Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-78c5997874-94fs2 Total loading time: 0 Render date: 2024-11-09T08:44:51.085Z Has data issue: false hasContentIssue false

42 - The Biology and Treatment of Metastatic Testicular Cancer

from PART II - CLINICAL RESEARCH

Published online by Cambridge University Press:  05 June 2012

By
M. Houman Fekrazad ,
Robert Hromas  and
Richard Lauer
Edited by
David Lyden ,
Danny R. Welch  and
Bethan Psaila
M. Houman Fekrazad
Affiliation:
University of New Mexico Health Science Center, United States
Robert Hromas
Affiliation:
University of New Mexico Health Science Center, United States
Richard Lauer
Affiliation:
University of New Mexico Health Science Center, United States
David Lyden
Affiliation:
Weill Cornell Medical College, New York
Danny R. Welch
Affiliation:
Weill Cornell Medical College, New York
Bethan Psaila
Affiliation:
Imperial College of Medicine, London
Get access

Summary

Despite remarkable advances in the past three decades, metastatic testicular cancer is still a leading cause of cancer death in young men. It is not clear why some patients are cured and others are not, and new treatments are still needed for this disease. Testicular cancer is not one disease but rather has multiple histologic subtypes. A better understanding of the biology of these different histologic subtypes of testicular cancer, and the use of a multidisciplinary approach, have significantly contributed to improving how we currently approach a young patient with testicular cancer. In addition, DNA microarray analysis has provided insight into the molecular pathobiology of the types of testicular cancer. Genetic and epigenetic alterations are two other important factors that could play a role in the behavior of the types of testicular cancer. Because of the multipotential nature of these tumors, patients with metastatic testicular cancer can present with different clinical scenarios, requiring different treatments. In this chapter, we discuss the biology and the treatment options for patients with metastatic testicular cancer based on tumor type and prognostic categories. Future directions and unmet needs for patients suffering from this disease are also discussed.

EPIDEMIOLOGY OF TESTICULAR CANCER

Human testicular cancers result from malignant transformation of premeiotic or early meiotic testicular germ cells. These cancers can demonstrate differentiation of all three germinal layers. Testicular cancers are the most common malignant neoplasm of males 15 to 34 years of age and a major cause of death from cancer in this age group.

Type
Chapter
Information
Cancer Metastasis
Biologic Basis and Therapeutics
 , pp. 465 - 474
Publisher: Cambridge University Press
Print publication year: 2011

