Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Conservative management of testicular germ-cell tumors

Abstract

Cure rates of germ-cell cancer have been greater than 95% for the last decade; therefore, over the past few years there has been a greater focus on 'conservative' approaches to treatment. The increased incidence of late non-germ-cell cancers in the era of radiotherapy and the incidence of subclinical testicular deficiency and metabolic syndrome in cured patients have accelerated this trend. Taking account of the increase in cure rates of primary chemotherapy failures from 5% to 60% with intensification of chemotherapy and surgery, this Review focuses on three areas: lessons from the initial failed trials of less-intensive treatment (i.e. bleomycin withdrawal and carboplatin substitution) that emphasised the need for improved salvage therapy; successes of reducing treatment of patients with metastases classed as good-risk from four cycles(20 days) to three cycles(9 days) and using 1 day carboplatin instead of 21 day radiotherapy as adjuvant for stage 1 seminoma; and the unexpected finding at 5 years of a 72% reduction of contralateral second germ-cell cancer. This finding provides the stimulus for the next generation of conservative trials using organ preservation, aiming to reduce occurrence of metabolic syndrome and using new radiological and minimal surgery techniques to accelerate the assessment of less toxic drugs and new approaches for combined medial and surgical treatment.

Key Points

  • In excess of 95% of all germ-cell cancers are cured by a combination of surgery and chemotherapy

  • 50% of patients who fail first line chemotherapy are cured by second line therapy, and a further 25% to 30% are cured by third line treatment

  • Successful trials in low-risk non-seminoma have reduced required treatment durations from 20 days in 12 weeks to 9 days in 9 weeks, and in stage 1 seminoma: from 20 days radiation to 1 day carboplatin

  • Studies of late complications from cancer treatments suggest there is still a need for future trials to be directed at further reducing the long term morbidity associated with chemotherapy and surgery

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Increase in the proportion of men presenting with testis tumors small enough for testis conservation.

Similar content being viewed by others

References

  1. Oliver RT et al. (1996) Testis conservation studies in germ cell cancer justified by improved primary chemotherapy response and reduced delay, 1978–1994. Br J Urol 78: 119–124

    Article  CAS  PubMed  Google Scholar 

  2. Robinson D et al. (2007) Mortality and incidence of second cancers following treatment for testicular cancer. Br J Cancer 96: 529–533

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Heidenreich et al. (2003) Complications of primary nerve sparing retroperitoneal lymph node dissection for clinical stage I nonseminomatous germ cell tumors of the testis: experience of the German Testicular Cancer Study Group. J Urol 169: 1710–1714

    Article  PubMed  Google Scholar 

  4. Hoff Wanderas E et al. (1990) Serum follicle stimulating hormone—predictor of cancer in the remaining testis in patients with unilateral testicular cancer. Br J Urol 66: 315–317

    Article  Google Scholar 

  5. Heidenreich A et al. (2001) The German Testicular Cancer Study G. Organ sparing surgery for malignant germ cell tumor of the testis. J Urol 166: 2161–2165

    Article  CAS  PubMed  Google Scholar 

  6. Oliver RT et al. (2003) Testis conserving chemotherapy in germ cell cancer: its potential to increase understanding of the biology and treatment of carcinoma-in-situ. APMIS 111: 86–92

    Article  CAS  PubMed  Google Scholar 

  7. Satoh M et al. (2005) Intraoperative, radio-guided sentinel lymph node mapping in laparoscopic lymph node dissection for Stage I testicular carcinoma. Cancer 103: 2067–2072

    Article  PubMed  Google Scholar 

  8. Shamash J et al. (2002) GAMEC—a novel protocol for IGCCCG poor prognosis and relapsing germ cell tumours. In Germ Cell Tumours V, 240–241 (Eds Harnden P et al.) London: Springer

    Chapter  Google Scholar 

  9. Shamash J et al. (2007) A phase II study using a topoisomerase I-based approach in patients with multiply relapsed germ-cell tumours. Ann Oncol 18: 925–930

    Article  CAS  PubMed  Google Scholar 

  10. Albers P et al. (1999) Positron emission tomography in the clinical staging of patients with Stage I and II testicular germ cell tumors. Urology 53: 808–811

