Annals of Surgical Oncology

, Volume 25, Issue 8, pp 2418–2427 | Cite as

Neoadjuvant Therapy Improves Outcomes in Locally Advanced Signet-Ring-Cell Containing Esophagogastric Adenocarcinomas

  • Ulrike Heger
  • Leila Sisic
  • Henrik Nienhüser
  • Susanne Blank
  • Ulf Hinz
  • Georg Martin Haag
  • Katja Ott
  • Alexis Ulrich
  • Markus W. Büchler
  • Thomas Schmidt
Gastrointestinal Oncology



Only a few studies have analyzed multimodal treatment concepts in the subgroup of signet-ring-cell containing upper gastrointestinal (GI) cancer. Recent retrospective, multicentric data favor primary resection without neoadjuvant chemotherapy for gastric signet-ring-cell containing carcinomas (SRCs). We compared the outcomes of primarily resected carcinomas with neoadjuvantly treated, locally advanced esophagogastric SRCs.


A total of 310 patients with esophagogastric SRC-staged cT3/4/Nany/Many from a prospective unicentric database were included in this study; 192 (61.9%) received neoadjuvant therapy (NEO group) and 118 (38.1%) were primarily resected (RES group).


Overall, 128 (41.3%) patients presented with adenocarcinoma of the esophagogastric junction (AEG) and 182 (58.7%) presented with gastric cancer. Neoadjuvant therapy was significantly associated with resection in curative intent (NEO: 91.1%; RES: 75.4%; P = 0.001), improved (y)pT category (P = 0.035), improved (y)pN category (P < 0.001), and R0 resections (curative intent cohort: 76.0% in NEO vs. 60.7% in RES; P = 0.010), among others, but not with postoperative complications. Overall survival was significantly improved by neoadjuvant treatment {median survival 28.5 months (95% confidence interval [CI] 14.4–39.6) vs. RES: 14.9 months (10.6–17.5); P < 0.001}, as well as in subgroups (AEG and gastric tumors, R0-resected patients, and patients with and without relevant comorbidities). Independent prognostic factors were neoadjuvant therapy (hazard ratio [HR] 0.66; P = 0.023), pT4 category (HR 1.71; P = 0.041), pN2 category (HR 1.86; P = 0.013), pN3 category (HR 2.40; P < 0.001), pM1 category (HR 1.95; P = 0.003), age > 70 years (HR 1.79; P = 0.006), gastric localization (HR 0.69; P = 0.032), American Society of Anesthesiologists classification 3/4 (HR 1.71; P = 0.004), and incomplete resection R1/2 (HR 1.6; P = 0.014).


Our results demonstrate a survival advantage for advanced-stage esophagogastric SRC patients by neoadjuvant treatment.



Leila Sisic received funding through a grant from the Faculty of Medicine, University of Heidelberg, however this has no relationship to the submitted work.

Supplementary material

10434_2018_6541_MOESM1_ESM.docx (801 kb)
Supplementary material 1 (DOCX 800 kb)


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Copyright information

© Society of Surgical Oncology 2018

Authors and Affiliations

  1. 1.Department of General, Visceral and Transplant SurgeryUniversity HospitalHeidelbergGermany
  2. 2.National Center for Tumor Diseases (NCT)University HospitalHeidelbergGermany
  3. 3.Department of SurgeryRosenheimGermany

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