Investigating the association between pretreatment thrombocytosis and ovarian cancer recurrence and survival

Thrombocytosis is frequently observed among cancer patients and can be attributed to increased platelet production.1 While the underlying pathophysiology has not been completely elucidated, it is believed that platelet activation is essential for tumor progression due to the release of several platelet-derived growth factors that can promote cellular proliferation, neo-vascularization, and ultimately tumor growth, tissue invasion, and metastasis.1 Although thrombocytosis in ovarian cancer patients has been viewed as a sign of advanced-stage disease since 1994 when it was reported to be frequently seen in patients with marked ascites, its role in ovarian cancer progression has not been fully investigated.1 As such, a systematic review was conducted aiming to summarize the current evidence related to the incidence of thrombocytosis in ovarian cancer patients and investigate its association with factors that predispose to decreased ovarian cancer survival, including advanced stage at diagnosis, presence of ascites, and successful complete tumor reduction.1

In this study, the Medline, Scopus, Medline, Scopus,, Cochrane Central Register of Controlled Trials CENTRAL and Google Scholar databases were searched for relevant studies.1 14 articles were selected for inclusion which included 5,414 ovarian cancer patients.1  The methodological quality of included studies ranged between moderate and high as some studies failed to report differences in disease stage or the optimal radicality of the procedure.1 The meta-analysis of 7 studies revealed that pre-treatment thrombocytosis was significantly associated with increased odds of ovarian cancer recurrence after exclusion of outliers (HR=1.67; 95% CI: 1.25-2.53).1  The interval to recurrence was also shorter in patients with thrombocytosis based on 4 studies, but this result did not reach statistical significance (mean difference = -6.61 months; 95% CI: -14.65-1.141; p=0.079).1

The meta-analysis of 11 studies revealed that thrombocytosis was associated with poorer overall survival after removing outliers (HR=2.08; 95% CI: 1.49-2.90).1 However, funnel plot analysis and Egger’s test analysis indicated the existence of potential publication bias.1  An additional 7 studies were included for the trim and fill analysis to adjust for publication bias, which led to a non-significant association between thrombocytosis and overall survival in ovarian cancer patients (HR=1.13, 95% CI: 0.53-2.34).1 The interval to death did not differ among cases with or without thrombocytosis based on 4 studies (mean difference: -0.26 months; 95% CI: -6.89-6.36; p=0.908), although the sample size was too small to reach firm conclusions.1

In summary, the findings of this study suggest that pre-treatment thrombocytosis may be associated with increased rates of disease recurrence and death in ovarian cancer patients.1 Since thrombocytosis is more frequently encountered during the advanced stages of the disease, it may be predictive of suboptimal tumor debulking.1 Although cancer-specific overall survival was not available among the included studies, it is unlikely that the increased risk of mortality observed is attributable to cardiovascular incidents since there was no significant increase in thromboembolic disease among patients with thrombocytosis.1 The relationship between thrombocytosis and platinum resistance remains unknown and further research in this field is needed.1

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