Multicentre cohort study to define and validate pathological assessment of response to neoadjuvant therapy in oesophagogastric adenocarcinoma

BackgroundThis multicentre cohort study sought to define a robust pathological indicator of clinically meaningful response to neoadjuvant chemotherapy in oesophageal adenocarcinoma. MethodsA questionnaire was distributed to 11 UK upper gastrointestinal cancer centres to determine the use of assessment of response to neoadjuvant chemotherapy. Records of consecutive patients undergoing oesophagogastric resection at seven centres between January 2000 and December 2013 were reviewed. Pathological response to neoadjuvant chemotherapy was assessed using the Mandard Tumour Regression Grade (TRG) and lymph node downstaging. ResultsTRG (8 of 11 centres) was the most widely used system to assess response to neoadjuvant chemotherapy, but there was discordance on how it was used in practice. Of 1392 patients, 1293 had TRG assessment; data were available for clinical and pathological nodal status (cN and pN) in 981 patients, and TRG, cN and pN in 885. There was a significant difference in survival between responders (TRG 1-2; median overall survival (OS) not reached) and non-responders (TRG 3-5; median OS 222 (95 per cent c.i. 194 to 251) years; P<0001); the hazard ratio was 246 (95 per cent c.i. 122 to 495; P=0012). Among local non-responders, the presence of lymph node downstaging was associated with significantly improved OS compared with that of patients without lymph node downstaging (median OS not reached versus 192 (168 to 216) years; P<0001). ConclusionA clinically meaningful local response to neoadjuvant chemotherapy was restricted to the small minority of patients (148 per cent) with TRG 1-2. Among local non-responders, a subset of patients (213 per cent) derived benefit from neoadjuvant chemotherapy by lymph node downstaging and their survival mirrored that of local responders. Response associated with survival