Skip to main content

Advertisement

SpringerLink
Log in

Late Relapse of Testis Cancer

  • Testis and Penile Cancer (M Manoharan and J Sheinfeld, Section Editors)
  • Published:
Current Urology Reports Aims and scope Submit manuscript

    We’re sorry, something doesn't seem to be working properly.

    Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.

Abstract

Most relapses of germ-cell tumors occur within 2 years of initial treatment. In 2 % to 4 % of patients, relapse may occur later. The retroperitoneum is the primary site of late relapses, and alpha-fetoprotein is the predominant marker. These tumors are highly resistant to chemotherapy. Surgical resection is the preferred treatment. If the recurrent disease is inoperable, salvage chemotherapy may be instituted, followed by resection of the residual disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as:• Of importance, •• Of outstanding importance

  1. Einhorn LH. Testicular cancer as a model for a curable neoplasm: the Richard and Hinda Rosenthal Foundation Award Lecture. Cancer Res. 1981;41(9 Pt 1):3275–80.

    PubMed  CAS  Google Scholar 

  2. Bosl GJ, Motzer RJ. Testicular germ-cell cancer. N Engl J Med. 1997;337(4):242–53.

    Article  PubMed  CAS  Google Scholar 

  3. Williams SD, Birch R, Einhorn LH, et al. Treatment of disseminated germ-cell tumors with cisplatin, bleomycin, and either vinblastine or etoposide. N Engl J Med. 1987;316(23):1435–40.

    Article  PubMed  CAS  Google Scholar 

  4. Bosl GJ, Gluckman R, Geller NL, et al. VAB-6: an effective chemotherapy regimen for patients with germ-cell tumors. J Clin Oncol. 1986;4(10):1493–9.

    PubMed  CAS  Google Scholar 

  5. Lipphardt ME, Albers P. Late relapse of testicular cancer. World J Urol. 2004;22(1):47–54.

    Article  PubMed  Google Scholar 

  6. •• Baniel J, Foster RS, Gonin R, et al. Late relapse of testicular cancer. J Clin Oncol. 1995;13(5):1170–6. Indiana University was the first to report late relapse as a distinct clinical entity.

    PubMed  CAS  Google Scholar 

  7. Odell WD, Griffin J. Pulsatile secretion of human chorionic gonadotropin in normal adults. N Engl J Med. 1987;317:1688–91.

    Article  PubMed  CAS  Google Scholar 

  8. Stenman UH, Alfthan H, Ranta T, Vartiainen E, Jalkanen J, Seppala M. Serum levels of human chorionic gonadotropin in nonpregnant women and men are modulated by gonadotropin-releasing hormone and sex steroids. J Clin Endocrinol Metab. 1987;64:730–6.

    Article  PubMed  CAS  Google Scholar 

  9. Catalona WJ, Vaitukaitis JL, Fair WR. Falsely positive specific human chorionic gonadotropin assays in patients with testicular tumors: conversion to negative with testosterone administration. J Urol. 1979;122:126–8.

    PubMed  CAS  Google Scholar 

  10. Garnick MB. Spurious rise in human chorionic gonadotropin induced by marihuana in patients with testicular cancer. N Engl J Med. 1980;303:1177.

    PubMed  CAS  Google Scholar 

  11. Braunstein GD, Thompson R, Gross S, Soares JR. Marijuana use does not spuriously elevate serum human chorionic gonadotropin levels. Urology. 1985;25:605–6.

    Article  PubMed  CAS  Google Scholar 

  12. Bell H. Alpha-fetoprotein and carcinoembryonic antigen in patients with primary liver carcinoma, metastatic liver disease, and alcoholic liver disease. Scand J Gastroenterol. 1982;17:897–903.

    Article  PubMed  CAS  Google Scholar 

  13. Waldmann TA, McIntire KR. The use of a radioimmunoassay for alpha-fetoprotein in the diagnosis of malignancy. Cancer. 1974;34(suppl):1510–5.

    Article  PubMed  CAS  Google Scholar 

  14. Masopust J, Kithier K, Rádl J, Koutecký J, Kotál L. Occurrence of fetoprotein in patients with neoplasms and non-neoplastic diseases. Int J Cancer. 1968;3:364–73.

    Article  PubMed  CAS  Google Scholar 

  15. Kitau MJ, Grint PC, Heath RB, Chard T. Serum alphafetoprotein levels in subjects infected with hepatitis B virus. J Med Virol. 1988;26:437–42.

