International Journal of Radiation Oncology*Biology*Physics
Clinical investigationRectumCan histopathologic assessment of circumferential margin after preoperative pelvic chemoradiotherapy for T3-T4 rectal cancer predict for 3-year disease-free survival?
Introduction
The optimal management of Stage II and III rectal cancer continues to be an increasing challenge for oncologists. Although surgery remains the mainstay of treatment, historically a high risk of local recurrence and poor survival has been reported for these patients. Randomized studies in the era before total mesorectal excision (TME) demonstrated local recurrence rates of 15–35% and a 5-year overall survival (OS) rate of approximately 60% for Dukes B2 and only 25% for Dukes C after surgery (1). The 5-year survival rate remains in the region of 40–55% in most modern series (2, 3), even when patients have undergone curative resection. Recent advances in surgical technique have resulted in a significant reduction in the risk of local recurrence; however, these improvements do not appear to have had an affect on OS (4, 5).
One-third of rectal cancer patients will present with locally advanced tumors (T3 and T4), and in up to 20% of cases, curative (histologically confirmed) R0 resection will not be achieved (6, 7). Approximately 40–50% of patients who undergo potentially curative surgery for rectal cancer will ultimately relapse and die of subsequent metastatic disease (8). TME alone is, therefore, insufficient for more locally advanced rectal cancer, and further improvements in survival are only likely to be gained with the use of better chemotherapy and radiotherapy (RT) combinations.
The main prognostic factors remain the extent of the primary tumor (T stage), regional lymph node status (N stage), and whether the circumferential resection margin (CRM) is sufficient. Previous studies (9) have confirmed that the greatest relapse rates were found in patients with nodal involvement and tumor extension beyond the rectal wall. Data from the Norwegian Rectal Cancer Project showed that at a median follow-up of 29 months, 40% of patients who had a positive CRM developed metastatic disease compared with 12% in whom the margin was >1 mm (10).
Methods of identifying and selecting which patients may benefit from preoperative chemoradiotherapy (CRT) have focused on digital rectal examination (DRE) and cross-sectional imaging using CT or MRI. DRE by an experienced coloproctologist can identify fixity as an indicator of locally advanced disease. Pelvic MRI using a surface phased array coil can demonstrate the relationship of the primary tumor to the mesorectum and the surrounding mesorectal fascia and appears to be able to predict the circumferential margin preoperatively and achieve good correlation with pathologic measurements (11, 12, 13, 14). Thus, preoperative CRT is increasingly offered to patients with rectal cancer who are expected on the basis of MRI criteria to have a close or involved resection margin with current surgical techniques.
Neoadjuvant CRT has been shown to downstage tumors, with more cases of Dukes A staging, a better surgical resection (R0) rate, and more sphincter-sparing procedures (15, 16). Controversy exists as to whether this correlates with improved survival (17, 18). In a recent large study of resectable rectal cancer cases (19), preoperative CRT was associated with a significantly improved local control rate compared with postoperative CRT, but OS was not improved. Downstaging after preoperative CRT also appears to be a significant prognostic factor, and patients with pT0, T1, or T2 disease appear to have a better prognosis (20, 21).
The aim of this study was to determine the rates of pathologic downstaging and negative circumferential margins and to define their relationship to local recurrence and disease-free survival (DFS) and OS.
Section snippets
Methods and materials
The Mount Vernon Cancer Centre serves a population of 1.8 million. A prospective database confirmed that 150 consecutive patients with primary, locally advanced rectal cancer received synchronous 5-fluorouracil (5-FU)–based CRT between January 1995 and December 2002. All patients were considered to have borderline resectable or unresectable disease by the referring surgeons.
Tumors were defined as rectal if the lower limit was located within 12 cm of the anal verge on rigid sigmoidoscopy.
Results
A total of 150 patients underwent CRT and 122 subsequently underwent surgery (81%). Five patients who had had a complete clinical response refused surgery, 4 patients died before surgery, 11 patients’ disease remained unresectable, and 4 patients had widespread peritoneal metastases at exploration and, therefore, did not undergo radical resection. One patient did not undergo surgery because of comorbidity, and three were lost to follow-up (Fig. 1).
