Review for 10.1186/s12876-025-03849-4 (2025)

Title: Meta-analysis of the efficacy of applying reduced surgery for the treatment of
asymptomatic unresectable advanced gastric cancer
Version: 3 Date: 29 Jan 2025
Reviewer's report:
This meta-analysis evaluates the efficacy and safety of reduction surgery in patients with
asymptomatic unresectable advanced gastric cancer (AGC). The study systematically reviews
data from five studies, including one randomized controlled trial (RCT) and four retrospective
studies, with a total sample size of 1,717 patients. Among them, 701 patients underwent
reduction surgery, while 1,016 received non-surgical treatment. The findings indicate that
reduction surgery does not provide a significant long-term survival benefit compared to non-
surgical treatment in terms of 1-year, 3-year, and 5-year survival rates. However, the median
survival time was prolonged by 11.58 months in the reduction surgery group. The incidence
of perioperative complications and mortality rates were higher in the reduction surgery group
(15% and 4%, respectively). Additionally, 3% of patients in the non-surgical treatment group
eventually required palliative surgery due to complications from the primary tumor. The authors
conclude that while reduction surgery might offer a modest survival advantage, it does not
provide a definitive long-term survival benefit for asymptomatic unresectable AGC patients.
They emphasize the need for more high-quality RCTs to establish stronger evidence supporting
clinical decision-making.
The topic is clinically significant, addressing the controversial role of reduction surgery in AGC.
However, the manuscript requires major revisions to improve methodological transparency,
statistical interpretation, and discussion clarity.
Limited Number of Studies & Study Design Bias: The meta-analysis includes only five studies,
with only one RCT, while the rest are retrospective. This limits the strength of the conclusions.
Suggestion: Acknowledge this limitation more explicitly and discuss its potential impact on bias.
Heterogeneity Not Fully Addressed: The study presents significant heterogeneity (I² > 50%) in
several outcomes, particularly 3-, 4-, and 5-year survival rates. Consider conducting subgroup
analyses (e.g., stratification by chemotherapy regimens) to explore sources of heterogeneity.
Lack of Standardized Chemotherapy Regimens Across Studies: The included studies likely
used different systemic therapy protocols, which may impact survival outcomes. Provide a table
summarizing chemotherapy regimens used in each study and discuss their potential impact.
Survival Data Interpretation Issues: The manuscript reports hazard ratios (HRs) but does not
adequately explain whether they were extracted directly or derived from reconstructed survival
curves. Clearly describe the methods used to extract survival data and discuss the reliability of
these HR estimates.
Publication Bias Assessment is Missing: The manuscript states that a funnel plot was used, but
no detailed discussion on publication bias is provided. Discuss whether asymmetry was detected
in the funnel plot, and if so, how it may have influenced the results.
No Sensitivity Analysis for Non-Surgical Group: While sensitivity analyses were performed for
surgical outcomes, there is no exploration of heterogeneity within the non-surgical treatment
group. Conduct a sensitivity analysis for non-surgical patients to assess how differences in
chemotherapy protocols might influence survival rates.
Causal Language Needs Refinement: The manuscript implies a causal relationship between
reduction surgery and survival outcomes, which is inappropriate for a meta-analysis of mostly
retrospective studies. Use more cautious language (e.g., "associated with" rather than "improves"
or "prolongs survival").
Failure to Discuss the Potential Role of Selection Bias: The patients who underwent reduction
surgery may have had better baseline performance status than those receiving non-surgical
treatment. Acknowledge potential selection bias and discuss whether baseline characteristics
(e.g., ECOG performance status, tumor burden) were adequately matched.
Limited Clinical Implications and Practical Recommendations: The discussion does not provide
clear clinical recommendations on when reduction surgery might be considered. Elaborate on
which patients might benefit most from reduction surgery based on tumor burden, age, or
chemotherapy response.
Need for More Comparison with Recent Trials: The discussion does not adequately compare
findings with other recent trials on non-surgical treatment options for AGC. Provide a brief
comparison with recent studies exploring conversion therapy, immunotherapy, or targeted
therapy.
The Concept of "Reduction Surgery" Needs Clearer Definition: The distinction between
reduction surgery and palliative surgery is somewhat unclear in certain sections. Clarify whether
debulking surgery and palliative gastrectomy were considered interchangeable in the included
studies.
Grammar and Terminology Refinement: Minor grammatical errors and awkward phrasing
appear throughout the manuscript.  A language revision is recommended to enhance readability
and coherence.
Consistency in Terminology: Terms like "reduction surgery," "debulking surgery," and
"palliative surgery" are used interchangeably. Define and use a consistent term throughout the
manuscript.
To enhance the discussion on surgical outcomes in gastric cancer, it is recommended to cite
and discuss the findings from Marano et al.'s study, "Current Trends in Volume and Surgical
Outcomes in Gastric Cancer" (J Clin Med. 2023 Apr 4;12(7):2708. doi: 10.3390/jcm12072708).
This comprehensive review emphasizes the association between hospital surgical volume and
patient outcomes, highlighting that higher-volume centers tend to achieve better postoperative
results. The study also discusses the concept of "textbook outcomes" as a multidimensional
measure of quality care, suggesting that centralization of gastric cancer surgeries to specialized,
high-volume hospitals may improve patient prognosis. Incorporating these insights could
provide a broader context for understanding factors influencing surgical success rates and
support discussions on healthcare policy and centralization strategies in gastric cancer treatment.