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Garner, MJ, Turner, MC, Ghadirian, P, Krewski, D (2005) Epidemiology of testicular cancer: an overview. Int J Cancer. 116(3): 331–39.CrossRefGoogle ScholarPubMed
Jemal, A, Siegel, R, Ward, E et al. (2008) Cancer statistics, 2008. CA Cancer J Clin. 58: 71–96.CrossRefGoogle ScholarPubMed
Holmes, LJ, Escalante, C, Garrison, O et al. (2008) Testicular cancer incidence trends in the USA (1975–2004): plateau or shifting racial paradigm?Public Health. 122(9): 862–72.CrossRefGoogle ScholarPubMed
Parkin, DM, Bray, F, Ferlay, J, Pisani, P. (2001) Estimating the world cancer burden: Globocan 2000. Int J Cancer. 94(2):153–6.CrossRefGoogle ScholarPubMed
Fosså, SD, Chen, J, Schonfeld, SJ et al. (2005) Risk of contralateral testicular cancer: a population-based study of 29,515 U.S. men. J Natl Cancer Inst. 97(14): 1056–66.CrossRefGoogle ScholarPubMed
Kanto, S, Hiramatsu, M, Suzuki, K et al. (2004) Risk factors in past histories and familial episodes related to development of testicular germ cell tumor. Int J Urol. 11: 640.CrossRefGoogle ScholarPubMed
Prener, A, Engholm, G, Jensen, OM (1996) Genital anomalies and risk for testicular cancer in Danish men. Epidemiology 7: 14.CrossRefGoogle ScholarPubMed
Wood, HM, Elder, JS (2009) Cryptorchidism and testicular cancer: separating fact from fiction. J Urol. 81(2): 452–61.CrossRefGoogle Scholar
Pettersson, A, Richiardi, L, Nordenskjold, A et al. (2007) Age at surgery for undescended testis and risk of testicular cancer. N Engl J Med. 356(18): 1835–41.CrossRefGoogle ScholarPubMed
Aguirre, D, Nieto, K, Lazos, M et al. (2006) Extragonadal germ cell tumors are often associated with Klinefelter syndrome. Hum Pathol. 37(4): 477–80.CrossRefGoogle ScholarPubMed
Dexeus, FH, Logothetis, CJ, Chong, C et al. (1998) Genetic abnormalities in men with germ cell tumours. J Urol. 140: 80–84.CrossRefGoogle Scholar
Ulbright, TM (2005) Germ cell tumors of the gonads: a selective review emphasizing problems in differential diagnosis, newly appreciated, and controversial issues. Mod Pathol. 18 Suppl 2: S61–79.CrossRefGoogle ScholarPubMed
Houldsworth, J, Korkola, JE, Bosl, GJ, Chaganti, RS (2006) Biology and genetics of adult male germ cell tumors. J Clin Oncol. 24(35): 5512–8.CrossRefGoogle ScholarPubMed
Almstrup, K, Hoei-Hansen, CE, Wirkner, U et al. (2004) Embryonic stem cell-like features of testicular carcinoma in situ revealed by genome-wide gene expression profiling. Cancer Res. 64: 4736–43.CrossRefGoogle ScholarPubMed
Almstrup, K, Hoei-Hansen, CE, Nielsen, JE et al. (2005) Genome-wide gene expression profiling of testicular carcinoma in situ progression into overt tumours. Br J Cancer. 92: 1934–41.CrossRefGoogle ScholarPubMed
Cheng, L, Sung, MT, Cossu-Rocca, P et al. (2007) OCT4: biological functions and clinical applications as a marker of germ cell neoplasia. J Pathol. 211(1): 1–9.CrossRefGoogle ScholarPubMed
Forman, D, Oliver, RT, Brett, AR et al. (1992) Familial testicular cancer: a report of the UK family register, estimation of risk and an HLA class 1 sib-pair analysis. Br J Cancer. 65: 255–62.CrossRefGoogle ScholarPubMed
der Maase, H, Rørth, M, Walbom-Jørgensen, S et al. (1986) Carcinoma in situ of contralateral testis in patients with testicular germ cell cancer: study of 27 cases in 500 patients. Br Med J (Clin Res Ed). 293(6559): 1398–401.CrossRefGoogle Scholar
Atkin, NB, Baker, MC (1982) Specific chromosome change, i(12p), in testicular tumours? (Letter)Lancet. 320: 1349.CrossRefGoogle Scholar
Rodriguez, E, Mathew, S, Mukherjee, AB et al. (1992) Analysis of chromosome 12 aneuploidy in interphase cells from human male germ cell tumors by fluorescence in situ hybridization. Genes Chromosomes Cancer. 5: 21–29.CrossRefGoogle ScholarPubMed