    Article  PubMed  CAS  Google Scholar 

  16. Schefer H, Mattmann S, Joss RA. Hereditary persistence of alpha-fetoprotein. Case report and review of the literature. Ann Oncol. 1998;9:667–72.

    Article  PubMed  CAS  Google Scholar 

  17. Ronnen EA, Kondagunta GV, Bacik J, et al. Incidence of late-relapse germ cell tumor and outcome to salvage chemotherapy. J Clin Oncol. 2005;23(28):6999–7004.

    Article  PubMed  Google Scholar 

  18. George DW, Foster RS, Hromas RA, et al. Update on late relapse of germ cell tumor: a clinical and molecular analysis. J Clin Oncol. 2003;21(1):113–22.

    Article  PubMed  Google Scholar 

  19. Mukhtar S, Beatty J, Agrawal S, et al. Germ cell tumour: late recurrence after 43 years. Ann R Coll Surg Engl. 2011;93:e24–6.

    Article  PubMed  CAS  Google Scholar 

  20. • Dieckmann KP, Albers P, Classen J, et al. Late relapse of testicular germ cell neoplasms: a descriptive analysis of 122 cases. J Urol. 2005;173(3):824–9. A contemporary population based study of late relapse.

    Article  PubMed  Google Scholar 

  21. Oldenburg J, Alfsen GC, Waehre H, et al. Late recurrences of germ cell malignancies: a population-based experience over three decades. Br J Cancer. 2006;94:820–7.

    Article  PubMed  CAS  Google Scholar 

  22. Oldenburg J, Martin JM, Fosså SD. Late relapses of germ cell malignancies: incidence, management, and prognosis. J Clin Oncol. 2006;24:5503–11.

    Article  PubMed  Google Scholar 

  23. Gerl A, Clemm C, Schmeller N, et al. Late relapse of germ cell tumors after cisplatin-based chemotherapy. Ann Oncol. 1997;8(1):41–7.

    Article  PubMed  CAS  Google Scholar 

  24. Ravi R, Oliver RT, Ong J, et al. A single-centre observational study of surgery and late malignant events after chemotherapy for germ cell cancer. Br J Urol. 1997;80(4):647–52.

    Article  PubMed  CAS  Google Scholar 

  25. Kuczyk MA, Bokemeyer C, Kollmannsberger C, et al. Late relapse after treatment for nonseminomatous testicular germ cell tumors according to a single center based experience. World J Urol. 2004;22(1):55–9.

    Article  PubMed  CAS  Google Scholar 

  26. Michael H, Lucia J, Foster RS, et al. The pathology of late recurrence of testicular germ cell tumors. Am J Surg Pathol. 2000;24(2):257–73.

    Article  PubMed  CAS  Google Scholar 

  27. Shahidi M, Norman AR, Dearnaley DP, et al. Late recurrence in 1263 men with testicular germ cell tumors. Multivariate analysis of risk factors and implications for management. Cancer. 2002;95(3):520–30.

    Article  PubMed  Google Scholar 

  28. Beyer J, Albers P, Altena R, et al. Maintaining success, reducing treatment burden, focusing on survivorship: highlights from the third European consensus conference on diagnosis and treatment of germ-cell cancer. Ann Oncol. 2013;24:878–88.

    Article  PubMed  CAS  Google Scholar 

  29. Tandstad T, Smaaland R, Solberg A, et al. Management of seminomatous testicular cancer: a binational prospective population-based study from the Swedish norwegian testicular cancer study group. J Clin Oncol. 2011;29:719–25.

    Article  PubMed  Google Scholar 

  30. Jones WG, Fossa SD, Mead GM, et al. 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. 2005;23(6):1200–8.

    Article  PubMed  Google Scholar 

  31. Fossa SD, Horwich A, Russell JM, 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(4):1146–54.

    PubMed  CAS  Google Scholar 

  32. Mead GM, Fossa SD, Oliver RT, et al. Randomized trials in 2466 patients with stage I seminoma: patterns of relapse and follow-up. J Natl Cancer Inst. 2011;103:241–9.

    Article  PubMed  Google Scholar 

  33. Kollmannsberger C, Moore C, Chi KN, et al. Non-risk-adapted surveillance for patients with stage I nonseminomatous testicular germ-cell tumors: diminishing treatment-related morbidity while maintaining efficacy. Ann Oncol. 2010;21:1296–301.

