OBJECTIVETo investigate the associated high risk factors of postoperative relapse and metastasis for patients with confined tumors (grade pT1b-4a) without lymph-node metastases (pN0) in thoracic esophageal squamous cell carcinoma (ESCC).

METHODSClinicopathological and follow up data of ESCC patients undergoing radical surgical resection as primary treatment in the Department of Thoracic Surgery, Shanghai Chest Hospital between January 2004 and December 2012 from Hospital Database were retrospectively collected. The inclusion criteria were as follows: (1) the first development of ESCC confirmed by histopathology without lymphatic and distant metastasis; (2) pathological stage of pT1bN0M0 to pT4aN0M0 according to the Union for International Cancer Control (UICC) in 2009; (3) curative trans-thoracic esophagectomy with R0 (tumor-free surgical margin) resection, using the Ivor-Lewis or McKeown procedure; two-field lymphadenectomy or three-field lymph node dissection based on the positive results of preoperative cervical ultrasonography examination or CT scan; (4) without adjuvant chemotherapy and/or radiotherapy before and after operation; (5) complete follow-up data. Logistic regression analysis was employed to identify the clinicopathological factors affecting the postoperative relapse and metastasis.

RESULTSA total of 112 patients were eligible, including 94 male cases and 18 female cases; age of (58.6±7.7) years; squamous carcinoma of upper thorax in 25 cases, of middle thorax in 67 cases and of lower thorax segment in 20 cases; 12 cases of high-differentiated ESCC, 49 cases of moderate-differentiated ESCC, poorly-differentiated ESCC in 48 cases; 4 cases of I(a stage, 9 cases of I(b, 24 cases of II(a, 62 cases of II(b, 13 cases of III(a; the tumor length >4 cm in 43 cases, ≤4 cm in 69 cases. Forty-three (38.4%) patients presented relapse or metastasis during the follow-up, including 24 (21.4%) of loco-regional relapse, 13 (11.6%) of distant metastasis, and 6(5.4%) of both above. Multivariate regression analysis revealed that poorly-differentiated tumor (OR=1.899, 95%CI:1.233-2.925, P=0.004), upper-middle location (OR=2.351, 95%CI:1.188-4.653, P=0.014), and tumor length >4 cm (OR=2.381, 95%CI:1.009-5.618, P=0.048) were independent risk factors of overall postoperative relapse and metastasis for thoracic ESCC with stage pT1b N0M0-T4aN0M0. Further stratified analysis identified that only poorly-differentiated tumor (OR=1.730, 95%CI:1.121-2.671, P=0.013) was an independent risk factor of loco-regional relapse, whereas pathological stage II(b-III(a (OR=3.372, 95%CI:1.206-9.428, P=0.021) was an independent risk factor of distant metastasis.

CONCLUSIONSPoorly-differentiated tumor, tumor length >4 cm, and upper-middle location may be regarded as high risk factors for predicting overall relapse and metastasis of pN0 thoracic ESCC patients after esophagectomy. Moreover, poorly-differentiated tumor is the only independent risk factor of postoperative loco-regional relapse, meanwhile it should be noted that pathological stage II(b-III(a is closely related to postoperative distant metastasis.