Murty, VV, Renault, B, Falk, CT et al. (1996) Physical mapping of a commonly deleted region, the site of a candidate tumor suppressor gene, at 12q22 in human male germ cell tumors. Genomics 35: 562–70.CrossRefGoogle ScholarPubMed
Clark, AT, Rodriguez, RT, Bodnar, MS et al. (2004) Human STELLAR, NANOG, and GDF3 genes are expressed in pluripotent cells and map to chromosome 12p13, a hotspot for teratocarcinoma. Stem Cells. 22: 169–79.CrossRefGoogle ScholarPubMed
Nathanson, KL, Kanetsky, PA, Hawes, R et al. (2005) The Y deletion gr/gr and susceptibility to testicular germ cell tumor. Am Hum Genet. 77: 1034–43.CrossRefGoogle Scholar
Riou, G, Barrois, M, Prost, S et al. (1995) The p53 and mdm-2 genes in human testicular germ-cell tumors. Mol Carcinog. 12(3): 124–31.CrossRefGoogle ScholarPubMed
Baltaci, S, Orhan, D, Türkölmez, K et al. (2001) P53, bcl-2 and bax immunoreactivity as predictors of response and outcome after chemotherapy for metastatic germ cell testicular tumours. BJU Int. 87(7): 661–6.CrossRefGoogle ScholarPubMed
Tian, Q, Frierson, HF Jr, Krystal, GW et al. (1999) Activating c-kit gene mutations in human germ cell tumors. Am J Pathol 154: 1643–7.CrossRefGoogle ScholarPubMed
Devouassoux-Shisheboran, M, Mauduit, C, Tabone, E et al. (2003) Growth regulatory factors and signalling proteins in testicular germ cell tumours. APMIS. 111(1): 212–24.CrossRefGoogle ScholarPubMed
Sariola, H, Meng, X (2003) GDNF-induced seminomatous tumours in mouse–an experimental model for human seminomas?APMIS. 111(1): 192–6; discussion 196.CrossRefGoogle Scholar
Bernstein, BE, Mikkelsen, TS, Xie, X et al. (2006) A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell. 125: 315–26.CrossRefGoogle ScholarPubMed
Batata, MA, Chu, FC, Hilaris, BS et al. (1982) Therapy and prognosis of testicular carcinomas in relation to TNM classification. Int J Radiat Oncol Biol Phys. 8(8): 1287–93.CrossRefGoogle ScholarPubMed
,International Germ Cell Cancer Collaborative Group. (1997) International Germ Cell Consensus Classification: a prognostic factor-based staging system for metastatic germ cell cancers. J Clin Oncol. 15(2): 594–603.CrossRefGoogle Scholar
Toner, GC, Geller, NL, Lin, SY, et al. (1991) Extragonadal and poor risk nonseminomatous germ cell tumors. Survival and prognostic features. Cancer. 67(8): 2049–57.3.0.CO;2-H>CrossRefGoogle ScholarPubMed
Nichols, CR, Saxman, S, Williams, SD et al. (1990) Primary mediastinal nonseminomatous germ cell tumors. A modern single institution experience. Cancer. 65(7): 1641–6.3.0.CO;2-U>CrossRefGoogle ScholarPubMed
Hartmann, JT, Nichols, CR, Droz, JP et al. (2002) Prognostic variables for response and outcome in patients with extragonadal germ-cell tumors. Ann Oncol. 13: 1017–28 (EBM III).CrossRefGoogle ScholarPubMed
Warde, P, Specht, L, Horwich, A et al. (2002) Prognostic factors for relapse in stage I seminoma managed by surveillance. J Clin Oncol. 20: 4448–52.CrossRefGoogle Scholar
Albers, P, Siener, R, Kliesch, S et al. (2003) Risk factors for relapse in clinical stage I nonseminomatous testicular germ cell tumors: results of the German Testicular Cancer Study Group trial. J Clin Oncol. 21: 1505–12.CrossRefGoogle Scholar
Böhlen, D, Borner, M, Sonntag, RW et al. (1999) Longterm results following adjuvant chemotherapy in patients with clinical stage I testicular nonseminomatous malignant germ cell tumors with high risk factors. J Urol. 161: 1148–52.CrossRefGoogle Scholar
Pont, J, Höltl, W, Kosak, D et al. (1990) Risk-adapted treatment choice in stage I nonseminomatous testicular germ cell cancer by regarding vascular invasion in the primary tumor: a prospective trial. J Clin Oncol. 8: 16–19.CrossRefGoogle Scholar
Saxman, SB, Finch, D, Gonin, R, Einhorn, LH (1998) 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 Indiana University experience. J Clin Oncol. 16(2): 702–6.CrossRefGoogle Scholar
Motzer, RJ, Nichols, CJ, Margolin, KA et al. (2007) 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. 25(3): 247–56.CrossRefGoogle ScholarPubMed
