Risk Scores for Occult Cancer in Patients with Venous Thromboembolism: A Post Hoc Analysis of the Hokusai-VTE Study

Abstract

Venous thromboembolism (VTE) may be the first sign of an undiagnosed cancer. In patients with unprovoked VTE, the risk is approximately 5% in the year following VTE diagnosis. Cancer-specific screening is therefore often considered in these patients, but the optimal screening strategy remains controversial. Recently, two risk classification scores have been proposed that may help in identifying patients at high risk of occult cancer in whom extensive screening may be warranted. In the present post hoc analysis of the Hokusai-VTE study, we evaluated the performance of the Registro Informatizado de Pacientes con Enfermedad TromboEmbólica (RIETE) and Screening for Occult Malignancy in Patients with Idiopathic Venous Thromboembolism (SOME) scores for occult cancer in patients with acute VTE. A total of 8,032 patients were included in the analysis of whom 218 (2.7%; 95% confidence interval [CI], 2.4–3.1) developed cancer between 30-day and 12-month follow-up. The c-statistics of the RIETE and SOME scores were 0.62 (95% CI, 0.57–0.66) and 0.59 (95% CI, 0.55–0.62), respectively. In patients classified as ‘high risk’, the cumulative incidence of cancer diagnosis during follow-up was 2.9% (95% CI, 2.1–3.9) for the RIETE score and 2.7% (95% CI, 1.9–3.7) for the SOME score, corresponding to hazard ratios of 1.8 (95% CI, 1.3–2.5) and 1.5 (95% CI, 1.04–2.2), respectively. In conclusion, the performance of both scores was poor. When used dichotomously, the scores were able to identify a group of patients with a significantly higher risk of occult cancer, although it remains unknown whether this translates into improved clinical important outcomes.

Keywords

venous thrombosis - deep vein thrombosis - pulmonary embolism - cancer

Authors' Contributions

Study conception and design: N. Kraaijpoel, N. van Es, H.R. Büller, M. Di Nisio.

Data acquisition: N. Kraaijpoel, N. van Es, G. Zhang, M. Lin, M. Di Nisio.

Statistical analysis: G. Zhang, M. Lin.

Interpretation of the data: N. Kraaijpoel, N. van Es, G. E. Raskob, H.R. Büller, M. Carrier, G. Zhang, M. Lin, M.A. Grosso, M. Di Nisio.

Drafting of the manuscript: N. Kraaijpoel, N. van Es, M. Di Nisio.

Critical revision of the manuscript for important intellectual content: N. Kraaijpoel, N. van Es, G.E. Raskob, H.R. Büller, M. Carrier, G. Zhang, M. Lin, M.A. Grosso, M. Di Nisio.

Final approval of the manuscript: N. Kraaijpoel, N. van Es, G. E. Raskob, H.R. Büller, M. Carrier, G. Zhang, M. Lin, M.A. Grosso, M. Di Nisio.

• References

• 1 van Es N, Le Gal G, Otten H-M. , et al. Screening for occult cancer in patients with unprovoked venous thromboembolism: a systematic review and meta-analysis of individual patient data. Ann Intern Med 2017; 167 (06) 410-417
• 2 Robin P, Le Roux PY, Planquette B. , et al; MVTEP study group. Limited screening with versus without (18)F-fluorodeoxyglucose PET/CT for occult malignancy in unprovoked venous thromboembolism: an open-label randomised controlled trial. Lancet Oncol 2016; 17 (02) 193-199
• 3 Carrier M, Lazo-Langner A, Shivakumar S. , et al; SOME Investigators. Screening for occult cancer in unprovoked venous thromboembolism. N Engl J Med 2015; 373 (08) 697-704
• 4 Prandoni P, Bernardi E, Valle FD. , et al. Extensive computed tomography versus limited screening for detection of occult cancer in unprovoked venous thromboembolism: a multicenter, controlled, randomized clinical trial. Semin Thromb Hemost 2016; 42 (08) 884-890
• 5 Van Doormaal FF, Terpstra W, Van Der Griend R. , et al. Is extensive screening for cancer in idiopathic venous thromboembolism warranted?. J Thromb Haemost 2011; 9 (01) 79-84
• 6 Delluc A, Antic D, Lecumberri R, Ay C, Meyer G, Carrier M. Occult cancer screening in patients with venous thromboembolism: guidance from the SSC of the ISTH. J Thromb Haemost 2017; 15 (10) 2076-2079
• 7 Khorana AA, Carrier M, Garcia DA, Lee AYY. Guidance for the prevention and treatment of cancer-associated venous thromboembolism. J Thromb Thrombolysis 2016; 41 (01) 81-91
• 8 Jara-Palomares L, Otero R, Jimenez D. , et al; RIETE Investigators. Development of a risk prediction score for occult cancer in patients with VTE. Chest 2017; 151 (03) 564-571
• 9 Ihaddadene R, Corsi DJ, Lazo-Langner A. , et al. Risk factors predictive of occult cancer detection in patients with unprovoked venous thromboembolism. Blood 2016; 127 (16) 2035-2037
• 10 Büller HR, Décousus H, Grosso MA. , et al; Hokusai-VTE Investigators. Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med 2013; 369 (15) 1406-1415
• 11 Raskob G, Büller H, Prins M. , et al; Hokusai-VTE Investigators. Edoxaban for the long-term treatment of venous thromboembolism: rationale and design of the Hokusai-venous thromboembolism study--methodological implications for clinical trials. J Thromb Haemost 2013; 11 (07) 1287-1294
• 12 Lin DY, Wei LJ, Ying Z. Checking the Cox model with cumulative sums of martingale-based residuals. Biometrika 1993; 80 (03) 557-572
• 13 van Es N, Bertoletti L, Jara-Palomares L. , et al. External validation of a risk score for occult cancer in patients with unprovoked venous thromboembolism: results from an individual patient data meta-analysis. International Society on Thrombosis and Haemostasis Congress, Berlin, 2017
• 14 Jara-Palomares L, Otero R, Jimenez D. , et al. External validation of a prognostic score for occult cancer in patients with venous thromboembolism. International Society on Thrombosis and Haemostasis Congress, Berlin, 2017
• 15 Bertoletti L, Robin P, Jara-Palomares L. , et al; MVTEP investigators. Predicting the risk of cancer after unprovoked venous thromboembolism: external validation of the RIETE score. J Thromb Haemost 2017; 15 (11) 2184-2187
• 16 Kearon C, Ageno W, Cannegieter SC, Cosmi B, Geersing GJ, Kyrle PA. ; Subcommittees on Control of Anticoagulation, and Predictive and Diagnostic Variables in Thrombotic Disease. Categorization of patients as having provoked or unprovoked venous thromboembolism: guidance from the SSC of ISTH. J Thromb Haemost 2016; 14 (07) 1480-1483
• 17 Carrier M, Le Gal G, Wells PS, Fergusson D, Ramsay T, Rodger MA. Systematic review: the Trousseau syndrome revisited: should we screen extensively for cancer in patients with venous thromboembolism?. Ann Intern Med 2008; 149 (05) 323-333
• 18 Sørensen HT, Sværke C, Farkas DK. , et al. Superficial and deep venous thrombosis, pulmonary embolism and subsequent risk of cancer. Eur J Cancer 2012; 48 (04) 586-593
• 19 Prandoni P, Casiglia E, Piccioli A. , et al. The risk of cancer in patients with venous thromboembolism does not exceed that expected in the general population after the first 6 months. J Thromb Haemost 2010; 8 (05) 1126-1127