of MERCURY study - Journal of Clinical Oncology 2014; 32(1): AHS CPG GI-005 Early Stage Rectal Cancer. 5. AHS Colorectal Surveillance Guidelines * Refer to Surgeon for benign, non-endoscopically resectable mass or malignant lesion approaches to diagnosis, staging, treatment and follow-up for rectal cancer, derived from a review of relevant scientific literature. Disclaimer: This pathway is intended to be used for informational purposes only, is subject to independent medical judgment in consultation with the patient to

7 Diagnosis Treatment SUSPICION & DIAGNOSTIC PROCEDURES SCREENING Quality Metrics: PRE-OPERATIVE STAGING Refer to : AHS CPG GI-005 Early Stage Rectal Cancer % rectal cancer patients who received MRI % rectal cancer MRIs reported synoptically % rectal cancer MRIs performed using MERCURY protocol Rectal cancer MRI report completeness Time from requisition to procedure for rectal cancer MRI Time from MRI procedure to MRI report dictation DECISION TO TREAT NEOADJUVANT THERAPY Refer to : AHS CPG GI-005 Early Stage Rectal Cancer % rectal cancer patients discussed at MDCs % rectal cancer patients referred to cancer centre for consideration of neoadjuvant therapy % rectal cancer patients receiving neoadjuvant therapy Rectal cancer radiotherapy report completeness SURGICAL THERAPY Refer to : AHS CPG GI-005 Early Stage Rectal Cancer % rectal cancer patients undergoing appropriate mesorectal excision (TME or TSTME) % mesorectal excisions that are complete (Quirke 2 & 3) % rectal cancer surgeries reported synoptically Proximal/distal margin postivity rate CRM positivity rate APR rate Complication rates (Deaths, Anastomatic leaks, Abscesses, Pelvics, Sepsis, ICU Admissions, Postoperative MIs, Bowel obstructions, Need for reoperations, ASA status) PATHOLOGIC ASSESSMENT Refer to GI Pathology Special Interest Guidelines % rectal cancer specimens evaluated according to the Quirke method % rectal cancer pathologic assessments reported synoptically % mesorectal excision completeness assessments performed % CRM assessments performed for rectal cancer pathologic assessments Rectal cancer pathology report completeness % appropriate tumour sampling for rectal cancer pathologic assessments ADVJUVANT THERAPY Refer to : AHS CPG GI-005 Early Stage Rectal Cancer % rectal cancer patients receiving adjuvant therapy within 12 weeks of surgery Rectal cancer radiotherapy report completeness FOLLOW-UP Refer to : AHS CPG GI-005 Early Stage Rectal Cancer % local recurrence Overall survival rates Recurrence-free survival rates # patient hospitalizations due to complications posttherapy approaches to diagnosis, staging, treatment and follow-up for rectal cancer, derived from a review of relevant scientific literature. Disclaimer: This pathway is intended to be used for informational purposes only, is subject to independent medical judgment in consultation with the patient to

8 Standards of Care of the Clinical Pathway The Alberta Clinical Pathway for Rectal Cancer is divided into six sections: Diagnosis, Staging (Diagnostic Imaging), Neoadjuvant Therapy, Surgery, Pathology, and Adjuvant Therapy. It is based largely on the recently published Clinical Practice Guideline (CPG) on the Management of Rectal Cancer from the American Society of Colon and Rectal Surgeons (ASCRS) that has been endorsed by the Society of Surgical Oncology (SSO) and the Society for Surgery of the Alimentary Tract (SSAT). All recommendations are evidence based and use the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) system to evaluate the evidence. Standards of Care are strong recommendations based on high quality evidence. Best practice points are weak recommendations based on lower quality evidence and expert opinion where evidence is conflicting or missing. 8 P age

9 Diagnosis Clinical Standards of Care and Best Practice Points Standards of Care: A thorough disease history should be obtained to elicit disease-specific symptoms, associated symptoms, and family history for all patients. Routine laboratory values should be ordered as indicated by the history and physical examination. As part of a full physical examination, a digital rectal examination (DRE) should be performed in conjunction with a proctosigmoidoscopy to determine the distance of the lesion from the anal verge, its mobility, to assess its position circumferentially and in relation to the sphincter complex. When possible, all patients with rectal cancer should undergo a full colonic evaluation with histological assessment of all intraluminal lesions prior to treatment. Best Practice Points: CT colonography may be used when colonoscopy cannot be completed. 6-9 Double contrast barium enema may also be used 10 but is not recommended in the case of near obstructing lesions. Neither alternate method is as accurate as colonoscopy with respect to small polyps. All patients should have a completion colonoscopy within 12 months post-operatively to clear the colon. STANDARDS OF CARE FOR DIAGNOSIS Rationale A cancer-specific history can guide the surgeon to look for associated pathology or metastatic disease and to initiate additional workup. Lab work should include a CEA level. 1 Clinical evaluation by digital rectal examination (DRE) and sigmoidoscopy is an essential part of locoregional staging. It complements formal clinical staging by MRI and endorectal ultrasound, and helps to identify patients who may benefit from neoadjuvant therapy and to stratify patients for sphincter preservation. The incidence of synchronous polyps is 30% and of synchronous cancers is 1% to 3%. 2-5 Colonoscopy is the preferred option because it offers the opportunity to confirm the diagnosis histologically through biopsy and to endoscopically remove any synchronous polyps. 9 P age

