Recurrence patterns after curative gastrectomy for pStage II/III gastric cancer: Exploratory analysis of the randomized controlled JCOG1001 trial

Published:November 15, 2022DOI:



      Peritoneal, lymph node, and hematogenous recurrence patterns are common after potentially curative surgery for gastric cancer. However, clinicopathological characteristics associated with each recurrence type have rarely been comprehensively reported among patients who received a unified treatment strategy and follow-up protocol. Understanding these recurrence patterns would help with early detection of recurrence and a personalized follow-up plan. We investigated the initial recurrence patterns after curative gastrectomy using data from the randomized clinical JCOG1001 trial.


      Of 1204 patients enrolled in JCOG1001, 932 pStage II/III patients were included. Initial recurrence dates and patterns were recorded by attending physicians according to the protocol. Risk factors for hematogenous, lymph node, and peritoneal recurrence were determined by univariable and multivariable analyses using the Fine–Gray model.


      Overall, 253 patients developed recurrence. Hematogenous recurrence was the most frequent pattern (n = 115), followed by peritoneal (n = 104) and lymph node recurrence (n = 70). Differentiated type (p = 0.0028), pT4 (p = 0.0466), and pN3 (p < 0.0001) were associated with hematogenous recurrence; however, D2+ lymphadenectomy reduced it (p = 0.0161). Patients with large (≥5 cm) tumors (p = 0.0312), pT4 (p < 0.0001), pN3 (p = 0.0013), and undifferentiated histologic type (p = 0.0001) had significantly higher rates of peritoneal recurrence. Extended lymph node metastasis (pN3) was the only risk factor (p < 0.0001) for lymph node recurrence.


      Clinicopathological features differed according to the recurrence patterns. Vigilant follow-up with an understanding of recurrence patterns might be beneficial for some high-risk patients.



