Association between the thoroughness of the histopathological examination and survival in patients with esophageal squamous cell carcinoma who achieve pathological complete response after chemoradiotherapy

Abstract

The College of American Pathologists guidelines recommend examining at least four representative tumor blocks for determining pathological T stage in patients with primarily resected esophageal cancer. Whether the same pathological requirements are adequate in patients undergoing esophagectomy following neoadjuvant chemoradiotherapy (nCRT) remains unclear. We hypothesized that current examination protocols may underestimate the presence of microscopical residual disease after nCRT, potentially leading to under-staging. We retrospectively reviewed the records of patients with esophageal squamous cancer (ESCC) who were diagnosed as having pathological complete response (pCR) following nCRT. The thoroughness of the pathological examination in pCR patients was examined using (i) the number of blocks examined in suspicious tumor area (≤4 vs. >4), and (ii) the block quotient (calculated as the pretreatment tumor length divided by the number of blocks examined in suspicious tumor area). A total of 91 patients were enrolled. The mean number of blocks used to confirm pCR was 4.8 (range: 2-14). The 5-year overall survival (OS) and disease-free survival (DFS) in the entire cohort were 55% and 65%, respectively. Multivariate analyses identified the block quotient as the only independent predictor of OS and DFS. Receiver operating characteristic curve analysis indicated an optimal cutoff value of 1.4 for the block quotient. Among the patients who achieved pCR, the 5-year DFS differed significantly between subjects with a low (≤1.4) or high (>1.4) block quotient (76% vs. 47%, respectively, P = 0.03). The block quotient (calculated by the pretreatment tumor length divided by the number of blocks) - which reflects the meticulousness of the histopathological examination for confirming pCR - is associated with survival in ESCC patients.

Residual Cancer Volume Predicts Clinical Outcome in Patients With Esophageal Squamous Cell Carcinoma After Neoadjuvant Chemotherapy

“…In the present study, we evaluated RCV by examining whole stepwise sections, including non-cancerous region, for the purpose of determining the optimal cutoff values. Even though the previous studies recommended that the histopathological evaluation of preoperative treatment required the meticulous examination by a larger number of tissue sections than that for primarily resected esophagus, 9,21 the RCV evaluation in whole stepwise sections may present a very troublesome task in routine clinical practice. However, because the cutoff value of RCV (1.0 cm 3 ) was very small in comparison with the range of RCV (0-49.3 cm 3 ), we believe that the residual cancer measurement by the whole stepwise examination is unnecessary for macroscopically huge cancers in routine clinical practice.…”

Osteopontin Expression Is Associated with the Poor Prognosis in Patients with Locally Advanced Esophageal Squamous Cell Carcinoma Receiving Preoperative Chemoradiotherapy

“…For stage II or III localized thoracic ESCC, the recent meta-analysis showed that preoperative concurrent chemoradiotherapy followed by surgery reduces locoregional recurrence and has significant survival benefit compared to surgery alone [ 16 ]. The achievement of a pathological complete response is commonly considered an important prognostic factor after preoperative chemoradiation [ 17 ]. Until now, there is no clear prognostic factor to predict treatment response of preoperative chemoradiation.…”