Performance status as the central guide in managing primary gastrointestinal lymphoma

Abstract

Primary gastrointestinal lymphoma (PGIL) represents a unique and challenging frontier in oncologic care, sitting at the crossroads of hematology, gastroenterology, and surgery. Its rarity, anatomical diversity, and histological heterogeneity complicate the formulation of universal management guidelines and clear prognostic models. In this context, Buyuktalanci et al recently published a study in World Journal of Gastroenterology Oncology, the retrospective cohort study, provides a valuable, focused analysis of clinicopathological and prognostic factors in a Turkish cohort. Their work confirms the predominance of gastric location and diffuse large B-cell lymphoma histology while performing a rigorous statistical interrogation of survival determinants. The most salient finding-that a poor performance status (PS) (Eastern Cooperative Oncology Group score ≥ 2) stands as the sole independent prognostic factor for inferior overall survival in multivariate analysis-serves as the cornerstone for this editorial. This piece expands upon that finding, contextualizing it within the broader landscape of PGIL research. We explore the implications of this result for risk stratification, arguing for the renewed primacy of this simple clinical assessment in an era of complex molecular profiling. We dissect the study’s insights on the evolving role of surgery, the intriguing prognostic signal of Helicobacter pylori infection, and the notable absence of a survival difference between gastric and intestinal sites in this cohort. Finally, we propose an integrative model for future research, advocating for prospective, multinational registries that amalgamate traditional clinical parameters like PS with emerging molecular and genomic data. The ultimate goal is to refine a personalized, physiology-aware approach to PGIL that optimizes therapeutic intensity for those who can benefit while sparing others undue toxicity.

Key Words: Primary gastrointestinal lymphoma; Prognosis; Performance status; Diffuse large B-cell lymphoma; Helicobacter pylori; Surgical oncology; Risk stratification

Core Tip: This study discusses primary gastrointestinal lymphoma (PGIL), a rare and heterogeneous cancer. It highlights a key finding from a recent study: Poor performance status (Eastern Cooperative Oncology Group score ≥ 2) is the strongest independent predictor of survival. We argue for the renewed integration of this fundamental clinical assessment with modern molecular profiling to guide personalized, risk-adapted therapy for PGIL, ensuring treatment intensity matches the patient’s physiologic capacity.

This editorial refers to “Analysis of histopathological and clinical prognostic factors in lymphomas involving the gastrointestinal system” by Buyuktalanci et al, 2026; https://dx.doi.org/10.4251/wjgo.v18.i3.115912.

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INTRODUCTION

Primary gastrointestinal lymphomas (PGILs) represent a unique and challenging subset of non-Hodgkin lymphomas (NHL)[1]. As the most common form of extranodal NHL, accounting for 30%-45% of such cases, PGILs sit at the crossroads of hematologic oncology and gastroenterology[2,3]. Their clinical presentation is notoriously nonspecific, often mimicking more common benign conditions like peptic ulcer disease, irritable bowel syndrome, or inflammatory bowel disease. This diagnostic ambiguity, coupled with their relative rarity (constituting only 1%-4% of all gastrointestinal malignancies), frequently leads to delays in diagnosis[2,4-7].

The heterogeneity of PGIL is multi-faceted. It encompasses a wide spectrum of histologic subtypes, led by diffuse large B-cell lymphoma (DLBCL) and extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma), but also including mantle cell, Burkitt’s, and various T-cell lymphomas[8,9]. This histologic diversity is mirrored by anatomic diversity, with the stomach being the predominant site in Western series, while the small intestine assumes greater relative frequency in certain geographic regions, possibly linked to variations in the prevalence of infectious agents or celiac disease[10-12]. Furthermore, PGIL exhibits significant variability in clinical behavior, ranging from indolent, locally confined disease [e.g., Helicobacter pylori (H. pylori)-dependent gastric MALT lymphoma] to highly aggressive, disseminated illness[13,14].

This heterogeneity directly challenges clinicians tasked with prognostication and therapeutic decision-making. While established tools like the International Prognostic Index and the Lugano staging system provide a framework, their performance in the extranodal context of PGIL can be inconsistent[15,16]. The search for reliable, PGIL-specific prognostic markers is therefore a persistent theme in the literature. In this context, the study by Buyuktalanci et al[17] in World Journal of Gastroenterology Oncology, makes a timely and focused contribution by rigorously analyzing a well-defined cohort from a single Turkish institution. Their work identifies a fundamental clinical factor-the patient’s performance status (PS)-as the sole independent prognostic factor for overall survival in multivariate analysis. This finding serves as the cornerstone for this editorial, in which we offer our perspectives, evaluations, and critical comments on their study.

