Gastric| Volume 172, ISSUE 2, P593-601, August 2022

Significance of neoadjuvant downstaging in gastric adenocarcinoma

Published:April 07, 2022DOI:



      Neoadjuvant chemotherapy is established in the treatment of gastric adenocarcinoma. Histopathological regression may have important prognostic implications. There are little data comparing clinical outcomes of patients with gastric adenocarcinoma that received neoadjuvant treatment and those neoadjuvant naive. The aim of this study is to determine the impact of neoadjuvant chemotherapy upon prognosis of patients being treated for gastric adenocarcinoma.


      Consecutive patients with gastric cancer from a single center between 2007 and 2017 were evaluated. Patients were treated with either a subtotal or total gastrectomy with D2 lymphadenectomy. Stage-by-stage comparison of the extent of pathological downstaging was conducted for patients who received neoadjuvant treatment (ypTNM) and those who did not (pTNM) using the TNM eighth edition.


      Overall, 384 patients underwent gastrectomy, 141 patients received neoadjuvant chemotherapy, and 86 patients (58.1%) were downstaged. Downstaged patients had improved overall survival compared to patients who did not respond to neoadjuvant chemotherapy (not reported vs 66 months, P < .001). Downstaging by >3 stages was the strongest independent predictor of overall survival (hazard ratio: 0.17; 95% confidence interval 0.062–0.44). Overall survival was significantly better among patients in the ypTNM groups when a stage-by-stage comparison was performed with the pTNM group.


      Pathological stage is a more accurate predictor of prognosis compared clinical stage with downstaged patients benefiting from lower recurrence rates and improved overall survival. Patients downstaged due to neoadjuvant chemotherapy may potentially have more favorable clinical outcomes compared to stage-matched patients who did not receive this.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Surgery
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Etemadi A.
        • Safiri S.
        • Sepanlou S.G.
        • et al.
        The global, regional, and national burden of stomach cancer in 195 countries, 1990–2017: a systematic analysis for the Global Burden of Disease study 2017.
        Lancet Gastroenterol Hepatol. 2020; 5: 42-54
        • Cunningham D.
        • Allum W.H.
        • Stenning S.P.
        • et al.
        Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer.
        N Engl J Med. 2006; 355: 11-20
        • Al-Batran S.E.
        • Homann N.
        • Pauligk C.
        • et al.
        Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomised, phase 2/3 trial.
        Lancet. 2019; 393: 1948-1957
        • Mcdonald J.S.
        • Smalley S.R.
        • Benedetti J.
        • et al.
        Chemoradiotherapy plus surgery for gastric adenocarcinoma.
        N Engl J Med. 2001; 345: 725-730
        • Sano T.
        • Sasako M.
        • Yamamoto S.
        • et al.
        Gastric cancer surgery: morbidity and mortality results from a prospective randomized controlled trial comparing D2 and extended para-aortic lymphadenectomy: Japan Clinical Oncology Group study 9501.
        J Clin Oncol. 2004; 22: 2767-2773
        • Schuhmacher C.
        • Gretschel S.
        • Lordick F.
        • et al.
        Neoadjuvant chemotherapy compared with surgery alone for locally advanced cancer of the stomach and cardia: European organisation for research and treatment of cancer randomized trial 40954.
        J Clin Oncol. 2010; 28: 5210-5218
        • Smith D.D.
        • Schwarz R.R.
        • Schwarz R.E.
        Impact of total lymph node count on staging and survival after gastrectomy for gastric cancer: data from a large US-population database.
        J Clin Oncol. 2005; 23: 7114-7124
        • Hundahl S.A.
        • Phillips J.L.
        • Menck H.R.
        The National Cancer Data Base Report on poor survival of U.S. gastric carcinoma patients treated with gastrectomy: Fifth Edition American Joint Committee on Cancer staging, proximal disease, and the “different disease” hypothesis.
        Cancer. 2000; 88: 921-932
        • Edge S.B.
        • American Joint Committee on Cancer
        AJCC Cancer Staging Manual.
        7th edition. Springer, 2010
        • Hao Y.
        • Liu Y.
        • Ishibashi H.
        • Wakama S.
        • Nishino E.
        • Yonemura Y.
        Downstaging of lymph node metastasis after neoadjuvant intraperitoneal and systemic chemotherapy in gastric carcinoma with peritoneal metastasis.
        Eur J Surg Oncol. 2019; 45: 1493-1497
      1. AJCC Cancer Staging Form Supplement AJCC Cancer Staging Manual, eighth edition. (n.d.).

