Colorectal Cancer Association of Canada consensus meeting: raising the standards of care for early-stage rectal cancer.

The purpose of the meeting reported here was to develop a set of national evidence-based standards for assessing and managing patients with potentially resectable rectal cancer. This report represents the consensus of the multidisciplinary group of Canadian rectal cancer experts attending that meeting.

1. TERMS OF REFERENCE

1.1 Purpose

The purpose of the meeting reported here was to develop a set of national evidence-based standards for assessing and managing patients with potentially resectable rectal cancer. This report represents the consensus of the multidisciplinary group of Canadian rectal cancer experts attending that meeting.

1.2 Participants

A representative group of Canadian rectal cancer experts from the key disciplines (surgical, medical and radiation oncology, pathology, radiology) involved in managing resectable rectal cancer were invited (Table I).

TABLE I

Participants in the Colorectal Cancer Association of Canada consensus meeting, December 8, 2008, Montreal, Quebec

Chairs
Scott Berry	Medical Oncologist, Sunnybrook Health Sciences Center, Odette Cancer Center, Toronto, ON
Te Vuong	Radiation Oncologist, McGill Cancer Center, Montreal, QC
Andy Smith	Surgeon, Sunnybrook Health Sciences Center, Odette Cancer Center, Toronto, ON
Carole Richard	Surgeon, Centre hospitalier de l’Universite de Montreal, Montreal, QC
Celia Marginean	Pathologist, Ottawa Hospital, Ottawa, ON
Advisory Board members
Shun Wong	Radiation Oncologist, Sunnybrook Health Sciences Center, Odette Cancer Center, Toronto, ON
Jean Maroun	Medical Oncologist, Ottawa Hospital Cancer Center, Ottawa, ON
Barb Melosky	Medical Oncologist, British Columbia Cancer Agency, Vancouver, BC
Thiery Alcindor	Medical Oncologist, McGill Cancer Center, Montreal, QC
Rasmy Loungnarath	Surgical Oncologist, Centre hospitalier de l’Universite de Montreal, Montreal, QC
Ralph Wong	Medical Oncologist, Cancer Care Manitoba, Winnipeg, MB
Kartik Jhavery	Radiologist, University Health Network, Princess Margaret Hospital, Toronto, ON
Sophie Lavertu	Radiation Oncologist, Centre hospitalier de l’Universite de Montreal, Montreal, QC
Erin Kennedy	Surgeon, University Health Network, Princess Margaret Hospital, Toronto, ON
Pierre Major	Medical Oncologist, Juravinski Cancer Center, Hamilton, ON
Eric Chen	Medical Oncologist, University Health Network, Princess Margaret Hospital, Toronto, ON
Audet Pascale	Radiologist, Centre hospitalier de l’Universite de Montreal, Montreal, QC
David Donath	Radiation Oncologist, Centre hospitalier de l’Universite de Montreal, Montreal, QC
Hugo Villeneuve	Radiation Oncology Resident, Centre hospitalier de l’Universite de Montreal, Montreal QC
Aaron Pollett	Pathologist, Mt. Sinai Hospital, Toronto, ON
Eugene Hsieh	Pathologist, Sunnybrook Health Sciences Center, Odette Cancer Center, Toronto, ON
Christine Cripps	Medical Oncologist, Ottawa Hospital Cancer Center, Ottawa, ON
Host
Colorectal Cancer Association of Canada	Barry Stein, President
Meeting organizer and scribe
Shaniah Leduc	CancerInsight
Observers
Charles Pitts	OroAlliance
Patricia Brooks Lemoine	Colorectal Cancer Association of Canada
Manon Jobin	Amgen
Barb Burgess	Amgen
Nermine Ibrahim	Sanofi-Aventis
Therese Boucher	Sanofi-Aventis
Scott Leduc	CancerInsight

Health care professionals involved in the care of patients with potentially curable rectal cancer

Stakeholders (provincial cancer agencies, hospitals, and so on) responsible for program and funding decisions related to the management of potentially resectable cancer

Patient advocacy and education groups such as the Colorectal Cancer Association of Canada

1.4 Basis of Recommendations

All recommendations are based on a structured presentation and discussion of the best available evidence.