    Article  CAS  PubMed  Google Scholar 

  11. Oliver RTD et al. (2004) 20 year phase 1/2 study of single agent carboplatin in metastatic seminoma:could it have been accelerated by 72 hour PET scan response? [abstract]. J Clin Oncol 22 (suppl): 4763

    Article  Google Scholar 

  12. Powles T et al. (2007) Molecular positron emission tomography and PET/CT imaging in urological malignancies. Eur Urol 51: 1511–1521

    Article  PubMed  Google Scholar 

  13. Edmonds PM et al. (1993) Risk of a second non-testis malignancy following radiotherapy for stage 1 seminoma. In Abstracts of the BAUS Annual Meeting, 1993 June, Harrogate, 53

    Google Scholar 

  14. Zagars GK et al. (2004) Mortality after cure of testicular seminoma. J Clin Oncol 22: 640–647

    Article  PubMed  Google Scholar 

  15. Oliver RTD (1985) Testicular germ cell tumours—a model for a new approach to treatment of adult solid tumours. Postgrad Med J 61: 123–131

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Williams SD et al. (1987) Treatment of disseminated germ-cell tumours with Cisplatin, Bleomycin, and either Vinblastine or Etoposide. N Engl J Med 316: 1435–1440

    Article  CAS  PubMed  Google Scholar 

  17. Mead GM and Stenning S (1997) International germ cell cancer collaborative group prognostic factor scoring system. J Clin Oncol 15: 594–603

    Article  Google Scholar 

  18. Bajorin D et al. (1998) Metastatic germ cell tumours: modelling for response to chemotherapy. J Clin Oncol 16: 707–715

    Article  CAS  PubMed  Google Scholar 

  19. Kaye S et al. (1998) Intensive induction-sequential chemotherapy with BOP/VIP-B compared with treatment of metastatic nonseminomatous germ cell tumour. J Clin Oncol 16: 692–701

    Article  CAS  PubMed  Google Scholar 

  20. Hinton S et al. (2003) Cisplatin, etoposide and either bleomycin or ifosfamide in the treatment of disseminated germ cell tumors: final analysis of an intergroup trial. Cancer 97: 1869–1875

    Article  CAS  PubMed  Google Scholar 

  21. Boshoff CB et al. (1995) Secondary tumours following etoposide containing therapy for germ cell cancer. Ann Oncol 6: 35–40

    Article  CAS  PubMed  Google Scholar 

  22. Orchid website [www.orchid-cancer.org.uk]

  23. Bhardwa JM et al. (2005) Assessing the size and stage of testicular germ cell tumours: 1984–2003. BJU Int 96: 819–821

    Article  PubMed  Google Scholar 

  24. Agnarsson BA et al. (2006) Testicular germ cell tumours in Iceland: a nationwide clinicopathological study. APMIS 114: 779–783

    Article  PubMed  Google Scholar 

  25. Shamash J et al. (1999) 60% salvage rate for germ cell tumours using sequential m-BOP, surgery and ifosfamide based chemotherapy. Ann Oncol 10: 685–692

    Article  CAS  PubMed  Google Scholar 

  26. Pico JL et al. (2005) A randomised trial of high-dose chemotherapy in the salvage treatment of patients failing first-line platinum chemotherapy for advanced germ cell tumours. Ann Oncol 16: 1152–1159

    Article  PubMed  Google Scholar 

  27. Motzer RJ et al. (2000) Paclitaxel, ifosfamide, and cisplatin second-line therapy for patients with relapsed testicular germ cell cancer. J Clin Oncol 18: 2413–2418

    Article  CAS  PubMed  Google Scholar 

  28. Shamash J et al.: GAMEC—a new intensive protocol for untreated poor prognosis and relapsed or refractory germ cell tumours. Br J Cancer 97: 308–314

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Ravi R et al. (1998) Surgery as salvage therapy in chemotherapy-resistant nonseminomatous germ cell tumours. Br J Urol 81: 884–888

    Article  CAS  PubMed  Google Scholar 

  30. Beck SD et al. (2005) Pathologic findings and therapeutic outcome of desperation post-chemotherapy retroperitoneal lymph node dissection in advanced germ cell cancer. Urol Oncol 23: 423–430