Kondagunta, GV, Bacik, J, Donadio, A et al. (2005) Combination of paclitaxel, ifosfamide, and cisplatin is an effective second-line therapy for patients with relapsed testicular germ cell tumors. J Clin Oncol. 23(27): 6549–55.CrossRefGoogle ScholarPubMed
Fizazi, K, Oldenburg, J, Dunant, A et al. (2008) Assessing prognosis and optimizing treatment in patients with postchemotherapy viable nonseminomatous germ-cell tumors (NSGCT): results of the sCR2 international study. Ann Oncol. 19(2): 259–64. Epub 2007 Nov 27.CrossRefGoogle ScholarPubMed
Albers, P, Weissbach, L, Krege, S et al. (2004) Prediction of necrosis after chemotherapy of advanced germ cell tumors: results of a prospective multicenter trial of the German Testicular Cancer Study Group. J Urol. 171(5): 1835–8.CrossRefGoogle ScholarPubMed
Spiess, PE, Brown, GA, Liu, P et al. (2006) Predictors of outcome in patients undergoing postchemotherapy retroperitoneal lymph node dissection for testicular cancer. Cancer. 107(7): 1483–90.CrossRefGoogle ScholarPubMed
Albers, P, Ganz, A, Hannig, E, Miersch, WD, Muller, SC (2000) Salvage surgery of chemorefractory germ cell tumors with elevated tumor markers. J Urol. 164(2): 381–4.CrossRefGoogle ScholarPubMed
Hartmann, JT, Candelaria, M, Kuczyk, MA, Schmoll, HJ, Bokemeyer, C (1997) 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. 33(6): 843–7.CrossRefGoogle ScholarPubMed
Hartmann, JT, Rick, O, Oechsle, K et al. (2005) Role of postchemotherapy surgery in the management of patients with liver metastases from germ cell tumors. Ann Surg. 242(2): 260–6.CrossRefGoogle ScholarPubMed
McGuire, MS, Rabbani, F, Mohseni, H et al. The role of thoracotomy in managing postchemotherapy residual thoracic masses in patients with nonseminomatous germ cell tumours. BJU Int. 2003;91(6): 469–473.CrossRefGoogle ScholarPubMed
Fizazi, K, Tjulandin, S, Salvioni, R, et al. (2001) 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. 19(10): 2647–57.CrossRefGoogle ScholarPubMed
Santis, M, Becherer, A, Bokemeyer, C et al. (2004) 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. 22(6): 1034–9.CrossRefGoogle ScholarPubMed
Gels, ME, Hoekstra, HJ, Sleijfer, DTh et al. (1995) Detection of recurrence in patients with clinical stage I nonseminomatous testicular germ cell tumors and consequences for further follow-up: A single center 10-year experience. J Clin Oncol. 13(5): 1188–94.CrossRefGoogle Scholar
Brenner, DJ, Hall, EJ (2007) Computed tomography – an increasing source of radiation exposure. N Engl J Med. 357(22): 2277–84.CrossRefGoogle ScholarPubMed
Albers, P, Siener, R, Kliesch, S et al. (2003) Risk factors for relapse in clinical stage I nonseminomatous testicular germ cell tumors: Results of the German testicular cancer study group trial. J Clin Oncol. 21(8): 1505–12.CrossRefGoogle Scholar
Vergouwe, Y, Steyerberg, EW, Eijkermans, MJC et al. (2003) Predictors of occult metastasis in clinical stage I nonseminoma: a systematic review. J Clin Oncol. 21(22): 4092–9.CrossRefGoogle Scholar
Donohue, JP, Thronhill, JA, Foster, RS, et al. Retroperitoneal lymphadenectomy for clinical stage A testis cancer (1965–1989): Modifications of technique and impact on ejaculation. J Urol 149: 237–243, 1993.CrossRefGoogle Scholar
Pont, J, Albrecht, W, Postner, G et al. (1996) Adjuvant chemotherapy for high-risk clinical stage I nonseminomatous testicular germ cell cancer: long–term results of a prospective trial. J Clin Oncol. 14(2): 441–8.CrossRefGoogle Scholar
Cullen, MH, Stenning, SP, Parkinson, MC et al. (1996) Short-course adjuvant chemotherapy in high-risk stage I nonseminomatous germ cell tumors of the testis: A medical research council report. J Clin Oncol. 14(4): 1106–13.CrossRefGoogle Scholar
Toner, GC, Stockler, MR, Boyer, MJ et al. (2001) (Australian and New Zealand Germ Cell Trial Group) Comparison of two standard chemotherapy regimens for good-prognosis germ-cell tumours: a randomized trial. Lancet. 357(9258): 739–4.CrossRefGoogle Scholar