DECONSTRUCTING THE FINDINGS: EASTERN COOPERATIVE ONCOLOGY GROUP STATUS AS THE KEYSTONE

The retrospective analysis by Buyuktalanci et al[17] of 111 patients with gastrointestinal lymphoma, of which 62 met strict criteria for PGIL, yields findings that are both confirmatory and illuminating. As highlighted above, their multivariate analysis singles out PS as the sole independent prognostic factor for overall survival (OS), underscoring its central role in PGIL outcomes. The epidemiologic data-median age in the seventh decade, male predominance, gastric preponderance (69.3%), and DLBCL as the leading subtype (79%)-align closely with numerous reports from Europe and North America, providing a valuable regional benchmark for Türkiye[11,18,19].

The core analytical contribution lies in the survival analysis. In univariate models, elevated lactate dehydrogenase (LDH ≥ 270 U/L), undergoing surgical treatment, and an Eastern Cooperative Oncology Group (ECOG) PS ≥ 2 were all significantly associated with reduced OS. The multivariate Cox regression analysis, however, distilled this list to a single independent prognostic factor: An ECOG score of 2 or greater (P = 0.010). This finding is of paramount importance.

The ECOG PS scale is a simple, subjective measure of a patient’s functional capacity and general well-being[20,21]. An ECOG score of 2 denotes a patient who is “ambulatory and capable of all self-care but unable to carry out any work activities; up and about more than 50% of waking hours”. Its power as a prognostic marker lies in its integrative nature. It is a holistic biomarker that captures not only the systemic burden of the lymphoma itself (e.g., B symptoms, cytopenias, metabolic derangements) but also the patient’s physiologic age, comorbid disease burden, nutritional status, and even psychosocial resilience. It reflects the host as much as the tumor.

Within this PGIL cohort, the study’s finding that this metric supersedes laboratory values like LDH and treatment variables like surgery in prognostic strength underscores a fundamental oncologic principle: A patient’s ability to tolerate therapy and withstand the disease process is a primary determinant of outcome.

This reaffirmation of ECOG status’s centrality is consistent with several other PGIL studies. Wang et al[22] in a large series of primary gastric lymphoma, identified poor PS as a key predictor of reduced OS. Similarly, the multinational series analyzed by Koch et al[19] for the German Multicenter Study Group highlighted PS as a critical factor. The work by Buyuktalanci et al[17] therefore reinforces a universal clinical truth, providing robust, region-specific validation for patients with definitively diagnosed PGIL.

Table 1 summarizes the prognostic factors identified in the study by Buyuktalanci et al[17], contrasting univariate and multivariate results alongside our interpretive commentary. As shown in the table, ECOG PS ≥ 2 emerges as the sole independent predictor of overall survival-a finding that we argue should anchor clinical risk stratification.

Table 1 Summary of prognostic factors in the study by Buyuktalanci et al[17] and editorial commentary.

Prognostic factor	Univariate analysis	Multivariate analysis	Editorial commentary and interpretation
ECOG PS ≥ 2	P < 0.0001, significant	P = 0.010, independent prognostic factor	Core perspective: PS is the cornerstone of prognostic assessment, reflecting the integration of host status and tumor burden. It should be prioritized in risk stratification
LDH ≥ 270 U/L	P = 0.029, significant	P = 0.085, not significant	A marker of tumor burden, but not independent of PS in this cohort. Possible collinearity with PS
Surgical treatment	P = 0.002, significant (associated with worse OS)	P = 0.384, not significant	Critical commentary: Although propensity score matching was used, unmeasured confounders (e.g., emergency indications, perioperative complications) may remain. Surgery likely serves as a marker-not a cause-of poor prognosis
IPI ≥ 3	OS: P = 0.095, not significant; EFS: P = 0.024, significant	Not entered into multivariate model	Inconsistent performance in PGIL; significance for EFS suggests predictive value for disease progression, but OS is dominated by host factors such as PS
Age ≥ 60 years	P = 0.529, not significant	-	Age did not show prognostic significance in this cohort, possibly due to the integrating effect of PS
Anatomical site (gastric vs intestinal)	OS: P = 0.531; EFS: P = 0.720, both not significant	-	Contrasts with some prior reports; may reflect the specific histological distribution or homogenization of treatment approaches in this cohort

ECOG: Eastern Cooperative Oncology Group; PS: Performance status; LDH: Lactate dehydrogenase; OS: Overall survival; EFS: Event-free survival; IPI: International Prognostic Index; PGIL: Primary gastrointestinal lymphoma.

