Factors Associated With False-Negative Endoscopic Biopsy Results After Neoadjuvant Chemoradiotherapy in Patients With Esophageal Squamous Cell Carcinoma

Abstract

The usefulness of endoscopic biopsy following neoadjuvant chemoradiotherapy (nCRT) is limited because of its high false-negative (FN) rates. However, data on the factors associated with FN biopsy results remain scarce. The purpose of this study was to investigate factors associated with FN results on endoscopic biopsies in patients with esophageal squamous cell carcinoma (ESCC) following nCRT.We retrospectively reviewed the records of ESCC patients who were treated at the Chang Gung Memorial Hospital, Taoyuan, Taiwan, between 1999 and 2013. Inclusion criteria were receiving nCRT as first-line treatment before esophagectomy and having been preoperatively submitted to an endoscopic biopsy. Endoscopic findings at the lesion site were classified into 6 distinct categories: stricture, tumor, ulcer, scar, other findings, or normal. Univariate and multivariate analyses were used to identify factors associated with FN biopsy findings.A total of 227 patients were selected, of which 92 (41.9%) had positive biopsy results. Among patients with negative biopsy findings (n = 135), 85 were found to have residual cancer on the resected esophagus. Multivariate analysis identified endoscopic findings as the only independent predictor of FN biopsy results. The negative predictive values were 77.8%, 61.9%, 52.6%, 30.3%, 23.1%, and 20.0% for the normal, scar, other findings, ulcer, stricture, and tumor categories, respectively (P < 0.001).In ESCC patients, the FN rate of endoscopic biopsy after nCRT is associated with the type of residual lesion.

Predictive value of endoscopic esophageal findings for residual esophageal cancer after neoadjuvant chemoradiotherapy

“…The present study confirms that certain endoscopic findings (i. e. endoscopic suspicion of residual tumor) may contribute to a diagnostic strategy for detection of residual esophageal cancer. In addition, and similarly to findings by Chao et al [12], a substantial rate of false-negative biopsies was observed in patients with endoscopic suspicion of residual tumor after nCRT. Outcome should, however, be interpreted with caution because of the small number of patients with this finding in this study.…”

“…For the purpose of this retrospective study, endoscopy reports were independently reviewed by two blinded investigators (R.D.vdB., B.J.vdW.) based on a predefined case record form with input from upper gastrointestinal endoscopists and previous studies [9,11,12]. The following endoscopic findings were recorded: non-passable stenosis, passable stenosis, suspicion of residual tumor, scar tissue, and ulceration (▶ Fig.…”

“…Previous studies have shown that the overall endoscopic response after neoadjuvant therapy is of prognostic value [11,14]. Furthermore, Chao et al showed that negative biopsies were less reliable in cases with certain endoscopic findings [12]; specifically, NPVs of biopsies obtained in patients with a stenosis, endoscopic suspicion of residual tumor, or ulceration were 23 %, 20 %, and 31 %, respectively. Hence, the authors concluded that endoscopic biopsies should not play a role in these patients as residual disease cannot reliably be ruled out, and presence of any of these findings should therefore be considered as a sign of residual esophageal cancer.…”

“…Little is known on the predictive value of endoscopic findings during active surveillance for esophageal cancer. Previous studies in patients with esophageal squamous cell carcinoma have suggested that the degree of endoscopic response is related to the observed response in the resection specimen and that certain endoscopic findings (e. g. stenosis, ulceration) should be considered as a sign of residual disease [11,12]. In this light, endoscopic evaluation of the esophagus may be of added value in an active surveillance strategy.…”

Prognosis of Patients With Pathologic T0 N+ Esophageal Squamous Cell Carcinoma After Chemoradiotherapy and Surgical Resection: Results From a Nationwide Study

“…Owing to recent advances in CRT (resulting in improved pCR rates) and in light of morbidity-related concerns related to esophageal resection after CRT, there is growing debate about whether planned esophagectomy could be avoided in patients without clinically evident disease (clinical CR) after CRT [11][12][13]. The use of optimized panendoscopy examination protocols can improve the diagnostic confidence on the absence of residual cancer at the primary site [14]. However, the lack of residual neoplasms at the primary tumor site does not rule out the presence of regional LN involvement.…”