Predictors of thrombosis in testicular cancer during platinum-based chemotherapy

Abstract

Purpose

To identify potential risk factors for the development of venous thromboembolic events in testicular cancer patients receiving platinum-based chemotherapy.

Methods

We performed a retrospective analysis including 255 patients with testicular germ cell tumors who received platinum-based chemotherapy from 2003 to 2018 as a multi-center observational cohort study. Patient and tumor characteristics of patients with and without a thromboembolic event were analyzed.

Results

49 (19%) patients experienced a venous thromboembolic event, with the majority representing pulmonary embolism and deep venous thrombosis (47%). There were no significant differences regarding the development of a venous thromboembolic event between first- and second-line regimes. Multivariate analysis showed an increased risk for a venous thromboembolic event in patients with clinical stage ≥ IIC disease (OR 2.259 [95% CI 1.105–4.618], p = 0.026), elevated serum LDH (OR 2.162 [95% CI 1.018–4.593], p = 0.045), febrile neutropenia (OR 2.973 [95% CI 1.363–6.487], p = 0.006) and central venous access (OR 3.465 [95% CI 1.068–11.243], p = 0.039). Patients suffering from a venous thromboembolic event revealed a significantly reduced overall survival (p = 0.033) during a median follow-up of 8 months [IQR 2–18].

Conclusions

19% of all patients treated by platinum-based chemotherapy due to testicular cancer suffered from a venous thromboembolic event, associated with reduced overall survival. As a result, monitoring of cancer patients at risk as well as the improvement of patients’ awareness of a thromboembolic event should thus be the main goal of their treating physicians.

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Fig. 1

Abbreviations

AFP:

Alpha-Fetoprotein

BEP:

Bleomycin, etoposide, cisplatin

GCT:

Germ cell tumors

β-hCG:

Human chorionic gonadotropin

IGCCCG:

International germ cell cancer collaborative group

IQR:

Interquartile range

LDH:

Lactate dehydrogenase

PEI:

Cisplatin, etopside, ifosfamide

PC-RPLND:

Post-chemotherapy retroperitoneal lymph node dissection

TIP:

Cisplatin, ifosfamide, paclitaxel

References

  1. 1.

    Albers P, Albrecht W, Algaba F et al (2015) Guidelines on testicular cancer: 2015 update. Eur Urol 68:1054–1068. https://doi.org/10.1016/j.eururo.2015.07.044

    Article  PubMed  PubMed Central  Google Scholar 

  2. 2.

    Donnellan E, Khorana AA (2017) Cancer and venous thromboembolic disease: a review. Oncologist 22:199–207. https://doi.org/10.1634/theoncologist.2016-0214

    Article  PubMed  PubMed Central  Google Scholar 

  3. 3.

    Piketty A-C, Fléchon A, Laplanche A et al (2005) The risk of thrombo-embolic events is increased in patients with germ-cell tumours and can be predicted by serum lactate dehydrogenase and body surface area. Br J Cancer 93:909–914. https://doi.org/10.1038/sj.bjc.6602791

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  4. 4.

    Fosså SD, Aass N, Harvei S, Tretli S (2004) Increased mortality rates in young and middle-aged patients with malignant germ cell tumours. Br J Cancer 90:607–612. https://doi.org/10.1038/sj.bjc.6601558

    Article  PubMed  PubMed Central  Google Scholar 

  5. 5.

    Gizzi M, Oberic L, Massard C et al (2016) Predicting and preventing thromboembolic events in patients receiving cisplatin-based chemotherapy for germ cell tumours. Eur J Cancer 69:151–157. https://doi.org/10.1016/j.ejca.2016.10.003

    CAS  Article  PubMed  Google Scholar 

  6. 6.

    Heidegger I, Porres D, Veek N et al (2017) Predictive factors for developing venous thrombosis during cisplatin-based chemotherapy in testicular cancer. Urol Int 99:104–109. https://doi.org/10.1159/000471888

    CAS  Article  PubMed  Google Scholar 

  7. 7.

