Laparoscopic vs Open Distal Gastrectomy for Locally Advanced Gastric Cancer: 5-Year Outcomes of the KLASS-02 Randomized Clinical Trial
Sang-Yong Son, Hoon Hur, Woo Jin Hyung, Young-Kyu Park, Hyuk-Joon Lee, Ji Yeong An, Wook Kim, Hyoung-Il Kim, Hyung-Ho Kim, Seung Wan Ryu, Min-Chan Kim, Seong-Ho Kong, Gyu Seok Cho, Jin-Jo Kim, Do Joong Park, Keun Won Ryu, Young Woo Kim, Jong Won Kim, Joo-Ho Lee, Han-Kwang Yang, Sang-Uk Han, Korean Laparoendoscopic Gastrointestinal Surgery Study (KLASS) Group, HyeSeong Ahn, Sang-Hoon Ahn, Jae-Moon Bae, Jung Min Bae, Sung Joon Bae, Cheul Su Byun, Yeon Soo Chang, Hyunjin Cho, In Cho, Minah Cho, Chang In Choi, Kyeong-Woon Choi, Seohee Choi, Seung-Ho Choi, Sung Il Choi, Yun-Suck Choi, Ho-Young Chung, Joo Won Chung, Jung Kee Chung, Bang Wool Eom, Sang Soo Eom, Dongyeop Ha, Man Ho Ha, Taekyung Ha, Dong-Seok Han, Sang-Moon Han, Se Wung Han, Yeon-Ju Huh, Sun-Hwi Hwang, You-Jin Jang, Ye Seob Jee, Chul Hyo Jeon, Gui-Ae Jeong, Inho Jeong, Oh Jeong, Sang-Ho Jeong, Sung-Ho Jin, Ji Hoon Jo, Kyong Hwa Jun, Bong Soo Jung, Do Hyun Jung, Mi-Ran Jung, Yoonju Jung, Dongbaek Kang, Ji Hoon Kang, So Hyun Kang, Amy Kim, Beom Su Kim, Chan Young Kim, Chang Hyun Kim, Chee Young Kim, Dae Hoon Kim, Dong Jin Kim, Dong-Wook Kim, Eun Young Kim, Ho-Goon Kim, Hyun Il Kim, In Ho Kim, Ji Hoon Kim, Jong-Han Kim, Jun Young Kim, Kap-Jung Kim, Ki Han Kim, Kwang Hee Kim, Kyoung Hwan Kim, Min Gyu Kim, Sa-Hong Kim, Sang Woon Kim, Se Won Kim, Seong-Gon Kim, Su Mi Kim, Sung Kim, Sung Geun Kim, Sung Soo Kim, Tae Han Kim, Yong Ho Kim, Yongil Kim, Yoo Min Kim, You Na Kim, Jeong Hyun Ko, Sung Chan Kong, In Gyu Kwon, Ji Hyoung Kwon, Oh Kyoung Kwon, Chang Min Lee, Han Hong Lee, Joong Ho Lee, Jun Ho Lee, Jun Hyun Lee, In Seob Lee, Kyung-Goo Lee, Moon-Soo Lee, Myung Jae Lee, Sang Eok Lee, Sang Ho Lee, Sang-Il Lee, Si Hak Lee, Se Youl Lee, Seung Soo Lee, Sol Lee, Yoontaek Lee, Seung Hyun Lim, Man-Sup Lim, Jae Seok Min, Woo-Kyun Mok, Young-Jae Mok, Yoon-Hwan Nam, Seung Jong Oh, Sung Don Oh, Sung Eun Oh, Sung Jin Oh, Cho Hyung Park, Dong Jin Park, Ji Ho Park, Ji Yeon Park, Ji Hyun Park, Jong-Min Park, Joong-Min Park, Ki Bum Park, Seong-Heum Park, Sungsoo Park, Yong Eun Park, Young Suk Park, Chulkyu Roh, Kun Ho Roh, Hoon Ryu, Seong Yeop Ryu, Ho Seok Seo, Jeong Eun Seo, Kyung Won Seo, Sang Hyuk Seo, Won Jun Seo, Jang Won Seon, Dong Gue Shin, Dong Woo Shin, Ho-Jung Shin, Tae Sung Sohn, Myoung Won Son, Taeil Son, Young-Gil Son, Geum Jong Song, Jeong Ho Song, Kyo Young Song, Sun-Kyo Song, Byoung Jo Suh, Yun-Suhk Suh, Ji-Young Sul, Choon Kyung Sung, Jun Young Yang, Han Mo Yoo, Moon-Won Yoo, Jeong-Hwan Yook, Hong Man Yoon, Ki Young Yoon, Sang Il Youn, Wansik Yu, Sang-Yong Son, Hoon