Journal of Cancer Survivorship

, Volume 2, Issue 3, pp 128–137 | Cite as

Predicted cardiovascular mortality and reported cardiovascular morbidity in testicular cancer survivors

  • H. S. Haugnes
  • N. Aass
  • S. D. Fosså
  • O. Dahl
  • O. Klepp
  • E. A. Wist
  • T. Wilsgaard
  • R. M. Bremnes



We examined if testicular cancer (TC) treatment is associated with any risk for cardiovascular morbidity or predicted mortality according to the SCORE model, in which a 10-year future risk of ≥5% for developing a fatal cardiovascular event qualify for high-risk status.


One thousand one hundred thirty-four TC survivors treated 1980–1994 participated in this study (1998–2002). Patients were categorised in four treatment groups: surgery (n = 225), radiotherapy (n = 445), and two chemotherapy groups: cumulative cisplatin dose ≤850 mg (n = 375) and >850 mg (cis>850, n = 89). Patients with cardiovascular disease, diabetes or SCORE ≥5% constituted a high-risk group, and those with SCORE >1% an intermediate/high risk group.


Age-adjusted mean SCORE was 0.93% for the surgery group. In comparison, chemotherapy treated patients had significantly higher SCORE (1.07%, p = 0.01). Only 15% of patients were scored to be at high-risk, while 53% qualified for the intermediate/high risk group. Patients in the cis>850 group had increased odds for having intermediate/high risk, compared with the surgery group (OR 3.4, 95% CI 1.3–8.7). Only 23 cardiovascular events had occurred since the testicular cancer diagnosis.


The SCORE model indicates that patients treated with cisplatin-based chemotherapy have a significantly increased future risk of a fatal cardiovascular event.

Implications for cancer survivors

TC survivors should be followed regularly with respect to cardiovascular risk profile beyond the routine 10-year clinical follow-up.


Testicular cancer Cisplatin Cardiovascular Mortality Morbidity SCORE 


  1. 1.
    Bray F, Dahl T, van Dijk T, et al. Cancer in Norway 2006. Available at (2007).
  2. 2.
    Krege S, Beyer J, Souchon R, Albers P, Albrecht W, Algaba F, et al. European Consensus Conference on Diagnosis and Treatment of Germ Cell Cancer: a report of the second meeting of the European Germ Cell Cancer Consensus Group (EGCCCG): part I. Eur Urol. 2008;53:478–96.PubMedCrossRefGoogle Scholar
  3. 3.
    Gietema JA, Sleijfer DT, Willemse PH, Schraffordt KH, van Ittersum E, Verschuren WM, et al. Long-term follow-up of cardiovascular risk factors in patients given chemotherapy for disseminated nonseminomatous testicular cancer. Ann Intern Med. 1992;116:709–15.PubMedGoogle Scholar
  4. 4.
    Strumberg D, Brugge S, Korn MW, Koeppen S, Ranft J, Scheiber G, et al. Evaluation of long-term toxicity in patients after cisplatin-based chemotherapy for non-seminomatous testicular cancer. Ann Oncol. 2002;13:229–36.PubMedCrossRefGoogle Scholar
  5. 5.
    Sagstuen H, Aass N, Fosså SD, Dahl O, Klepp O, Wist EA, et al. Blood pressure and body mass index in long-term survivors of testicular cancer. J Clin Oncol. 2005;23:4980–90.PubMedCrossRefGoogle Scholar
  6. 6.
    Boyer M, Raghavan D, Harris PJ, Lietch J, Bleasel A, Walsh JC, et al. Lack of late toxicity in patients treated with cisplatin-containing combination chemotherapy for metastatic testicular cancer. J Clin Oncol. 1990;8:21–6.PubMedGoogle Scholar
  7. 7.
    Haugnes HS, Aass N, Fossa SD, Dahl O, Klepp O, Wist EA, et al. Components of the metabolic syndrome in long-term survivors of testicular cancer. Ann Oncol. 2007;18:241–8.PubMedCrossRefGoogle Scholar
  8. 8.
    Wethal T, Kjekshus J, Røislien J, Ueland T, Andreassen AK, Wergeland R, et al. Treatment-related differences in cardiovascular risk factors in long-term survivors of testicular cancer. Journal of Cancer Survivorship 2007;1:8–16.PubMedCrossRefGoogle Scholar
  9. 9.
    Meinardi MT, Gietema JA, van der Graaf WT, van Veldhuisen DJ, Runne MA, Sluiter WJ, et al. Cardiovascular morbidity in long-term survivors of metastatic testicular cancer. J Clin Oncol. 2000;18:1725–32.PubMedGoogle Scholar
  10. 10.
    Huddart RA, Norman A, Shahidi M, Horwich A, Coward D, Nicholls J, et al. Cardiovascular disease as a long-term complication of treatment for testicular cancer. J Clin Oncol. 2003;21:1513–23.PubMedCrossRefGoogle Scholar
  11. 11.
    van den Belt-Dusebout A, Nuver J, de Wit R, Gietema JA, Bokkel Huinink WW, Rodrigus PTR, et al. Long-term risk of cardiovascular disease in 5-year survivors of testicular cancer. J Clin Oncol. 2006;24:467–75.PubMedCrossRefGoogle Scholar
  12. 12.
    Zagars GK, Ballo MT, Lee AK, Strom SS. Mortality after cure of testicular seminoma. J Clin Oncol. 2004;22:640–7.PubMedCrossRefGoogle Scholar
  13. 13.
    Lederman GS, Sheldon TA, Chaffey JT, Herman TS, Gelman RS, Coleman CN. Cardiac disease after mediastinal irradiation for seminoma. Cancer 1987;60:772–6.PubMedCrossRefGoogle Scholar
  14. 14.
    Hanks GE, Peters T, Owen J. Seminoma of the testis: long-term beneficial and deleterious results of radiation. Int J Radiat Oncol Biol Phys. 1992;24:913–9.PubMedGoogle Scholar
  15. 15.
    Fossa SD, Gilbert E, Dores GM, Chen J, McGlynn KA, Schonfeld S, et al. Noncancer causes of death in survivors of testicular cancer. J Natl Cancer Inst. 2007;99:533–44.PubMedCrossRefGoogle Scholar
  16. 16.
    De Backer G, Ambrosioni E, Borch-Johnsen K, Brotons C, Cifkova R, Dallongeville J, et al. European guidelines on cardiovascular disease prevention in clinical practice. Third Joint Task Force of European and other Societies on Cardiovascular Disease Prevention in clinical practice. Eur Heart J. 2003;24:1601–10.PubMedCrossRefGoogle Scholar
  17. 17.
    Graham I, Atar D, Borch-Johnsen K, Boysen G, Burell G, Cifkova R, et al. European guidelines on cardiovascular disease prevention in clinical practice: executive summary. Fourth Joint Task Force of the European Society of Cardiology and other Societies on Cardiovascular Disease Prevention in clinical practice (constituted by representatives of nine societies and by invited experts). Eur J Cardiovasc Prev Rehabil. 2007;14(Suppl 2):E1–40.PubMedCrossRefGoogle Scholar
  18. 18.
    Conroy RM, Pyorala K, Fitzgerald AP, Sans S, Menotti A, De Backer G, et al. Estimation of ten-year risk of fatal cardiovascular disease in Europe: the SCORE project. Eur Heart J. 2003;24:987–1003.PubMedCrossRefGoogle Scholar
  19. 19.
    Brydoy M, Fossa SD, Klepp O, Bremnes RM, Wist EA, Wentzel-Larsen T, et al. Paternity following treatment for testicular cancer. J Natl Cancer Inst. 2005;97:1580–8.PubMedCrossRefGoogle Scholar
  20. 20.
    Hartz I, Njolstad I, Eggen AE. Does implementation of the European guidelines based on the SCORE model double the number of Norwegian adults who need cardiovascular drugs for primary prevention? The Tromso Study 2001. Eur Heart J. 2005;26:2673–80.PubMedCrossRefGoogle Scholar
  21. 21.
    Klepp O, Dahl O, Flodgren P, Stierner U, Olsson AM, Oldbring J, et al. Risk-adapted treatment of clinical stage 1 non-seminoma testis cancer. Eur J Cancer 1997;33:1038–44.PubMedCrossRefGoogle Scholar
  22. 22.
    Aass N, Klepp O, Cavallin-Stahl E, Dahl O, Wicklund H, Unsgaard B, et al. Prognostic factors in unselected patients with nonseminomatous metastatic testicular cancer: a multicenter experience. J Clin Oncol. 1991;9:818–26.PubMedGoogle Scholar
  23. 23.
    Klepp O, Olsson AM, Henrikson H, Aass N, Dahl O, Stenwig AE, et al. Prognostic factors in clinical stage I nonseminomatous germ cell tumors of the testis: multivariate analysis of a prospective multicenter study. Swedish–Norwegian testicular cancer group. J Clin Oncol. 1990;8:509–18.PubMedGoogle Scholar
  24. 24.
    Fossa SD, Droz JP, Stoter G, Kaye SB, Vermeylen K, Sylvester R. Cisplatin, vincristine and ifosphamide combination chemotherapy of metastatic seminoma: results of EORTC trial 30874. EORTC GU Group. Br J Cancer 1995;71:619–24.PubMedGoogle Scholar
  25. 25.
    Cullen MH, Stenning SP, Parkinson MC, Fossa SD, Kaye SB, Horwich AH, et al. Short-course adjuvant chemotherapy in high-risk stage I nonseminomatous germ cell tumors of the testis: a medical research council report. J Clin Oncol. 1996;14:1106–13.PubMedGoogle Scholar
  26. 26.
    Horwich A, Oliver RT, Wilkinson PM, Mead GM, Harland SJ, Cullen MH, et al. A medical research council randomized trial of single agent carboplatin versus etoposide and cisplatin for advanced metastatic seminoma. MRC Testicular Tumour Working Party. Br J Cancer 2000;83:1623–9.PubMedCrossRefGoogle Scholar
  27. 27.
    Horwich A, Sleijfer DT, Fossa SD, Kaye SB, Oliver RT, Cullen MH, et al. Randomized trial of bleomycin, etoposide, and cisplatin compared with bleomycin, etoposide, and carboplatin in good-prognosis metastatic nonseminomatous germ cell cancer: a multiinstitutional medical research council/European organization for research and treatment of cancer trial. J Clin Oncol. 1997;15:1844–52.PubMedGoogle Scholar
  28. 28.
    Fossa SD, Horwich A, Russell JM, Roberts JT, Cullen MH, Hodson NJ, et al. Optimal planning target volume for stage I testicular seminoma: a medical research council randomized trial. Medical Research Council Testicular Tumor Working Group. J Clin Oncol. 1999;17:1146.PubMedGoogle Scholar
  29. 29.
    Peckham MJ, McElwain TJ, Barrett A, Hendry WF. Combined management of malignant teratoma of the testis. Lancet 1979;2:267–70.PubMedCrossRefGoogle Scholar
  30. 30.
    Getz L, Sigurdsson JA, Hetlevik I, Kirkengen AL, Romundstad S, Holmen J. Estimating the high risk group for cardiovascular disease in the Norwegian HUNT 2 population according to the 2003 European guidelines: modelling study. BMJ 2005;331:551–6.PubMedCrossRefGoogle Scholar
  31. 31.
    Anderson KM, Odell PM, Wilson PW, Kannel WB. Cardiovascular disease risk profiles. Am Heart J. 1991;121:293–8.PubMedCrossRefGoogle Scholar
  32. 32.
    Anderson KM, Wilson PW, Odell PM, Kannel WB. An updated coronary risk profile. A statement for health professionals. Circulation 1991;83:356–62.PubMedGoogle Scholar
  33. 33.
    Brindle P, Emberson J, Lampe F, Walker M, Whincup P, Fahey T, et al. Predictive accuracy of the Framingham coronary risk score in British men: prospective cohort study. BMJ 2003;327:1267.PubMedCrossRefGoogle Scholar
  34. 34.