        • Park S.R.
        • Kim M.J.
        • Ryu K.W.
        • et al.
        Prognostic value of preoperative clinical staging assessed by computed tomography in resectable gastric cancer patients: a viewpoint in the era of preoperative treatment.
        Ann Surg. 2010; 251: 428-435
        • D’Ugo D.
        • Persiani R.
        • Rausei S.
        • et al.
        Response to neoadjuvant chemotherapy and effects of tumor regression in gastric cancer.
        Eur J Surg Oncol. 2006; 32: 1105-1109
        • Newman E.
        • Marcus S.G.
        • Potmesil M.
        • et al.
        Neoadjuvant chemotherapy with CPT-11 and cisplatin downstages locally advanced gastric cancer.
        J Gastrointest Surg. 2002; 6 (discussion 223): 212-223
        • Bradley N.A.
        • Wilson C.
        • Graham J.
        • et al.
        The downstaging approach to irresectable oesophageal and gastric cancer: a single centre experience.
        J Gastrointest Oncol. 2019; 10: 499-505
        • Navidi M.
        • Madhavan A.
        • Griffin S.M.
        • et al.
        Trainee performance in radical gastrectomy and its effect on outcomes.
        BJS Open. 2020; 4
        • Royal College of Pathologists
        G006 Dataset for histopathological reporting of oesophageal and gastric carcinoma. Version 3. 2019; : 1-23
        • Jemal A.
        • Bray F.
        • Center M.M.
        • Ferlay J.
        • Ward E.
        • Forman D.
        Global cancer statistics.
        CA Cancer J Clin. 2011; 61
        • Mokadem I.
        • Dijksterhuis W.P.M.
        • van Putten M.
        • et al.
        Recurrence after preoperative chemotherapy and surgery for gastric adenocarcinoma: a multicenter study.
        Gastric Cancer. 2019; 22
        • Davies A.R.
        • Gossage J.A.
        • Zylstra J.
        • et al.
        Tumor stage after neoadjuvant chemotherapy determines survival after surgery for adenocarcinoma of the esophagus and esophagogastric junction.
        J Clin Oncol. 2014; 32
        • Kamarajah S.K.
        • Navidi M.
        • Wahed S.
        • et al.
        Significance of neoadjuvant downstaging in carcinoma of esophagus and gastroesophageal junction.
        Ann Surg Oncol. 2020; 27
        • Badgwell B.
        • Blum M.
        • Estrella J.
        • et al.
        Predictors of survival in patients with resectable gastric cancer treated with preoperative chemoradiation therapy and gastrectomy.
        J Amer Coll Surg. 2015; 221
        • Navidi M.
        • Phillips A.W.
        • Griffin S.M.
        • et al.
        Cardiopulmonary fitness before and after neoadjuvant chemotherapy in patients with oesophagogastric cancer.
        Br J Surg. 2018; 105
        • Sinclair R.
        • Navidi M.
        • Griffin S.
        • Sumpter K.
        The impact of neoadjuvant chemotherapy on cardiopulmonary physical fitness in gastro-oesophageal adenocarcinoma.
        Ann Royal Coll Surg Eng. 2016; 98
        • Smyth E.
        • Wotherspoon A.
        • Peckitt C.
        • et al.
        Mismatch repair deficiency, microsatellite instability,and survival: an exploratory analysis of the Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) trial.
        JAMA Oncol. 2017; 3
        • Smyth E.
        • Verheij M.
        • Allum W.
        • Cunningham D.
        • Cervantes A.
        • Arnold D.
        Gastric cancer: ESMO practice guidelines for diagnosis, treatment and follow-up.
        Ann Oncol. 2016; 27
        • Leake P.
        • Cardoso R.
        • Seevaratnam R.
        • et al.
        A systematic review of the accuracy and utility of peritoneal cytology in patients with gastric cancer.
        Gastric Cancer. 2012; 15