The status of perineural invasion predicts the outcomes of postoperative radiotherapy in locally advanced esophageal squamous cell carcinoma.
BACKGROUND
Prognosis of locally advanced esophageal squamous cell carcinoma (ESCC) remains dismal even after curative resection and adjuvant radiotherapy. New biomarkers for predicting prognosis and treatment outcomes are needed for improved treatment stratification of patients with locally advanced ESCC. The prognostic and treatment predictive significance of perineural invasion (PNI) in the locally advanced ESCC remains unclear. This study aimed to examine the effect of PNI on the outcomes of locally advanced ESCC patients after curative resection with or without postoperative radiotherapy (PORT).


METHODS
We retrospectively reviewed 262 consecutive locally advanced ESCC patients who underwent curative resection. Tumors sections were re-evaluated for PNI by an independent pathologist blinded to the patients' outcomes. Overall survival (OS) and disease-free survival (DFS) were determined using the Kaplan-Meier method; univariate log-rank test and multivariate Cox proportional hazard model were used to evaluate the prognostic value of PNI.


RESULTS
Finally, 243 patients were analyzed and enrolled into this study, of which 132 received PORT. PNI was identified in 22.2% (54/243) of the pathologic sections. The 5-year DFS was favorable for PNI-negative patients versus PNI-positive patients (21.3% vs. 36.7%, respectively; P = 0.005). The 5-year OS was 40.3% for PNI-negative patients versus 21.7% for PNI-positive patients (P < 0.001). On multivariate analysis, PNI was an independent prognostic factor. In a subset analysis for patients received PORT, PNI was evaluated as a prognostic predictor as well (P < 0.05). In contrast to patients without PORT, PORT couldn't improve the disease recurrence and survival in locally advanced ESCC patients with PNI-positive (P > 0.05).


CONCLUSIONS
PNI could serve as an independent prognostic factor and prognosticate treatment outcomes in locally advanced ESCC patients. The PNI status should be considered when stratifying high-risk locally advanced ESCC patients for adjuvant radiotherapy. Future prospective study is warranted to confirm our results.
Department of Tumor Biological Treatment, The Third Affiliated Hospital, Soochow University 185 Juqian Road, Changzhou 213003, China ; Department of Radiation Oncology, The Third Affiliated Hospital, Soochow University 185 Juqian Road, Changzhou 213003, China.
Zhong-Hua
ZH
Ning
Department of Pathology, The Third Affiliated Hospital, Soochow University 185 Juqian Road, Changzhou 213003, China.
Wei
W
Zhao
Department of Tumor Biological Treatment, The Third Affiliated Hospital, Soochow University 185 Juqian Road, Changzhou 213003, China.
Xiao-Dong
XD
Li
Department of Tumor Biological Treatment, The Third Affiliated Hospital, Soochow University 185 Juqian Road, Changzhou 213003, China.
Lu-Jun
LJ
Chen
Department of Tumor Biological Treatment, The Third Affiliated Hospital, Soochow University 185 Juqian Road, Changzhou 213003, China.
Bin
B
Xu
Department of Radiation Oncology, The Third Affiliated Hospital, Soochow University 185 Juqian Road, Changzhou 213003, China.
Wen-Dong
WD
Gu
Department of Radiation Oncology, The Third Affiliated Hospital, Soochow University 185 Juqian Road, Changzhou 213003, China.
Ying-Jie
YJ
Shao
Department of Tumor Biological Treatment, The Third Affiliated Hospital, Soochow University 185 Juqian Road, Changzhou 213003, China.
Yun
Y
Xu
Department of Radiation Oncology, The Third Affiliated Hospital, Soochow University 185 Juqian Road, Changzhou 213003, China.
Jin
J
Huang
Department of Radiation Oncology, The Third Affiliated Hospital, Soochow University 185 Juqian Road, Changzhou 213003, China.
Hong-Lei
HL
Pei
Department of Tumor Biological Treatment, The Third Affiliated Hospital, Soochow University 185 Juqian Road, Changzhou 213003, China.
Jing-Ting
JT
Jiang
D000328:Adult; D000368:Aged; D001706:Biopsy; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery*; D018450:Disease Progression; D018572:Disease-Free Survival; D004938:Esophageal Neoplasms / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery*; D000077277:Esophageal Squamous Cell Carcinoma; D016629:Esophagectomy / Q000009:adverse effects / Q000401:mortality; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local; D010525:Peripheral Nerves / Q000473:pathology*; D016016:Proportional Hazards Models; D018714:Radiotherapy, Adjuvant; D020266:Radiotherapy, Conformal / Q000009:adverse effects / Q000401:mortality; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
Biomarkers; esophageal squamous cell carcinoma; perineural invasion; postoperative radiotherapy; prognosis