10 STANDARDS OF CARE FOR DIAGNOSIS (continued) References: 1. Sturgeon CM, Duffy MJ, Stenman UH et al. National Academy of Clinical Biochemistry. National Academy of Clinical Biochemistry laboratory medicine practice guidelines for use of tumor markers in testicular, prostate, colorectal, breast, and ovarian cancers. Clin Chem 2008;54:e11-e Barillari P, Ramacciato G, De Angelis R, et al. Effect of pre-operative colonoscopy on the incidence of synchronous and metachronous neoplasms. Acta Chir Scand 1990;156: Adloff M, Arnaud JP, Bergamaschi R, Schloegel M. Syncronous carcinoma of the colon and rectum: prognostic and therapeutic implications. Am J Surg. 1989;157: Bat L, Neumann G, Shemesh E. The association of synchronous neoplasms with occluding colorectal cancer. Dis Colon Rectum. 1985;28: Isler JT, Brown PC, Lewis FG, Billingham RP. The role of pre-operative colonoscopy in colorectal cancer. Dis Colon Rectum. 1987;30: Fenlon HM, McAneny DB, Nunes DP, Clarke PD, Ferruci JT. Occlusive colon carcinoma: virtual colonscopy in the preoperative evaluation of the proximal colon. Radiology. 1999;210: Macari M, Berman P, Dicker M, Milano A, Megibow AJ. Usefulness of CT colonography in patients with incomplete colonoscopy. AJR AM J Roentgenol. 1999;173: Neri E, Giusti P, Battolla L, et al. Colorectal cancer: role of CT colonography in preoperative evaluation after incomplete colonoscopy. Radiology. 2002;223: Sun L, Wu H, Guan YS. Colonography by CT, MRI and PET/CT combined with conventional colonoscopy in colorectal cancer screening and staging. World J Gastroenterol. 2008;14: Sosna J, Sella T, Sy O, et al. Critical analysis of the performance of double-contrast barium enema for detecting colorectal polyps > or = 6 mm in the era of CT colonography. AJR AM J Roentgenol. 2008;190: P age

11 Pre-operative Staging Clinical Standards of Care and Best Practice Points Standards of Care: All patients intended for curative surgery should receive, as a minimum standard, pre-operative clinical staging with a dedicated high resolution pelvic MRI (unless contraindicated), a Computed Tomography (CT) of Chest, Abdomen, and Pelvis and a preoperative CEA level Patients in whom transanal excision is being considered should also receive pre-operative clinical staging with endorectal ultrasound. All pelvic MRIs should be reported in a synoptic format using a specified template with or without additional data points (appendix x). Clinical staging is based on AJCCT NM seventh edition (appendix table) STANDARDS OF CARE FOR PRE-OPERATIVE STAGING Rationale Standard pelvic MRI may not provide the same information (e.g.: evaluation of tumor circumferential margin, identification of malignant lymph nodes) that MERCURY protocol or other related protocols provide. Endorectal ultrasound is more accurate than MRI in the assessment of T1 and T2 tumours. The liver and lungs are the most frequent sites of metastatic disease from rectal cancer. Detection and evaluation of local organ involvement or synchronous metastases may require a change in treatment strategy (e.g., chemotherapy rather than surgery first, potential simultaneous resection of both the primary tumor and the metastatic sites). Best Practice Points: There is a limited role for FDG-PET imaging in the primary clinical staging of rectal cancer. Patients with locally advanced disease who require an extended radical resection for cure may benefit from FDG-PET imaging prior to surgery. Chest x-ray and ultrasound abdomen should not be used for clinical staging of the chest as they are not as accurate as CT. The presence of unresectable metastatic disease may influence the decision to proceed with extended radical resection 11 P age