    Dieckmann K-P, Gerl A, Witt J et al (2010) Myocardial infarction and other major vascular events during chemotherapy for testicular cancer. Ann Oncol 21:1607–1611. https://doi.org/10.1093/annonc/mdp597

    Article  PubMed  Google Scholar 

  8. 8.

    Weijl NI, Rutten MFJ, Zwinderman AH et al (2000) Thromboembolic events during chemotherapy for germ cell cancer: a cohort study and review of the literature. J Clin Oncol 18:2169–2178. https://doi.org/10.1200/JCO.2000.18.10.2169

    CAS  Article  PubMed  Google Scholar 

  9. 9.

    Solari L, Krönig M, Ihorst G et al (2016) High rates of thromboembolic events in patients with germ cell cancer undergoing cisplatin-based polychemotherapy. Urol Int 96:399–405. https://doi.org/10.1159/000445126

    CAS  Article  PubMed  Google Scholar 

  10. 10.

    Bezan A, Posch F, Ploner F et al (2017) Risk stratification for venous thromboembolism in patients with testicular germ cell tumors. PLoS One 12:e0176283. https://doi.org/10.1371/journal.pone.0176283

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  11. 11.

    Mandala M, Falanga A, Roila F, ESMO Guidelines Working Group (2011) Management of venous thromboembolism (VTE) in cancer patients: ESMO clinical practice guidelines. Ann Oncol 22:vi85–vi92. https://doi.org/10.1093/annonc/mdr392

    Article  PubMed  Google Scholar 

  12. 12.

    Burness CB, Perry CM (2014) Rivaroxaban: a review of its use in the treatment of deep vein thrombosis or pulmonary embolism and the prevention of recurrent venous thromboembolism. Drugs 74:243–262. https://doi.org/10.1007/s40265-013-0174-4

    CAS  Article  PubMed  Google Scholar 

  13. 13.

    Babyak MA (2004) What you see may not be what you get: a brief, nontechnical introduction to overfitting in regression-type models. Psychosom Med 66:411–421

    PubMed  Google Scholar 

  14. 14.

    Moore RA, Adel N, Riedel E et al (2011) High incidence of thromboembolic events in patients treated with cisplatin-based chemotherapy: a large retrospective analysis. J Clin Oncol 29:3466–3473. https://doi.org/10.1200/JCO.2011.35.5669

    CAS  Article  PubMed  Google Scholar 

  15. 15.

    Shlebak AA, Smith DB (1997) Incidence of objectively diagnosed thromboembolic disease in cancer patients undergoing cytotoxic chemotherapy and/or hormonal therapy. Cancer Chemother Pharmacol 39:462–466. https://doi.org/10.1007/s002800050599

    CAS  Article  PubMed  Google Scholar 

  16. 16.

    Khorana AA (2010) Venous thromboembolism and prognosis in cancer. Thromb Res 125:490–493. https://doi.org/10.1016/j.thromres.2009.12.023

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  17. 17.

    Chaturvedi S, Sidana S, Elson P et al (2014) Symptomatic and incidental venous thromboembolic disease are both associated with mortality in patients with prostate cancer. PLoS One 9:e94048. https://doi.org/10.1371/journal.pone.0094048

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  18. 18.

    Honecker F, Koychev D, Luhmann AD et al (2013) Venous thromboembolic events in germ cell cancer patients undergoing platinum-based chemotherapy. Onkologie 36:7–7. https://doi.org/10.1159/000355652

    CAS  Article  Google Scholar 

  19. 19.

    Srikanthan A, Tran B, Beausoleil M et al (2015) Large retroperitoneal lymphadenopathy as a predictor of venous thromboembolism in patients with disseminated germ cell tumors treated with chemotherapy. J Clin Oncol 33:582–587. https://doi.org/10.1200/JCO.2014.58.6537

    Article  PubMed  Google Scholar 

  20. 20.

