Korean J Urol.  2013 Jan;54(1):2-10.

Current Management of Testicular Cancer

• Shin YS
• Kim HJ

Abstract

Germ cell tumors (GCTs) of the testis are rare, but are the most common cancer in young men. GCTs may consist of one predominant histologic pattern or may represent a mixture of multiple histologic types. For treatment purposes, two broad categories are recognized: 1) pure seminoma and 2) others, which together are termed nonseminomatous GCTs (NSGCTs). In general, seminoma tends to be less aggressive, to be diagnosed at an earlier stage, and to spread predictably along lymphatic channels to the retroperitoneum before spreading hematogenously to the lung or other organs. Compared with NSGCTs, seminoma is exquisitely sensitive to radiation therapy and platinum-based chemotherapy. NSGCTs are usually mixed tumors and teratoma often exists at the sites of metastasis with other GCT elements; cure often requires chemotherapy to kill the chemosensitive-components and surgery to remove the teratomatous components. The main factors contributing to excellent cure rates of GCTs are careful staging at diagnosis; adequate early treatment using chemotherapeutic combinations, with or without radiotherapy and surgery; and very strict follow-up and salvage therapy. We review several clinical studies and summarize the current trends in the management of GCTs.

Keyword

Neoplasms; Testis; Therapeutics

MeSH Terms

Follow-Up Studies
Humans
Lung
Male
Neoplasm Metastasis
Neoplasms, Germ Cell and Embryonal
Salvage Therapy
Seminoma
Teratoma
Testicular Neoplasms
Testis

Reference

1. Schottenfeld D, Warshauer ME, Sherlock S, Zauber AG, Leder M, Payne R. The epidemiology of testicular cancer in young adults. Am J Epidemiol. 1980. 112:232–246.

2. Huyghe E, Matsuda T, Thonneau P. Increasing incidence of testicular cancer worldwide: a review. J Urol. 2003. 170:5–11.

3. Bosl GJ, Motzer RJ. Testicular germ-cell cancer. N Engl J Med. 1997. 337:242–253.

4. Forman D, Oliver RT, Brett AR, Marsh SG, Moses JH, Bodmer JG, et al. Familial testicular cancer: a report of the UK family register, estimation of risk and an HLA class 1 sib-pair analysis. Br J Cancer. 1992. 65:255–262.

5. Westergaard T, Olsen JH, Frisch M, Kroman N, Nielsen JW, Melbye M. Cancer risk in fathers and brothers of testicular cancer patients in Denmark. A population-based study. Int J Cancer. 1996. 66:627–631.

6. Dieckmann KP, Loy V, Buttner P. Prevalence of bilateral testicular germ cell tumours and early detection based on contralateral testicular intra-epithelial neoplasia. Br J Urol. 1993. 71:340–345.

7. Germa-Lluch JR, Garcia del Muro X, Maroto P, Paz-Ares L, Arranz JA, Guma J, et al. Clinical pattern and therapeutic results achieved in 1490 patients with germ-cell tumours of the testis: the experience of the Spanish Germ-Cell Cancer Group (GG). Eur Urol. 2002. 42:553–562.

8. Skakkebaek NE. Possible carcinoma-in-situ of the testis. Lancet. 1972. 2:516–517.

9. Klein EA. Tumor markers in testis cancer. Urol Clin North Am. 1993. 20:67–73.

10. Wanderas EH, Tretli S, Fossa SD. Trends in incidence of testicular cancer in Norway 1955-1992. Eur J Cancer. 1995. 31A:2044–2048.

11. Peyret C. Tumeurs du testicule. Synthèse et recommandations en onco-urologie. Prog Urol. 1993. 2:60–64.

12. Martin JM, Panzarella T, Zwahlen DR, Chung P, Warde P. Evidence-based guidelines for following stage 1 seminoma. Cancer. 2007. 109:2248–2256.

13. Ellis JH, Bies JR, Kopecky KK, Klatte EC, Rowland RG, Donohue JP. Comparison of NMR and CT imaging in the evaluation of metastatic retroperitoneal lymphadenopathy from testicular carcinoma. J Comput Assist Tomogr. 1984. 8:709–719.

14. Thurnher S, Hricak H, Carroll PR, Pobiel RS, Filly RA. Imaging the testis: comparison between MR imaging and US. Radiology. 1988. 167:631–636.