12 STANDARDS OF CARE FOR PRE-OPERATIVE STAGING (continued) References: 1. MERCURY Study Group. Diagnostic Accuracy of preoperative magnetic reconance imaging in predicting curative resection of rectal cancer: prospective observational study. Br J Radiol. 2005;333: Taylor FGM, Quirke P, Heald RJ, Moran BJ, Blomqvist L, Swift IR, Sebag-Montefiore D, Tekkis P, and Brown G. Preoperative magnetic resonance imaging assessment of circumferential resection margin predicts disease-free survival and local recurrence: 5-year follow-up results of the MERCURY study. J Clin Oncol 2014;32: Brown G, Daniels IR, Richardson C, Revell P, Peppercorn D, Bourne M. Techniques and trouble-shooting in high spatial resolution thin slice MRI for rectal cancer. Br J Radiol. 2005;78: Kennedy ED, Milot L, Fruitman M, Al-Sukhni E, Heine G, Schmocker S, Brown G, McLeod RS. Development and implementation of a synoptic MRI report for preoperative staging of rectal cancer on a population-based level. Dis Colon Rectum. 2014;57: Garcia-Aguilar J, Pollack J, Lee SH, et al. Accuracy of endorectal ultrasonography in preoperative staging of rectal tumors. Dis Colon Rectum. 2002;45: Marush F, Koch A, Schmidt U, et al. Routine use of transrectal ultrasound in rectal carcinoma: results of a prospective multi-center study. Endoscopy. 2002;34: Scheele J, Stang R, Altendorf-Hofmann A, Paul M. Resection of colorectal liver metastases. World J Surg. 1995;19: Mehta S, Johnson RJ, Schofield PF. Staging of colorectal cancer. Clin Radiol. 1994;49: Colorectal Cancer (Contemporary Issues in Cancer Imaging). 1 st ed. New York, NY: Cambridge University Press; P age

13 Neoadjuvant Therapy Clinical Standards of Care and Best Practice Points Standards of Care: All patients with locally advanced operable rectal cancer should have the opportunity to be discussed at a Multidisciplinary Tumor Group Conference (MDC) and offered neoadjuvant (pre-operative) therapy, when appropriate. Patients should have appropriate imaging performed prior to this discussion. Neoadjuvant therapy should be considered for clinical T3, clinical T4, and node positive cancers of the mid to distal rectum. Patients with an obstructing lesion who require neoadjuvant chemoradiation should be defunctioned with a proximal loop ostomy prior to starting treatment. There are two possible approaches: o Short-course pre-operative radiotherapy includes 5 Gray daily over 5 days (total 25 Gray) without chemotherapy followed by surgery within 1 week; o Long-course pre-operative chemoradiotherapy includes conventional 1.8 to 2 Gray per fraction over 5 to 6 weeks to a total dose of 45 to 50.4 Gray with concurrent administration of fluoropyrimidine-based chemotherapy followed by surgery at 8 to 12 weeks. STANDARDS OF CARE FOR NEOADJUVANT THERAPY Rationale The decision to offer multimodality therapy requires input from experts in all therapeutic modalities. MDC should include representation from Radiology, Pathology, Radiation Oncology, Medical Oncology, and Surgery. The advantages of long-course chemoradiotherapy include downsizing which is associated with improved local control and reduced rates of local recurrence. It may alter the surgical treatment plan in favor of a sphincter-preserving procedure due to tumour involution. Short-course pre-operative radiotherapy can be considered in patients whose tumor margin appears close to but free from the mesorectal fascia on imaging and where tumor regression and downsizing would not improve resection or sphincter preservation. While short-course pre-operative radiotherapy appears to be well tolerated with less acute grade 3/4 toxicities and better 13 P age

14 STANDARDS OF CARE FOR NEOADJUVANT THERAPY Clinical Standards of Care and Best Practice Points Best Practice Points: Following long-course pre-operative chemoradiotherapy and prior to surgery, consideration should be given to restaging with CT scan and pelvic MRI. Rationale compliance when compared to long-course pre-operative chemoradiotherapy, it may lead to more long-term complications. Tumour involution may have altered the surgical plan. 14 P age

15 STANDARDS OF CARE FOR NEOADJUVANT THERAPY Clinical Standards of Care and Best Practice Points Rationale References: 1. Fleming FJ, Påhlman L, Monson JR. Neoadjuvant therapy in rectal cancer. Dis Colon Rectum Jul;54(7): Sebag-Montefiore D, Stephens RJ, Steele R, et al. Preoperative radiotherapy versus selective postoperative chemoradiotherapy in 550 patients with rectal cancer (MRC CR07 and NCIC-CTG C016): a multicentre, randomised trial. Lancet. 2009;373: Improved survival with preoperative radiotherapy in resectable rectal cancer. Swedish Rectal Cancer Trial. N Engl J Med. 1997;336: Folkesson J, Birgisson H, Pahlman L, Cedermark B, Glimelius B, Gunnarsson U. Swedish Rectal Cancer Trial: long lasting benefits from radiotherapy on survival and local recurrence rate. J Clin Oncol. 2005;23: Birgisson H, Påhlman L, Gunnarsson U, Glimelius B; Swedish Rectal Cancer Trial Group. Adverse effects of preoperative radiation therapy for rectal cancer: long-term follow-up of the Swedish Rectal Cancer Trial. J Clin Oncol. 2005;23: Kapiteijn E, Marijnen CA, Nagtegaal ID, et al; Dutch Colorectal Cancer Group. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med. 2001;345: van Gijn W, Marijnen CA, Nagtegaal ID, et al; Dutch Colorectal Cancer Group. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer: 12-year follow-up of the multicentre, randomised controlled TME trial. Lancet Oncol. 2011;12: Ceelen WP, Van Nieuwenhove Y, Fierens K. Preoperative chemoradiation versus radiation alone for stage II and III resectable rectal cancer. Cochrane Database Syst Rev. 2009:CD Quah HM, Chou JF, Gonen M, et al. Pathologic stage is most prognostic of disease-free survival in locally advanced rectal cancer patients after preoperative chemoradiation. Cancer. 2008;113: Weiser MR, Quah HM, Shia J, et al. Sphincter preservation in low rectal cancer is facilitated by preoperative chemoradiation and intersphincteric dissection. Ann Surg. 2009;249: Sauer R, Becker H, Hohenberger W, et al; German Rectal Cancer Study Group. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med. 2004;351: P age

