Seminal Articles—Germ Cell Tumors

Based on our expert's review, here are the must-read articles for every oncologist about patients with germ cell tumors.

General Review

1. Journal of Clinical Oncology: Issue on Genitourinary Cancers. J Clin Oncol. 2006;24(35):5479-5621.

2. Bosl GJ, Motzer RJ. Testicular germ-cell cancer. N Engl J Med. 1997;337(4):242–253.

3. Kondagunta GV, Motzer RJ. Chemotherapy for advanced germ cell tumors. J Clin Oncol. 2006;24(35):5493-5502.

4. Feldman DR, Bosl GJ, Sheinfeld J, et al. Medical treatment of advanced testicular cancer. JAMA. 2008;299(6):672-684. Free

Epidemiology/Risk Factors

5. Lutke-Holzik MF, Rapley EA, Hoekstra HJ, et al. Genetic predisposition to testicular germ-cell tumours. Lancet Oncol. 2004;5(6):363-371.

6. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin. 2012;62(1):10-29. Free

7. Siegel R, DeSantis C, Virgo K, et al. Cancer treatment and survivorship statistics, 2012. CA Cancer J Clin. 2012;62(4):220-241. Free

8. Daling JR, Doody DR, Sun X, et al. Association of marijuana use and the incidence of testicular germ cell tumors. Cancer. 2009;115(6):1215-1223. Free

9. Trabert B, Sigurdson AJ, Sweeney AM, et al. Marijuana use and testicular germ cell tumors. Cancer. 2011;117(4):848-853. Free

Underlying Biology

10. Houldsworth J, Korkola JE, Bosl GJ, et al. Biology and genetics of adult male germ cell tumors. J Clin Oncol. 2006;24(35):5512-5518.

11. Reuter VE. Origins and molecular biology of testicular germ cell tumors. Mod Pathol. 2005;18(Suppl 2):S51-60. Free

Staging/Prognosis

12. Garnick MB. Spurious rise in human chorionic gonadotropin induced by marihuana in patients with testicular cancer. N Engl J Med. 1980;303(20):1177.

13. International Germ Cell Consensus Classification: a prognostic factor-based staging system for metastatic germ cell cancers. International Germ Cell Cancer Collaborative Group. J Clin Oncol. 1997;15(2):594-603.

14. Testis. In: Edge SB, Byrd DR, Compton CC, et al, eds. AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer; 2010:469-478.

Early-Stage Seminomatous Germ Cell Tumors

15. Fosså 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.

16. Jones WG, Fosså 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 Origanisation for the Research and Treatment of Cancer Trial 30942 (ISRCTN18525328). J Clin Oncol. 2005;23(6):1200-1208.

17. Oliver RT, Mead GM, Rustin GJ, et al. Randomized trial of carboplatin versus radiotherapy for stage I seminoma: mature results on relapse and contralateral testis cancer rates in MRC TE19/EORTC 30982 study (ISRCTN27163214). J Clin Oncol. 2011;29(8):957-962.

18. Bosl GJ, Patil S. Carboplatin in clinical stage I seminoma: too much and too little at the same time. J Clin Oncol. 2011;29(8):949-952.

19. Garcia-del-Muro X, Maroto P, Gumá J, et al. Chemotherapy as an alternative to radiotherapy in the treatment of stage IIA and IIB testicular seminoma: a Spanish Germ Cell Cancer Group Study. J Clin Oncol. 2008;26(33):5416-5421.

Early-Stage Non-Seminomatous Germ Cell Tumors

20. Motzer RJ, Sheinfeld J, Mazumdar M, et al. Etoposide and cisplatin adjuvant therapy for patients with pathologic stage II germ cell tumors. J Clin Oncol. 1995;13(11):2700-2704.

21. Kondagunta GV, Motzer RJ. Adjuvant chemotherapy for stage II nonseminomatous germ-cell tumors. Urol Clin North Am. 2002;34(2):179-185.