    Article  PubMed  CAS  Google Scholar 

  34. Sturgeon JF, Moore MJ, Kakiashvili DM, et al. Non-risk-adapted surveillance in clinical stage I nonseminomatous germ cell tumors: the Princess Margaret Hospital's experience. Eur Urol. 2011;59:556–62.

    Article  PubMed  Google Scholar 

  35. Nolan L, Wheater M, Kirby J, et al. Late relapse (>2 years) on surveillance in stage I non-seminomatous germ cell tumours; predominant seminoma only histology. BJU Int. 2010;106:1648–51.

    Article  PubMed  Google Scholar 

  36. Tandstad T, Dahl O, Cohn-Cedermark G, et al. Risk-adapted treatment in clinical stage I nonseminomatous germ cell testicular cancer: the SWENOTECA management program. J Clin Oncol. 2009;27:2122–8.

    Article  PubMed  Google Scholar 

  37. Nicolai N, Miceli R, Necchi A, et al. Retroperitoneal lymph node dissection with no adjuvant chemotherapy in clinical stage I nonseminomatous germ cell tumours: long-term outcome and analysis of risk factors of recurrence. Eur Urol. 2010;58:912–8.

    Article  PubMed  Google Scholar 

  38. Kondagunta GV, Bacik J, Bajorin D, et al. Etoposide and cisplatin chemotherapy for metastatic good-risk germ cell tumors. J Clin Oncol. 2005;23(36):9290–4.

    Article  PubMed  CAS  Google Scholar 

  39. Ehrlich Y, Beck SDW, Ulbright TM, et al. Outcome analysis of patients with transformed teratoma to primitive neuroectodermal tumor. Ann Oncol. 2010;21:1846–50.

    Article  PubMed  CAS  Google Scholar 

  40. Loehrer Sr PJ, Hui S, Clark S, et al. Teratoma following cisplatin-based combination chemotherapy for nonseminomatous germ cell tumors: a clinicopathological correlation. J Urol. 1986;135(6):1183–9.

    PubMed  Google Scholar 

  41. Leibovitch I, Foster RS, Ulbright TM, et al. Adult primary pure teratoma of the testis. The Indiana experience. Cancer. 1995;75:2244–50.

    Article  PubMed  CAS  Google Scholar 

  42. Kernek KM, Ulbright TM, Zhang S, et al. Identical allelic losses in mature teratoma and other histologic components of malignant mixed germ cell tumors of the testis. Am J Pathol. 2003;163:2477–84.

    Article  PubMed  CAS  Google Scholar 

  43. van Echten J, van der Vloedt WS, van de Pol M, et al. Comparison of the chromosomal pattern of primary testicular nonseminomas and residual mature teratomas after chemotherapy. Cancer Genet Cytogenet. 1997;99:59–67.

    Article  PubMed  Google Scholar 

  44. Fizazi K, Tjulandin S, Salvioni R, et al. Viable malignant cells after primary chemotherapy for disseminated nonseminomatous germ cell tumors: prognostic factors and role of postsurgery chemotherapy results from an international study group. J Clin Oncol. 2001;19(10):2647–57.

    PubMed  CAS  Google Scholar 

  45. Sonneveld DJ, Sleijfer DT, Koops HS, et al. Mature teratoma identified after postchemotherapy surgery in patients with disseminated nonseminomatous testicular germ cell tumors: a plea for an aggressive surgical approach. Cancer. 1998;82(7):1343–51.

    Article  PubMed  CAS  Google Scholar 

  46. Hendry WF, Norman AR, Dearnaley DP, et al. Metastatic nonseminomatous germ cell tumors of the testis: Results of elective and salvage surgery for patients with residual retroperitoneal masses. Cancer. 2002;94:1668–76.

    Article  PubMed  Google Scholar 

  47. Debono DJ, Heilman DK, Einhorn LH, et al. Decision analysis for avoiding postchemotherapy surgery in patients with disseminated nonseminomatous germ cell tumors. J Clin Oncol. 1997;15:1455–64.

    PubMed  CAS  Google Scholar 

  48. Bosl GJ, Motzer RJ. Weighing risks and benefits of postchemotherapy retroperitoneal lymph node dissection: not so easy. J Clin Oncol. 2010;28:519–2.

