Observational Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Surg. Nov 27, 2021; 13(11): 1463-1483
Published online Nov 27, 2021. doi: 10.4240/wjgs.v13.i11.1463
Long-term survival of patients with stage II and III gastric cancer who underwent gastrectomy with inadequate nodal assessment
Jacopo Desiderio, Andrea Sagnotta, Irene Terrenato, Eleonora Garofoli, Claudia Mosillo, Stefano Trastulli, Federica Arteritano, Federico Tozzi, Vito D'Andrea, Yuman Fong, Yanghee Woo, Sergio Bracarda, Amilcare Parisi
Jacopo Desiderio, Stefano Trastulli, Federica Arteritano, Amilcare Parisi, Department of Digestive Surgery, St. Mary’s Hospital, Terni 05100, Italy
Jacopo Desiderio, Vito D'Andrea, Department of Surgical Sciences, Sapienza University of Rome, Rome 00161, Italy
Andrea Sagnotta, Department of General Surgery and Surgical Oncology, San Filippo Neri Hospital, Rome 00135, Italy
Irene Terrenato, Biostatistics and Bioinformatic Unit, Scientific Direction, IRCCS Regina Elena National Cancer Institute, Rome 00144, Italy
Eleonora Garofoli, Claudia Mosillo, Sergio Bracarda, Department of Medical Oncology, St. Mary’s Hospital, Terni 05100, Italy
Federico Tozzi, Division of Surgical Oncology and Endocrine Surgery, Mays Cancer Center, University of Texas Health Science Center San Antonio, San Antonio, TX 78229, United States
Yuman Fong, Yanghee Woo, Division of Surgical Oncology, Department of Surgery, City of Hope National Medical Center, Duarte, LA, 91010, United States
Author contributions: Desiderio J, Sagnotta A and Terrenato I designed the study, conducted the research, collected the data, analyzed the results and drafted the manuscript; Terrenato I performed the statistics; Parisi A, D'Andrea V, Bracarda S, Woo Y and Fong Y supervised the study, and revised the manuscript; Trastulli S, Garofoli E, Mosillo C, Tozzi F confirmed the statistics, interpreted the data, and revised the manuscript; All authors read and approved the final manuscript.
Institutional review board statement: This is a study using a population-based registry, so institutional review board was not applicable.
Informed consent statement: This is a study using a population-based registry, so informed consent was not applicable.
Conflict-of-interest statement: The authors declare that they have no conflicting interests.
Data sharing statement: Further information is available from the corresponding author on reasonable request.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Jacopo Desiderio, PhD, Academic Research, Surgeon, Surgical Oncologist, Department of Digestive Surgery, St. Mary’s Hospital, Via Tristano di Joannuccio 1, Terni 05100, Italy. j.desiderio@aospterni.it
Received: April 28, 2021
Peer-review started: April 28, 2021
First decision: June 17, 2021
Revised: June 30, 2021
Accepted: October 22, 2021
Article in press: October 22, 2021
Published online: November 27, 2021
Processing time: 211 Days and 22.8 Hours
Abstract
BACKGROUND

Gastric cancer is an aggressive disease with frequent lymph node (LN) involvement. The NCCN recommends a D2 lymphadenectomy and the harvesting of at least 16 LNs. This threshold has been the subject of great debate, not only for the extent of surgery but also for more appropriate staging. The reclassification of stage IIB through IIIC based on N3b nodal staging in the eighth edition of the American Joint Committee on Cancer (AJCC) staging system highlights the efforts to more accurately discriminate survival expectancy based on nodal number. Furthermore, studies have suggested that pathologic assessment of 30 or more LNs improve prognostic accuracy and is required for proper staging of gastric cancer.

AIM

To evaluate the long-term survival of advanced gastric cancer patients who deviated from expected survival curves because of inadequate nodal evaluation.

METHODS

Eligible patients were identified from the Surveillance, Epidemiology, and End Results database. Those with stage II–III gastric cancer were considered for inclusion. Three groups were compared based on the number of analyzed LNs. They were inadequate LN assessment (ILA, < 16 LNs), adequate LN assessment (ALA, 16-29 LNs), and optimal LN assessment (OLA, ≥ 30 LNs). The main outcomes were overall survival (OS) and cancer-specific survival. Data were analyzed by the Kaplan-Meier product-limit method, log-rank test, hazard risk, and Cox proportional univariate and multivariate models. Propensity score matching (PSM) was used to compare the ALA and OLA groups.

RESULTS

The analysis included 11607 patients. Most had advanced T stages (T3 = 48%; T4 = 42%). The pathological AJCC stage distribution was IIA = 22%, IIB = 18%, IIIA = 26%, IIIB = 22%, and IIIC = 12%. The overall sample divided by the study objective included ILA (50%), ALA (35%), and OLA (15%). Median OS was 24 mo for the ILA group, 29 mo for the ALA group, and 34 mo for the OLA group (P < 0.001). Univariate analysis showed that the ALA and OLA groups had better OS than the ILA group [ALA hazard ratio (HR) = 0.84, 95% confidence interval (CI): 0.79–0.88, P < 0.001 and OLA HR = 0.73, 95%CI: 0.68–0.79, P < 0.001]. The OS outcome was confirmed by multivariate analysis (ALA HR = 0.68, 95%CI: 0.64–0.71, P < 0.001 and OLA: HR = 0.48, 95%CI: 0.44–0.52, P < 0.001). A 1:1 PSM analysis in 3428 patients found that the OLA group had better survival than the ALA group (OS: OLA median = 34 mo vs ALA median = 26 mo, P < 0.001, which was confirmed by univariate analysis (HR = 0.81, 95%CI: 0.75–0.89, P < 0.001) and multivariate analysis: (HR = 0.71, 95%CI: 0.65–0.78, P < 0.001).

CONCLUSION

Proper nodal staging is a critical issue in gastric cancer. Assessment of an inadequate number of LNs places patients at high risk of adverse long-term survival outcomes.

Keywords: Gastric Cancer; Lymphadenectomy; Gastrectomy; Staging; N stage; Surveillance, Epidemiology, and End Results

Core Tip: A large database was analyzed to investigate survival outcomes related to lymph node assessment in locally advanced gastric cancer patients with radical gastrectomy. Independent of TNM-stage, the group with assessment of < 16 lymph nodes (LNs) had significantly worse survival than two other groups, 16-29 LNs and ≥ 30 LNs. Stage migration because of inadequate specimen analysis and improper lymphadenectomy was the main root cause.