Hur, Woo Jin Hyung, Young-Kyu Park, Hyuk-Joon Lee, Ji Yeong An, Wook Kim, Hyoung-Il Kim, Hyung-Ho Kim, Seung Wan Ryu, Min-Chan Kim, Seong-Ho Kong, Gyu Seok Cho, Jin-Jo Kim, Do Joong Park, Keun Won Ryu, Young Woo Kim, Jong Won Kim, Joo-Ho Lee, Han-Kwang Yang, Sang-Uk Han, Korean Laparoendoscopic Gastrointestinal Surgery Study (KLASS) Group, HyeSeong Ahn, Sang-Hoon Ahn, Jae-Moon Bae, Jung Min Bae, Sung Joon Bae, Cheul Su Byun, Yeon Soo Chang, Hyunjin Cho, In Cho, Minah Cho, Chang In Choi, Kyeong-Woon Choi, Seohee Choi, Seung-Ho Choi, Sung Il Choi, Yun-Suck Choi, Ho-Young Chung, Joo Won Chung, Jung Kee Chung, Bang Wool Eom, Sang Soo Eom, Dongyeop Ha, Man Ho Ha, Taekyung Ha, Dong-Seok Han, Sang-Moon Han, Se Wung Han, Yeon-Ju Huh, Sun-Hwi Hwang, You-Jin Jang, Ye Seob Jee, Chul Hyo Jeon, Gui-Ae Jeong, Inho Jeong, Oh Jeong, Sang-Ho Jeong, Sung-Ho Jin, Ji Hoon Jo, Kyong Hwa Jun, Bong Soo Jung, Do Hyun Jung, Mi-Ran Jung, Yoonju Jung, Dongbaek Kang, Ji Hoon Kang, So Hyun Kang, Amy Kim, Beom Su Kim, Chan Young Kim, Chang Hyun Kim, Chee Young Kim, Dae Hoon Kim, Dong Jin Kim, Dong-Wook Kim, Eun Young Kim, Ho-Goon Kim, Hyun Il Kim, In Ho Kim, Ji Hoon Kim, Jong-Han Kim, Jun Young Kim, Kap-Jung Kim, Ki Han Kim, Kwang Hee Kim, Kyoung Hwan Kim, Min Gyu Kim, Sa-Hong Kim, Sang Woon Kim, Se Won Kim, Seong-Gon Kim, Su Mi Kim, Sung Kim, Sung Geun Kim, Sung Soo Kim, Tae Han Kim, Yong Ho Kim, Yongil Kim, Yoo Min Kim, You Na Kim, Jeong Hyun Ko, Sung Chan Kong, In Gyu Kwon, Ji Hyoung Kwon, Oh Kyoung Kwon, Chang Min Lee, Han Hong Lee, Joong Ho Lee, Jun Ho Lee, Jun Hyun Lee, In Seob Lee, Kyung-Goo Lee, Moon-Soo Lee, Myung Jae Lee, Sang Eok Lee, Sang Ho Lee, Sang-Il Lee, Si Hak Lee, Se Youl Lee, Seung Soo Lee, Sol Lee, Yoontaek Lee, Seung Hyun Lim, Man-Sup Lim, Jae Seok Min, Woo-Kyun Mok, Young-Jae Mok, Yoon-Hwan Nam, Seung Jong Oh, Sung Don Oh, Sung Eun Oh, Sung Jin Oh, Cho Hyung Park, Dong Jin Park, Ji Ho Park, Ji Yeon Park, Ji Hyun Park, Jong-Min Park, Joong-Min Park, Ki Bum Park, Seong-Heum Park, Sungsoo Park, Yong Eun Park, Young Suk Park, Chulkyu Roh, Kun Ho Roh, Hoon Ryu, Seong Yeop Ryu, Ho Seok Seo, Jeong Eun Seo, Kyung Won Seo, Sang Hyuk Seo, Won Jun Seo, Jang Won Seon, Dong Gue Shin, Dong Woo Shin, Ho-Jung Shin, Tae Sung Sohn, Myoung Won Son, Taeil Son, Young-Gil Son, Geum Jong Song, Jeong Ho Song, Kyo Young Song, Sun-Kyo Song, Byoung Jo Suh, Yun-Suhk Suh, Ji-Young Sul, Choon Kyung Sung, Jun Young Yang, Han Mo Yoo, Moon-Won Yoo, Jeong-Hwan Yook, Hong Man Yoon, Ki Young Yoon, Sang Il Youn, Wansik Yu
Abstract
Importance: The long-term safety of laparoscopic distal gastrectomy for locally advanced gastric cancer (AGC) remains uncertain given the lack of 5-year follow-up results.
