Initial risk-stratified treatment for advanced testicular germ cell tumors
- Timothy D Gilligan, MD
Timothy D Gilligan, MD
- Associate Professor of Medicine
- Cleveland Clinic Lerner College of Medicine
- Vice-Chair for Education
- Cleveland Clinic Taussig Cancer Institute
- Director of Coaching, Center for Excellence in Healthcare Communication
- Cleveland Clinic
- Philip W Kantoff, MD
Philip W Kantoff, MD
- Section Editor — Testicular Cancer
- Chairman of Medicine
- Memorial Sloan Kettering Cancer Center
Testicular cancers are one of the most curable solid neoplasms. In the United States, the five-year survival rate is over 95 percent, and approximately 400 deaths from testicular cancer are seen per year . (See "Clinical manifestations, diagnosis, and staging of testicular germ cell tumors" and "Epidemiology of and risk factors for testicular germ cell tumors".)
Factors that have likely contributed to the declining mortality rate for testicular cancer include the development and use of effective chemotherapy, a trend toward earlier stage disease at presentation, and an increasing proportion of tumors that are pure seminomas .
The risk stratification of advanced testicular germ cell tumors (GCTs) and initial management based on risk will be reviewed here. The clinical manifestations, diagnosis, and staging, and an overview of the general approach to treatment of testicular GCTs are reviewed separately. In addition, chemotherapy protocols used in the management of GCTs are also covered separately.
- Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA Cancer J Clin 2017; 67:7.
- Powles TB, Bhardwa J, Shamash J, et al. The changing presentation of germ cell tumours of the testis between 1983 and 2002. BJU Int 2005; 95:1197.
- 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; 15:594.
- Brimo F, Srigley JR, Ryan CJ, et al. Testis. In: AJCC Cancer Staging Manual, 8th, Amin MB. (Ed), Springer, New York 2017. p.727.
- Testis. In: AJCC Cancer Staging Handbook, 6th, Green FL, Page DL, Fleming ID, et al (Eds), Springer Verlag, New York 2002. p.347.
- Klepp O, Flodgren P, Maartman-Moe 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.
- Feldman DR, Bosl GJ, Sheinfeld J, Motzer RJ. Medical treatment of advanced testicular cancer. JAMA 2008; 299:672.
- Einhorn LH, Williams SD, Loehrer PJ, 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.
- Saxman SB, Finch D, Gonin R, Einhorn LH. Long-term follow-up of a phase III study of three versus four cycles of bleomycin, etoposide, and cisplatin in favorable-prognosis germ-cell tumors: the Indian University experience. J Clin Oncol 1998; 16:702.
- de Wit R, Roberts JT, Wilkinson PM, et al. 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 2001; 19:1629.
- Toner GC, Stockler MR, Boyer MJ, et al. Comparison of two standard chemotherapy regimens for good-prognosis germ-cell tumours: a randomised trial. Australian and New Zealand Germ Cell Trial Group. Lancet 2001; 357:739.
- 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.
- 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; 15:1837.
- 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; 18:917.
- 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; 11:598.
- 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; 15:1844.
- Bokemeyer C, Köhrmann O, Tischler J, 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.
- 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; 316:1435.
- Massard C, Plantade A, Gross-Goupil M, et al. Poor prognosis nonseminomatous germ-cell tumours (NSGCTs): should chemotherapy doses be reduced at first cycle to prevent acute respiratory distress syndrome in patients with multiple lung metastases? Ann Oncol 2010; 21:1585.
- Nichols CR, Catalano PJ, Crawford ED, et al. Randomized comparison of cisplatin and etoposide and either bleomycin or ifosfamide in treatment of advanced disseminated germ cell tumors: an Eastern Cooperative Oncology Group, Southwest Oncology Group, and Cancer and Leukemia Group B Study. J Clin Oncol 1998; 16:1287.
- 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; 97:1869.
- 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; 78:828.
- Culine S, Kramar A, Théodore C, et al. Randomized trial comparing bleomycin/etoposide/cisplatin with alternating cisplatin/cyclophosphamide/doxorubicin and vinblastine/bleomycin regimens of chemotherapy for patients with intermediate- and poor-risk metastatic nonseminomatous germ cell tumors: Genito-Urinary Group of the French Federation of Cancer Centers Trial T93MP. J Clin Oncol 2008; 26:421.
- Kaye SB, Mead GM, Fossa S, 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.
- Fosså SD, Paluchowska B, Horwich A, et al. Intensive induction chemotherapy with C-BOP/BEP for intermediate- and poor-risk metastatic germ cell tumours (EORTC trial 30948). Br J Cancer 2005; 93:1209.
- 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; 25:247.
- 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; 22:1054.
- Fizazi K, Pagliaro L, Laplanche A, et al. Personalised chemotherapy based on tumour marker decline in poor prognosis germ-cell tumours (GETUG 13): a phase 3, multicentre, randomised trial. Lancet Oncol 2014; 15:1442.
- Fizazi K, Flechon A, Le Teuff G, et al. Mature results of the GETUG 13 phase III trial in poor-prognosis germ-cell tumors (GCT). Abstract 4504, 2016 American Society Of Clinical Oncology meeting.
- Gilligan T. Testicular cancer survivorship. Hematol Oncol Clin North Am 2011; 25:627.
- van Dijk MR, Steyerberg EW, Habbema JD. Survival of non-seminomatous germ cell cancer patients according to the IGCC classification: An update based on meta-analysis. Eur J Cancer 2006; 42:820.
- Ko JJ, Bernard B, Tran B, et al. Conditional Survival of Patients With Metastatic Testicular Germ Cell Tumors Treated With First-Line Curative Therapy. J Clin Oncol 2016; 34:714.
- Kier MG, Lauritsen J, Mortensen MS, et al. Prognostic Factors and Treatment Results After Bleomycin, Etoposide, and Cisplatin in Germ Cell Cancer: A Population-based Study. Eur Urol 2017; 71:290.
- GENERAL APPROACH TO ADVANCED DISEASE
- DEFINITION OF RISK
- Nonseminomatous germ cell tumors
- - Good risk
- - Intermediate risk
- - Poor risk
- TREATMENT OPTIONS
- Good risk
- - Bleomycin, etoposide, and cisplatin
- - Etoposide and cisplatin
- - Decreased efficacy with carboplatin
- - Chemotherapy-related toxicity
- Intermediate- and poor-risk advanced disease
- - BEP
- - VIP
- Chemotherapy-related toxicity
- MONITORING RESPONSE TO TREATMENT
- Nonseminomatous germ cell tumors
- Long-term prognosis
- SUMMARY AND RECOMMENDATIONS