Can Clinical Response Predict Pathologic Response Following Neoadjuvant Chemoradiation for Esophageal Cancer?

Approximately 20-40% of patients with locally advanced esophageal cancer will achieve a pathologic complete response (ypCR) following neoadjuvant chemoradiotherapy (nCRT). Predicting ypCR based on a clinical complete response (ycCR) has been a challenge. This study assessed the correlation between ycCR and ypCR, as determined from esophagectomy specimens.

Patients undergoing esophagectomy following nCRT at three major institutions between 2005 and 2018 were reviewed. Restaging, including PET/CT, endoscopy with biopsy, and esophageal ultrasound (EUS), was performed to determine ycCR.

Six hundred sixty patients were included, with 93.3% with esophageal adenocarcinoma histology. Six hundred fifty-eight of these patients underwent PET, 304 EUS, and 584 underwent a biopsy. Following nCRT, 148 (22.4%) were found to have a ypCR. Only 12/32 (37.5%) determined to have a ycCR were found to have a ypCR, while 136/628 (21.6%) with a non-ycCR were found to have a ypCR (p 0.075). Individual modality PPV was 28% for PET, 54% for EUS, and 26% for biopsy. When PET was combined with EUS, 168 reports were concordant and the PPV of ypCR was 50%, though the number of patients was low (1/2). With all 3 re-staging modalities combined, the PPV and NPV both rose to 100%.

Current restaging tools cannot reliably predict ypCR after nCRT. While multimodal restaging appears to be a more accurate predictor of ypCR than any testing modality alone, patients cannot reliably be advised to avoid an esophagectomy on the assumption that ycCR predicts ypCR at this time.