22. Albers P, Siener R, Krege S, et al. Randomized phase III trial comparing retroperitoneal lymph node dissection with one course of bleomycin and etoposide plus cisplatin chemotherapy in the adjuvant treatment of clinical stage I Nonseminomatous testicular germ cell tumors: AUO trial AH 01/94 by the German Testicular Cancer Study Group. J Clin Oncol. 2008;26(18):2966-2972.

23. Stephenson AJ, Bosl GJ, Motzer RJ, et al. 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(35):5597-5602.

Advanced Disease (Nonseminoma and Seminoma)

Good Risk

24. Bosl GJ, Geller NL, Bajorin D, et al. A randomized trial of etoposide + cisplatin versus vinblastine + bleomycin + cisplatin + cyclophosphamide + dactinomycin in patients with good-prognosis germ cell tumors. J Clin Oncol. 1988;6(8):1231-1238.

25. Bajorin DF, Sarosdy MF, Pfister DG, et al. Randomized trial of etoposide and cisplatin versus etoposide and carboplatin in patients with good-risk germ cell tumors: a multiinstitutional study. J Clin Oncol. 1993;11(4):598-606.

26. Loehrer PJ Sr, Johnson D, Elson P, et al. Importance of bleomycin in favorable-prognosis disseminated germ cell tumors: an Eastern Cooperative Oncology Group trial. J Clin Oncol. 1995;13(2):470-476.

27. de Wit R, Stoter G, Kaye SB et al. Importance of bleomycin in combination chemotherapy for good-prognosis testicular nonseminoma: a randomized study of the European Organization for Research and Treatment of Cancer Genitourinary Tract Cancer Cooperative Group. J Clin Oncol. 1997;15(5):1837-1843.

28. Horwich A, Sleijfer DT, Fosså SD, 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(5):1844-1852.

29. Grimison PS, Stockler MR, Thomson DB, et al. Comparison of two standard chemotherapy regimens for good-prognosis germ cell tumors: updated analysis of a randomized trial. J Natl Cancer Inst. 2010;102:1253. Free

30. 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):9290-9294.

31. Culine S, Kerbrat P, Kramar A, et al. Refining the optimal chemotherapy regimen for good-risk metastatic nonseminomatous germ-cell tumors: a randomized trial of the Genito-Urinary Group of the French Federation of Cancer Centers (GETUG T93BP). Ann Oncol. 2007;18(5):917-924. Free

Intermediate/Poor Risk

32. 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):1435-1440.

33. Nichols CR, Williams SD, Loehrer PJ, et al. Randomized study of cisplatin dose intensity of poor-risk germ cell tumors: a Southeastern Cancer Study Group and Southwest Oncology Group protocol. J Clin Oncol. 1991;9(7):1163-1172.

34. De Wit R, Stoter G, Sleijfer DT, et al. Four cycles of BEP versus an alternating regime of PVB and BEP in patients with poor-prognosis metastatic testicular non-seminoma; a randomized study of the EORTC Genitourinary Tract Cancer Cooperative Group. Br J Cancer. 1995;71(6):1311-1314. Free

35. de Wit R, Stoter G, Sleijfer DT, 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(6):828-832. Free

36. Kaye SB, Mead GM, Fosså SD, 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(2):692-701.

37. Hinton S, Catalano PJ, Einhorn LH, et al. Cisplatin, etoposide and either bleomycin or ifosfamide in the treatment of disseminated germ cell tumors: final analysis of an intergroup trial. Cancer. 2003;97(8):1869-1875. Free

38. Motzer RJ, Nichols CJ, Margolin KA, et al. Phase III randomized trial of conventional-dose chemotherapy with or without high-dose chemotherapy and autologous hematopoietic stem-cell rescue as first-line treatment for patients with poor-prognosis metastatic germ cell tumors. J Clin Oncol. 2007;25(3):247-256.

39. Droz JP, Kramar A, Biron P, et al. Failure of high-dose cyclophosphamide and etoposide combined with double-dose cisplatin and bone marrow support in patients with high-volume metastatic nonseminomatous germ-cell tumours: mature results of a randomised trial. Eur Urol. 2007;51(3):739-746.