    Article  PubMed  Google Scholar 

  31. Zuk RJ et al. (1989) Findings in lymph nodes of patients with germ cell tumours after chemotherapy and their relation to prognosis. J Clin Pathol 42: 1049–1054

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Loehrer PJ Sr et al. (1986) Teratoma following cisplatin-based combination chemotherapy for nonseminomatous germ cell tumors: a clinicopathological correlation. J Urol 135: 1183–1189

    Article  PubMed  Google Scholar 

  33. Oliver RT (2001) Testicular cancer. Curr Opin Oncol 13: 191–198

    Article  CAS  PubMed  Google Scholar 

  34. Shelley M et al. (2003) Testicular germ cell cancer. Evidence-based Oncology 34: 365–373

    Article  Google Scholar 

  35. Horwich A et al. (1997) 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 15: 1844–1852

    Article  CAS  PubMed  Google Scholar 

  36. De Wit R et al. (2001) Equivalence of three or four cycles of bleomycin, etoposide, and cisplatin chemotherapy and of a 3- or 5-day schedule in good-prognosis germ cell cancer: a randomized Study of the European Organization for Research and Treatment of Cancer Genitourinary Tract Cancer Cooperative Group and the Medical Research Council. J Clin Oncol 19: 1629–1640

    Article  CAS  PubMed  Google Scholar 

  37. Fossa SD et al. (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 21: 1107–1118

    Article  PubMed  Google Scholar 

  38. Freedman L et al. (1985) Prognostic factors in advanced non-seminomatous germ cell testicular tumours: results of a multicentre study. Lancet 1: 8–11

    Google Scholar 

  39. Freedman LS et al. (1987) Histopathology in the prediction of relapse of patients with stage 1 testicular teratoma treated by orchidectomy alone. On behalf of MRC Testicular Tumour Subgroup (Urological Working Party). Lancet 2: 294–298

    Article  CAS  PubMed  Google Scholar 

  40. Leiter E and Brendler H (1967) Loss of ejaculation following bilateral retroperitoneal lymphadenectomy. J Urol 98: 375–378

    Article  CAS  PubMed  Google Scholar 

  41. Williams SD et al. (1987) Immediate adjuvant chemotherapy versus observation with treatment at relapse in pathological stage II testicular cancer. N Engl J Med 317: 1433

    Article  CAS  PubMed  Google Scholar 

  42. Oliver R et al. (2004) Long term follow up of Anglian Germ Cell Cancer Group surveillance versus adjuvant chemotherapy treated stage 1 non-seminoma patients. Urology 63: 556–561

    Article  CAS  PubMed  Google Scholar 

  43. Albers P (2007) Management of stage I testis cancer. Eur Urol 51: 34–43

    Article  PubMed  Google Scholar 

  44. Steiner H et al. (2004) Long-term results of laparoscopic retroperitoneal lymph node dissection: a single-center 10-year experience. Urology 63: 550–555

    Article  PubMed  Google Scholar 

  45. Rassweiler J et al. (2006) Laparoscopic and robotic assisted radical prostatectomy—critical analysis of the results. Eur Urol 49: 612–624

    Article  PubMed  Google Scholar 

  46. Stephenson AJ et al. (2005) Retroperitoneal lymph node dissection for nonseminomatous germ cell testicular cancer: impact of patient selection factors on outcome. J Clin Oncol 23: 2781–2788

    Article  PubMed  Google Scholar 

  47. Donohue JP et al. (1987) Correlation of computerized tomographic changes and histological findings in 80 patients having radical retroperitoneal lymph node dissection after chemotherapy for testis cancer. J Urol 137: 1176–1179

    Article  CAS  PubMed  Google Scholar 

  48. Albers P et al. (2006) One course adjuvant PEB chemotherapy versus retroperitoneal lymph node dissection in patients with stage I non-seminoma [abstract]. J Clin Oncol 24: 4512

    Google Scholar 

  49. Tyrrell CJ and Peckham MJ (1976) The response of lymph node metastases of testicular teratoma to radiation therapy. Br J Urol 48: 363–370