2. PREAMBLE

2.1 Application of Recommendations

These standards provide the basis for a discussion with patients regarding management options. Treatment plans will depend on a more complete discussion of the risks and benefits of proposed therapies with individual patients.

Significant progress has been made in improving outcomes for patients with potentially resectable rectal cancer; however, further improvement is necessary. Offering patients the option of participating in clinical trials should be a priority.

Optimally, the approach for assessing and managing patients with rectal cancer should involve a collaborative, multidisciplinary team (including all relevant medical specialties and allied health professionals). For example, optimal rectal cancer management is predicated on open communication and quality assurance between the surgeon and the pathologist describing the extent of disease of the surgical specimen for optimal postsurgical treatment choices.

Radiologic assessment and imaging should be completed within 2–3 weeks to ensure that the appropriate information is available to make timely management decisions.

3. QUESTIONS AND CONSENSUS STATEMENTS

Question 1

For complete clinical staging of rectal cancer, what should the standard diagnostics and reporting be (preoperative assessment)?

Consensus Statement 1

All diagnostics should be completed within a timely period (42 days to treatment, including imaging within the first 2–3 weeks), starting from the date of biopsy.

Services should include:

Colonoscopy

Imaging

Computed axial tomography of thorax, abdomen, and pelvis AND magnetic resonance imaging (mri)

Slices of 3–4 mm should be routine

Mesorectal margin measurements or circumferential resection margin (crm) with tumour distance should be reported

Measurements for staging criteria should be provided (see the radiology protocol in Appendix A)

When available, endorectal ultrasonography may be complementary to mri in some T1/2 patients to better delineate T-stage

This statement utilizes Beets–Tan et al. 2001 1, Brown et al. 2003 2, Filippone et al. 2004 3, Nagtegaal et al. 2002 4, Iafrate et al. 2006 5, Kapiteijn et al. 2001 6, and Harisinghani et al. 2003 7.

Question 2

For complete clinical staging of rectal cancer, what should constitute standard pathology reporting?

Consensus Statement 2

For complete clinical staging of rectal cancer, synoptic reporting in accordance with the College of American Pathologists (cap) protocol for the examination of specimens from patients with primary carcinomas of colon and rectum, based on the American Joint Committee on Cancer and International Union Against Cancer TNM, to include these points:

Total mesorectal excision (tme) quality

Macroscopic assessment of mesorectum (complete, partially complete, or incomplete)

crm status

Positive if tumour is at 1 mm or less from the crm or if a lymph node with metastasis is at 1 mm or less from the crm

If neoadjuvant therapy was received, pathologic tumour response grading should be recorded

For the complete protocol, see the cap template (Appendix B).

This statement utilizes Nagtegaal and van Krieken 2002 8, Quirke 1998 9, Heald and Ryall 1986 10, Dworak et al. 1997 11, Washington et al. 2008 13, Smith et al. 2008 14, Kapiteijn et al. 2001 15, Nagtegaal and Quirke 2008 16, Rödel et al. 2005 17, Glynne–Jones et al. 2006 18,19, Ruo et al. 2002 20, Nagtegaal et al. 2002 21, and Parfitt and Driman 2007 22.

Question 3

Which neoadjuvant radiation protocol or protocols should be standard when combined with chemotherapy?

Consensus Statement 3

Preoperative neoadjuvant radiotherapy is the standard of care for clinically staged ii and iii patients. Long-course radiation (minimum of 45 cGy over 5 weeks) with fluoropyrimidine chemotherapy or short-course radiation without chemotherapy can be considered. A multidisciplinary team approach (with or without a tumour board) is important to review individual cases and reach consensus on the appropriate course of treatment (short- vs. long-course radiation).

This statement utilizes Bujko et al. 2004 23, Marijnen et al. 2003 24, Swedish Rectal Cancer Trial 1997 25, Bosset et al. 2006 26, Gérard et al. 2006 27, and Sauer et al. 2004 28.

