Revisiting the association between pretreatment thrombocytosis and cancer survival outcomes: an umbrella review of meta-analyses

Our plain-English summary of Revisiting the association between pretreatment thrombocytosis and cancer survival outcomes: an umbrella review of meta-analyses, by C. Shu, X. Wang, C. Li, et al (BMC Cancer, 2024).

The study

• Authors: C. Shu, X. Wang, C. Li, J. Huang, X. Xie, H. Li, J. Zhao, Z. Wang, Y. He, Y. Zhou
• Journal: BMC Cancer
• Published: 2024;24(1):1246
• Type of article: Systematic review
• Cited by: 7 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Although associations have been reported linking pretreatment thrombocytosis to cancer survival outcomes, the validity and strength of existing observational evidence have been contested. This study aimed to conduct an umbrella review to comprehensively appraise the strength, validity and credibility of these reported associations.

Methods: We searched Medline, Embase and Cochrane Database of Systematic Reviews from inception to 8 April 2023 to retrieve meta-analyses of observational studies. Meta-analyses were re-performed using a random-effect model and the strength of evidence was graded as convincing, highly suggestive, suggestive and weak according to seven pre-defined quantitative criteria reflecting statistical significance, amount of data, heterogeneity, and evidence of bias. The quality of review was appraised using the AMSTAR2 checklist. The umbrella review was reported adhering to the PRISMA guideline and was registered on PROSPERO (CRD42023455391).

Results: A total of 21 unique meta-analyses investigating ten cancer subtypes were included. All meta-analyses reported inferior survival outcome in cancer patients with pretreatment thrombocytosis, and 18 of them (85.7%) yielded statistically significant results (P < 0.05). Consistent effects were observed across meta-analyses that adopted different cut-off values (i.e. platelet count > 300 or 400 × 109 /L) to define thrombocytosis. Although evidence appraisal did not identify convincing evidence (Class I), the associations of thrombocytosis with inferior overall survival of lung, gastric, colorectal cancer and malignant mesothelioma were classified as highly suggestive evidence (Class II). According to AMSTAR2 ratings, no meta-analysis was identified with high or moderate quality.

Conclusions: Our findings consolidated the association between pretreatment thrombocytosis and poor survival outcomes in various cancers. Nonetheless, the absence of convincing associations indicates a need for further large-scale, high-quality evidence to confirm whether platelets can serve as a prognostic predictor or a therapeutic target.

© 2024. The Author(s).

In plain English

This article was an umbrella review: the authors gathered published meta-analyses (studies that pool earlier studies) on whether a high platelet count before treatment, called thrombocytosis, was linked to survival in cancer patients. They kept 21 unique meta-analyses from 15 publications, covering ten cancer types, re-ran each one and graded the strength of the evidence. Depending on the meta-analysis, thrombocytosis meant a platelet count above 300 or above 400 × 10^9 per litre. All 21 meta-analyses pointed toward worse survival with thrombocytosis, and 18 were statistically significant. None reached the top grade, convincing. Links with worse overall survival in lung, gastric and colorectal cancer and malignant mesothelioma were graded highly suggestive. For malignant mesothelioma, one meta-analysis of 14 studies and 3,127 patients gave an effect size of 1.58 (95% confidence interval 1.39 to 1.77 in the article's table). No meta-analysis was rated high or moderate quality. The authors concluded that more high-quality evidence is needed. They noted they could not tell whether the link reflects cause, reverse causation or confounding. The article did not study asbestos exposure.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Umbrella review (systematic review of published meta-analyses of observational studies), with each meta-analysis re-performed using a random-effects model and the evidence graded into classes
• Who was studied: 21 unique meta-analyses from 15 publications, covering ten cancer types (including malignant mesothelioma), found in database searches from inception to 8 April 2023
• Exposure: Pretreatment thrombocytosis (an abnormally high platelet count), analysed separately by cut-off value: platelet count above 300 or above 400 × 10^9 per litre. No asbestos or fiber exposure was studied.
• Main results:
  • All 21 meta-analyses showed effects in the same direction (worse survival with thrombocytosis), with effect sizes from 1.28 to 3.14. 18 of 21 (85.7%) were statistically significant (p less than 0.05).
  • No association was graded convincing (Class I). Associations with worse overall survival in colorectal, lung and gastric cancer and malignant mesothelioma were graded highly suggestive (Class II), one association was graded suggestive (Class III), and 13 were graded weak (Class IV).
  • Malignant mesothelioma (meta-analysis by Zhuo, 2017; cut-off 400): 14 studies, 3,127 patients, 2,151 events; effect size for overall survival 1.58 (95% CI 1.39–1.77 in Table 2); between-study heterogeneity I2 51.0%; AMSTAR2 quality rated critically low.
  • Large heterogeneity (I2 above 50%) was seen in ten (47.6%) meta-analyses, including those on malignant mesothelioma.
  • By AMSTAR2, none of the reviews reached high or moderate quality. Four of the 21 meta-analyses were rated low and 17 critically low.
• The authors' conclusion: The authors concluded that highly suggestive evidence linked thrombocytosis with worse overall survival in lung, gastric and colorectal cancer and malignant mesothelioma. Because no evidence was convincing and all included meta-analyses were of low credibility by AMSTAR2, they said more high-quality evidence is needed before platelet count could become a valid prognostic predictor or treatment target.
• Limitations the authors state:
  • The review could not determine whether the association reflects causation, reverse causation or confounding.
  • Earlier studies mostly measured platelets after cancer diagnosis, so the timing (temporality) of the association could not be addressed.
  • The review could not assess the influence of effect modifiers or confounders, and did not examine all primary studies.
  • The grading system used needs further validation.
  • Only peer-reviewed meta-analyses were included. Grey literature, conference abstracts, letters and comments were excluded, and cancers without enough evidence for a systematic review were not covered.
  • Turning platelet count into a yes/no category at a cut-off may lose information and introduce bias.

Topics

Medical terms in this study, explained in our Lexicon: Systematic Review, Statistical Significance, Overall Survival, Colorectal Cancer, Mesothelioma, Meta-Analysis.

Related studies

• Pretreatment thrombocytosis as a significant prognostic factor in malignant mesothelioma: a meta-analysis — Y. Zhuo, L. Lin, et al. (2017)
• Is ADC a rising star in solid tumor? An umbrella review of systematic reviews and meta-analyses — H. Wei, Y. Zhang, et al. (2025)
• Preoperative Thrombocytosis Predicts Shortened Survival in Patients with Malignant Peritoneal Mesothelioma Undergoing Operative Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy — Y.C. Li, T. Khashab, et al. (2017)
• HMGB1 overexpression as a prognostic factor for survival in cancer: a meta-analysis and systematic review — T. Wu, W. Zhang, et al. (2016)
• Pretreatment elevated serum lactate dehydrogenase as a significant prognostic factor in malignant mesothelioma: A meta-analysis — Y. Zhuo, L. Lin, et al. (2016)
• Outcomes of Cytoreductive Surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) in patients older than 70 years; survival benefit at considerable morbidity and mortality — K.I. Votanopoulos, N.A. Newman, et al. (2013)

Browse more research in BMC Cancer, or return to medical research.