title: Histological tumour response to pre-operative combined modality therapy in locally advanced rectal cancer.
abstract: BACKGROUND: Pre-operative combined modality therapy (CMT) is used in locally advanced rectal cancer. Its use affects the clinicopathological staging based on the resected specimen. Assessment of the tumour response in the resected specimen may provide prognostic information. This study was undertaken to determine the histological response to pre-operative chemoradiation and to assess the interobserver reliability of a newly developed tumour response grading system for rectal cancer. METHODS: Pre-operative biopsy specimens and the resected specimens of 21 patients with low rectal cancer were assessed. The patients underwent pre-operative CMT consisting of radiotherapy (45 Gy) with 5-FU either as a continuous infusion or as a bolus intravenous infusion with leucovorin. After four to six weeks tumour response was assessed by comparing pre-operative transrectal ultrasound (TRUS) findings (uT1-4, uN0-1) with postoperative histopathological assessment (pT1-4, pN0-1) using UICC TNM characteristics. Tumour response was defined as a decrease in T status. The histological response to CMT was based on the tumour regression grade (TRG) and ranged from fibrosis extending through the rectal wall with no residual cancer (TRG 1), to no evidence of tumour response (TRG 5). Inter-observer reliability was assessed using weighted and unweighted kappa statistics. RESULTS: Local downstaging was demonstrated in 11/21 (52%) of patients. Three of 21 patients had a TRG 1 response. Thirteen of 21 (62%) patients had TRG 1-3 responses to CMT. There was no significant correlation between local downstaging and TRG. The interobserver correlation coefficient for assessment of TRG was 0.88 (unweighted kappa). CONCLUSIONS: Local downstaging by pre-operative CMT can be demonstrated if pre-operative TRUS staging is compared to standard pathology staging in patients with rectal cancer. Local downstaging is not directly related to histologic response as assessed by TRG. Inter-observer reporting of tumour regression grade (TRG) is reliable.
authors.affiliation: University of Sydney, Royal Prince Alfred Hospital, Sydney NSW Australia, Department of Surgery, Royal Prince Alfred Hospital, Sydney NSW Australia, Department of Gastroenterology, Royal Prince Alfred Hospital, Sydney NSW Australia, Department of Pathology, Royal Prince Alfred Hospital, Sydney NSW Australia, Department of Radiation Oncology, Royal Prince Alfred Hospital, Sydney NSW Australia, Wellington Cancer Centre, Wellington Hospital, New Zealand.
authors.forename: M. J
authors.initials: MJ
authors.lastname: Morgan
authors.forename: D. J
authors.initials: DJ
authors.lastname: Koorey
authors.forename: D
authors.initials: D
authors.lastname: Painter
authors.forename: M
authors.initials: M
authors.lastname: Findlay
authors.forename: K
authors.initials: K
authors.lastname: Tran
authors.forename: G
authors.initials: G
authors.lastname: Stevens
authors.forename: M. J
authors.initials: MJ
authors.lastname: Solomon