Response: P-selectin ready for the “News at Six”

Response

We thank Rana et al for their comments on our study.¹  In this prospective observational cohort study, we demonstrated that high levels of soluble P-selectin (sP-selectin) are predictive of venous thromboembolism (VTE) in cancer patients. In previous studies our group reported that high plasma levels of sP-selectin, which are modulated by variations of the P-selectin gene, are strongly associated with VTE in non–cancer patients.^2,3 

Initially we enrolled 812 patients in the Vienna Cancer and Thrombosis Study (CATS) for investigation of sP-selectin. From this group, 135 were excluded because, after reevaluation. they did not exactly fulfill the inclusion and exclusion criteria of the study. Reasons for exclusion are clearly outlined in the “Methods” section of our paper¹  (eg, long-term prophylaxis with low molecular weight heparin [LMWH] or tumor not confirmed by histology [n = 52], no complete information on follow-up [n = 61], or no adequate material for sP-selectin measurement was available [n = 12]). None of the clinicians conducting initial interviews, regular follow-up, and the diagnosis of VTE was aware of test results at any time. The technicians who performed testing of sP-selectin levels were also unaware at all times of our patients' characteristics. Moreover, the samples for serial measurements were blinded.

The cumulative probability of developing VTE after 6 months was analyzed not only because of the high risk for occurrence of VTE in cancer patients in the first 3 to 6 months after diagnosis, but also because we believe that this time period seems to be feasible for a prophylactic anticoagulation of cancer patients.

Use of the 75th percentile to dichotomize sP-selectin levels in our current study (53.1 ng/mL) was chosen because the cutoff level matched closely to the 95th percentile of sP-selectin in the control group of healthy individuals (55.1 ng/mL).²  This cutoff level was associated with an odds ratio of 10.6 for VTE.² 

We agree with Rana et al that the sensitivity and specificity of sP-selectin is low, which is also true for any other biomarker that has been reported to be associated with VTE risk. However, this was not a diagnostic study but an observational study with the aim to investigate predictive parameters associated with the risk of VTE in cancer patients. We think that sP-selectin might help to detect a cohort of cancer patients at high risk of VTE, although we are fully aware that the positive predictive value for an individual patient is rather low.

Finally, based on results of this study, we concluded that measurement of sP-selectin at diagnosis of cancer would help identify cancer patients at increased risk for VTE. However, we are in line with Rana and colleagues that our results require validation in a larger prospective cohort study. Furthermore, the benefit of prophylactic anticoagulant treatment for cancer patients with high levels of sP-selectin needs to be evaluated in appropriately designed randomized controlled trials. Currently, P-selectin may not yet be ready for “prime time,” but the promising results of CATS justify P-selectin to be aired shortly before prime time.