Objective: To compare the 5-year follow-up results in patients with clinically AGC enrolled in the Korean Laparoendoscopic Gastrointestinal Surgery Study (KLASS)-02 randomized clinical trial who underwent laparoscopic or open distal gastrectomy.
Design, setting, and participants: The KLASS-02, a multicenter randomized clinical trial, showed that laparoscopic surgery was noninferior to open surgery for patients with locally AGC. The present study assessed the 5-year follow-up results, including 5-year overall survival (OS) and relapse-free survival (RFS) rates and long-term complications, in patients enrolled in KLASS-02. From November 21, 2011, to April 29, 2015, patients aged 20 to 80 years diagnosed preoperatively with locally AGC were enrolled. Final follow-up was on June 15, 2021. Data were analyzed June 24 to September 9, 2021.
Interventions: Patients were treated with R0 resection either by laparoscopic gastrectomy or open gastrectomy as the full analysis set of the KLASS-02 trial.
Main outcomes and measures: Five-year OS and RFS rates, recurrence patterns, and long-term surgical complications were evaluated.
Results: This study enrolled a total of 1050 patients. A total of 974 patients were treated with R0 resection; 492 (50.5%) in the laparoscopic gastrectomy group (mean [SD] age, 59.8 [11.0] years; 351 men [71.3%]) and 482 (49.5%) in the open gastrectomy group (mean [SD] age, 59.4 [11.5] years; 335 men [69.5%]). In patients who underwent laparoscopic and open distal gastrectomy, the 5-year OS (88.9% vs 88.7%) and RFS (79.5% vs 81.1%) rates did not differ significantly. The most common types of recurrence were peritoneal carcinomatosis (73 of 173 [42.1%]), hematogenous metastases (36 of 173 [20.8%]), and locoregional recurrence (23 of 173 [13.2%]), with no between-group differences in types of recurrence at each cancer stage. The correlation between 3-year RFS and 5-year OS at the individual level was highest in patients with stage III gastric cancer (ρ = 0.720). The late complication rate was significantly lower in the laparoscopic than in the open surgery group (32 of 492 [6.5%] vs 53 of 482 [11.0%]). The most common type of complication in both groups was intestinal obstruction (13 of 492 [2.6%] vs 24 of 482 [5.0%]).
Conclusions and relevance: The 5-year outcomes of the KLASS-02 trial support the 3-year results, which is the noninferiority of laparoscopic surgery compared with open gastrectomy for locally AGC. The laparoscopic approach can be recommended in patients with locally AGC to achieve the benefit of low incidence of late complications.
Trial registration: ClinicalTrials.gov Identifier: NCT01456598.
Conflict of interest statement
Conflict of Interest Disclosures: Dr Hyung reported receiving grants from Medtronic and GC pharma; stocks from Hutom; and personal fees from SK Hynix (Wuxi) outside the submitted work. Dr Kong reported receiving grants from Medtronic and Stryker outside the submitted work. Dr D. Park reported receiving grants from Daewoong Pharmaceuticals, JW Pharmaceuticals, and Medtronic outside the submitted work. Dr J.W. Kim reported receiving grants from DN Company Co Ltd research fund outside the submitted work. Dr Han reported receiving grants from the National R&D Program for Cancer Control and Ethicon Endo-Surgery, a Johnson & Johnson Company, during the conduct of the study. No other disclosures were reported.
Figures
![Figure 1.. Kaplan-Meier Analyses of Overall Survival…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/9301593/bin/jamasurg-e222749-g001.jpg)
![Figure 2.. Cumulative Incidence Rates of Patients…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/9301593/bin/jamasurg-e222749-g002.jpg)
References
- Hur H, Lee HY, Lee HJ, et al. . Efficacy of laparoscopic subtotal gastrectomy with D2 lymphadenectomy for locally advanced gastric cancer: the protocol of the KLASS-02 multicenter randomized controlled clinical trial. BMC Cancer. 2015;15:355. doi:10.1186/s12885-015-1365-z
- Han SU, Hur H, Lee HJ, et al. ; Korean Laparoendoscopic Gastrointestinal Surgery Study (KLASS) Group . Surgeon quality control and standardization of D2 lymphadenectomy for gastric cancer: a prospective multicenter observational study (KLASS-02-QC). Ann Surg. 2021;273(2):315-324. doi:10.1097/SLA.0000000000003883
- Kim HI, Hur H, Kim YN, et al. . Standardization of D2 lymphadenectomy and surgical quality control (KLASS-02-QC): a prospective, observational, multicenter study [NCT01283893]. BMC Cancer. 2014;14:209. doi:10.1186/1471-2407-14-209
- Hyung WJ, Yang HK, Park YK, et al. ; Korean Laparoendoscopic Gastrointestinal Surgery Study Group . Long-term outcomes of laparoscopic distal gastrectomy for locally advanced gastric cancer: the KLASS-02-RCT randomized clinical trial. J Clin Oncol. 2020;38(28):3304-3313. doi:10.1200/JCO.20.01210
- Kim HS, Jeong CW, Kwak C, Kim HH, Ku JH. Disease-free survival at 2 and 3 years is a significant early surrogate marker predicting the 5-year overall survival in patients treated with radical cystectomy for urothelial carcinoma of the bladder: external evaluation and validation in a cohort of Korean patients. Front Oncol. 2015;5:246. doi:10.3389/fonc.2015.00246
- Saad ED, Squifflet P, Burzykowski T, et al. . Disease-free survival as a surrogate for overall survival in patients with HER2-positive, early breast cancer in trials of adjuvant trastuzumab for up to 1 year: a systematic review and meta-analysis. Lancet Oncol. 2019;20(3):361-370. doi:10.1016/S1470-2045(18)30750-2
- Sargent DJ, Wieand HS, Haller DG, et al. . Disease-free survival vs overall survival as a primary end point for adjuvant colon cancer studies: individual patient data from 20 898 patients on 18 randomized trials. J Clin Oncol. 2005;23(34):8664-8670. doi:10.1200/JCO.2005.01.6071
- Oba K, Paoletti X, Alberts S, et al. ; GASTRIC group . Disease-free survival as a surrogate for overall survival in adjuvant trials of gastric cancer: a meta-analysis. J Natl Cancer Inst. 2013;105(21):1600-1607. doi:10.1093/jnci/djt270
- Bang YJ, Van Cutsem E, Feyereislova A, et al. ; ToGA Trial Investigators . Trastuzumab in combination with chemotherapy vs chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010;376(9742):687-697. doi:10.1016/S0140-6736(10)61121-X
- Janjigian YY, Shitara K, Moehler M, et al. . First-line nivolumab plus chemotherapy vs chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial. Lancet. 2021;398(10294):27-40. doi:10.1016/S0140-6736(21)00797-2
- Wilke H, Muro K, Van Cutsem E, et al. ; RAINBOW Study Group . Ramucirumab plus paclitaxel vs placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol. 2014;15(11):1224-1235. doi:10.1016/S1470-2045(14)70420-6
- Ellis H, Moran BJ, Thompson JN, et al. . Adhesion-related hospital readmissions after abdominal and pelvic surgery: a retrospective cohort study. Lancet. 1999;353(9163):1476-1480. doi:10.1016/S0140-6736(98)09337-4
- Sakari T, Christersson M, Karlbom U. Mechanisms of adhesive small bowel obstruction and outcome of surgery; a population-based study. BMC Surg. 2020;20(1):62. doi:10.1186/s12893-020-00724-9
- Lee HJ, Hyung WJ, Yang HK, et al. ; Korean Laparo-endoscopic Gastrointestinal Surgery Study (KLASS) Group . Short-term outcomes of a multicenter randomized controlled trial comparing laparoscopic distal gastrectomy with D2 lymphadenectomy to open distal gastrectomy for locally advanced gastric cancer (KLASS-02-RCT). Ann Surg. 2019;270(6):983-991. doi:10.1097/SLA.0000000000003217
- Sakamoto Y, Sano T, Shimada K, et al. . Favorable indications for hepatectomy in patients with liver metastasis from gastric cancer. J Surg Oncol. 2007;95(7):534-539. doi:10.1002/jso.20739
- Kemp R, Prasad V. Surrogate endpoints in oncology: when are they acceptable for regulatory and clinical decisions, and are they currently overused? BMC Med. 2017;15(1):134. doi:10.1186/s12916-017-0902-9
- Oba M, Hasegawa K, Matsuyama Y, et al. . Discrepancy between recurrence-free survival and overall survival in patients with resectable colorectal liver metastases: a potential surrogate endpoint for time to surgical failure. Ann Surg Oncol. 2014;21(6):1817-1824. doi:10.1245/s10434-014-3504-1
- Kano Y, Ohashi M, Muneoka Y, et al. . Different risk factors for 3 major recurrence patterns of pathological stage II or III gastric cancer patients who completed adjuvant S-1 monotherapy. Eur J Surg Oncol. 2021;47(12):3097-3104. doi:10.1016/j.ejso.2021.04.018
- Takahashi R, Ohashi M, Kano Y, et al. . Timing and site-specific trends of recurrence in patients with pathological stage II or III gastric cancer after curative gastrectomy followed by adjuvant S-1 monotherapy. Gastric Cancer. 2019;22(6):1256-1262. doi:10.1007/s10120-019-00953-9
- Yu J, Huang C, Sun Y, et al. ; Chinese Laparoscopic Gastrointestinal Surgery Study (CLASS) Group . Effect of laparoscopic vs open distal gastrectomy on 3-year disease-free survival in patients with locally advanced gastric cancer: the CLASS-01 randomized clinical trial. JAMA. 2019;321(20):1983-1992. doi:10.1001/jama.2019.5359
- Park YK, Yoon HM, Kim YW, et al. ; COACT group . Laparoscopy-assisted vs open D2 distal gastrectomy for advanced gastric cancer: results from a randomized phase II multicenter clinical trial (COACT 1001). Ann Surg. 2018;267(4):638-645. doi:10.1097/SLA.0000000000002168
- Kim HH, Han SU, Kim MC, et al. ; Korean Laparoendoscopic Gastrointestinal Surgery Study (KLASS) Group . Effect of laparoscopic distal gastrectomy vs open distal gastrectomy on long-term survival among patients with stage I gastric cancer: the KLASS-01 randomized clinical trial. JAMA Oncol. 2019;5(4):506-513. doi:10.1001/jamaoncol.2018.6727
- Chen X, Feng X, Wang M, Yao X. Laparoscopic vs open distal gastrectomy for advanced gastric cancer: a meta-analysis of randomized controlled trials and high-quality nonrandomized comparative studies. Eur J Surg Oncol. 2020;46(11):1998-2010. doi:10.1016/j.ejso.2020.06.046
- Wang JB, Zhong Q, Chen QY, et al. . Well-designed retrospective study vs small-sample prospective study in research based on laparoscopic and open radical distal gastrectomy for advanced gastric cancer. Surg Endosc. 2020;34(10):4504-4515. doi:10.1007/s00464-019-07237-4
- Bang YJ, Kim YW, Yang HK, et al. ; CLASSIC trial investigators . Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label, randomised controlled trial. Lancet. 2012;379(9813):315-321. doi:10.1016/S0140-6736(11)61873-4
- Sakuramoto S, Sasako M, Yamaguchi T, et al. ; ACTS-GC Group . Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. N Engl J Med. 2007;357(18):1810-1820. doi:10.1056/NEJMoa072252
- Oh SJ, Choi WB, Song J, Hyung WJ, Choi SH, Noh SH; Yonsei Gastric Cancer Clinic . Complications requiring reoperation after gastrectomy for gastric cancer: 17 years’ experience in a single institute. J Gastrointest Surg. 2009;13(2):239-245. doi:10.1007/s11605-008-0716-3
- Kim SG, Song KY, Lee HH, et al. . Efficacy of an antiadhesive agent for the prevention of intra-abdominal adhesions after radical gastrectomy: a prospective randomized, multicenter trial. Medicine (Baltimore). 2019;98(19):e15141. doi:10.1097/MD.0000000000015141
- Jang SH, Jung YK, Choi SJ, Ha TK. Postoperative mechanical small bowel obstruction induced by V-Loc barbed absorbable suture after laparoscopic distal gastrectomy. Ann Surg Treat Res. 2017;92(5):380-382. doi:10.4174/astr.2017.92.5.380
- Kinoshita T, Uyama I, Terashima M, et al. ; LOC-A Study Group . Long-term outcomes of laparoscopic vs open surgery for clinical stage II/III gastric cancer: a multicenter cohort study in Japan (LOC-A Study). Ann Surg. 2019;269(5):887-894. doi:10.1097/SLA.0000000000002768
- Huang ZN, Ma Y, Chen QY, et al. . Potential survival benefits of open over laparoscopic radical gastrectomy for gastric cancer patients beyond 3 years after surgery: result from multicenter in-depth analysis based on propensity matching. Surg Endosc. 2022;36(2):1456-1465. doi:10.1007/s00464-021-08430-0
Source: PubMed