Question 4

Which neoadjuvant chemotherapy protocol or protocols should be standard when combined with long-course radiation?

Consensus Statement 4

The optimal fluoropyrimidine-based chemotherapy is based on extrapolation of data from randomized trials of combined-modality chemoradiation used in the postoperative setting. Use fluoropyrimidine-based chemotherapy with long-course radiation. Protracted fluoropyrimidine is preferable to bolus 5-fluorouracil because of improved tolerability and similar efficacy, as seen in the largest and most recent randomized trial (int 0144) 29.

This statement utilizes Smalley et al. 2006 29, Wong et al. 2008 30, and O’Connell 1994 31.

Question 5

What should be the surgical standard of care for rectal cancer?

Consensus Statement 5

All stage ii–iii rectal cancers should be considered for neoadjuvant treatment. For all rectal cancers undergoing radical surgery, tme principles must be followed. Surgeons treating rectal cancer patients should be familiar with the tme surgery. Quality should be assured through independent evaluations by the surgeon and the pathologist. Synoptic operative reporting is encouraged.

Trans-anal excision represents an oncologic compromise for most rectal cancer patients. Consider it only in patients with comorbidities, realizing that it requires excellent preoperative assessment and high intraoperative expertise.

Because trans-anal endoscopic microsurgery is a new approach for local excision, patients being treated using this approach should preferably be enrolled in trials or prospective follow-up studies.

This statement utilizes MacFarlane et al. 1993 32, Cecil et al. 2004 33, Dahlberg et al. 1998 34, Martling et al. 2000 35, Brown and Daniels 2005 36, Dubé et al. 1997 37, Karanjia et al. 1992 38, Ricciardi 2007 39, Murphy 2008 40, Ptok 2007 41, van den Brink 2004 42, Wibe 2002 43, Okabe 2004 44, and Nash 2009 45.

Question 6

What criteria should be standard for handling, evaluating, and reporting on the surgical specimen?

Consensus Statement 6

The surgeon should be aware of the standard macroscopic evaluation (grades 1, 2, 3) of the surgical specimen immediately after removal of the rectum. The pathologist receiving the specimen should also grade the macroscopic quality of the excision, independently of grading by the surgeon. Optimal management is predicated on productive, open communication between the surgeon and the pathologist so that quality assurance and appropriate mechanisms for evaluation and improvement can be achieved (see also consensus statement 5). Collaboration is mandatory for optimal evaluation; that is, margin assessment, surgical difficulty encountered, neoadjuvant treatment given to the patient must be communicated. (For optimal assessment of the specimen, the pathologist has to be informed if neoadjuvant therapy was administered.)

This statement takes account of Nagtegaal and van Krieken 2002 8, Quirke 1998 9, Dworak 1997 11, Washington et al. 2008 13, Smith 2008 14, Kapiteijn 2001 15, Nagtegaal and Quirke 2008 16, Nagtegaal 2002 21, and Parfitt and Driman 2007 22.

Question 7

What is the standard adjuvant chemotherapy post neoadjuvant treatment and surgery?

Consensus Statement 7

All patients should be considered for 4–6 months of fluoropyrimidine-based therapy. Based on extrapolation of phase III trials for adjuvant treatment of colon cancer, adjuvant oxaliplatin-based therapy should be considered for patients at high risk for recurrence, including, but not limited to those who are

ypN-positive.

crm-positive.

This statement utilizes Sauer et al. 2004 28, Wong et al. 2008 29, André et al. 2009 46, and Kuebler et al. 2007 47.

5. CONFLICTS OF INTEREST

Participants disclosed potential conflicts of interest within the past 2 years:

Scott Berry: Advisory boards for Sanofi–Aventis

Celia Marginean: None

Carole Richard: None

Andrew Smith: None

Te Vuong: Work as a consultant for Sanofi–Aventis

The Colorectal Cancer Association of Canada and the authors acknowledge the sponsors who provided unrestricted grants: Sanofi–Aventis, Bristol–Myers Squibb, and Amgen.