Loehrer, PJ, Lauer, R, Roth, BJ et al. (1988) Salvage therapy in recurrent germ cell cancer: ifosfamide and cisplatin plus either vinblastine or etoposide. Ann Intern Med. 109(7): 540–6.CrossRefGoogle ScholarPubMed
Nichols, CR, Williams, SD, Loehrer, PJ et al. (1991) 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. 9(7): 1163–72.CrossRefGoogle Scholar
Kaye, SB, Mead, GM, Fossa, S et al. (1998) 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. 16(2): 692–701.CrossRefGoogle ScholarPubMed
Lewis, CR, Fossa, SD, Mead, G et al. (1991) BOP/VIP – a new platinum-intensive chemotherapy regimen for poor prognosis germ cell tumours. Ann Oncol. 2(3): 203–11.CrossRefGoogle ScholarPubMed
Culine, S, Kramar, A, Theodore, C et al. (2008) 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. 26(3): 421–7.CrossRefGoogle ScholarPubMed
Hernandez, CH Sr (2006) Role of XPA, ERCC1, mtTFA on the survival of patients with metastatic germ cell tumors of testis treated with cisplatin. J Clin Oncol. 24(35): 5512–8.Google Scholar
Koul, S, Mcklernana, IM, Narayan, G et al. (2004) Role of promoter hypermethylation in cisplatin treatment response of male germ cell tumors. Mol Cancer. 3: 16.CrossRefGoogle ScholarPubMed
Mead, GM, Cullen, MH, Huddart, R et al. (2005). A Phase II trial of TIP (paclitaxel, ifosfamide and cisplatin) given as a second-line (post-BEP) salvage chemotherapy for patients with metastatic germ cell cancer: A Medical Research Council trial. Br J Cancer. 93(2): 178–84.CrossRefGoogle ScholarPubMed
Einhorn, LH, Williams, SD, Chamness, A et al. (2007) High-dose chemotherapy and stem-cell rescue for metastatic germ-cell tumors. N Engl J Med. 357(4): 340–8.CrossRefGoogle ScholarPubMed
Lorch, A, Kollmannsberger, C, Hartmann, JT et al. (2007) A prospective randomized multicenter trial of the German testicular cancer study group. J Clin Oncol. 25(19): 2778–84.CrossRefGoogle ScholarPubMed
Beyer, J, Kramar, A, Mandanas, R et al. (1996) High-dose chemotherapy as salvage treatment in germ cell tumors: A multivariate analysis of prognostic variables. J Clin Oncol. 14(10): 2638–45.CrossRefGoogle ScholarPubMed
Hinton, S, Catalano, P, Einhorn, LH et al. (2002) Phase II study of paclitaxel plus gemcitabine in refractory germ cell tumors (E9897): A trial of the Eastern Cooperative Oncology Group. J Clin Oncol. 20(7): 1859–63.CrossRefGoogle ScholarPubMed
Bedano, PM, Brames, MJ, Williams, SD et al. (2006) Phase II study of cisplatin plus epirubicin salvage chemotherapy in refractory germ cell tumors. J Clin Oncol. 24(34): 5403–7.CrossRefGoogle ScholarPubMed
Kollmannsberger, C, Beyer, J, Liersch, R et al. (2004) 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. 22(1): 108–14.CrossRefGoogle ScholarPubMed
Fenner, MH, Beutel, G, Grünwald, V (2008) Targeted therapies for patients with germ cell tumors. Exp Opin Invest Drugs. 17(4): 511–22.CrossRefGoogle ScholarPubMed
Dahl, AA, Haaland, CF, Mykletun, A et al. (2005) Study of anxiety disorder and depression in long-term survivors of testicular cancer. J Clin Oncol. 23(10): 2389–95.CrossRefGoogle ScholarPubMed
Lampe, H, Horwich, A, Norman, A et al. (1997) Fertility after chemotherapy for testicular germ cell cancers. J Clin Oncol. 15(1): 239–45.CrossRefGoogle ScholarPubMed
Belt-Dusebout, AW, Wit, R, Gietema, JA et al. (2006) Treatment-specific risks of second malignancies and cardiovascular disease in 5-year survivors of testicular cancer. J Clin Oncol. 25(28): 4370–8.CrossRefGoogle Scholar
Vaughn, DJ, Palmer, SC, Carver, JR. (2008) Cardiovascular risk in long-term survivors of testicular cancer. Cancer. 112(9): 1949–53.CrossRefGoogle ScholarPubMed

Save book to Kindle

To save this book to your Kindle, first ensure [email protected] is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×