40. Daugaard G, Skoneczna I, Aass N, et al. A randomized phase III study comparing standard dose BEP with sequential high-dose cisplatin, etoposide, and ifosfamide (VIP) plus stem-cell support in males with poor-prognosis germ-cell cancer. An intergroup study of EORTC, GTCSG, and Grupo Germinal (EORTC 30974). Ann Oncol. 2011;22(5):1054-1061. Free

41. Collette L, Sylvester RJ, Stenning SP, et al. Impact of the treating institution on survival of patients with poor-prognosis metastatic nonseminoma. European Organization for Research and Treatment of Cancer Genito-Urinary Tract Cancer Collaborative Group and the Medical Research Council Testicular Cancer Working Party. J Natl Cancer Inst. 1999;91(10):839-846. Free

42. Donadio AC, Motzer RJ, Bajorin DF, et al. Chemotherapy for teratoma with malignant transformation. J Clin Oncol. 2003;21(23):4285-4291.

Post-Chemotherapy Surgery

43. Beck SD, Foster RS, Bihrle R, et al. Teratoma in the orchiectomy specimen and volume of metastasis are predictors of retroperitoneal teratoma in post-chemotherapy nonseminomatous testis cancer. J Urol. 2002;168(4 Pt 1):1402-1404.

44. Oldenburg J, Alfsen GC, Lien HH, et al. Postchemotherapy retroperitoneal surgery remains necessary in patients with nonseminomatous testicular cancer and minimal residual tumor masses. J Clin Oncol. 2003;21(17):3310-3317.

45. De Santis M, Becherer A, Bokemeyer C, et al. 2-18fluoro-deoxy-D-glucose positron emission tomography is a reliable predictor for viable tumor in postchemotherapy seminoma: an update of the prospective multicentric SEMPET trial. J Clin Oncol. 2004;22(6):1034-1039.

46. Carver BS, Shayegan B, Serio A, et al. Long-term clinical outcome after postchemotherapy retroperitoneal lymph node dissection in men with residual teratoma. J Clin Oncol. 2007;25(9):1033-1037.

47. Eggener SE, Carver BS, Loeb S, et al. Pathologic findings and clinical outcome of patients undergoing retroperitoneal lymph node dissection after multiple chemotherapy regimens for metastatic testicular germ cell tumors. Cancer. 2007;109(3):528-535. Free

48. Bosl GJ, Motzer RJ. Weighing risks and benefits of postchemotherapy retroperitoneal lymph node dissection: not so easy. J Clin Oncol. 2010;28(4):519-521.

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 postchemotherapy retroperitoneal lymph node dissection needed after complete remission? J Clin Oncol. 2010;28(4):531-536.

50. Hartmann JT, Candelaria M, Kuczyk MA, et al. Comparison of histological results from the resection of residual masses at different sites after chemotherapy for metastatic non-seminomatous germ cell tumours. Eur J Cancer. 1997;33(6):843-847.

51. Fox EP, Weathers TD, Williams SD, et al. Outcome analysis for patients with persistent nonteratomatous germ cell tumor in post chemotherapy retroperitoneal lymph node dissections. J Clin Oncol. 2003;11(7):1294-1299.

52. Mosharafa AA, Foster RS, Leibovich BC, et al. Is post-chemotherapy resection of seminomatous elements associated with higher acute morbidity? J Urol. 2003;169(6):2126-2128.

Relapsed-Disease/Salvage Therapy

53. Motzer RJ, Geller NL, Tan CC, et al. Salvage chemotherapy for patients with germ cell tumors. The Memorial Sloan-Kettering Cancer Center experience (1979-1989). Cancer. 1991;67(5):1305-1310.

54. Loehrer PJ, Gonin R, Nichols CR, et al. Vinblastine plus ifosfamide plus cisplatin as initial salvage therapy in recurrent germ cell tumor. J Clin Oncol. 1998;16(7):2500-2504.

55. Kollmannsberger C, Beyer J, Liersch R, et al. Combination chemotherapy with gemcitabine plus oxaliplatin in patients with intensively pretreated or refractory germ cell cancer: a study of the German Testicular Cancer Study Group. J Clin Oncol. 2004;22(1):108-114.