15. Mattrey RF. Magnetic resonance imaging of the scrotum. Semin Ultrasound CT MR. 1991. 12:95–108.

16. Heidenreich A, Weissbach L, Holtl W, Albers P, Kliesch S, Kohrmann KU, et al. Organ sparing surgery for malignant germ cell tumor of the testis. J Urol. 2001. 166:2161–2165.

17. Sobin LH, Gospodarowicz MK, Wittekind C, editors. TNM classification of malignant tumours. 2009. 7th ed. Chichester (UK): Wiley-Blackwell.

18. Zagars GK. Horwich A, editor. Management of stage I seminoma: radiotherapy. Testicular cancer: investigation and management. 1999. 2nd ed. London: Chapman & Hall Medical;99.

19. Klepp O, Flodgren P, Maartman-Moe H, Lindholm CE, Unsgaard B, Teigum H, et al. Early clinical stages (CS1, CS1Mk+ and CS2A) of non-seminomatous testis cancer. Value of pre- and post-orchiectomy serum tumor marker information in prediction of retroperitoneal lymph node metastases. Swedish-Norwegian Testicular Cancer Project (SWENOTECA). Ann Oncol. 1990. 1:281–288.

20. International Germ Cell Cancer Collaborative Group. International Germ Cell Consensus Classification: a prognostic factor-based staging system for metastatic germ cell cancers. J Clin Oncol. 1997. 15:594–603.

21. Warde P, Specht L, Horwich A, Oliver T, Panzarella T, Gospodarowicz M, et al. Prognostic factors for relapse in stage I seminoma managed by surveillance: a pooled analysis. J Clin Oncol. 2002. 20:4448–4452.

22. Bokemeyer C, Kuczyk MA, Serth J, Hartmann JT, Schmoll HJ, Jonas U, et al. Treatment of clinical stage I testicular cancer and a possible role for new biological prognostic parameters. J Cancer Res Clin Oncol. 1996. 122:575–584.

23. Albers P, Siener R, Kliesch S, Weissbach L, Krege S, Sparwasser C, et al. Risk factors for relapse in clinical stage I non-seminomatous testicular germ cell tumors: results of the German Testicular Cancer Study Group Trial. J Clin Oncol. 2003. 21:1505–1512.

24. Zagars GK, Ballo MT, Lee AK, Strom SS. Mortality after cure of testicular seminoma. J Clin Oncol. 2004. 22:640–647.

25. van Leeuwen FE, Stiggelbout AM, van den Belt-Dusebout AW, Noyon R, Eliel MR, van Kerkhoff EH, et al. Second cancer risk following testicular cancer: a follow-up study of 1,909 patients. J Clin Oncol. 1993. 11:415–424.

26. van den Belt-Dusebout AW, de Wit R, Gietema JA, Horenblas S, Louwman MW, Ribot JG, et al. Treatment-specific risks of second malignancies and cardiovascular disease in 5-year survivors of testicular cancer. J Clin Oncol. 2007. 25:4370–4378.

27. van den Belt-Dusebout AW, Nuver J, de Wit R, Gietema JA, ten Bokkel Huinink WW, Rodrigus PT, et al. Long-term risk of cardiovascular disease in 5-year survivors of testicular cancer. J Clin Oncol. 2006. 24:467–475.

28. Travis LB, Fossa SD, Schonfeld SJ, McMaster ML, Lynch CF, Storm H, et al. Second cancers among 40,576 testicular cancer patients: focus on long-term survivors. J Natl Cancer Inst. 2005. 97:1354–1365.

29. 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. 21:1513–1523.

30. Oliver RT, Mason MD, Mead GM, von der Maase H, Rustin GJ, Joffe JK, et al. Radiotherapy versus single-dose carboplatin in adjuvant treatment of stage I seminoma: a randomised trial. Lancet. 2005. 366:293–300.

31. Aparicio J, Germa JR, Garcia del Muro X, Maroto P, Arranz JA, Saenz A, et al. Risk-adapted management for patients with clinical stage I seminoma: the Second Spanish Germ Cell Cancer Cooperative Group study. J Clin Oncol. 2005. 23:8717–8723.

32. Tolan S, Vesprini D, Jewett MA, Warde PR, O'Malley M, Panzarella T, et al. No role for routine chest radiography in stage I seminoma surveillance. Eur Urol. 2010. 57:474–479.

33. Santoni R, Barbera F, Bertoni F, De Stefani A, Livi L, Paiar F, et al. Stage I seminoma of the testis: a bi-institutional retrospective analysis of patients treated with radiation therapy only. BJU Int. 2003. 92:47–52.

34. Jones WG, Fossa SD, Mead GM, Roberts JT, Sokal M, Horwich A, 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 (ISRCTN 18525328). J Clin Oncol. 2005. 23:1200–1208.

35. Fossa SD, Horwich A, Russell JM, Roberts JT, Cullen MH, Hodson NJ, et al. Medical Research Council Testicular Tumor Working Group. Optimal planning target volume for stage I testicular seminoma: a Medical Research Council randomized trial. J Clin Oncol. 1999. 17:1146.

36. Chung PW, Gospodarowicz MK, Panzarella T, Jewett MA, Tew-George B, et al. Stage II testicular seminoma: patterns of recurrence and outcome of treatment. Eur Urol. 2004. 45:754–759.

37. Gilbert DC, Vanas NJ, Beesley S, Bloomfield D, Money-Kyrle J, Norman A, et al. Treating IIA/B seminoma with combination carboplatin and radiotherapy. J Clin Oncol. 2009. 27:2101–2102.

38. 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. 99:533–544.

39. Mosharafa AA, Foster RS, Leibovich BC, Bihrle R, Johnson C, Donohue JP. Is post-chemotherapy resection of seminomatous elements associated with higher acute morbidity? J Urol. 2003. 169:2126–2128.

40. Herr HW, Sheinfeld J, Puc HS, Heelan R, Bajorin DF, Mencel P, et al. Surgery for a post-chemotherapy residual mass in seminoma. J Urol. 1997. 157:860–862.

41. Steyerberg EW, Keizer HJ, Fossa SD, Sleijfer DT, Toner GC, Schraffordt Koops H, et al. Prediction of residual retroperitoneal mass histology after chemotherapy for metastatic nonseminomatous germ cell tumor: multivariate analysis of individual patient data from six study groups. J Clin Oncol. 1995. 13:1177–1187.

42. Oldenburg J, Alfsen GC, Lien HH, Aass N, Waehre H, Fossa SD. Postchemotherapy retroperitoneal surgery remains necessary in patients with nonseminomatous testicular cancer and minimal residual tumor masses. J Clin Oncol. 2003. 21:3310–3317.

43. Stephenson AJ, Bosl GJ, Motzer RJ, Bajorin DF, Stasi JP, Sheinfeld J. Nonrandomized comparison of primary chemotherapy and retroperitoneal lymph node dissection for clinical stage IIA and IIB nonseminomatous germ cell testicular cancer. J Clin Oncol. 2007. 25:5597–5602.

44. Toner GC, Neerhut GJ, Schwarz MA, Thursfield VJ, Sandeman TF, Giles GG, et al. The management of testicular cancer in Victoria, 1988-1993. Urology Study Committee of the Victorian Co-operative Oncology Group. Med J Aust. 2001. 174:328–331.

45. Abratt RP, Pontin AR, Barnes RD, Reddi BV. Adjuvant chemotherapy for stage I non-seminomatous testicular cancer. S Afr Med J. 1994. 84:605–607.

46. Amato RJ, Ro JY, Ayala AG, Swanson DA. Risk-adapted treatment for patients with clinical stage I nonseminomatous germ cell tumor of the testis. Urology. 2004. 63:144–148.

47. Bohlen D, Borner M, Sonntag RW, Fey MF, Studer UE. Long-term results following adjuvant chemotherapy in patients with clinical stage I testicular nonseminomatous malignant germ cell tumors with high risk factors. J Urol. 1999. 161:1148–1152.

48. Chevreau C, Mazerolles C, Soulie M, Gaspard MH, Mourey L, Bujan L, et al. Long-term efficacy of two cycles of BEP regimen in high-risk stage I nonseminomatous testicular germ cell tumors with embryonal carcinoma and/or vascular invasion. Eur Urol. 2004. 46:209–214.

49. 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. 14:1106–1113.

50. Dearnaley DP, Fossa SD, Kaye SB, Cullen MH, Harland SJ, Sokal MP, et al. Adjuvant bleomycin, vincristine and cisplatin (BOP) for high-risk stage I non-seminomatous germ cell tumours: a prospective trial (MRC TE17). Br J Cancer. 2005. 92:2107–2113.

51. Oliver RT, Ong J, Shamash J, Ravi R, Nagund V, Harper P, et al. Long-term follow-up of Anglian Germ Cell Cancer Group surveillance versus patients with Stage 1 nonseminoma treated with adjuvant chemotherapy. Urology. 2004. 63:556–561.

