A Pathological Study of Residual Cancer in the Esophageal Wall Following Neoadjuvant Chemoradiotherapy: Focus on Esophageal Squamous Cell Carcinoma Patients with False Negative Preoperative Endoscopic Biopsies.

BACKGROUND: Endoscopic biopsy examinations after neoadjuvant chemoradiotherapy (nCRT) are of limited value in patients with esophageal cancer due to the high rates of false negative (FN) findings. We sought to investigate the anatomical locations of residual tumors in esophageal squamous cell carcinoma (ESCC) patients with FN endoscopic biopsies with the ultimate goal of improving their clinical management. METHODS: ESCC patients with residual cancers after nCRT which were not identified by preoperative endoscopic biopsy were deemed eligible. All of the surgical specimens were re-reviewed with a special focus on (1) distribution of residual cancer in each esophageal layer; (2) tumor regression grade (TRG); and (3) shortest distance between the lumen and the residual tumor. RESULTS: Among the 49 ESCC patients with FN biopsy results, a strong 'layer-dependent' tumor regression was observed. There was a preferential clearing of esophageal cancer cells located in the adventitia, followed by muscle and the submucosal (SM) and mucosal (M) layers (p < 0.001). Residual malignancies located in the muscle layer or the adventitia without simultaneous involvement of the M/SM layers were rare (n = 3; 6.1 %). TRG following nCRT did not affect the rate of M/SM involvement (p = 0.55) but was inversely associated with the distance between the lumen and residual cancer (mean distance in patients with TRG of 2, 3, and 4 was 1.1, 0.82, and 0.37 mm, respectively; p = 0.041). CONCLUSION: Most ESCC patients who show FN endoscopic biopsies following nCRT still have detectable lesions in the M/SM layers. Aggressive biopsy protocols may potentially improve detection rates.

Pretreatment clinical stage predicts locoregional recurrence in patients with esophageal cancer who achieved a complete clinical response to chemoradiotherapy.

OBJECTIVE: Definitive chemoradiotherapy (dCRT) represents a curative nonsurgical treatment option for patients with esophageal cancer. However, tumor recurrence is common after dCRT, even when clinical complete response (cCR) is achieved. Here, we investigated the timing, patterns, and risk factors for recurrence in patients with esophageal squamous cell carcinoma (ESCC) who achieved cCR following dCRT. METHODS: We retrospectively examined the clinical records of patients with ESCC who achieved cCR following dCRT between 2001 and 2014. Locoregional recurrence (LR) was defined as a recurrence occurring in the esophageal lumen and/or locoregional lymph nodes. Recurrences at any other sites were considered as distant recurrences (DRs). RESULTS: A total of 102 patients who achieved cCR were included. After a mean follow-up of 54.5 months, 51 patients developed recurrences (34 LRs, 6 combined LR and DR, and 11 DRs). The cumulative 1-, 3-, and 5-year recurrence rates were 35%, 46%, and 50%, respectively. The mean time to recurrence for the 40 patients with LRs (including LRs plus LRs/DRs) was significantly shorter (281.4 days) compared with that of patients with DRs (643.6 days; P = .006), with 95% of the former being diagnosed within 2 years. Multivariate Cox regression analysis identified pretreatment clinical stage III as the only independent risk factor for LR (hazard ratio, 2.732; 95% confidence interval; 1.063-7.020; P = .037). CONCLUSIONS: Disease recurrence occurs in 50% of ESCC patients who achieve cCR following dCRT, with LR being the most common pattern. Advanced pretreatment clinical stage is an independent risk factor for LR.