    Article  PubMed  Google Scholar 

  49. Ehrlich Y, Brames MJ, Beck SD, et al. Long-term follow-up of cisplatin combination chemotherapy in patients with disseminated nonseminomatous germ cell tumors: Is a post-chemotherapy retroperitoneal lymph node dissection needed following complete remission? J Clin Oncol. 2010;28:531–6.

    Article  PubMed  CAS  Google Scholar 

  50. •• Sharp DS, Carver BS, Eggener SE, et al. Clinical outcome and predictors of survival in late relapse of germ cell tumor. J Clin Oncol. 2008;26:5524–9. Contemporary late relapse series from MSKCC emphasizing the importance of complete surgical excision of late relapse masses.

    Article  PubMed  Google Scholar 

  51. Schmoll HJ. SouchonR, Krege S, et al.: European consensus on diagnosis and treatment of germ cell cancer: a report of the European Germ Cell Cancer Consensus Group (EGCCCG). Ann Oncol. 2004;15(9):1377–99.

    Article  PubMed  CAS  Google Scholar 

  52. Geldart TR, Gale J, McKendrick J, et al. Late relapse of metastatic testicular nonseminomatous germ cell cancer: surgery is needed for cure. BJU Int. 2006;98:353–8.

    Article  PubMed  Google Scholar 

  53. •• Lorch A, Rick O, Wündisch T, et al. High dose chemotherapy as salvage treatment for unresectable late relapse germ cell tumors. J Urol. 2010;184:168–73. Late relapse not suitable for surgery is chemoresistant and response to high dose chemotherapy is usually not durable.

    Article  PubMed  Google Scholar 

  54. Aparicio J. Garcia del Muro X, Maroto P, et al.: Multicenter study evaluating a dual policy of postorchiectomy surveillance and selective adjuvant single-agent carboplatin for patients with clinical stage I seminoma. Ann Oncol. 2003;14(6):867–72.

    Article  PubMed  CAS  Google Scholar 

  55. Oliver RT, Mason MD, Mead GM, et al. Radiotherapy versus single-dose carboplatin in adjuvant treatment of stage I seminoma: a randomised trial. Lancet. 2005;366(9482):293–300.

    Article  PubMed  CAS  Google Scholar 

  56. Muramaki M, Hara I, Miyake H, et al. Clinical study of six cases showing late relapse of germ cell tumors. Int J Urol. 2005;12(9):855–8.

    Article  PubMed  Google Scholar 

  57. Rao PH, Houldsworth J, Palanisamy N, et al. Chromosomal amplification is associated with cisplatin resistance of human male germ cell tumors. Cancer Res. 1998;58(19):4260–3.

    PubMed  CAS  Google Scholar 

  58. Madani A, Kemmer K, Sweeney C, et al. Expression of KIT and epidermal growth factor receptor in chemotherapy refractory non-seminomatous germ-cell tumors. Ann Oncol. 2003;14(6):873–80.

    Article  PubMed  CAS  Google Scholar 

  59. Mayer F, Wermann H, Albers P, et al. Histopathological and molecular features of late relapses in non-seminomas. BJU Int. 2011;107:936–43.

    Article  PubMed  Google Scholar 

  60. Sugimura J, Foster RS, Cummings OW, et al. Gene expression profiling of early- and late-relapse nonseminomatous germ cell tumor and primitive neuroectodermal tumor of the testis. Clin Cancer Res. 2004;10(7):2368–78.

    Article  PubMed  CAS  Google Scholar 

Download references

Compliance with Ethics Guidelines

Conflict of Interest

Dr. Yaron Ehrlich, Dr. Eli Rosenbaum, and Dr. Jack Baniel reported no potential conflicts of interest relevant to this article.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Author information

Authors and Affiliations

  1. Department of Urology and Oncology, Rabin Medical Center, Petach Tikva, 49100, Israel

    Yaron Ehrlich, Eli Rosenbaum & Jack Baniel

  2. Sackler Medical School, Tel Aviv University, P.O. Box 39040, Tel Aviv, 69978, Israel

    Yaron Ehrlich, Eli Rosenbaum & Jack Baniel

Authors
  1. Yaron Ehrlich
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Eli Rosenbaum
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jack Baniel
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yaron Ehrlich.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ehrlich, Y., Rosenbaum, E. & Baniel, J. Late Relapse of Testis Cancer. Curr Urol Rep 14, 518–524 (2013). https://doi.org/10.1007/s11934-013-0355-4

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11934-013-0355-4

Keywords

Search

Navigation