    Article  CAS  PubMed  Google Scholar 

  50. Williams C (1977) Current dilemmas in the management of non-seminomatous germ cell tumors of the testis. Cancer Treat Rev 4: 275–297

    Article  CAS  PubMed  Google Scholar 

  51. Oliver RTD et al. (1984) Possible new approaches to the management of seminoma of the testis. Br J Urol 56: 729–733

    Article  CAS  PubMed  Google Scholar 

  52. Logothetis CJ et al. (1987) Cyclophosphamide and sequential cisplatin for advanced seminoma: long term follow up 52 patients. J Urol 138: 789–794

    Article  CAS  PubMed  Google Scholar 

  53. Bokemeyer C et al. (2004) Metastatic seminoma treated with either single agent carboplatin or cisplatin-based combination chemotherapy: a pooled analysis of two randomised trials. Br J Cancer 91: 683–687

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Travis LB et al. (2005) Second cancers among 40,576 testicular cancer patients: focus on long-term survivors. J Natl Cancer Inst 97: 1354–1365

    Article  PubMed  Google Scholar 

  55. Warde P et al. (2002) Prognostic factors for relapse in stage I seminoma managed by surveillance: a pooled analysis. J Clin Oncol 20: 4448–4452

    Article  PubMed  Google Scholar 

  56. Oliver RTD (2005) One-dose carboplatin in seminoma. Lancet 366: 1526

    Article  PubMed  Google Scholar 

  57. Fossa SD et al. (1999) 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 17: 1146

    Article  CAS  PubMed  Google Scholar 

  58. Jones WG et al. (2005) Randomized trial of 30 versus 20 Gy in the adjuvant treatment of stage I testicular seminoma: a report on Medical Research Council Trial TE18, European Organisation for the Research and Treatment of Cancer Trial 30942 (ISRCTN18525328). J Clin Oncol 23: 1200–1208

    Article  PubMed  Google Scholar 

  59. Logue JP et al. (2003) Short course para-aortic radiation for stage I seminoma of the testis. Int J Radiat Oncol Biol Phys 57: 1304–1309

    Article  PubMed  Google Scholar 

  60. Classen J et al. (2004) Para-aortic irradiation for stage I testicular seminoma: results of a prospective study in 675 patients. A trial of the German testicular cancer study group (GTCSG). Br J Cancer 90: 2305–2311

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Oliver RT et al. (1994) Pilot studies of 2 and 1 course carboplatin as adjuvant for stage I seminoma: should it be tested in a randomized trial against radiotherapy? Int J Radiat Oncol Biol Phys 29: 3–8

    Article  CAS  PubMed  Google Scholar 

  62. Dieckmann K et al. (2000) Adjuvant treatment of clinical stage 1 seminoma: is a single course of carboplatin sufficient? Urology 55: 102–106

    Article  CAS  PubMed  Google Scholar 

  63. Krege S et al. (2006) Single agent carboplatin for CS IIA/B testicular seminoma. A phase II study of the German Testicular Cancer Study Group (GTCSG). Ann Oncol 17: 276–280

    Article  CAS  PubMed  Google Scholar 

  64. Sant M et al. (2007) Ten-year survival and risk of relapse for testicular cancer: a EUROCARE high resolution study. Eur J Cancer 43: 585–592

    Article  PubMed  Google Scholar 

  65. Oliver TD et al. (2005) Pooled analysis of phase II reports of 2 vs 1 course of carboplatin as adjuvant for stage 1 seminoma [abstract]. J Clin Oncol 23: 4572

    Article  Google Scholar 

  66. Oliver RTD et al. (2005) Radiotherapy versus single-dose carboplatin in adjuvant treatment of stage 1 seminoma: a randomised trial. Lancet 366: 293–300

    Article  CAS  PubMed  Google Scholar 

  67. Warde P (2006) Are carboplatin and radiotherapy equally effective for the adjuvant treatment of stage I seminoma? Nat Clin Pract Oncol 3: 18–19

    Article  CAS  PubMed  Google Scholar 

  68. Loehrer PJ Sr and Bosl GJ (2005) Carboplatin for stage I seminoma and the sword of Damocles. J Clin Oncol 23: 8566–8569