    Hense HW, Schulte H, Lowel H, Assmann G, Keil U. Framingham risk function overestimates risk of coronary heart disease in men and women from Germany—results from the MONICA Augsburg and the PROCAM cohorts. Eur Heart J. 2003;24:937–45.PubMedCrossRefGoogle Scholar
  35. 35.
    Hense HW. Observations, predictions and decisions—assessing cardiovascular risk assessment. Int J Epidemiol. 2004;33:235–9.PubMedCrossRefGoogle Scholar
  36. 36.
    Hubert HB, Feinleib M, McNamara PM, Castelli WP. Obesity as an independent risk factor for cardiovascular disease: a 26-year follow-up of participants in the Framingham Heart Study. Circulation 1983;67:968–77.PubMedGoogle Scholar
  37. 37.
    Tunstall-Pedoe H, Kuulasmaa K, Mahonen M, Tolonen H, Ruokokoski E. Contribution of trends in survival and coronary-event rates to changes in coronary heart disease mortality: 10-year results from 37 WHO MONICA Project populations. The Lancet 1999;353:1547–57.CrossRefGoogle Scholar
  38. 38.
    Ergin A, Muntner P, Sherwin R, He J. Secular trends in cardiovascular disease mortality, incidence, and case fatality rates in adults in the United States. Am J Med. 2004;117:219–27.PubMedCrossRefGoogle Scholar
  39. 39.
    Nord C, Bjoro T, Ellingsen D, Mykletun A, Dahl O, Klepp O, et al. Gonadal hormones in long-term survivors 10 years after treatment for unilateral testicular cancer. Eur Urol. 2003;44:322–8.PubMedCrossRefGoogle Scholar
  40. 40.
    Svartberg J, von Muhlen D, Schirmer H, Barrett-Connor E, Sundfjord J, Jorde R. Association of endogenous testosterone with blood pressure and left ventricular mass in men. The Tromso Study. Eur J Endocrinol. 2004;150:65–71.PubMedCrossRefGoogle Scholar
  41. 41.
    Svartberg J, Midtby M, Bonaa KH, Sundsfjord J, Joakimsen RM, Jorde R. The associations of age, lifestyle factors and chronic disease with testosterone in men: the Tromso Study. Eur J Endocrinol. 2003;149:145–52.PubMedCrossRefGoogle Scholar
  42. 42.
    Laaksonen DE, Niskanen L, Punnonen K, Nyyssonen K, Tuomainen TP, Valkonen VP, et al. Testosterone and sex hormone-binding globulin predict the metabolic syndrome and diabetes in middle-aged men. Diabetes Care 2004;27:1036–41.PubMedCrossRefGoogle Scholar
  43. 43.
    Khaw KT, Dowsett M, Folkerd E, Bingham S, Wareham N, Luben R, et al. Endogenous testosterone and mortality due to all causes, cardiovascular disease, and cancer in men. European prospective investigation into cancer in Norfolk (EPIC-Norfolk) prospective population study. Circulation 2007;116:2694–701.PubMedCrossRefGoogle Scholar
  44. 44.
    Laughlin GA, Barrett-Connor E, Bergstrom J. Low serum testosterone and mortality in older men. J Clin Endocrinol Metab. 2008;93:68–75.PubMedCrossRefGoogle Scholar
  45. 45.
    Nuver J, Smit AJ, Wolffenbuttel BH, Sluiter WJ, Hoekstra HJ, Sleijfer DT, et al. The metabolic syndrome and disturbances in hormone levels in long-term survivors of disseminated testicular cancer. J Clin Oncol. 2005;23:3718–25.PubMedCrossRefGoogle Scholar
  46. 46.
    Nuver J, Smit AJ, Sleijfer DT, van Gessel AI, van Roon AM, van der MJ, et al. Microalbuminuria, decreased fibrinolysis, and inflammation as early signs of atherosclerosis in long-term survivors of disseminated testicular cancer. Eur J Cancer 2004;40:701–6.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • H. S. Haugnes
    • 1
  • N. Aass
    • 2
  • S. D. Fosså
    • 3
    • 4
  • O. Dahl
    • 5
    • 6
  • O. Klepp
    • 7
  • E. A. Wist
    • 8
  • T. Wilsgaard
    • 9
  • R. M. Bremnes
    • 1
    • 10
  1. 1.Department of Oncology, Institute of Clinical MedicineUniversity of TromsøTromsøNorway
  2. 2.Department of OncologyRikshospitalet Medical CenterOsloNorway
  3. 3.Department of Clinical Cancer ResearchRikshospitalet Medical CenterOsloNorway
  4. 4.Medical FacultyUniversity of OsloOsloNorway
  5. 5.Section of Oncology, Institute of MedicineUniversity of BergenBergenNorway
  6. 6.Department of OncologyHaukeland University HospitalBergenNorway
  7. 7.Department of OncologySt. Olav University HospitalTrondheimNorway
  8. 8.Department of OncologyUllevål University HospitalOsloNorway
  9. 9.Institute of Community MedicineUniversity of TromsøTromsøNorway
  10. 10.Department of OncologyUniversity Hospital of North NorwayTromsøNorway

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