The 10-year outcome and prognostic factors of laparoscopic D₂ radical distal gastrectomy for locally advanced gastric cancer: a CLASS multicenter study

To investigate the 10-year outcome and prognostic factors of laparo-scopic D₂ radical distal gastrectomy for locally advanced gastric cancer.

The retrospec-tive cohort study was conducted. The clinicopathological data of 652 patients with locally advanced gastric cancer who were admitted to 16 hospitals from the multicenter database of laparoscopic gastric cancer surgery in the Chinese Laparoscopic Gastrointestinal Surgery Study (CLASS) Group, including 214 cases in the First Affiliated Hospital of Army Medical University, 191 cases in Fujian Medical University Union Hospital, 52 cases in Nanfang Hospital of Southern Medical University, 49 cases in West China Hospital of Sichuan University, 43 cases in Xijing Hospital of Air Force Medical University, 25 cases in Jiangsu Province Hospital of Chinese Medicine, 14 cases in the First Medical Center of the Chinese PLA General Hospital, 12 cases in No.989 Hospital of PLA, 12 cases in the Third Affiliated Hospital of Sun Yat-Sen University, 10 cases in the First Affiliated Hospital of Nanchang University, 9 cases in the First People's Hospital of Foshan, 7 cases in Zhujiang Hospital of Southern Medical University, 7 cases in Fujian Medical University Cancer Hospital, 3 cases in Zhongshan Hospital of Fudan University, 2 cases in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 2 cases in Peking University Cancer Hospital & Institute, from February 2004 to December 2010 were collected. There were 442 males and 210 females, aged (57±12)years. All patients underwent laparoscopic D₂ radical distal gastrectomy. Observation indicators: (1) surgical situations; (2) postoperative pathological examination; (3) postoperative recovery and complications; (4) follow-up; (5) prognostic factors analysis. Follow-up was conducted by outpatient examination and telephone interview to detect the tumor recurrence and metastasis, postoperative survival of patients up to March 2020. Measurement data with normal distribution were represented as Mean±SD, and measurement data with skewed distribution were represented as M(Q₁,Q₃) or M(range). Count data were described as absolute numbers or percen-tages, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data was analyzed using the rank sum test. The life table method was used to calculate survival rates and the Kaplan-Meier method was used to draw survival curves. Log-Rank test was used for survival analysis. Univariate and multivariate analyses were analyzed using the COX hazard regression model.