16 Surgical Therapy Clinical Standards of Care and Best Practice Points Standards of Care: Local excision is an appropriate treatment modality for carefully selected T1 rectal cancers without high-risk features (e.g.: absence of lymphovascular or perineural invasion, low to moderate grade of differentiation, tumors less than 3 cm in diameter occupying less than one third of the circumference of the bowel lumen). A thorough surgical exploration should be performed during radical excision and the findings documented in the operative report. The surgical report should include information regarding the diagnostic workup, intraoperative findings, and technical details of the procedure, preferably in a synoptic format. All patients with operable rectal cancer who require radical resection should undergo a complete mesorectal excision (ME). Total mesorectal excision (TME) should be used for curative resection of tumors of the middle and lower thirds of the rectum, either as part of low anterior or abdominoperineal resection (APR). For tumors of the upper third of the rectum, a tumor-specific mesorectal excision should be used with the mesorectum divided ideally no less than 5 cm below the lower margin of the tumor. STANDARDS OF CARE FOR SURGICAL THERAPY Rationale Accurate pre-operative staging is essential for the selection of patients for local excision. T1 cancers with low risk features have a low risk of mesorectal lymph node spread The surgical exploration includes a thorough assessment of the peritoneal cavity and the abdominal organs to detect or rule out synchronous lesions, more advanced malignant disease (e.g.: carcinomatosis, adjacent organ involvement, occult metastasis), or coexisting pathology. Appropriate surgical technique, including sharp mesorectal excision, is integral to optimizing oncologic outcome and minimizing morbidity in rectal cancer surgery. It is important to recognize that distal mesorectal spread often extends further than intramural spread, with deposits found up to 3 to 4 cm distal to the primary cancer. Obtaining an adequate radial or circumferential resection margin (CRM) is critical for local control. 16 P age

17 STANDARDS OF CARE FOR SURGICAL THERAPY Clinical Standards of Care and Best Practice Points A 2-cm distal mural margin is adequate for most rectal cancers when combined with a TME. For cancers located at or below the distal mesorectal margin, a 1-cm distal mural margin is acceptable. Proximal vascular ligation at the origin of the superior rectal artery with resection of all associated lymphatic drainage is appropriate for most rectal cancer resections. In the absence of any obvious clinical involvement, an extended lateral lymph node dissection is not necessary in addition to TME Patients with an apparent complete clinical response to neoadjuvant therapy should be offered a definitive resection. A watch and wait approach is not standard of care. It should only be offered in the context of either a registry or a trial and only after thorough discussion at a multidisciplinary conference. Intraoperative anastomotic leak testing should be performed to help identify an anastomosis at increased risk of a subsequent clinical leak. Rationale Distal intramural spread is uncommon and is found beyond 1 cm in only 4% to 10% of rectal cancers; this is usually accompanied by adverse pathologic features. Thus, a distal margin of 2 cm will remove all microscopic disease in the majority of cases. If the tumour is at or below the distal mesorectum and confined to the rectal wall, a 1 cm margin is acceptable. Low ligation distal to the left colic is sufficient for nodal sampling. High ligation of the inferior mesenteric artery (IMA) at the origin at the aorta may provide superior mobilization for a tension-free coloanal anastomosis. Lateral lymph node dissection is associated with increased urinary and sexual dysfunction without conferring a significant oncological benefit. Neither clinical examination involving DRE nor current imaging modalities (MRI, CT, or PET scanning) can reliably predict pathological complete response. Anastomotic leaks are associated with decreased survival and a significant increase in risk for local recurrence. A diverting ostomy has been shown to reduce the risk of anastomotic leak and reduce its consequences. A diverting ileostomy should be considered in low rectal anastomoses below the peritoneal reflection and following neoadjuvant radiation or chemoradiation. 17 P age