Of the 122 patients who underwent surgery, 75
Discussion
Chemoradiotherapy before surgery is now a common approach in the treatment of locally advanced rectal cancers (15, 16, 18), which has focused on the potential for downstaging to enable a curative surgical resection or a sphincter-sparing procedure. Standard surgical resection, even with TME, in cancers that are partially or totally fixed is usually associated with very high rates of incomplete excision and almost universal local recurrence at a later date. For this reason, most surgeons accept
Conclusion
The results of this study have suggested that preoperative 5-FU–based CRT can produce effective downstaging and improve the R0 resection rates with a negative CRM in patients with locally advanced rectal carcinoma. A positive CRM is associated with very poor OS and DFS. However, of all the currently recognized risk factors for local recurrence and metastatic disease, the circumferential margin is the only one that could potentially be influenced by all forms of treatment (surgery, chemotherapy,
Acknowledgments
We acknowledge the help and cooperation of the following surgeons who also contributed to this study: J. Nicholls, R. Phillips, D. Cairns, R. Hallan, J. Gilbert, and J. McCue.
References (39)
- et al.
Defining the needs for adjuvant therapy of rectal and colonic cancer
Surg Clin North Am
(1981) - et al.
Radiotherapy does not compensate for positive resection margins in rectal cancer patientsReport of a multicenter randomized trial
Int J Radiat Oncol Biol Phys
(2003) - et al.
Sphincter preservation following preoperative radiotherapy for rectal cancerReport of a randomised trial comparing short-term radiotherapy vs. conventionally fractionated radiochemotherapy
Radiother Oncol
(2004) - et al.
Impact of T and N substage on survival and disease relapse in adjuvant rectal cancerA pooled analysis
Int J Radiat Oncol Biol Phys
(2002) - et al.
Accuracy of magnetic resonance imaging in prediction of tumour-free resection margin in rectal cancer surgery
Lancet
(2001) - et al.
Does downstaging predict improved outcome after preoperative chemoradiation for extraperitoneal locally advanced rectal cancer? A long-term analysis of 165 patients
Int J Radiat Oncol Biol Phys
(2002) - et al.
Prognostic significance of postchemoradiation stage following preoperative chemotherapy and radiation for advanced/recurrent rectal cancers
Int J Radiat Oncol Biol Phys
(2000) - et al.
Local recurrence of rectal adenocarcinoma due to inadequate surgical resectionHistopathological study of lateral tumour spread and surgical excision
Lancet
(1986) - et al.
Effect of preoperative irradiation on resectability of colorectal carcinomas
Int J Radiat Oncol Biol Phys
(1982) - et al.
Residual, unresectable, or recurrent colorectal cancerExternal beam irradiation and intraoperative electron beam boost ± resection
Int J Radiat Oncol Biol Phys
(1983)
Effects of positive resection margin and tumor distance from anus on rectal cancer treatment outcomes
Am J Surg
Role of circumferential margin involvement in the local recurrence of rectal cancer
Lancet
Preoperative chemoradiotherapy versus preoperative radiotherapy in rectal cancer patientsAssessment of acute toxicity and treatment compliance—Report of the 22921 randomised trial conducted by the EORTC Radiotherapy Group
Eur J Cancer
Pathologic complete response predicts long-term survival following preoperative radiotherapy for rectal cancer [Abstract]
Int J Radiat Biol Phys
Postoperative adjuvant chemotherapy or radiation therapy for rectal cancerResults from NSABP protocol R-01
J Natl Cancer Inst
Local recurrence after curative excision of the rectum for cancer without adjuvant therapyRole of total anatomical dissection
Br J Surg
Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer
N Engl J Med
Prospective multicenter study of the quality of oncologic resections in patients undergoing laparoscopic colorectal surgery for cancer
Dis Colon Rectum
Adjuvant therapy in rectal cancerAnalysis of stage, sex, and local control—Final report of intergroup 0114
J Clin Oncol
Cited by (104)
Oncological strategy following R1 sphincter-saving resection in low rectal cancer after chemoradiotherapy
2021, European Journal of Surgical OncologyManagement of the positive pathologic circumferential resection margin in rectal cancer: A national cancer database (NCDB) study
2021, European Journal of Surgical OncologyHow to measure tumour response in rectal cancer? An explanation of discrepancies and suggestions for improvement
2020, Cancer Treatment ReviewsContinuous Effect of Radial Resection Margin on Recurrence and Survival in Rectal Cancer Patients Who Receive Preoperative Chemoradiation and Curative Surgery: A Multicenter Retrospective Analysis
2017, International Journal of Radiation Oncology Biology Physics