    Mead GM, Stenning SP (1997) The international germ cell consensus classification: a new prognostic factor-based staging classification for metastatic germ cell tumours. Clin Oncol (R Coll Radiol) 9:207–209

    CAS  Article  Google Scholar 

  21. 21.

    Kyriazi V, Theodoulou E (2013) Assessing the risk and prognosis of thrombotic complications in cancer patients. Arch Pathol Lab Med 137:1286–1295. https://doi.org/10.5858/arpa.2012-0490-RA

    Article  PubMed  Google Scholar 

  22. 22.

    Khorana AA, Francis CW, Culakova E et al (2006) Thromboembolism in hospitalized neutropenic cancer patients. J Clin Oncol 24:484–490. https://doi.org/10.1200/JCO.2005.03.8877

    Article  PubMed  Google Scholar 

  23. 23.

    Lin J, Proctor MC, Varma M et al (2003) Factors associated with recurrent venous thromboembolism in patients with malignant disease. J Vasc Surg 37:976–983. https://doi.org/10.1067/mva.2003.191

    Article  PubMed  Google Scholar 

  24. 24.

    Nestler T, Huber J, Laury AM et al (2018) Thromboprophylaxis and the route of administration of chemotherapy in testicular cancer patients in German-speaking countries. World J Urol. https://doi.org/10.1007/s00345-018-2222-x

    Article  PubMed  Google Scholar 

  25. 25.

    Carrier M, Lee AY (2009) Prophylactic and therapeutic anticoagulation for thrombosis—major issues in oncology. Nat Clin Pract Oncol 6:74–84. https://doi.org/10.1038/ncponc1244

    CAS  Article  PubMed  Google Scholar 

  26. 26.

    Yamashita Y, Wada H, Nomura H et al (2014) Elevated fibrin-related markers in patients with malignant diseases frequently associated with disseminated intravascular coagulation and venous thromboembolism. Intern Med 53:413–419

    Article  CAS  PubMed  Google Scholar 

  27. 27.

    Li XD, Guo SJ, Chen SL et al (2017) Clinical outcome of postchemotherapy retroperitoneal lymph node dissection and predicting retroperitoneal histology in advanced nonseminomatous germ cell tumours of the testis. Zhonghua Wai Ke Za Zhi 55:603–607. https://doi.org/10.3760/cma.j.issn.0529-5815.2017.08.010

    CAS  Article  PubMed  Google Scholar 

  28. 28.

    Madoiwa S (2017) Management of venous thromboembolism in cancer patients. Gan To Kagaku Ryoho 44:2064–2071

    PubMed  Google Scholar 

  29. 29.

    Noble S, Prout H, Nelson A (2015) Patients’ Experiences of LIving with CANcer-associated thrombosis: the PELICAN study. Patient Prefer Adherence 9:337. https://doi.org/10.2147/PPA.S79373

    Article  PubMed  PubMed Central  Google Scholar 

  30. 30.

    Cushman M (2007) Epidemiology and risk factors for venous thrombosis. Semin Hematol 44:62–69. https://doi.org/10.1053/j.seminhematol.2007.02.004

    Article  PubMed  PubMed Central  Google Scholar 

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Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors

Contributions

MG: manuscript editing. KG: data collection or management, data analysis. IH: manuscript editing. AH: project development, manuscript editing, supervision. MH: data analysis, manuscript editing. TN: manuscript editing. PP: project development, data collection or management, data analysis, manuscript writing/editing. DP: project development, manuscript editing, supervision. JS: manuscript editing.

Corresponding author

Correspondence to Axel Heidenreich.

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The authors declare that they have no conflict of interest.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study formal consent is not required.

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Paffenholz, P., Grein, K., Heidegger, I. et al. Predictors of thrombosis in testicular cancer during platinum-based chemotherapy. World J Urol 37, 1907–1916 (2019). https://doi.org/10.1007/s00345-018-2598-7

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Keywords

  • Thrombosis
  • Germ cell tumor
  • Cisplatin
  • Chemotherapy