18 STANDARDS OF CARE FOR SURGICAL THERAPY Clinical Standards of Care and Best Practice Points A diverting ostomy should be considered for patients undergoing a TME for rectal cancer especially after neoadjuvant therapy. In patients with T4 rectal cancers, resection of any involved adjacent organs should be performed with an en bloc technique. Current evidence indicates that laparoscopic TME/TSTME can be performed with equivalent oncological outcomes in comparison with open TME/TSTME when performed by an experienced laparoscopic surgeon with the necessary technical expertise especially for tumours in the lower third where there is an increase risk of a positive margin. While oophorectomy is advised for grossly abnormal ovaries or contiguous extension of a rectal cancer, routine prophylactic oophorectomy is not necessary. In patients with a large bowel obstruction, an expanding intraluminal stent is an acceptable treatment option in the palliative setting or as a bridge to definitive resection. Best Practice Points: After low anterior resection and TME, the formation of a colonic reservoir may be considered. Rationale Diverting ostomy will ameliorate the effects of a clinical leak and may prevent some clinical leaks. Ileostomies are more prone to diarrhea and may predispose to dehydration and electrolyte abnormalities during the course of chemotherapy but are easier to close. TME/SPTME are technical operations with specific oncologic principles that must be respected to maximize oncologic outcomes for the patient. A laparoscopic approach must adhere to the same oncologic principles without compromise or the surgery should be converted to open or laparoscopic assisted. Current evidence suggests that a laparoscopic approach may be associated with an increased risk of positive margins. A colonic reservoir has been shown to decrease the effects of low anterior resection syndrome in the short term. 18 P age

19 STANDARDS OF CARE FOR SURGICAL THERAPY Clinical Standards of Care and Best Practice Points Rationale In patients undergoing a TME, an intraoperative rectal washout may be considered. References: 1. Quirke P, Durdey P, Dixon MF, Williams NS. Local recurrence of rectal adenocarcinoma due to inadequate surgical resection. Histopathological study of lateral tumour spread and surgical excision. Lancet. 1986;2: Adam IJ, Mohamdee MO, Martin IG, et al. Role of circumferential margin involvement in the local recurrence of rectal cancer. Lancet. 1994;344: Quirke P, Steele R, Monson J, et al; MRC CR07/NCIC-CTG CO16 Trial Investigators; NCRI Colorectal Cancer Study Group. 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: Slanetz CA Jr. The effect of inadvertent intraoperative perforation on survival and recurrence in colorectal cancer. Dis Colon Rectum. 1984;27: P age

20 Pathologic Assessment STANDARDS OF CARE FOR PATHOLOGIC ASSESSMENT Clinical Standards of Care and Best Practice Points Standards of Care: Assessment of the quality of ME (TME/TSTME) should be performed on the fresh specimen when it is received by the pathology lab, and it should be assessed by either a designated pathologist or a pathology assistant who is familiar with the mesorectal quality assessment criteria. The assessment should be documented and included in the final pathology report. The bowel should be fixed with the tumour containing segment unopened followed by cross sectional slicing when fully fixed (Quirke). Rationale The surgeon should facilitate this process by ensuring that specimens are orientated correctly and delivered to the histopathology laboratory promptly, consistent with unit protocol There should be appropriate tumour sampling with at least 5 tumour containing blocks which include: o Minimum of 3 tumor blocks showing the relationship to the CRM o Minimum of 2 tumour blocks containing the luminal aspect of the tumour o Minimum of 2 blocks with the closest serosal surface (tumours at or above the peritoneal reflection only) o Tumours that are grossly > 5 mm from the CRM and or serosal surface require only one block of each provided that a total of 3 blocks with the deepest invasion are submitted 20 P age

21 Clinical Standards of Care and Best Practice Points Pathology report must be in synoptic format based on the standards accepted by the Alberta Association of Pathologists All mandatory elements described in the College of American Pathologists (CAP) Colorectal checklist are contained in the report The CRM is assessed for distance from tumor The distal margin is assessed: o It is recommended that the measurement for distal limit of tumor to the distal margin be measured in the fresh state o If the procedure is completed after weekday working hours or on the weekend, the specimen should be placed in formalin o The Pathologist / Pathology Assistant should state if the distal margin measurement was made with the specimen in the fresh state or fixed state o It is preferable to obtain Pathologist consultation if the status of the distal margin is uncertain at the time of the surgery rather than opening of the bowel by the surgeon STANDARDS OF CARE FOR PATHOLOGIC ASSESSMENT Rationale The use of such structured protocols has been shown to improve the information content of pathology reports. The pathologist plays a key role in patient management (e.g.: confirmation of the initial diagnosis, determination of final tumor stage, assessment of margin involvement, response to neoadjuvant therapy). 21 P age