(1) Surgical situations: among 652 patients, 617 cases underwent D₂ lymph node dissection and 35 cases underwent D₂₊ lymph node dissection. There were 348 cases with Billroth Ⅱ anastomosis, 218 cases with Billroth Ⅰ anastomosis, 25 cases with Roux-en-Y anastomosis and 61 cases with other digestive tract reconstruction methods. Twelve patients had combined visceral resection. There were 569 patients with intraoperative blood transfusion and 83 cases without blood transfusion. The operation time of 652 patients was 187(155,240)minutes and volume of intraoperative blood loss was 100(50,150)mL. (2) Postoperative pathological examina-tion: the maximum diameter of tumor was (4.5±2.0)cm of 652 patients. The number of lymph node dissected of 652 patients was 26(19,35), in which the number of lymph node dissected was >15 of 570 cases and ≤15 of 82 cases. The number of metastatic lymph node was 4(1,9). The proximal tumor margin was (4.8±1.6)cm and the distal tumor margin was (4.5±1.5)cm. Among 652 patients, 255 cases were classified as Borrmann type Ⅰ-Ⅱ, 334 cases were classified as Borrmann type Ⅲ-Ⅳ, and 63 cases had missing Borrmann classification data. The degree of tumor differentiation was high or medium in 171 cases, low or undifferentiated in 430 cases, and the tumor differentiation data was missing in 51 cases. There were 123, 253 and 276 cases in pathological stage T2, T3 and T4a, respectively. There were 116, 131, 214 and 191 cases in pathological stage N0, N1, N2 and N3, respectively. There were 260 and 392 cases in pathological TNM stage Ⅱ and Ⅲ, respectively. (3) Postoperative recovery and complications: the time to postoperative first out-of-bed activities, time to postoperative first flatus, time to the initial liquid food intake, duration of postoperative hospital stay of 652 patients were 3(2,4)days, 4(3,5)days, 5(4,6)days, 10(9,13)days, respectively. Among 652 patients, 69 cases had postoperative complications. Clavien-Dindo grade Ⅰ-Ⅱ, grade Ⅲa, grade Ⅲb, and grade Ⅳa complications occurred in 60, 3, 5 and 1 cases, respectively (some patients could have multiple complications). The duodenal stump leakage was the most common surgical complication, with the incidence of 3.07%(20/652). Respiratory complication was the most common systemic complication, with the incidence of 2.91%(19/652). All the 69 patients were recovered and discharged successfully after treatment. (4) Follow-up: 652 patients were followed up for 110-193 months, with a median follow-up time of 124 months. There were 298 cases with postoperative recurrence and metastasis. Of the 255 patients with the time to postoperative recurrence and metastasis ≤5 years, there were 21 cases with distant metastasis, 69 cases with peritoneal metastasis, 37 cases with local recurrence, 52 cases with multiple recurrence and metastasis, 76 cases with recurrence and metastasis at other locations. The above indicators were 5, 9, 10, 4, 15 of the 43 patients with the time to postoperative recurrence and metastasis >5 years. There was no significant difference in the type of recurrence and metastasis between them (χ²=5.52, P>0.05). Cases in pathological TNM stage Ⅱ and Ⅲ were 62 and 193 of the patients with the time to postoperative recurrence and metastasis ≤5 years, versus 23 and 20 of the patients with the time to postoperative recurrence and metastasis >5 years, showing a significant difference in pathological TNM staging between them (χ²=15.36, P<0.05). Cases in pathological stage T2, T3, T4a were 42, 95, 118 of the patients with the time to postoperative recurrence and metastasis ≤5 years, versus 9, 21, 13 of the patients with the time to postoperative recurrence and metastasis >5 years, showing no significant difference in pathological T staging between them (Z=-1.80, P>0.05). Further analysis showed no significant difference in cases in pathological stage T2 or T3 (χ²=0.52, 2.08, P>0.05) but a significant difference in cases in pathological stage T4a between them (χ²=3.84, P<0.05). Cases in pathological stage N0, N1, N2, N3 were 19, 44, 85, 107 of the patients with the time to postoperative recurrence and metastasis ≤5 years, versus 12, 5, 18, 8 of the patients with the time to postoperative recurrence and metastasis >5 years, showing a significant difference in pathological N staging between them (Z=-3.34, P<0.05). Further analysis showed significant differences in cases in pathological stage N0 and N3 (χ²=16.52, 8.47, P<0.05) but no significant difference in cases in pathological stage N1 or N2 (χ²=0.85, 1.18, P>0.05). The median overall survival time was 81 months after surgery and 10-year overall survival rate was 46.1% of 652 patients. The 10-year overall survival rates of patients in TNM stage Ⅱ and Ⅲ were 59.6% and 37.5%, respectively, showing a significant difference between them (χ²=35.29, P<0.05). In further analysis, the 10-year overall survival rates of patients in pathological TNM stage ⅡA, ⅡB, ⅢA, ⅢB and ⅢC were 65.6%, 55.8%, 46.9%, 37.1% and 24.0%, respectively, showing a significant difference between them (χ²=55.06, P<0.05). The 10-year overall survival rates of patients in patholo-gical stage T2, T3 and T4a were 55.2%, 46.5% and 41.5%, respectively, showing a significant difference between them (χ²=8.39, P<0.05). The 10-year overall survival rates of patients in patholo-gical stage N0, N1, N2 and N3 were 63.7%, 56.2%, 48.5% and 26.4%, respectively, showing a signifi-cant difference between them (χ²=54.89, P<0.05). (5) Prognostic factors analysis: results of univariate analysis showed that age, maximum diameter of tumor, degree of tumor differentiation as low or undifferentiated, pathological TNM staging, pathological T staging, pathological stage N2 or N3, post-operative chemotherapy were related factors for the 10-year overall survival rate of locally advanced gastric cancer patients undergoing laparoscopic D₂ radical distal gastrectomy (hazard ratio=1.45, 1.64, 1.37, 2.05, 1.30, 1.68, 3.08, 0.56, 95% confidence interval as 1.15-1.84, 1.32-2.03, 1.05-1.77, 1.62-2.59, 1.05-1.61, 1.17-2.42, 2.15-4.41, 0.44-0.70, P<0.05). Results of multivariate analysis showed that maximum diameter of tumor >4 cm, low-differentiated or undifferentiated tumor, pathological TNM stage Ⅲ were independent risk factors for the 10-year overall survival rate of locally advanced gastric cancer patients undergoing laparoscopic D₂ radical distal gastrectomy (hazard ratio=1.48,1.44, 1.81, 95% confidence interval as 1.19-1.84, 1.11-1.88, 1.42-2.30, P<0.05) and postoperative chemotherapy was a independent protective factor for the 10-year overall survi-val rate of locally advanced gastric cancer patients undergoing laparoscopic D₂ radical distal gastrec-tomy (hazard ratio=0.57, 95% confidence interval as 045-0.73, P<0.05).

Laparoscopic assisted D₂ radical distal gastrectomy for locally advanced gastric cancer has satisfactory 10-year oncologic outcomes. A high proportion of patients in pathological TNM stage Ⅲ, pathological stage T4a, pathological stage N3 have the time to postoperative recurrence and metastasis ≤5 years, whereas a high proportion of patients in pathological TNM stage Ⅱ or pathological stage N0 have the time to postoperative recurrence and metastasis >5 years. Maximum diameter of tumor >4 cm, low-differentiated or undifferentiated tumor, pathological TNM stage Ⅲ are independent risk factors for the 10-year overall survival rate of locally advanced gastric cancer patients undergoing laparos-copic D₂ radical distal gastrectomy. Postoperative chemotherapy is a independent protective factor for the 10-year overall survival rate of locally advanced gastric cancer patients undergoing laparos-copic D₂ radical distal gastrectomy.