    Article  PubMed  Google Scholar 

  69. Motzer RJ et al. (2006) Testicular cancer. Clinical practice guidelines in oncology. J Natl Compr Canc Netw 4: 1038–1058

    Article  CAS  PubMed  Google Scholar 

  70. Huddart RA and Joffe JK (2006) Preferred treatment for stage I seminoma: a survey of Canadian radiation oncologists. Clin Oncol (R Coll Radiol) 18: 693–695

    Article  CAS  Google Scholar 

  71. Sternswald J et al. (1978) Lymphopenia and change in distribution of human B and T lymphocyte in peripheral blood induced by irradiation for mammary carcinoma. Lancet 1: 1352–1356

    Google Scholar 

  72. Fossa S et al. (1989) Long term mobidity after infradiaphragmatic radiotherapy in young men with testicular cancer. Cancer 64: 404–408

    Article  CAS  PubMed  Google Scholar 

  73. Nuver J et al. (2005) The metabolic syndrome and disturbances in hormone levels in long-term survivors of disseminated testicular cancer. J Clin Oncol 23: 3718–3725

    Article  CAS  PubMed  Google Scholar 

  74. Mardiak J et al. (2007) Damage of bone metabolism and osteoporosis in testicular cancer patients[abstract]. J Clin Oncol 25 (suppl): 5052

    Google Scholar 

  75. Willemse P-PM (2007) Bone abnormalities in male germ-cell cancer survivors [abstract]. J Clin Oncol 25 (suppl): 5053

    Google Scholar 

  76. Oliver R (2006) Epidemiology of testis cancer. In Comprehensive Textbook of Genitourinary Oncology, edn 3, 547–558 (Eds Vogelzang N et al.) Philadephia: Lippincott Williams & Wilkins

    Google Scholar 

  77. Oliver RTD (1990) Atrophy, hormones, genes and viruses in aetiology of germ cell tumours. Cancer Surv 9: 263–268

    CAS  PubMed  Google Scholar 

  78. Skakkebaek NE et al. (2001) Testicular dysgenesis syndrome: an increasingly common developmental disorder with environmental aspects. Hum Reprod 16: 972–978

    Article  CAS  PubMed  Google Scholar 

  79. Sharpe RM (2003) The 'oestrogen hypothesis'—where do we stand now? Int J Androl 26: 2–15

    Article  CAS  PubMed  Google Scholar 

  80. Mahood IK et al. (2006) Cellular origins of testicular dysgenesis in rats exposed in utero to di(n-butyl) phthalate. Int J Androl 29: 148–154

    Article  CAS  PubMed  Google Scholar 

  81. Rajpert-De Meyts E (2006) Developmental model for the pathogenesis of testicular carcinoma in situ: genetic and environmental aspects. Hum Reprod Update 12: 303–323

    Article  CAS  PubMed  Google Scholar 

  82. Petersen PM et al. (1999) Semen quality and reproductive hormones before orchiectomy in men with testicular cancer. J Clin Oncol 17: 941–947

    Article  CAS  PubMed  Google Scholar 

  83. Hoei-Hansen CE et al. (2007) Towards a non-invasive method for early detection of testicular neoplasia in semen samples by identification of fetal germ cell-specific markers. Hum Reprod 22: 167–173

    Article  CAS  PubMed  Google Scholar 

  84. Harisinghani MG et al. (2005) A pilot study of lymphotrophic nanoparticle-enhanced magnetic resonance imaging technique in early stage testicular cancer: a new method for noninvasive lymph node evaluation. Urology 66: 1066–1071

    Article  PubMed  Google Scholar 

  85. Eggener SE et al. (2007) Incidence of disease outside modified retroperitoneal lymph node dissection templates in clinical stage I or IIA nonseminomatous germ cell testicular cancer. J Urol 177: 937–942

    Article  PubMed  Google Scholar 

  86. Powles T et al. (2003) Novel in-vitro approaches to the treatment of cisplatin resistant germ cell tumours [abstract]. Proc Am Soc Clin Oncol 22: 547

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Ethics declarations

Competing interests

The author declares no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Oliver, T. Conservative management of testicular germ-cell tumors. Nat Rev Urol 4, 550–560 (2007). https://doi.org/10.1038/ncpuro0905

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ncpuro0905

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing