Supportive Care in Cancer

, Volume 27, Issue 2, pp 373–382 | Cite as

Exploring the spectrum of late effects following radical orchidectomy for stage I testicular seminoma: a systematic review of the literature

  • Jennifer A. Soon
  • Angelyn Anton
  • Javier Torres
  • Ruth Lawrence
  • Phillip Parente
  • Joseph McKendrick
  • Ian D. Davis
  • Carmel PezaroEmail author
Review Article



Testicular seminomas occur in young men and are highly curable. Toxicities following treatment for men with extensive stage II-III seminomas may cause long-term morbidities. However, it is not clear whether the risk of late effects also increases following surgery for testis-confined seminoma. In this systematic review, we examined the available literature regarding the incidence of late effects in our target population of patients with stage I seminoma treated with orchidectomy alone.


Publications were identified through an electronic literature search using the MEDLINE, EMBASE and PsychInfo databases, identifying cohorts treated for stage I seminoma. Data on late effects were collected and classified as physical or psychological.


Six hundred and four articles were screened to identify 100 studies. In the target population, available evidence suggests no increased risk of cardiovascular disease, metabolic syndrome, or renal dysfunction compared to the general population. Sperm counts were initially lower than an age-matched cohort; however, counts normalised when re-assessed 5 years later. Data were not specifically reported for the target population regarding bone health, second malignancy, hypogonadism, fertility and all psychological domains. Heterogeneity of study design and reporting methods contributed to uncertainty regarding the true incidence and clinical significance of late effects.


The curability of stage I seminoma and the wide range of potential late effects of treatment suggest the need for long-term monitoring alongside standard cancer surveillance. Important data are needed on the prevalence of late effects, specifically related to testicular cancer survivors undergoing surveillance following orchidectomy.

Implications for cancer survivors

Awareness and screening for relevant late effects may prevent further morbidity in men treated for stage I seminoma.


Systematic review Seminoma Testicular cancer Late effects Survivorship Germ cell tumour 



IDD is supported by a National Health and Medical Research Council Practitioner Fellowship (APP1102604).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

520_2018_4492_MOESM1_ESM.docx (62 kb)
ESM 1 (DOCX 62 kb)


  1. 1.
    Australian Institute of Health and Welfare (AIHW) (2017) Australian Cancer Incidence and Mortality (ACIM) books: testicular cancer. AIHW, Canberra <>Google Scholar
  2. 2.
    Gilbert DC, Van As NJ, Huddart RA (2009) Reducing treatment toxicities in the management of good prognosis testicular germ cell tumors. Expert Rev Anticancer Ther 9(2):223–233PubMedCrossRefGoogle Scholar
  3. 3.
    Znaor A, Lortet-Tieulent J, Jemal A, Bray F (2014) International variations and trends in testicular cancer incidence and mortality. Eur Urol 65(6):1095–1106PubMedCrossRefGoogle Scholar
  4. 4.
    Beard CJ, Gupta S, Motzer RJ, O’Donnell EK, Plimack ER, Margolin KA, Ryan CJ, Sheinfeld J, Feldman DR (2015) Follow-up management of patients with testicular cancer: a multidisciplinary consensus-based approach. J Natl Compr Cancer Netw 13(6):811–822CrossRefGoogle Scholar
  5. 5.
    Warde PGM (2009) Evolving concepts in stage I seminoma. BJU Int 104:1357–1361PubMedCrossRefGoogle Scholar
  6. 6.
    Dong W, Gang W, Liu M, Zhang H (2016) Analysis of the prognosis of patients with testicular seminoma. Oncol Lett 11(2):1361–1366PubMedCrossRefGoogle Scholar
  7. 7.
    Travis LBBC, Allan JM, Dahl AA, Feldman DR, Oldenburg J, Daugaard G, Kelly JL, Dolan ME, Hannigan R, Constine LS, Oeffinger KC, Okunieff P, Armstrong G, Wiljer D, Miller RC, Gietema JA, van Leeuwen FE, Williams JP, Nichols CR, Einhorn LH, Fossa SD (2010) Testicular cancer survivorship: research strategies and recommendations. J Natl Cancer Inst 102:1114–1130PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Kvammen OTM, Solberg A, Møller B, Klepp OH, Fosså S, Tandstad T (2017) Long-term causes of relative excess mortality after diagnosis of testicular germ cell tumor. J Clin Oncol 35(suppl; abstr 4553):4553CrossRefGoogle Scholar
  9. 9.
    Lubberts SKL, Steggink LC, Steursma G, Nuver J, Oosting S, van Ginkel RJ, de Jong IJ, Eulenburg C, Lefrandt JD, Meijer C, Sluiter WJ, Gietema JA (2017) Life expectancy 20 years after cisplatin-based treatment for testicular cancer (TC). J Clin Oncol 35(suppl; abstr 4550):4550CrossRefGoogle Scholar
  10. 10.
    Peckham MJBA, Liew KH, Horwich A, Robinson B, Dobbs HJ, McElwain TJ, Hendry WF (1983) The treatment of metastatic germ-cell testicular tumours with bleomycin, etoposide and cis-platin (BEP). Br J Cancer 1983(47):613–619CrossRefGoogle Scholar
  11. 11.
    Gilligan T (2011) Testicular cancer survivorship. Hematol Oncol Clin North Am 25(3):627–639PubMedCrossRefGoogle Scholar
  12. 12.
    Pearce SM, Liauw SL, Eggener SE (2015) Management of low-stage testicular seminoma. Urol Clin North Am 42(3):287–298PubMedCrossRefGoogle Scholar
  13. 13.
    Glaser SM, Vargo JA, Balasubramani GK, Beriwal S (2016) Surveillance and radiation therapy for stage I seminoma-have we learned from the evidence? Int J Radiat Oncol Biol Phys 94(1):75–84PubMedCrossRefGoogle Scholar
  14. 14.
    Huddart RA, Norman A, Moynihan C, Horwich A, Parker C, Nicholls E, Dearnaley DP (2005) Fertility, gonadal and sexual function in survivors of testicular cancer. Br J Cancer 93(2):200–207PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    LA Moher D, Tetzlaff J, Altman DG (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med 151(4):264–269PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Higgins JPT, Green S (eds) (2011) Cochrane handbook for systematic reviews of interventions version 5.1.0 [updated March 2011]. The Cochrane Collaboration. Available from Accessed 15 June 2018
  17. 17.
    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(3):607–612PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    van den Belt-Dusebout AW, Nuver J, de Wit R, Gietema JA, ten Bokkel Huinink WW, Rodrigus PTR, Schimmel EC, Aleman BMP, van Leeuwen FE (2006) Long-term risk of cardiovascular disease in 5-year survivors of testicular cancer. J Clin Oncol Off J Am Soc Clin Oncol 24(3):467–475CrossRefGoogle Scholar
  19. 19.
    Willemse PM, Hamdy NAT, De Kam ML, Burggraaf J, Osanto S (2014) Changes in bone mineral density in newly diagnosed testicular cancer patients after anticancer treatment. J Clin Endocrinol Metab 99(11):4101–4108PubMedCrossRefGoogle Scholar
  20. 20.
    Murugaesu N, Powles T, Bestwick J, Oliver RTD, Shamash J (2009) Long-term follow-up of testicular cancer patients shows no predisposition to osteoporosis. Osteoporos Int 20(9):1627–1630PubMedCrossRefGoogle Scholar
  21. 21.
    Ondrusova M, Ondrus D, Dusek L, Spanikova B (2009) Damage of hormonal function and bone metabolism in long-term survivors of testicular cancer. Neoplasma 56(6):473–479PubMedCrossRefGoogle Scholar
  22. 22.
    Sagstuen H, Aass N, Fosså SD, Dahl O, Klepp O, Wist EA, Wilsgaard T, Bremnes RM (2005) Blood pressure and body mass index in long-term survivors of testicular cancer. J Clin Oncol Off J Am Soc Clin Oncol 23(22):4980–4990CrossRefGoogle Scholar
  23. 23.
    Fosså SD, Chen J, Schonfeld SJ, McGlynn KA, McMaster ML, Gail MH et al (2005) Risk of contralateral testicular cancer: a population-based study of 29,515 U.S. men. J Natl Cancer Inst 97(14):1056–1066PubMedCrossRefGoogle Scholar
  24. 24.
    Ondrus D, Ondrusova M, Friedova L (2014) Second malignancies in long-term testicular cancer survivors. Int Urol Nephrol 46(4):749–756PubMedCrossRefGoogle Scholar
  25. 25.
    van Leeuwen FE, Stiggelbout AM, van den Belt-Dusebout AW, Noyon R, Eliel MR, van Kerkhoff EH, Delemarre JF, Somers R (1993) Second cancer risk following testicular cancer: a follow-up study of 1,909 patients. J Clin Oncol Off J Am Soc Clin Oncol 11(3):415–424CrossRefGoogle Scholar
  26. 26.
    Travis LB, Curtis RE, Storm H, Hall P, Holowaty E, Van Leeuwen FE et al (1997) Risk of second malignant neoplasms among long-term survivors of testicular cancer. J Natl Cancer Inst 89(19):1429–1439PubMedCrossRefGoogle Scholar
  27. 27.
    Travis LB, Fosså SD, Schonfeld SJ, McMaster ML, Lynch CF, Storm H et al (2005) Second cancers among 40,576 testicular cancer patients: focus on long-term survivors. J Natl Cancer Inst 97(18):1354–1365PubMedCrossRefGoogle Scholar
  28. 28.
    Hansen PV, Trykker H, Helkjoer PE, Andersen J (1989) Testicular function in patients with testicular cancer treated with orchiectomy alone or orchiectomy plus cisplatin-based chemotherapy. J Natl Cancer Inst 81(16):1246–1250PubMedCrossRefGoogle Scholar
  29. 29.
    Fosså SD, Aabyholm T, Vespestad S, Norman N, Ous S (1993) Semen quality after treatment for testicular cancer. Eur Urol 23(1):172–176PubMedCrossRefGoogle Scholar
  30. 30.
    Brydoy M, Fosså SD, Klepp O, Bremnes RM, Wist EA, Bjoro T et al (2012) Sperm counts and endocrinological markers of spermatogenesis in long-term survivors of testicular cancer. Br J Cancer 107(11):1833–1839PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Ping P, Gu B-H, Li P, Huang Y-R, Li Z (2014) Fertility outcome of patients with testicular tumor: before and after treatment. Asian J Androl 16(1):107–111PubMedCrossRefGoogle Scholar
  32. 32.
    Huyghe E, Matsuda T, Daudin M, Chevreau C, Bachaud J-M, Plante P, Bujan L, Thonneau P (2004) Fertility after testicular cancer treatments: results of a large multicenter study. Cancer 100(4):732–737PubMedCrossRefGoogle Scholar
  33. 33.
    Brydøy M, Fosså SD, Klepp O, Bremnes RM, Wist EA, Wentzel-Larsen T, Dahl O (2005) Paternity following treatment for testicular cancer. J Natl Cancer Inst 97(21):1580–1588PubMedCrossRefGoogle Scholar
  34. 34.
    Thonneau P, Marchand S, Tallec A, Ferial ML, Ducot B, Lansac J, Lopes P, Tabaste JM, Spira A (1991) Incidence and main causes of infertility in a resident population (1,850,000) of three French regions (1988–1989). Hum Reprod 6(6):811–816PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Kim C, McGlynn KA, McCorkle R, Li Y, Erickson RL, Ma S et al (2012) Sexual functioning among testicular cancer survivors: a case-control study in the U.S. J Psychosom Res 73(1):68–73PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Dahl AA, Bremnes R, Dahl O, Klepp O, Wist E, Fosså SD (2007) Is the sexual function compromised in long-term testicular cancer survivors? Eur Urol 52(5):1438–1447PubMedCrossRefGoogle Scholar
  37. 37.
    Arai Y, Kawakita M, Okada Y, Yoshida O (1997) Sexuality and fertility in long-term survivors of testicular cancer. J Clin Oncol Off J Am Soc Clin Oncol 15(4):1444–1448CrossRefGoogle Scholar
  38. 38.
    Beard CJ, Travis LB, Chen M-H, Arvold ND, Nguyen PL, Martin NE, Kuban DA, Ng AK, Hoffman KE (2013) Outcomes in stage I testicular seminoma: a population-based study of 9193 patients. Cancer 119(15):2771–2777PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Nord C, Bjøro T, Ellingsen D, Mykletun A, Dahl O, Klepp O, Bremnes RM, Wist E, Fosså SD (2003) Gonadal hormones in long-term survivors 10 years after treatment for unilateral testicular cancer. Eur Urol 44(3):322–328PubMedCrossRefGoogle Scholar
  40. 40.
    Sprauten M, Brydøy M, Haugnes HS, Cvancarova M, Bjøro T, Bjerner J, Fosså SD, Oldenburg J (2014) Longitudinal serum testosterone, luteinizing hormone, and follicle-stimulating hormone levels in a population-based sample of long-term testicular cancer survivors. J Clin Oncol Off J Am Soc Clin Oncol 32(6):571–578CrossRefGoogle Scholar
  41. 41.
    Hansen SW, Berthelsen JG, von der Maase H (1990) Long-term fertility and Leydig cell function in patients treated for germ cell cancer with cisplatin, vinblastine, and bleomycin versus surveillance. J Clin Oncol Off J Am Soc Clin Oncol 8(10):1695–1698CrossRefGoogle Scholar
  42. 42.
    Pühse G, Secker A, Kemper S, Hertle L, Kliesch S (2011) Testosterone deficiency in testicular germ-cell cancer patients is not influenced by oncological treatment. Int J Androl 34(5 Pt 2):e351–e3e7PubMedCrossRefGoogle Scholar
  43. 43.
    O’Carrigan B, Fournier M, Olver IN, Stockler MR, Whitford H, Toner GC, Thomson DB, Davis ID, Hanning F, Singhal N, Underhill C, Clingan P, McDonald A, Boland A, Grimison P, Australian and New Zealand Urogenital and Prostate Cancer Trials Group (2014) Testosterone deficiency and quality of life in Australasian testicular cancer survivors: a prospective cohort study. Intern Med J 44(8):813–817PubMedCrossRefGoogle Scholar
  44. 44.
    Nuver J, Smit AJ, Wolffenbuttel BHR, Sluiter WJ, Hoekstra HJ, Sleijfer DT, Gietema JA (2005) The metabolic syndrome and disturbances in hormone levels in long-term survivors of disseminated testicular cancer. J Clin Oncol Off J Am Soc Clin Oncol 23(16):3718–3725CrossRefGoogle Scholar
  45. 45.
    Rossen P, Pedersen AF, Zachariae R, von der Maase H (2012) Sexuality and body image in long-term survivors of testicular cancer. Eur J Cancer 48(4):571–578PubMedCrossRefGoogle Scholar
  46. 46.
    Tuinman MA, Fleer J, Sleijfer DT, Hoekstra HJ, Hoekstra-Weebers JEHM (2005) Marital and sexual satisfaction in testicular cancer survivors and their spouses. Support Care Cancer 13(7):540–548PubMedCrossRefGoogle Scholar
  47. 47.
    Alacacioglu A, Ulger E, Varol U, Yavuzsen T, Akyol M, Yildiz Y et al (2014) Sexual satisfaction, anxiety, depression and quality of life in testicular cancer survivors. Med Oncol 31(7):43PubMedCrossRefGoogle Scholar
  48. 48.
    Rieker PP, Fitzgerald EM, Kalish LA, Richie JP, Lederman GS, Edbril SD, Garnick MB (1989) Psychosocial factors, curative therapies, and behavioral outcomes. A comparison of testis cancer survivors and a control group of healthy men. Cancer 64(11):2399–2407PubMedCrossRefGoogle Scholar
  49. 49.
    Gritz ER, Wellisch DK, Siau J, Wang HJ (1990) Long-term effects of testicular cancer on marital relationships. Psychosomatics 31(3):301–312PubMedCrossRefGoogle Scholar
  50. 50.
    Grov EK, Fosså SD, Bremnes RM, Dahl O, Klepp O, Wist E et al (2009) The personality trait of neuroticism is strongly associated with long-term morbidity in testicular cancer survivors. Acta Oncol 48(6):842–849PubMedCrossRefGoogle Scholar
  51. 51.
    Smith ABRC, Butow P et al (2018) A systematic review of quantitative observational studies investigating psychological distress in testicular cancer survivors. Psycho-Oncology 27(5):1129–1138PubMedCrossRefGoogle Scholar
  52. 52.
    Rieker PP, Edbril SD, Garnick MB (1985) Curative testis cancer therapy: psychosocial sequelae. J Clin Oncol Off J Am Soc Clin Oncol 3(8):1117–1126CrossRefGoogle Scholar
  53. 53.
    Eberhard J, Ståhl O, Cohn-Cedermark G, Cavallin-Ståhl E, Giwercman Y, Rastkhani H, Rylander L, Eberhard-Gran M, Kvist U, Giwercman A (2010) Emotional disorders in testicular cancer survivors in relation to hypogonadism, androgen receptor polymorphism and treatment modality. J Affect Disord 122(3):260–266PubMedCrossRefGoogle Scholar
  54. 54.
    Thorsen L, Nystad W, Stigum H, Dahl O, Klepp O, Bremnes RM, Wist E, Fosså SD (2005) The association between self-reported physical activity and prevalence of depression and anxiety disorder in long-term survivors of testicular cancer and men in a general population sample. Support Care Cancer 13(8):637–646PubMedCrossRefGoogle Scholar
  55. 55.
    Thorsen L, Nystad W, Dahl O, Klepp O, Bremnes RM, Wist E et al (2003) The level of physical activity in long-term survivors of testicular cancer. Eur J Cancer 39(9):1216–1221PubMedCrossRefGoogle Scholar
  56. 56.
    Rutskij R, Gaarden T, Bremnes R, Dahl O, Finset A, Fossa SD, Klepp O, Sorebo O, Wist E, Dahl AA (2010) A study of coping in long-term testicular cancer survivors. Psychol Health Med 15(2):146–158PubMedCrossRefGoogle Scholar
  57. 57.
    Rudberg L, Nilsson S, Wikblad K (2000) Health-related quality of life in survivors of testicular cancer 3 to 13 years after treatment. J Psychosoc Oncol 18(3):19–31CrossRefGoogle Scholar
  58. 58.
    Tuinman MA, Fleer J, Hoekstra HJ, Sleijfer DT, Hoekstra-Weebers JEHM (2004) Quality of life and stress response symptoms in long-term and recent spouses of testicular cancer survivors. Eur J Cancer 40(11):1696–1703PubMedCrossRefGoogle Scholar
  59. 59.
    Rossen PB, Pedersen AF, Zachariae R, von der Maase H (2009) Health-related quality of life in long-term survivors of testicular cancer. J Clin Oncol Off J Am Soc Clin Oncol 27(35):5993–5999CrossRefGoogle Scholar
