The clinical significance of the circumferential resection margin following preoperative pelvic chemo-radiotherapy in rectal cancer: why we need a common language.
ABSTRACT The presence of microscopic tumour cells within 1 mm of the circumferential surgical resection margin (CRM) is the endpoint most strongly associated with local recurrence in rectal cancer and doubles the risk of developing distant metastases. Reporting on the CRM can monitor surgical quality assurance and over the past two decades has driven advances in surgical technique with the increasing use of total mesorectal excision. The aim of this review was to use the evidence from both phase II and phase III randomized trials of preoperative radiotherapy and chemoradiation in rectal cancer, to assess how often CRM involvement is currently documented and examine its utility as an early predictor of both disease-free and overall survival.
A literature search identified both randomized and nonrandomized trials of preoperative radiation therapy and chemoradiation therapy in rectal cancer since 1993. The aim was to find those studies, which documented the distance from the periphery of the tumour and the CRM. Small trials treating < 20 patients were excluded.
One hundred and eighty-seven phase II and 28 phase III trials of preoperative radiotherapy or chemoradiation were identified. Most trials documented the degree of response but only 10 of 187 phase II/retrospective studies and four of 28 phase III trials presented data on the achievement of a negative CRM. Few defined this early pathological endpoint prospectively with accurate measurements. However, the majority of studies did use the definition of <or= 1 mm as an involved CRM. Discussion Pathological parameters have been used as early endpoints to compare studies of preoperative radiotherapy or chemoradiation. It remains uncertain whether the degree of response to chemoradiation (e.g. complete pathological response, downsizing the primary tumour, sterilizing the regional nodes, tumour regression grades or residual cell density) or the achievement of a curative resection (uninvolved CRM) is the best early clinical endpoint. Retrospective studies in rectal cancer have confirmed a strong association between the presence of microscopic tumour cells within 1 mm of the CRM and increased risks of both local recurrence and distant metastases. However, as yet this early pathological endpoint lacks structured measurement and analysis techniques to control for intra- and inter-observer variation and has not been validated as a potential surrogate for local control and survival. Recommendations are made as to the most appropriate information, which should be documented in future trials.
The CRM status predicts outcome after surgery alone, preoperative radiotherapy and preoperative chemoradiation. Yet CRM status and its measurement has been poorly documented in the literature, and rarely as a prospective measure of outcome. The CRM should be measured and documented in all cases, using the definition of <or= 1 mm to denote an involved CRM. This definition should also be incorporated into future rectal cancer studies with the use of a standardized proforma.
- SourceAvailable from: Yojiro Hashiguchi[show abstract] [hide abstract]
ABSTRACT: To clarify the characteristics related to long-term survival in patients with lateral nodal involvement. Few reports have addressed the prognostic determinants in patients with actual lateral nodal involvement, which are important in determining treatment. Review of a prospective colorectal database at a single institution for a 10-year period (1987-1996) identified 53 patients with lateral nodal involvement. All nine patients who underwent resection of synchronous distant metastases developed recurrence and died within 3 years. Of the 44 patients without distant metastases, 25 (57%) developed locoregional recurrence, and the overall 5-year survival rate was 32%. Multivariate analysis showed that age, total number of involved nodes (mesorectal and lateral), and circumferential surgical margin involvement had independently predicted postoperative survival. Patients with three or fewer nodes involved accounted for one third of lateral-positive patients, with a 5-year survival rate of 75%, whereas the 18 patients with four or more involved nodes had a 5-year survival rate of 4%. All eight patients with circumferential margin involvement died of carcinoma, and seven developed locoregional recurrences. Involvement of other pelvic organs had no effect on prognosis, nor were adverse prognostic outcomes noted by the region of lateral involvement. For patients with lateral involvement, the most important prognostic variables are distant metastases, the total number of nodes involved, circumferential margin involvement, and age. Selection of patients based on these variables may lead to the identification of a subgroup for whom lateral nodal dissection could be the first treatment choice.Annals of Surgery 09/2001; 234(2):190-7. · 6.33 Impact Factor
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ABSTRACT: This study examines the prognostic significance of circumferential margin involvement by tumor in resected specimens after potentially curative rectal cancer surgery. During an eight-year period, all patients with rectal cancer were prospectively audited. For tumors of the middle and lower thirds of the rectum, a total mesorectal excision was performed; for tumor of the upper third, mesorectal excision proceeded at least 5 cm distal to the primary tumor. Resected specimens were subjected to careful histologic assessment, and patients undergoing curative procedures were entered into a surveillance program to detect both local and distant recurrence. Of 218 patients in the cohort, 9 had no resection, 14 underwent local excision, 1 had pre-operative radiotherapy, and 42 patients (20 percent) had palliative resections and were excluded from further analysis. This left 152 patients having a curative resection, of whom 20 (13 percent) had tumor within 1 mm of the circumferential margin. After follow-up until death or a median period of 41 months, recurrent disease was seen in 24 percent of patients with a negative margin and 50 percent with a positive margin. Both disease-free survival and mortality were significantly related to margin involvement (log-rank, P = 0.01 and P = 0.005, respectively). Local recurrence, however, was not significantly different in the two groups (11 and 15 percent, respectively; log-rank, P = 0.38). When mesorectal excision is performed, circumferential margin involvement is more an indicator of advance disease than inadequate local surgery. Patients with an involved margin may die from distant disease before local recurrence becomes apparent.Diseases of the Colon & Rectum 09/1998; 41(8):979-83. · 3.34 Impact Factor
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ABSTRACT: To analyze the potential variability in rates of circumferential resection margin (CRM) involvement between different surgeons and time periods and to determine the suitability of using CRM status as an immediate predictor of outcome after rectal cancer surgery. After disease stage has been taken into account, survival in rectal cancer has been shown to be very variable between surgeons and institutions. One of the major factors influencing survival is local recurrence, and this in turn is strongly related to inadequate tumor excision, particularly at the CRM. In a study involving 608 patients who underwent surgery for rectal cancer in Leeds during the 12-year period 1986 to 1997, the authors examined the role of CRM status as an immediate predictor of likely outcome, paying particular attention to its relationships with different surgeons and time periods. Of 586 patients on whom full clinical follow-up was obtained, 165 (28.2%) had CRM involvement by carcinoma on pathologic examination. Up to the end of 1998, 105 (17.9%) patients had developed local recurrence. A significantly higher proportion (38.2%) of CRM-positive patients developed local recurrence than CRM-negative ones (10.0%). Kaplan-Meier survival analysis showed significant improvements in survival for CRM-negative patients over CRM-positive patients. Survival analysis in relation to two gastrointestinal surgeons and a group of other surgeons showed survival improvements that paralleled a reduction in the rates of CRM involvement for the two gastrointestinal surgeons during the period of the study. No improvement in survival or reduction in rates of CRM involvement was seen in the group of other surgeons. These results show that CRM status may be used as an immediate predictor of survival after rectal cancer surgery and serves as a useful indicator of the quality of surgery. The frequency of CRM involvement can be used both for overall surgical audit and for monitoring the value of training programs in improving rectal surgery by individual surgeons. Its use in the current MRC CR07 study is valid and the best indicator of a requirement for further local therapy.Annals of Surgery 05/2002; 235(4):449-57. · 6.33 Impact Factor