CONTEXTUALIZING CONTRADICTORY OBSERVATIONS: SURGERY AND H. PYLORI

The study presents two ancillary findings that warrant careful interpretation: The negative association of surgery with survival and the positive association of H. pylori infection with survival.

The surgery paradox

The observation that patients undergoing surgery (followed by chemotherapy) had worse OS and event-free survival than those treated with chemotherapy or chemoradiation alone (P = 0.002 and 0.013, respectively) is intriguing and likely reflects profound selection bias rather than a deleterious effect of surgery. The authors correctly employ propensity score matching to address this, a sophisticated methodological strength. Historically, surgery was the cornerstone of PGIL management. However, over the past two decades, its role has dramatically diminished, reserved primarily for emergencies (perforation, hemorrhage, obstruction) or diagnostic dilemmas[23,24]. Consequently, in a modern cohort like this one (spanning 2006-2018), the “surgery group” almost certainly represents a negative selection of patients with more complicated, advanced, or bulky disease at presentation. The multivariate analysis, where the significance of surgery was attenuated (P = 0.384), supports the interpretation that surgery is a marker for adverse disease biology or presentation, not an independent cause of poor outcome. This finding aligns with the broader trend in oncology favoring organ-preserving, systemic approaches where effective.

However, we caution that propensity score matching can only adjust for measured confounders. Unmeasured factors-such as the specific indication for surgery (e.g., perforation, hemorrhage, obstruction, or diagnostic uncertainty), the urgency of the procedure, and postoperative complications-may still differ systematically between groups. These unmeasured biases likely contribute to the observed survival disadvantage in the surgery group. Therefore, while the authors’ conclusion that surgery is a marker rather than a cause of poor prognosis is reasonable, it should be interpreted with this residual confounding in mind.

The H. pylori survival advantage

The report that H. pylori infection was detected in 48% of gastric PGIL cases and was associated with significantly better OS (P < 0.0001) is provocative. A causative link between H. pylori and gastric MALT lymphoma is well-established, and eradication therapy is the first-line treatment for localized disease[25]. However, the extension of a survival benefit to a mixed cohort (predominantly DLBCL) is less clear. The authors appropriately caution that the small sample size of H. pylori-positive patients (n = 21) precludes definitive conclusions. This finding may be confounded by several factors: H. pylori-positive status might be associated with earlier-stage disease or a distinct molecular subtype of DLBCL with better prognosis[26]. Alternatively, it may reflect lead-time bias or the benefits of eradication therapy itself on the gastric microenvironment[27]. This intriguing signal highlights the need for systematic H. pylori testing and reporting in future PGIL studies to clarify its potential role as more than an etiologic agent in MALT lymphoma[28-30].

We would add that the survival benefit observed in H. pylori-positive patients may be confounded by several factors beyond sample size. First, H. pylori positivity might be associated with earlier-stage disease, which independently predicts better outcomes. Second, the majority of H. pylori-positive patients in this cohort had DLBCL rather than MALT lymphoma, yet the biological rationale for a survival benefit in DLBCL remains speculative. Third, all H. pylori-positive patients received eradication therapy, but whether this therapy directly contributed to improved survival-or merely served as a marker for more favorable disease biology-cannot be determined from this study. We therefore urge readers to view this finding as hypothesis-generating rather than conclusive.

THE GEOGRAPHIC AND BIOLOGICAL TAPESTRY OF PGIL

The discussion by Buyuktalanci et al[17] rightly situates their findings within the global landscape of PGIL, which exhibits notable geographic variation. The predominance of gastric involvement in their Turkish cohort contrasts with patterns in parts of the Middle East and the Pacific region, where intestinal lymphomas are more frequent[10,31]. This variation is a powerful reminder of the role of environmental and genetic factors. The high prevalence of immunoproliferative small intestinal disease in the Mediterranean and Middle East, the link between celiac disease and enteropathy-associated T-cell lymphoma in Northern Europe, and the association of H. pylori with gastric lymphomas worldwide illustrate how the local biologic milieu shapes disease epidemiology[32-34].

Furthermore, the study’s failure to find a significant survival difference between gastric and intestinal lymphomas contrasts with some previous reports[11,35]. This may reflect the specific histologic mix and stage distribution within their cohort or evolving treatment paradigms that have equalized outcomes. It underscores that while anatomic site influences presentation and management, overarching host factors like PS may ultimately exert a stronger influence on survival across subtypes.