52. Donohue JP, Foster RS. Retroperitoneal lymphadenectomy in staging and treatment. The development of nerve-sparing techniques. Urol Clin North Am. 1998. 25:461–468.

53. Eggener SE, Carver BS, Sharp DS, Motzer RJ, Bosl GJ, Sheinfeld J. Incidence of disease outside modified retroperitoneal lymph node dissection templates in clinical stage I or IIA nonseminomatous germ cell testicular cancer. J Urol. 2007. 177:937–942.

54. Jewett MA, Kong YS, Goldberg SD, Sturgeon JF, Thomas GM, Alison RE, et al. Retroperitoneal lymphadenectomy for testis tumor with nerve sparing for ejaculation. J Urol. 1988. 139:1220–1224.

55. Ondrus D, Hornak M, Matoska J, Kausitz J, Belan V. Primary chemotherapy in the management of low stage (IIA and IIB) non-seminomatous germ cell testicular tumours. Int Urol Nephrol. 1992. 24:299–304.

56. Pont J, Albrecht W, Postner G, Sellner F, Angel K, Holtl W. Adjuvant chemotherapy for high-risk clinical stage I non-seminomatous testicular germ cell cancer: long-term results of a prospective trial. J Clin Oncol. 1996. 14:441–448.

57. Davis BE, Herr HW, Fair WR, Bosl GJ. The management of patients with nonseminomatous germ cell tumors of the testis with serologic disease only after orchiectomy. J Urol. 1994. 152:111–113.

58. Saxman SB, Nichols CR, Foster RS, Messemer JE, Donohue JP, Einhorn LH. The management of patients with clinical stage I nonseminomatous testicular tumors and persistently elevated serologic markers. J Urol. 1996. 155:587–589.

59. Culine S, Theodore C, Terrier-Lacombe MJ, Droz JP. Primary chemotherapy in patients with nonseminomatous germ cell tumors of the testis and biological disease only after orchiectomy. J Urol. 1996. 155:1296–1298.

60. Lerner SE, Mann BS, Blute ML, Richardson RL, Zincke H. Primary chemotherapy for clinical stage II nonseminomatous germ cell testicular tumors: selection criteria and long-term results. Mayo Clin Proc. 1995. 70:821–828.

61. Socinski MA, Garnick MB, Stomper PC, Fung CY, Richie JP. Stage II nonseminomatous germ cell tumors of the testis: an analysis of treatment options in patients with low volume retroperitoneal disease. J Urol. 1988. 140:1437–1441.

62. Einhorn LH, Williams SD, Loehrer PJ, Birch R, Drasga R, Omura G, et al. Evaluation of optimal duration of chemotherapy in favorable-prognosis disseminated germ cell tumors: a Southeastern Cancer Study Group protocol. J Clin Oncol. 1989. 7:387–391.

63. Bokemeyer C, Kohrmann O, Tischler J, Weissbach L, Rath U, Haupt A, et al. A randomized trial of cisplatin, etoposide and bleomycin (PEB) versus carboplatin, etoposide and bleomycin (CEB) for patients with 'good-risk' metastatic non-seminomatous germ cell tumors. Ann Oncol. 1996. 7:1015–1021.

64. 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. 15:1844–1852.

65. 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. 83:1623–1629.

66. de Wit R, Stoter G, Sleijfer DT, Neijt JP, ten Bokkel Huinink WW, de Prijck L, et al. Four cycles of BEP vs four cycles of VIP in patients with intermediate-prognosis metastatic testicular non-seminoma: a randomized study of the EORTC Genitourinary Tract Cancer Cooperative Group. European Organization for Research and Treatment of Cancer. Br J Cancer. 1998. 78:828–832.

67. Nichols CR, Williams SD, Loehrer PJ, Greco FA, Crawford ED, Weetlaufer J, et al. Randomized study of cisplatin dose intensity in poor-risk germ cell tumors: a Southeastern Cancer Study Group and Southwest Oncology Group protocol. J Clin Oncol. 1991. 9:1163–1172.

68. Kaye SB, Mead GM, Fossa S, Cullen M, de Wit R, Bodrogi I, et al. Intensive induction-sequential chemotherapy with BOP/VIP-B compared with treatment with BEP/EP for poor-prognosis metastatic nonseminomatous germ cell tumor: a Randomized Medical Research Council/European Organization for Research and Treatment of Cancer study. J Clin Oncol. 1998. 16:692–701.