22 Clinical Standards of Care and Best Practice Points Location of the rectosigmoid junction should be determined as follows: o The Surgeon should place a suture where he/she feels the rectosigmoid junction is most likely located o The Pathologist should also attempt to determine the location of the rectosigmoid junction by determining: 1. where the taenia coli splay 2. where the mesosigmoid begins to flare out to form the mesorectum The relationship of the tumor to the anterior peritoneal reflection (APR) should be made as follows: o Distance of closest point of tumour to the APR o o It should be stated if the tumour is above or below the APR If the tumour straddles the APR, a comment should be made with respect to the following: 1. Is the tumor centered above, below, or at the APR? 2. Measurement of the length of the tumor below the APR STANDARDS OF CARE FOR PATHOLOGIC ASSESSMENT Rationale The Pathologist may not be able to determine the location of the rectosigmoid junction: o It may not be possible to see where the taenia coli splay o The mesenteric fat of both the mesorectum and mesosigmoid may be too tattered to make this observation 22 P age

23 Clinical Standards of Care and Best Practice Points Specimen submission to Pathology: o Specimens should be submitted in the fresh state to pathology immediately after the procedure to allow assessment of the distal margin (during working hours). o Specimens should be placed in formalin after hours. It is permissible for the Surgeon to open the bowel along the anterior serosal surface proximal to the tumour to ensure complete exposure to formalin. Specimens with < 12 lymph nodes identified must be reexamined. Assessment of pathologic response to neoadjuvant therapy requires (Ref. 1-4): o Minimum of 5 blocks o If no tumor cells, x3 deeper sections o If still no tumor cells, submit all gross tumor tissue o If still no tumor cells, x3 deeper sections on each block Lymphovascular invasion is reported Large vessel venous invasion and discontinuous extramural tumor extension are reported when identified When venous invasion is suspected on H and E, Elastin stains will be performed Pathology report is issued in a timely manner (within 2 weeks of surgery). Lynch syndrome screening according to current provincial guidelines STANDARDS OF CARE FOR PATHOLOGIC ASSESSMENT Rationale Opening of the bowel below the tumour will prevent mesorectal assessment and could make an accurate circumferential margin measurement impossible The report is central for quality assurance for Radiologists, Surgeons, Radiation oncologists, and Medical oncologists 23 P age

24 REFERENCES 1. Nagtegaal I D, van Krieken J H J M. The role of pathologists in the quality control of diagnosis and treatment of rectal cancer an overview. Eur J Cancer 2002; Quirke P. The pathologist, the surgeon and colorectal cancer: get it right because it matters. Prog Pathol 1998; (This is a book chapter, I don t have a copy of this reference, but it is often cited for this standard of care. 3. Valentini V, Aristei C, Glimelius B, Minsky BD, Beets-Tan R, Borras JM, et al. Multidisciplinary Rectal Cancer Management: 2nd European Rectal Cancer Consensus Conference (EURECA-CC2). Radiother Oncol Aug;92(2): O'Neil M, Damjanov I. Histopathology of Colorectal Cancer after Neoadjuvant Chemoradiation Therapy. The Open Pathology Journal. 2009;3: Thies S, Langer R. Tumor regression grading of gastrointestinal carcinomas after neoadjuvant treatment. Front Oncol. 2013;3: Loughrey M, B., Quirke P, Shepherd N, A. Dataset for colorectal cancer histopathology reports. Royal College of Pathologists online publication P age

25 Adjuvant Therapy STANDARDS OF CARE FOR ADJUVANT THERAPY Clinical Standards of Care and Best Practice Points Rationale Standards of Care: All patients should be evaluated by a Medical Oncologist for adjuvant chemotherapy. Chemotherapy when indicated should be started within 12 weeks of surgery to maximize effect. The risks and benefits of adjuvant chemotherapy should be discussed with all patients with stage II and III rectal cancer References: 1. Valentini V, Beets-Tan R, Borras JM, et al. Evidence and research in rectal cancer. Radiother Oncol. 2008;87: Quasar Collaborative Group, Gray G, Barnwell J, et al. Adjuvant chemotherapy versus observation in patients with colorectal cancer: a randomized study. Lancet 2007;370: André T, Boni C, Mounedji-Boudiaf L, et al; Multicenter International Study of Oxaliplatin/5-Fluorouracil/Leucovorin in the Adjuvant Treatment of Colon Cancer (MOSAIC) Investigators. Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med. 2004; 350: André T, Boni C, Navarro M, et al. Improved overall survival with oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment in stage II or III colon cancer in the MOSAIC trial. J Clin Oncol. 2009;27: Kuebler JP, Wieand HS, O Connell MJ, et al. Oxaliplatin combined with weekly bolus fluoruoracil and leukovorin as surgical adjuvant chemotherapy for stage II and III colon cancer: results from NSABP C-07. J Clin Oncol. 2007;25: F ietkau R, Klautke G. Adjuvant chemotherapy following neoadjuvant therapy of rectal cancer: the type of neoadjuvant therapy (chemoradiotherapy or radiotherapy) may be important for selection of patients. J Clin Oncol. 2008; 26: Collette L, Bosset JF, den Dulk M, et al; European Organisation for Research and Treatment of Cancer Radiation Oncology Group. Patients with curative resection of ct3-4 rectal cancer after preoperative radiotherapy or radiochemotherapy: does anybody benefit from adjuvant fluorouracil-based chemotherapy? A trial of the European Organisation for Research and Treatment of Cancer Radiation Oncology Group. J Clin Oncol. 2007;25: P age