LIMITATIONS AS A SPRINGBOARD FOR FUTURE RESEARCH

The authors transparently acknowledge the limitations inherent to their work: Its retrospective, single-center design and the relatively modest sample size, particularly for subgroup analyses (e.g., only 7 patients with ECOG ≥ 2). These limitations are typical of research into rare diseases but do not invalidate the primary conclusion. Instead, they chart a course for future investigation.

The limitations of the study by Buyuktalanci et al[17]-its retrospective design, single-center setting, relatively modest sample size (particularly for subgroup analyses such as the 7 patients with ECOG ≥ 2 and the 6 with MALT lymphoma), and the absence of centralized pathology review-chart a clear course for future investigation. Building on these limitations, we propose the following priorities: (1) Prospective, multicenter validation: The finding that ECOG PS is the sole independent prognostic factor requires validation in larger, geographically diverse cohorts that include adequate numbers of patients with poor PS and rare histologic subtypes; (2) Integration with molecular profiling: The interplay between clinical PS and tumor biology remains unexplored. Does ECOG ≥ 2 correlate with high-risk molecular subtypes (e.g., non-GCB DLBCL, double-hit lymphomas) in PGIL, or does PS provide independent prognostic information beyond genetics? Future studies should prospectively collect tissue for centralized molecular analysis; (3) Clarification of the H. pylori signal: The provocative association between H. pylori positivity and improved survival-limited by small numbers and the predominance of DLBCL in this cohort-warrants dedicated investigation in larger gastric PGIL cohorts with standardized H. pylori testing and documentation of eradication therapy; and (4) Refinement of surgical indications: To overcome the residual confounding inherent in retrospective analyses of surgery, future studies should prospectively record surgical indications, urgency, and perioperative complications to clarify the true role of surgery in the modern treatment era.

CONCLUSION

The study by Buyuktalanci et al[17] delivers a powerful, practice-oriented message. In an era of rapid advancement in genomic sequencing and targeted therapeutics, it reaffirms the irreplaceable value of a fundamental clinical skill: The careful assessment of the patient before us. The ECOG PS is a low-cost, high-yield prognostic tool that encapsulates the dynamic interaction between tumor and host.

Building on the finding that ECOG PS is the central prognostic factor in PGIL, we propose a clinical decision framework that places PS at the core of individualized management (Figure 1). This framework integrates PS with molecular profiling, H. pylori status, anatomic site, and comorbidity burden to guide treatment intensity, while emphasizing dynamic reassessment throughout the treatment course.

Figure 1 An Eastern Cooperative Oncology Group performance status -centered framework for individualized management of primary gastrointestinal lymphoma. A proposed clinical decision framework for primary gastrointestinal lymphoma that places Eastern Cooperative Oncology Group (ECOG) Performance status (PS) at the center of individualized management. Treatment intensity is stratified according to ECOG PS, with integration of molecular subtype, Helicobacter pylori status, anatomical site, and comorbidity burden. Continuous reassessment throughout the treatment course allows for dynamic adaptation of therapeutic strategies. H. pylori: Helicobacter pylori; PGIL: Primary gastrointestinal lymphoma; ECOG: Eastern Cooperative Oncology Group; PS: Performance status; GCB: Germinal center B-cell; non-GCB: Non-germinal center B-cell; R-CHOP: The name of a combination of cancer drugs; R: Rituximab; C: Cyclophosphamide; H: Doxorubicin; O: Vincristine; P: Prednisolone.

This editorial posits that the future of PGIL management lies not in choosing between clinical acumen and molecular precision, but in their deliberate integration. The foundational prognostic pillar of PS must be the bedrock upon which more nuanced molecular stratification is built. The patient with ECOG 0 and a low-risk genetic profile may be candidates for de-escalated or novel therapies, while the patient with ECOG ≥ 2 may require intensified supportive care alongside aggressive treatment, regardless of tumor genetics.

Therefore, we commend Buyuktalanci et al[17] for their contribution. Despite the inherent limitations of a retrospective, single-center design, their study provides robust, region-specific validation of PS as a key prognostic factor in PGIL-a finding with immediate clinical applicability. At the same time, the study’s limitations highlight the need for continued investigation. The negative association of surgery with survival, while likely driven by selection bias, reminds us of the importance of rigorous confounding control. The intriguing but inconclusive H. pylori signal calls for dedicated prospective studies. By both confirming a clinical truth and illuminating unanswered questions, Buyuktalanci et al[17] have made a valuable contribution that should encourage clinicians to place PS at the forefront of PGIL assessment while inspiring future collaborative research.