Glynne-Jones R, Mawdsley S, Novell JRThe clinical significance of the circumferential resection margin following preoperative pelvic chemo-radiotherapy in rectal cancer: why we need a common language. Colorectal Dis 8: 800-807

Luton and Dunstable Hospital NHS Foundation Trust, Luton, England, United Kingdom
Colorectal Disease (Impact Factor: 2.35). 12/2006; 8(9):800-7. DOI: 10.1111/j.1463-1318.2006.01139.x
Source: PubMed


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.

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    • "Local treatment approach such as postoperative radiotherapy or CRT has failed to compensate for positive CRM according to previous studies [2,4]. Systemic therapy may be required because positive CRM is related with high risk for distant metastasis as demonstrated in the current study as well as other studies [6,7,9,10,14]. EORTC 22921 showed that the tumor biology could be linked to the effect of chemotherapy [18]. "
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    ABSTRACT: Circumferential resection margin (CRM) and distal resection margin (DRM) have different impact on clinical outcomes after preoperative chemoradiotherapy (CRT) followed by surgery. Effect and adequate length of resection margin as well as impact of treatment response after preoperative CRT was evaluated. Total of 403 patients with rectal cancer underwent preoperative CRT followed by total mesorectal excision between January 2004 and December 2010. After applying the criterion of margin less than 0.5 cm for CRM or less than 1 cm for DRM, 151 cases with locally advanced rectal cancer were included as a study cohort. All patients underwent conventionally fractionated radiation with radiation dose over 50 Gy and concurrent chemotherapy with 5-fluorouracil or capecitabine. Postoperative chemotherapy was administered to 142 patients (94.0%). Median follow-up duration was 43.1 months. The 5-year overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS) rates, and locoregional control rates (LRC) were 84.5%, 72.8%, 74.2%, and 86.3%, respectively. CRM of 1.5 mm and DRM of 7 mm were cutting points showing maximal difference in a maximally selected rank method. In univariate analysis, CRM of 1.5 mm was significantly related with worse clinical outcomes, whereas DRM of 7 mm was not. In multivariate analysis, CRM of 1.5 mm, and ypN were prognosticators for all studied endpoints. However, CRM was not a significant prognostic factor for good responders, defined as patients with near total regression or T down-staging, which was found in 16.5% and 40.5% among studied patients, respectively. In contrast, poor responders demonstrated a significant difference according to the CRM status for all studied end-points. Close CRM, defined as 1.5 mm, was a significant prognosticator, but the impact was only prominent for poor responders in subgroup analysis. Postoperative treatment strategy may be individualized based on this finding. However, findings from this study need to be validated with larger cohort.
    Full-text · Article · Dec 2013 · BMC Cancer
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    ABSTRACT: The improvement in local control by preoperative radiotherapy for rectal cancer can be at the cost of substantial morbidity. The aim of this study was to determine the impact of short-course preoperative radiotherapy on morbidity and mortality after total mesorectal excision in a low-volume hospital. From 2000 to 2007, 104 patients underwent rectal resection for a proven malignancy. Outcome parameters including anastomotic leakage rate, duration of hospital stay, and survival were retrospectively compared between patients who received radiotherapy followed by resection and patients who underwent resection alone. Anastomotic leakage occurred in 11 of 28 patients (39%) who underwent radiotherapy and in 10 of 54 patients (19%) in the surgery-alone group (P = 0.04). The length of hospital stay was significantly longer in the radiotherapy group in comparison with the surgery-alone group (median 22 vs. 12 days; P = 0.002). Independent predictors of decreased overall survival were high American Society of Anesthesiologists classification, application of preoperative radiotherapy, necessity of Intensive Care Unit admission, and advanced pathological stage. A negative impact of preoperative radiotherapy on morbidity and mortality after rectal cancer surgery with an annual caseload of 16 was observed. Auditing of local practices is essential for quality control and potential improvement of clinical outcome.
    Full-text · Article · Feb 2007 · Journal of Gastrointestinal Cancer
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    ABSTRACT: After preoperative (radio)chemotherapy, histologic determinants for prognostication have changed. It is unclear which variables, including assessment of tumor regression, are the best indicators for local recurrence and survival. A series of 201 patients with locally advanced rectal cancer (cT3/T4, M0) presenting with an involved or at least threatened circumferential margin (CRM) on preoperative imaging (<2 mm) were evaluated using standard histopathologic variables and four different histologic regression systems. All patients received neoadjuvant radiochemotherapy or radiotherapy. The prognostic value of all factors was tested with univariate survival analysis of time to local recurrence and overall survival. Local recurrence occurred in only 8% of the patients with a free CRM compared with 43% in case of CRM involvement (P < 0.0001). None of the four regression systems were associated with prognosis, not even when corrected for CRM status. However, we did observe a higher degree of tumor regression after radiochemotherapy compared with radiotherapy (P < 0.001). Absence of tumor regression was associated with increasing invasion depth and a positive CRM (P = 0.02 and 0.03, respectively). Assessment of CRM involvement is the most important pathologic variable after radiochemotherapy. Although tumor regression increases the chance on a free CRM, in cases with positive resection margins prognosis is poor irrespective of the degree of therapy-induced regression.
    Full-text · Article · Nov 2007 · Clinical Cancer Research
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