26 Key Metrics for Monitoring Quality of the Clinical Pathway PRE-OPERATIVE STAGING - QUALITY METRICS Standard of Care Key Quality Metrics Data Sources Targets All patients intended for curative surgery for rectal cancer should receive, as a minimum standard, pre-operative clinical staging with a dedicated high resolution pelvic MRI using the MERCURY protocol, unless contraindicated. % rectal cancer patients undergoing MRI by stage (Surgeon metric) Alberta Cancer Registry rectal cancer diagnosis (pathology report at biopsy) Netcare Lab post-operative pathology report chart review (exclude rectosigmoid, include curative-intent resections) Netcare Diagnostic imaging chart review Stage 1 100% Stage 2 100% Stage 3 100% % rectal cancer MRIs performed using mercury or modified mercury protocol (Radiologist metric) Alberta Cancer Registry rectal cancer diagnosis (pathology report at biopsy) Netcare Lab post-operative pathology report chart review (exclude rectosigmoid, include curative-intent resections) Netcare Diagnostic imaging MRI report chart review Stage 1 100% Stage 2 100% Stage 3 100% 26 P age

27 PRE-OPERATIVE STAGING - QUALITY METRICS (continued) Standard of Care Key Quality Metrics Data Sources Targets All pelvic MRIs should be reported in a synoptic format. % rectal cancer MRIs reported synoptically (Radiologist metric) Rectal cancer MRI report completeness % inclusion of all items below (Radiologist metric): 1. T-category & N-category 2. Distance to the mesorectal fascia 3. Assessment of extramural venous invasion (EMVI) 4. Assessment of tumour height 5. Relationship to anterior peritoneal reflection 6. Relationship to anal sphincter Note: report completeness does not reflect whether or not the indicated assessment was performed, only whether it was included in the report. Alberta Cancer Registry rectal cancer diagnosis (pathology report at biopsy) Netcare Lab post-operative pathology report chart review (exclude rectosigmoid, include curative-intent resections) Netcare Diagnostic imaging MRI report chart review 100% 100% 27 P age

28 PRE-OPERATIVE STAGING - QUALITY METRICS (continued) Standard of Care Key Quality Metrics Data Sources Targets Not applicable quality metric for educational purposes % concordant T-stage between MRI and pathology reports for rectal cancer patients treated with short-course neoadjuvant therapy or no pre-operative radiotherapy (Radiologist & Pathologist metric) % concordant distance to the CRM assessments between MRI and pathology reports for rectal cancer patients treated with short-course radiotherapy (Radiologist and Pathologist metric) % concordant EMVI assessment between MRI and pathology reports for rectal cancer patients treated with short-course radiotherapy (Radiologist & Pathologist metric) Alberta Cancer Registry rectal cancer diagnosis (pathology report at biopsy) Netcare Lab post-operative pathology report chart review (exclude rectosigmoid, include curative-intent resections) ARIA RO / ARIA MO chart review Netcare Diagnostic Imaging MRI report 28 P age

29 NEOADJUVANT THERAPY - QUALITY METRICS Standard of Care Key Quality Metrics Data Sources Targets All patients with locally advanced operable rectal cancer should have the opportunity to be discussed at a Multidisciplinary Tumor Group Conference (MDC) and offered neoadjuvant (pre-operative) therapy, when appropriate. Patients should have appropriate imaging performed prior to this discussion. % rectal cancer patients discussed at multidisciplinary tumour boards (Surgeon metric) Prospective Data Collection 80% of all cases Neoadjuvant therapy should be considered for clinical T3, clinical T4, and node positive cancers of the mid to distal rectum. % appropriate Stage II and III rectal cancer patients that received consult for consideration of neoadjuvant therapy ACRegistry extract, NetCare chart review 80% of clinical stage II and III % appropriate stage II and III rectal cancer patients receiving neoadjuvant therapy (Radiation and Medical Oncologist metric) ACRegistry extract (Stage II and III), ARIA MO/RO 80% of clinical stage II and III 29 P age

30 NEOADJUVANT THERAPY - QUALITY METRICS (continued) Standard of Care Key Quality Metrics Data Sources Targets Not applicable quality metric for educational purposes Rectal cancer radiotherapy report completeness % inclusion of all items below (Radiation Oncologist metric): 1. Planned/Delivered Dose and Fractionation 2. Technique (Field-Based 3D conformal or IMRT) 3. Start date/completion Date 4. Delay/disruption in treatment (for any reason) 5. Documentation of acute side effects Rectal cancer chemotherapy report completeness - % inclusion of all items below (Medical Oncologist metric): 1. Delivered dose Note: report completeness does not reflect whether or not the indicated assessment was performed, only whether it was included in the report. ACRegistry extract (Stage II and III), ARIA RO 30 P age

