Accuracy of detecting residual disease after neoadjuvant chemoradiotherapy for esophageal squamous cell carcinoma (preSINO trial): a prospective multicenter diagnostic cohort study

Abstract

Background: After neoadjuvant chemoradiotherapy (nCRT) for esophageal cancer, high pathologically complete response (pCR) rates are being achieved especially in patients with squamous cell carcinoma (SCC). An active surveillance strategy has been proposed for SCC patients with clinically complete response (cCR) after nCRT. To justify omitting surgical resection, patients with residual disease should be accurately identified. The aim of this study is to assess the accuracy of response evaluations after nCRT based on the preSANO trial, including positron emission tomography with computed tomography (PET-CT), endoscopy with bite-on-bite biopsies and endoscopic ultrasonography (EUS) with fine-needle aspiration (FNA) in patients with potentially curable esophageal SCC. Methods: Operable esophageal SCC patients who are planned to undergo nCRT according to the CROSS regimen and are planned to undergo surgery will be recruited from four Asian centers. Four to 6 weeks after completion of nCRT, patients will undergo a first clinical response evaluation (CRE-1) consisting of endoscopy with bite-on-bite biopsies. In patients without histological evidence of residual tumor (i.e. without positive biopsies), surgery will be postponed another 6 weeks. A second clinical response evaluation (CRE-2) will be performed 10-12 weeks after completion of nCRT, consisting of PET-CT, endoscopy with bite-on-bite biopsies and EUS with FNA. Immediately after CRE-2 all patients without evidence of distant metastases will undergo esophagectomy. Results of CRE-1 and CRE-2 as well as results of the three single diagnostic modalities will be correlated to pathological response in the resection specimen (gold standard) for calculation of sensitivity, specificity, negative predictive value and positive predictive value.

Moderately differentiated esophageal squamous cell carcinoma has a poor prognosis after neoadjuvant chemoradiotherapy

“…We first assessed the pathological characteristics of patients with ESCC who received NCRT using the Japanese residual tumor pattern, Mandard-TRG system, local inflammatory infiltration classification, and lymph node status. We found that patients with poorly differentiated tumors showed a better response to NCRT than those with well or moderately differentiated tumors, which is in line with the findings of a previous study (15). A possible reason for this is that poorly differentiated tumors have a high turnover of cells, which increases their likelihood of being affected by DNA damage and apoptosis following NCRT (16).…”

Diffusion-weighted MRI and 18F-FDG PET/CT in assessing the response to neoadjuvant chemoradiotherapy in locally advanced esophageal squamous cell carcinoma

“…The recently published preSANO study [ 19 ] reported that the clinical response evaluation using endoscopic ultrasonography, bite-on-bite biopsies, and fine-needle aspiration of suspicious lymph nodes was adequate for detection of locoregional residual disease, with PET-CT for detection of interval metastases. This evaluation system is now being utilized in patients with esophageal squamous cell cancer recruited from four Asian centers (pre-SINO study [ 29 ]). An additional multicenter prospective observational study developed a multimodal prediction modality, of which ctDNA and MRI were added, that accurately predicted histopathological response to nCRT (PRIDE study [ 30 ]).…”

Advances in the curative management of oesophageal cancer

“…The French Esostrate-Prodige 32 study is similar in design to SANO, but the randomisation method differs [ 73 ]. For SCC alone, in four Asian Centres, a preliminary study preSINO (surgery if needed for oesophageal cancer) is also underway based on preSANO principles; this might progress to an RCT [ 74 ].…”