The clinical significance of the circumferential resection margin following preoperative pelvic chemo-radiotherapy in rectal cancer: why we need a common language.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Glynne-Jones
R
R
Centre for Cancer Treatment, Mount Vernon Hospital, Northwood, Middlesex, UK. rob.glynne-jones@whht.nhs.uk
Mawdsley
S
S
Novell
J R
JR
D017024:Chemotherapy, Adjuvant; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D023381:Endpoint Determination; D006651:Histocytochemistry; D006801:Humans; D018365:Neoplasm, Residual / Q000473:pathology*; D018714:Radiotherapy, Adjuvant; D012004:Rectal Neoplasms / Q000188:drug therapy / Q000473:pathology* / Q000532:radiotherapy / Q000601:surgery; D009626:Terminology as Topic; D016896:Treatment Outcome