31 SURGICAL THERAPY - QUALITY METRICS Standard of Care Key Quality Metrics Data Sources Targets All patients with operable rectal cancer who require radical resection should undergo a complete mesorectal excision (ME). Total mesorectal excision (TME) should be used for curative resection of tumors of the middle and lower thirds of the rectum, either as part of low anterior or abdominoperineal resection (APR). For tumors of the upper third of the rectum, a tumorspecific mesorectal excision should be used with the mesorectum divided ideally no less than 5 cm below the lower margin of the tumor. % rectal cancer patients undergoing appropriate mesorectal excision (Surgeon metric) total mesorectal excision for curative resection of tumor of the middle and lower thirds of the rectum (based on pathology report) tumor-specific mesorectal excision for proximal rectal cancer % mesorectal excisions that are near complete and complete (Quirke 2 & 3 grade based on mesorectal excision evaluation in pathology report) (Surgeon metric) for total mesorectal excision for tumor-specific mesorectal excision ACRegistry extract, NetCare Postoperative pathology report chart review, Synpotec colorectal surgical synoptic report 100% 90% - Due to technical reasons nots all mesorectal excision can be completed as Grade 2 or P age

32 SURGICAL THERAPY - QUALITY METRICS (continued) Standard of Care Key Quality Metrics Data Sources Targets The surgical report should include information regarding the diagnostic workup, intraoperative findings, and technical details of the procedure, preferably in a synoptic format. % rectal cancer surgeries reported synoptically (Surgeon metric) Rectal cancer surgical report completeness % inclusion of all items in provincial surgical synoptic report template (Surgeon metric) ACRegistry extract, Netcare postoperative pathology report chart review, Synoptec colorectal surgical synoptic report 100% 100% A 2-cm distal mural margin is adequate for most rectal cancers when combined with a TME. For cancers located at or below the distal mesorectal margin, a 1-cm distal mural margin is acceptable. Proximal/distal margin positivity rate (Surgeon metric) ACRegistry extract, Netcare postoperative pathology report chart review 1-2% Obtaining an adequate radial or circumferential resection margin (CRM) is critical for local control. CRM positivity rate (Surgeon metric) < 7% provincially. Ideally ~ 5% in select high volume groups Total mesorectal excision (TME) should be used for curative resection of tumors of the middle and lower thirds of the rectum, either as part of low anterior or abdominoperineal resection (APR). APR rate (Surgeon metric) < 25% provincially. Select high volume centers could be less than 20% 32 P age

33 PATHOLOGIC ASSESSMENT - QUALITY METRICS Standard of Care Key Quality Metrics Data Sources Targets The tumour is fixed with the tumour containing segment unopened followed by cross sectional slicing when fully fixed (Quirke). % rectal specimens evaluated according to the Quirke method (Pathologist metric) ACRegistry extract, NetCare postoperative pathology report chart review 100% Assessment of the quality of ME (TME/TSTME) should be performed on the fresh specimen when it is received by the pathology lab, and it should be assessed by either a designated pathologist or a pathologist assistant who is familiar with the ME quality assessment criteria. % mesorectal excision completeness assessments performed for rectal cancer pathologic assessments (Pathologist metric) for total mesorectal excision for tumor-specific mesorectal excision ACRegistry extract, NetCare postoperative pathology report chart review 100% Not applicable quality metric for educational purposes % disconcordant mesorectal excision grading between surgical and pathology reports for rectal cancer patients (Surgeon and Pathologist metric) ACRegistry extract, Netcare postoperative pathology report chart review, Synoptec colorectal surgical synoptic report The CRM is assessed for distance from tumor % CRM assessments performed for rectal cancer pathologic assessments (Pathologist metric) ACRegistry extract, NetCare postoperative pathology report chart review 100% 33 P age

34 PATHOLOGIC ASSESSMENT - QUALITY METRICS (continued) Standard of Care Key Quality Metrics Data Sources Targets There is appropriate tumour sampling with at least 5 tumour containing blocks which include: Minimum of 3 tumor blocks showing the relationship to the CRM Minimum of 2 tumour blocks containing the luminal aspect of the tumour Minimum of 2 blocks with the closest serosal surface (tumours at or above the peritoneal reflection only) Tumours that are grossly > 5 mm from the CRM and or serosal surface require only one block of each provided that a total of 3 blocks with the deepest invasion are submitted % appropriate tumour sampling for rectal cancer pathologic assessments (Pathologist metric) at least 5 tumour containing blocks which include: 1. Minimum 3 tumour blocks showing relationship to CRM 2. Minimum 2 blocks with closest serosal surface (tumours at or above the peritoneal reflection only) Note: Tumours that are grossly 5 mm of the CRM and/or serosal surface require only one block of each provided that a total of 3 blocks with the deepest invasion are submitted ACRegistry extract, NetCare postoperative pathology report chart review To be determined by the Gastrointestinal Pathology Special Interest Group 34 P age