Residual disease after neoadjuvant chemoradiotherapy for oesophageal cancer: locations undetected by endoscopic biopsies in the preSANO trial.

BACKGROUND: Active surveillance has been proposed for patients with oesophageal cancer in whom there is a complete clinical response after neoadjuvant chemoradiotherapy (nCRT). However, endoscopic biopsies have limited negative predictive value in detecting residual disease. This study determined the location of residual tumour following surgery to improve surveillance and endoscopic strategies. METHODS: The present study was based on patients who participated in the prospective preSANO trial with adenocarcinoma or squamous cell carcinoma of the oesophagus or oesophagogastric junction treated in four Dutch hospitals between 2013 and 2016. Resection specimens and endoscopic biopsies taken during clinical response evaluations after nCRT were reviewed by two expert gastrointestinal pathologists. The exact location of residual disease in the oesophageal wall was determined in resection specimens. Endoscopic biopsies were assessed for the presence of structures representing the submucosal layer of the oesophageal wall. RESULTS: In total, 119 eligible patients underwent clinical response evaluations after nCRT followed by standard surgery. Residual tumour was present in endoscopic biopsies from 70 patients, confirmed on histological analysis of the resected organ. Residual tumour was present in the resection specimen from 27 of the other 49 patients, despite endoscopic biopsies being negative. Of these 27 patients, residual tumour was located in the mucosa in 18, and in the submucosa beneath tumour-free mucosa in eight. One patient had tumour in muscle beneath tumour-free mucosa and submucosa. CONCLUSION: Most residual disease after nCRT missed by endoscopic biopsies was located in the mucosa. Active surveillance could be improved by more sampling and considering submucosal biopsies.

ANTECEDENTES: Se ha propuesto un seguimiento activo para los pacientes con cáncer de esófago en los que se logra una respuesta clínica completa tras quimiorradioterapia neoadyuvante (neoadjuvant chemoradiotherapy, nCRT). Sin embargo, las biopsias endoscópicas tienen un valor predictivo limitado para detectar la enfermedad residual. En este estudio se evaluó la localización del tumor residual tras la cirugía para poder determinar estrategias de seguimiento y endoscópicas. MÉTODOS: Este estudio se basa en pacientes que participaron en el ensayo prospectivo preSANO (adenocarcinoma o carcinoma escamoso del esófago o unión esofagogástrica en cuatro hospitales de los Países Bajos entre 2013 y 2016). Los especímenes quirúrgicos, así como las biopsias endoscópicas efectuadas durante las evaluaciones de la respuesta clínica después de nCRT fueron revisadas por dos patólogos gastrointestinales expertos. En los especímenes de resección, se determinó la localización exacta de la enfermedad residual en la pared del esófago. Se evaluaron las biopsias endoscópicas para identificar estructuras que constituyeran la capa submucosa de la pared del esófago. RESULTADOS: En total, 119 pacientes elegibles fueron sometidos a evaluaciones de la respuesta clínica tras nCRT seguida de cirugía estándar. Se detectó tumor residual en las biopsias endoscópicas de 70 pacientes, luego confirmadas en la histología de la pieza extirpada. Se identificó tumor residual en la pieza de resección de 27 de los otros 49 pacientes, a pesar de que las biopsias endoscópicas fueron negativas. En estos 27 pacientes, 18 presentaban tumor residual en la mucosa y ocho pacientes en la submucosa mas allá de una mucosa libre de tumor. Un paciente tenía tumor en el músculo más allá de una mucosa y submucosa libres de tumor. CONCLUSIÓN: La mayoría de los casos de enfermedad residual tras nCRT que no se detectaron en las biopsias endoscópicas, se localizaban en la mucosa. El seguimiento activo podría mejorar con la toma de más muestras y considerando las biopsias submucosas.

Pattern of recurrence in patients with a pathologically complete response after neoadjuvant chemoradiotherapy and surgery for oesophageal cancer.

BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) and surgery is a widely used treatment for locally advanced resectable oesophageal cancer, with 20-50 per cent of patients having a pathological complete response (pCR). Disease, however, still recurs in 20-30 per cent of these patients. The aim of this study was to assess the pattern of recurrence in patients with a pCR after nCRT and surgery. METHODS: All patients with a pCR after nCRT and surgery included in the phase II and III CROSS (ChemoRadiotherapy for Oesophageal followed by Surgery Study) trials (April 2001 to December 2008) and after the CROSS trials (September 2009 to October 2017) were identified. The site of recurrence was compared with the applied radiation and surgical fields. Outcomes were median time to recurrence, and overall and progression-free survival. RESULTS: A total of 141 patients with a median follow-up of 100 (i.q.r. 64-134) months were included. Some 29 of 141 patients (20,6 per cent) developed recurrence. Of these, four had isolated locoregional recurrence, 15 had distant recurrence only, and ten had both locoregional and distant recurrence. Among the 14 patients with locoregional recurrences, five had recurrence within the radiation field, seven outside the radiation field, and two at the border. Median time to recurrence was 24 (10-62) months. The 5-year overall survival rate was 74 per cent and the recurrence-free survival rate was 70 per cent. CONCLUSION: Despite good overall survival, recurrence still occurred in 21 per cent of patients. Most recurrences were distant, outside the radiation and surgical fields.

Neoadjuvant chemoradiotherapy for resectable oesophageal cancer.

At present, treatment of potentially curable oesophageal cancer includes neoadjuvant chemoradiotherapy followed by oesophagectomy. Alternatively, neoadjuvant chemotherapy is used. To date, strong evidence on the superiority of one modality over the other has not been provided. Currently, up to one-third of patients show a pathologically complete response after neoadjuvant chemoradiotherapy. To optimise the efficacy of neoadjuvant treatment for individual patients, prediction of response to neoadjuvant treatment is highly desired. Therefore, several clinical diagnostic modalities have been investigated for early response evaluation, of which positron emission tomography (PET) has been studied most extensively. To identify patients who might benefit from postponing or even omitting surgery, recent advances have been made in evaluating response after completion of neoadjuvant chemoradiotherapy. This review provides an overview of current evidence and recent advances in neoadjuvant chemoradiotherapy for oesophageal cancer and discusses the use of neoadjuvant chemotherapy compared to chemoradiotherapy. Moreover, clinical response evaluation to neoadjuvant chemoradiotherapy is reviewed.