Krishnan A. Rethinking carcinoembryonic antigen and carbohydrate antigen 19-9 in gastric cancer surveillance: From statistical association to clinical utility. World J Gastrointest Oncol 2026; 18(10): 119774 [DOI: 10.4251/wjgo.119774]
Corresponding Author of This Article
Arunkumar Krishnan, Department of Supportive Oncology, Atrium Health Levine Cancer, Atrium Health Wake Forest Baptist Comprehensive Cancer Center, 1021 Morehead Medical Dr, Charlotte, NC 28204, United States. dr.arunkumar.krishnan@gmail.com
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Oncology
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review-article
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Krishnan A. Rethinking carcinoembryonic antigen and carbohydrate antigen 19-9 in gastric cancer surveillance: From statistical association to clinical utility. World J Gastrointest Oncol 2026; 18(10): 119774 [DOI: 10.4251/wjgo.119774]
World J Gastrointest Oncol. Oct 15, 2026; 18(10): 119774 Published online Oct 15, 2026. doi: 10.4251/wjgo.119774
Rethinking carcinoembryonic antigen and carbohydrate antigen 19-9 in gastric cancer surveillance: From statistical association to clinical utility
Arunkumar Krishnan
Arunkumar Krishnan, Department of Supportive Oncology, Atrium Health Levine Cancer, Atrium Health Wake Forest Baptist Comprehensive Cancer Center, Charlotte, NC 28204, United States
Author contributions: Krishnan A conceptualized the manuscript and conducted the assessment; Krishnan A prepared the manuscript draft, which was subsequently reviewed and approved for final publication.
AI contribution statement: AI-based tools were used in this manuscript for language refinement and editorial polishing - improving grammar and readability - consistent with most current publisher policies on AI-assisted language editing. No AI tool was used to generate the substantive analysis, conclusions, or scientific arguments or writing.
Conflict-of-interest statement: The author reports no relevant conflicts of interest for this article.
Corresponding author: Arunkumar Krishnan, Department of Supportive Oncology, Atrium Health Levine Cancer, Atrium Health Wake Forest Baptist Comprehensive Cancer Center, 1021 Morehead Medical Dr, Charlotte, NC 28204, United States. dr.arunkumar.krishnan@gmail.com
Received: February 5, 2026 Revised: February 23, 2026 Accepted: March 9, 2026 Published online: October 15, 2026 Processing time: 223 Days and 12.6 Hours
Abstract
Gastric cancer (GC) remains a leading cause of cancer-related mortality worldwide, and identifying reliable prognostic biomarkers for postoperative surveillance is a persistent clinical challenge. Serum carcinoembryonic antigen and carbohydrate antigen 19-9 have long been studied for their potential to predict recurrence and guide treatment in this context, yet their clinical utility remains incompletely validated. A recent study examined these biomarkers as predictors of early recurrence and gastrointestinal chemotherapy toxicity in patients receiving adjuvant S-1 plus oxaliplatin therapy after gastrectomy. While the study provides clinically interesting data, several methodological and statistical shortcomings limit the strength and generalizability of its conclusions. In this opinion review, we undertake a comprehensive critical reappraisal of the study’s design, analytical approach, and interpretive framework. We examine five key areas of concern: selection bias arising from exclusion of poorly compliant patients, temporal ambiguity in biomarker-outcome relationships, inadequate control of clinically relevant confounders, fundamental flaws in survival analysis methodology, and the absence of predictive performance evaluation. Beyond the specific critique, we place these issues within the broader landscape of biomarker research in GC, discussing the evolving role of molecular subtypes, liquid biopsy technologies such as circulating tumor DNA, and modern statistical frameworks, including decision curve analysis and the TRIPOD guidelines. We argue that the field must move beyond simple correlative biomarker studies toward methodologically rigorous, prospectively validated, and clinically actionable prognostic models. Finally, we outline a practical roadmap for future research, identifying the key steps required to translate promising biomarker signals into tools that can meaningfully improve postoperative decision-making in gastrointestinal oncology.
Core Tip: This opinion review critically examines a recent study linking carcinoembryonic antigen and carbohydrate antigen 19-9 to gastric cancer recurrence and chemotherapy toxicity, identifying fundamental methodological gaps that limit clinical applicability. The concerns raised-selection bias, reverse causality, inadequate confounding control, mishandled survival analysis, and absent predictive performance assessment-are not unique to one study; they represent recurring weaknesses across the biomarker literature in gastrointestinal oncology. We argue that the field must embrace modern biostatistical frameworks, integrate molecular subtyping and liquid biopsy technologies, and adopt rigorous validation standards before any single biomarker can reliably guide postoperative management.