  60. 60.
    Shinn EH, Swartz RJ, Thornton BB, Spiess PE, Pisters LL, Basen-Engquist KM (2010) Testis cancer survivors’ health behaviors: comparison with age-matched relative and demographically matched population controls. J Clin Oncol Off J Am Soc Clin Oncol 28(13):2274–2279CrossRefGoogle Scholar
  61. 61.
    Kim C, McGlynn KA, McCorkle R, Erickson RL, Niebuhr DW, Ma S et al (2011) Quality of life among testicular cancer survivors: a case-control study in the United States. Qual Life Res Int J Qual Life Asp Treat Care Rehab 20(10):1629–1637Google Scholar
  62. 62.
    Stuart NS, Woodroffe CM, Grundy R, Cullen MH (1990) Long-term toxicity of chemotherapy for testicular cancer—the cost of cure. Br J Cancer 61(3):479–484PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Fleer J, Hoekstra HJ, Sleijfer DT, Tuinman MA, Klip EC, Hoekstra-Weebers JEHM (2006) Quality of life of testicular cancer survivors and the relationship with sociodemographics, cancer-related variables, and life events. Support Care Cancer 14(3):251–259PubMedCrossRefGoogle Scholar
  64. 64.
    Alanee S, Russo P (2012) Suicide in men with testis cancer. Eur J Cancer Care 21(6):817–821CrossRefGoogle Scholar
  65. 65.
    Fosså SD, de Wit R, Roberts JT, Wilkinson PM, de Mulder PHM, Mead GM, Cook P, de Prijck L, Stenning S, Aaronson NK, Bottomley A, Collette L, European Organization for Research and Treatment of Cancer Genitourinary Group 30941, Medical Research Council Testicular Cancer Study Group TE20 (2003) Quality of life in good prognosis patients with metastatic germ cell cancer: a prospective study of the European Organization for Research and Treatment of Cancer Genitourinary Group/Medical Research Council Testicular Cancer Study Group (30941/TE20). J Clin Oncol Off J Am Soc Clin Oncol 21(6):1107–1118CrossRefGoogle Scholar
  66. 66.
    Stouten-Kemperman MM, de Ruiter MB, Caan MWA, Boogerd W, Kerst MJ, Reneman L, Schagen SB (2015) Lower cognitive performance and white matter changes in testicular cancer survivors 10 years after chemotherapy. Hum Brain Mapp 36:4638–4647PubMedCrossRefGoogle Scholar
  67. 67.
    Skaali T, Fosså SD, Andersson S, Cvancarova M, Langberg CW, Lehne G, Dahl AA (2011) Self-reported cognitive problems in testicular cancer patients: relation to neuropsychological performance, fatigue, and psychological distress. J Psychosom Res 70(5):403–410PubMedCrossRefGoogle Scholar
  68. 68.
    Amidi A, Wu LM, Pedersen AD, Mehlsen M, Pedersen CG, Rossen P, Agerbæk M, Zachariae R (2015) Cognitive impairment in testicular cancer survivors 2 to 7 years after treatment. Support Care Cancer 23(10):2973–2979PubMedCrossRefGoogle Scholar
  69. 69.
    Schagen SB, Boogerd W, Muller MJ, Huinink WTB, Moonen L, Meinhardt W et al (2008) Cognitive complaints and cognitive impairment following BEP chemotherapy in patients with testicular cancer. Acta Oncol 47(1):63–70PubMedCrossRefGoogle Scholar
  70. 70.
    Pedersen AD, Rossen P, Mehlsen MY, Pedersen CG, Zachariae R, von der Maase H (2009) Long-term cognitive function following chemotherapy in patients with testicular cancer. J Int Neuropsychol Soc 15(2):296–301PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Eastern Health Cancer ServicesBox HillAustralia
  2. 2.Eastern Health Library ServicesBox HillAustralia
  3. 3.Monash University Eastern Health Clinical SchoolBox HillAustralia

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