When and where: A study on gastric cancer recurrence after neoadjuvant/perioperative chemotherapy

doi:10.3748/wjg.117778

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Randomized Controlled Trial

Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Gastroenterol. Aug 14, 2026; 32(30): 117778
Published online Aug 14, 2026. doi: 10.3748/wjg.117778

When and where: A study on gastric cancer recurrence after neoadjuvant/perioperative chemotherapy

Manlio Monti, Bianca Ceredi, Flavia Foca, Paolo Morgagni, Massimo Framarini, Bernadette Vertogen, Daniele Marrelli, Franco Roviello, Uberto Fumagalli Romario, Silvia Bozzarelli, Annibale Donini, Luigina Graziosi, Federica Filippini, Maria Bencivenga, Carlo Milandri, Gianni Mura, Gian Luca Baiocchi, Stefano Rausei, Chiara Molinari, Alessandro Passardi

Manlio Monti, Bianca Ceredi, Alessandro Passardi, Department of Medical Oncology, IRCCS Istituto Scientifico Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola 47014, Emilia-Romagna, Italy

Flavia Foca, Bernadette Vertogen, Unit of Biostatistics and Clinical Trials, IRCCS Istituto Scientifico Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola 47014, Emilia-Romagna, Italy

Paolo Morgagni, Massimo Framarini, Department of General Surgery, “Morgagni-Pierantoni” Hospital, Forlì 47121, Emilia-Romagna, Italy

Daniele Marrelli, Unit of Surgical Oncology, University of Siena, Siena 53100, Provincia di Siena, Italy

Franco Roviello, Department of Surgical Oncology, University of Siena, Siena 53100, Provincia di Siena, Italy

Uberto Fumagalli Romario, Department of Digestive Surgery, European Institute of Oncology, IRCCS, Milano 20141, Lombardia, Italy

Silvia Bozzarelli, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Rozzano 20089, Lombardia, Italy

Annibale Donini, Luigina Graziosi, Department of General and Emergency Surgery, University of Perugia, Perugia 06129, Umbria, Italy

Federica Filippini, Maria Bencivenga, General and Upper GI Surgery Division, University of Verona, Verona 37129, Veneto, Italy

Carlo Milandri, Department of Oncology, “San Donato” Hospital, Arezzo 52100, Tuscany, Italy

Gianni Mura, Department of General Surgery, “San Donato” Hospital, Arezzo 52100, Tuscany, Italy

Gian Luca Baiocchi, Department of Clinical and Experimental Sciences, University of Brescia, Brescia 25123, Lombardia, Italy

Stefano Rausei, General Surgery Unit, Cittiglio/Angera Hospital, ASST Sette Laghi, Cittiglio 21033, Varese, Italy

Chiara Molinari, Biosciences Laboratory, IRCCS Istituto Scientifico Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola 47014, Emilia-Romagna, Italy

Author contributions: Monti M designed the research study; Monti M, Morgagni P, Framarini M, Marrelli D, Roviello F, Fumagalli Romario U, Bozzarelli S, Donini A, Graziosi L, Filippini F, Bencivenga M, Milandri C, Mura G, Baiocchi GL, Rausei S acquired the data; Monti M and Morgagni P interpreted the data; Vertogen B managed the data; Foca F performed the statistical analysis; Monti M, Ceredi B, Foca F, Molinari C drafted the manuscript; Bozzarelli S, Passardi A, Morgagni P, Baiocchi GL and Rausei S critically revised the manuscript for important intellectual content; all authors have read and agreed to the published version of the manuscript.

Institutional review board statement: The study was approved by the IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori” Institutional review board (No. 471 of 21/07/2010) and by the Local Ethics Committees.

Clinical trial registration statement: The trial was registered on ClinicalTrial.gov website (No. NCT01876927) and in the EudraCT database (No. 2010-020189-37).

Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.

Conflict-of-interest statement: The authors declare that they have no conflict of interest.

CONSORT 2010 statement: The authors have read the CONSORT 2010 Statement, and the manuscript was prepared and revised according to the CONSORT 2010 Statement.

Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at flavia.foca@irst.emr.it. Participants gave informed consent for data sharing.

Corresponding author: Flavia Foca, BStat, Researcher, Unit of Biostatistics and Clinical Trials, IRCCS Istituto Scientifico Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Via P. Maroncelli 40, Meldola 47014, Emilia-Romagna, Italy. flavia.foca@irst.emr.it

Received: December 24, 2025
Revised: February 12, 2026
Accepted: April 21, 2026
Published online: August 14, 2026
Processing time: 211 Days and 18.4 Hours

Abstract

BACKGROUND

Neoadjuvant chemotherapy is the standard of care for locally advanced gastric cancer (GC) in the Western countries. However, limited data are available on the timing and patterns of recurrence in this setting.

AIM

To evaluate recurrence patterns and timing of neoadjuvant/perioperative chemotherapy in patients with GC, analyze factors influencing recurrence, update relapse-free survival (RFS) and overall survival (OS) estimates.

METHODS

A total of 91 patients with resectable GC were enrolled between September 2010 and August 2016. Participants were then randomized in a 1:1 ratio to receive either 4 cycles of neoadjuvant chemotherapy (arm A) or a preoperative plus postoperative consisting of 2 cycles of docetaxel, oxaliplatin, and capecitabine chemotherapy, followed by 2 additional cycles after surgery (arm B).

RESULTS

Fifty-two out of 84 patients (61.9%) experienced disease recurrence, and for 41 the site of disease was identified. Distant, peritoneal, and local relapses occurred in 21 (51.2%), 11 (26.8%), and 5 (12.2%) patients, respectively. The median follow-up was 79 months (range: 4.2-120 months). The 5-years RFS was 39.0% [95% confidence interval (CI): 27.9-49.9]. cT4 tumors had a higher risk of recurrence compared to those with cT2-3 tumors (hazard ratio = 1.92; 95%CI: 1.03-3.56; P = 0.038). The 5-years and 7-years OS was 58.7% (95%CI: 41.9-72.2) and 47.3% (95%CI: 29.4-63.2) in arm A and it was 55.0% (95%CI: 38.4-68.9; P = 0.806) and 46.8% (95%CI: 30.7-61.5; P = 0.806) in arm B, respectively.

CONCLUSION

Distant metastases are the most common relapse sites, within two years after surgery; RFS depends on tumor size, histology and treatment response; median OS was 69.6 months with favorable long-term outcomes.

Keywords: Gastric cancer; Neoadjuvant chemotherapy; Perioperative chemotherapy; Time of recurrence; Site of recurrence; Postoperative recurrence

Core Tip: This randomized study provides long-term data on recurrence patterns after neoadjuvant or perioperative chemotherapy for resectable gastric cancer. Most relapses occurred at distant sites, with the highest risk within the first two years after surgery. These findings support risk stratification particularly given by interaction between tumor regression score and lymph nodes involvement. Time-dependent modelling suggested that the intestinal subtype is associated with a decreasing recurrence risk over time; however, this finding requires further validation.