      CD (Clavien–Dindo), CI (confidence interval), HR (hazard ratio), JCOG (Japan Clinical Oncology Group)
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        • Bray F.
        • Ferlay J.
        • Soerjomataram I.
        • Siegel R.L.
        • Torre L.A.
        • Jemal A.
        Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.
        CA A Cancer J Clin. 2018; 68: 394-424
        • Ikoma N.
        • Chen H.C.
        • Wang X.
        • Blum M.
        • Estrella J.S.
        • Fournier K.
        • et al.
        Patterns of initial recurrence in gastric adenocarcinoma in the era of preoperative therapy.
        Ann Surg Oncol. 2017; 24: 2679-2687
        • Lee J.H.
        • Son S.Y.
        • Lee C.M.
        • Ahn S.H.
        • Park D.J.
        • Kim H.H.
        Factors predicting peritoneal recurrence in advanced gastric cancer: implication for adjuvant intraperitoneal chemotherapy.
        Gastric Cancer. 2014; 17: 529-536
        • Fujiya K.
        • Tokunaga M.
        • Makuuchi R.
        • Nishiwaki N.
        • Omori H.
        • Takagi W.
        • et al.
        Early detection of nonperitoneal recurrence may contribute to survival benefit after curative gastrectomy for gastric cancer.
        Gastric Cancer. 2017; 20 (S1): 141-149
        • Tan I.T.
        • So B.Y.
        Value of intensive follow-up of patients after curative surgery for gastric carcinoma.
        J Surg Oncol. 2007; 96: 503-506
        • Park C.H.
        • Park J.C.
        • Chung H.
        • Shin S.K.
        • Lee S.K.
        • Cheong J.H.
        • et al.
        Impact of the surveillance interval on the survival of patients who undergo curative surgery for gastric cancer.
        Ann Surg Oncol. 2016; 23: 539-545
        • Dong Y.
        • Ma S.
        • Yang S.
        • Luo F.
        • Wang Z.
        • Guo F.
        Non-curative surgery for patients with gastric cancer with local peritoneal metastasis: a retrospective cohort study.
        Med (Baltim). 2016; 95e5607
        • Terashima M.
        • Ichikawa W.
        • Ochiai A.
        • Kitada K.
        • Kurahashi I.
        • Sakuramoto S.
        • et al.
        • ACTS-GC Group
        TOP2A, GGH, and PECAM1 are associated with hematogenous, lymph node, and peritoneal recurrence in stage II/III gastric cancer patients enrolled in the ACTS-GC study.
        Oncotarget. 2017; 8: 57574-57582
        • Lee J.H.
        • Chang K.K.
        • Yoon C.
        • Tang L.H.
        • Strong V.E.
        • Yoon S.S.
        Lauren histologic type is the most important factor associated with pattern of recurrence following resection of gastric adenocarcinoma.
        Ann Surg. 2018; 267: 105-113
        • Liu D.
        • Lu M.
        • Li J.
        • Yang Z.
        • Feng Q.
        • Zhou M.
        • et al.
        The patterns and timing of recurrence after curative resection for gastric cancer in China.
        World J Surg Oncol. 2016; 14: 305
        • Kurokawa Y.
        • Doki Y.
        • Mizusawa J.
        • Terashima M.
        • Katai H.
        • Yoshikawa T.
        • et al.
        Bursectomy versus omentectomy alone for resectable gastric cancer (JCOG1001): a phase 3, open-label, randomised controlled trial.
        Lancet Gastroenterol Hepatol. 2018; 3: 460-468
        • Sasako M.
        • Sakuramoto S.
        • Katai H.
        • Kinoshita T.
        • Furukawa H.
        • Yamaguchi T.
        • et al.
        Five-year outcomes of a randomized phase III trial comparing adjuvant chemotherapy with S-1 versus surgery alone in stage II or III gastric cancer.
        J Clin Oncol. 2011; 29: 4387-4393
        • Sasako M.
        • Sano T.
        • Yamamoto S.
        • Kurokawa Y.
        • Nashimoto A.
        • Kurita A.
        • et al.
        • Japan Clinical Oncology Group
        D2 lymphadenectomy alone or with para-aortic nodal dissection for gastric cancer.
        N Engl J Med. 2008; 359: 453-462
        • D'Angelica M.
        • Gonen M.
        • Brennan M.F.
        • Turnbull A.D.
        • Bains M.
        • Karpeh M.S.
        Patterns of initial recurrence in completely resected gastric adenocarcinoma.
        Ann Surg. 2004; 240: 808-816
        • Aoyama T.
        • Yoshikawa T.
        • Hayashi T.
        • Kuwabara H.
        • Mikayama Y.
        • Ogata T.
        • et al.
        Risk factors for peritoneal recurrence in stage II/III gastric cancer patients who received S-1 adjuvant chemotherapy after D2 gastrectomy.
        Ann Surg Oncol. 2012; 19: 1568-1574
        • Wada T.
        • Kunisaki C.
        • Hasegawa S.
        • Takagawa R.
        • Momiyama M.
        • Kosaka T.
        • et al.
        Factors predictive of recurrence after surgery for gastric cancer followed by adjuvant S-1 chemotherapy.
        Anticancer Res. 2013; 33: 1747-1751
        • Sun Z.
        • Xu Y.Y.
        • Wang Z.N.
        • Zhu Z.
        • Zhang H.
        • Huang B.J.
        • et al.
        Macroscopic serosal classification predicts peritoneal recurrence for patients with gastric cancer underwent potentially curative surgery.
        Ann Surg Oncol. 2011; 18: 1068-1080
        • Tokunaga M.
        • Kurokawa Y.
        • Machida R.
        • Sato Y.
        • Takiguchi S.
        • Doki Y.
        • et al.
        Impact of postoperative complications on survival outcomes in patients with gastric cancer: exploratory analysis of a randomized controlled JCOG1001 trial.
        Gastric Cancer. 2021; 24: 214-223
        • Katai H.
        • Maruyama K.
        • Sasako M.
        • Sano T.
        • Okajima K.
        • Kinoshita T.
        • et al.
        Mode of recurrence after gastric cancer surgery.
        Dig Surg. 1994; 11: 99-103
        • Association J.G.C.
        Japanese gastric cancer treatment guidelines 2018.
        fifth ed. Gastric Cancer, 2020
        • Baiocchi G.L.
        • D'Ugo D.
        • Coit D.
        • Hardwick R.
        • Kassab P.
        • Nashimoto A.
        • et al.
        Follow-up after gastrectomy for cancer: the charter scaligero consensus conference.
        Gastric Cancer. 2016; 19: 15-20
        • Smyth E.C.
        • Verheij M.
        • Allum W.
        • Cunningham D.
        • Cervantes A.
        • Arnold D.
        • ESMO Guidelines Committee
        Gastric cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.
        Ann Oncol. 2016; 27: v38-v49