56. 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.

57. Kondagunta GV, Bacik J, Donadio D, et al. Combination of paclitaxel, ifosfamide, and cisplatin is an effective second-line therapy for patients with relapsed testicular germ cell tumors. J Clin Oncol. 2005;23(27):6549-6555.

58. Oldenburg J, Martin JM, Fosså SD. Late relapses of germ cell malignancies: incidence management, and prognosis. J Clin Oncol. 2006;24(35):5503-5511.

59. Einhorn LH, Brames MJ, Juliar B, et al. Phase II study of paclitaxel plus gemcitabine salvage chemotherapy for germ cell tumors after progression following high-dose chemotherapy with tandem transplant. J Clin Oncol. 2007;25(5):513-516.

60. Einhorn LH, Williams SD, Chamness A, et al. High-dose chemotherapy and stem-cell rescue for metastatic germ-cell tumors. N Engl J Med. 2007;357(4):340-348. Free

61. 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(34):5524-5529. Free

62. Feldman DR, Sheinfeld J, Bajorin DF, et al. TI-CE high dose chemotherapy for patients with previously treated germ cell tumors. J Clin Oncol. 2010;28(10):1706-1713.

63. Pico JL, Rosti G, Kramar A, et al. 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. 2005;16(7):1152-1159. Free

64. International Prognostic Factors Study Group, Lorch A, Beyer J, Bascoul-Mollevi C, et al. Prognostic factors in patients with metastatic germ cell tumors who experienced treatment failure with cisplatin-based first-line chemotherapy. J Clin Oncol. 2010;28(33):4906-4911.

65. Lorch A, Kollmannsberger C, Hartmann JT, et al. Single versus sequential high-dose chemotherapy in patients with relapsed or refractory germ cell tumors: a prospective randomized multicenter trial of the German Testicular Cancer Study Group. J Clin Oncol. 2007;25(19):2778-2784.

66. Lorch A, Bascoul-Mollevi C, Kramar A, et al. Conventional-dose versus high-dose chemotherapy as first salvage treatment in male patients with metastatic germ cell tumors: evidence from a large international database. J Clin Oncol. 2011;29(16):2178-2184.

67. Kondagunta GV, Sheinfeld J, Motzer RJ. Recommendations of follow-up after treatment of germ cell tumors. Semin Oncol. 2003;30(3):382-389.

Survivorship

68. Hartmann JT, Albrecht C, Schmoll HJ, et al. Long-term effects on sexual function and fertility after treatment of testicular cancer. Br J Cancer. 1999;80(5-6):801-807. Free

69. Nuver J, Smit AJ, van der Meer J, et al. Acute chemotherapy-induced cardiovascular changes in patients with testicular cancer. J Clin Oncol. 2005;23(36):9130-9137.

70. Meinardi MT, Gietema JA, van der Graaf WT, et al. Cardiovascular morbidity in long-term survivors of metastatic testicular cancer. J Clin Oncol. 2000;18(8):1725-1732.

71. van den Belt-Dusebout AW, Nuver J, de Wit R, et al. Long-term risk of cardiovascular disease in 5-year survivors of testicular cancer. J Clin Oncol. 2006;24(3):467-475.

72. Nuver J, Smit AJ, Wolffenbuttel BH, et al. The metabolic syndrome and disturbances in hormone levels in long-term survivors of disseminated testicular cancer. J Clin Oncol. 2005;23(16):3718-3725.

73. Travis LB, Fosså SD, Schonfeld SJ, et al. Second cancers among 40,576 testicular cancer patients: focus on long-term survivors. J Natl Cancer Inst. 2005;97(18):1354-1365. Free

74. van den Belt-Dusebout AW, de Wit R, Gietema JA, et al. Treatment-specific risks of second malignancies and cardiovascular disease in 5-year survivors of testicular cancer. J Clin Oncol. 2007;25(28):4370-4378.

75. Dahl AA, Haaland CF, Mykletun A, et al. Study of anxiety disorder and depression in long-term survivors of testicular cancer. J Clin Oncol. 2005;23(10):2389-2395.