Testicular Cancer, Version 2.2020, NCCN Clinical Practice Guidelines in Oncology

Authors:
Timothy Gilligan Case Comprehensive Cancer Center/University Hospitals Seidman Cancer Center and Cleveland Clinic Taussig Cancer Institute;

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Daniel W. Lin University of Washington/Seattle Cancer Care Alliance;

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Rahul Aggarwal UCSF Helen Diller Family Comprehensive Cancer Center;

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David Chism Vanderbilt-Ingram Cancer Center;

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Nicholas Cost University of Colorado Cancer Center;

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Ithaar H. Derweesh UC San Diego Moores Cancer Center;

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Hamid Emamekhoo University of Wisconsin Carbone Cancer Center;

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Darren R. Feldman Memorial Sloan Kettering Cancer Center;

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Daniel M. Geynisman Fox Chase Cancer Center;

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Steven L. Hancock Stanford Cancer Institute;

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Chad LaGrange Fred & Pamela Buffett Cancer Center;

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Ellis G. Levine Roswell Park Cancer Institute;

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Thomas Longo Duke Cancer Institute;

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Will Lowrance Huntsman Cancer Institute at the University of Utah;

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Bradley McGregor Dana-Farber/Brigham and Women's Cancer Center;

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Paul Monk The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute;

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Joel Picus Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine;

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Phillip Pierorazio The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins;

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Soroush Rais-Bahrami O'Neal Comprehensive Cancer Center at UAB;

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Philip Saylor Massachusetts General Hospital Cancer Center;

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Kanishka Sircar The University of Texas MD Anderson Cancer Center;

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David C. Smith University of Michigan Rogel Cancer Center;

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Katherine Tzou Mayo Clinic Cancer Center;

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Daniel Vaena St. Jude Children’s Research Hospital/The University of Tennessee Health Science Center;

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David Vaughn Abramson Cancer Center at the University of Pennsylvania;

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Kosj Yamoah Moffitt Cancer Center;

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Jonathan Yamzon City of Hope National Medical Center; and

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Alyse Johnson-Chilla National Comprehensive Cancer Network.

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Jennifer Keller National Comprehensive Cancer Network.

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Lenora A. Pluchino National Comprehensive Cancer Network.

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Testicular cancer is relatively uncommon and accounts for <1% of all male tumors. However, it is the most common solid tumor in men between the ages of 20 and 34 years, and the global incidence has been steadily rising over the past several decades. Several risk factors for testicular cancer have been identified, including personal or family history of testicular cancer and cryptorchidism. Testicular germ cell tumors (GCTs) comprise 95% of malignant tumors arising in the testes and are categorized into 2 main histologic subtypes: seminoma and nonseminoma. Although nonseminoma is the more clinically aggressive tumor subtype, 5-year survival rates exceed 70% with current treatment options, even in patients with advanced or metastatic disease. Radical inguinal orchiectomy is the primary treatment for most patients with testicular GCTs. Postorchiectomy management is dictated by stage, histology, and risk classification; treatment options for nonseminoma include surveillance, systemic therapy, and nerve-sparing retroperitoneal lymph node dissection. Although rarely occurring, prognosis for patients with brain metastases remains poor, with >50% of patients dying within 1 year of diagnosis. This selection from the NCCN Guidelines for Testicular Cancer focuses on recommendations for the management of adult patients with nonseminomatous GCTs.

Individual Disclosures for the NCCN Testicular Cancer Panel

TU1

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  • 1.

    Cancer Statistics Factsheets SEER. Testicular Cancer. National Cancer Institute, Bethesda, MD. 2019. Available at: https://seer.cancer.gov/statfacts/html/testis.html. Accessed September 5, 2019.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2.

    Sarıcı H, Telli O, Eroğlu M. Bilateral testicular germ cell tumors. Turk J Urol 2013;39:249252.

  • 3.

    Huyghe E, Matsuda T, Thonneau P. Increasing incidence of testicular cancer worldwide: a review. J Urol 2003;170:511.

  • 4.

    Shanmugalingam T, Soultati A, Chowdhury S, et al.. Global incidence and outcome of testicular cancer. Clin Epidemiol 2013;5:417427.

  • 5.

    Verhoeven RH, Gondos A, Janssen-Heijnen ML, et al.. Testicular cancer in Europe and the USA: survival still rising among older patients. Ann Oncol 2013;24:508513.

  • 6.

    Chia VM, Quraishi SM, Devesa SS, et al.. International trends in the incidence of testicular cancer, 1973-2002. Cancer Epidemiol Biomarkers Prev 2010;19:11511159.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7.

    Pishgar F, Haj-Mirzaian A, Ebrahimi H, et al.. Global, regional and national burden of testicular cancer, 1990-2016: results from the Global Burden of Disease Study 2016. BJU Int 2019;124:386394.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8.

    Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin 2019;69:734.

  • 9.

    Turnbull C, Rahman N. Genome-wide association studies provide new insights into the genetic basis of testicular germ-cell tumour. Int J Androl 2011;34:e86e97.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10.

    Greene MH, Kratz CP, Mai PL, et al.. Familial testicular germ cell tumors in adults: 2010 summary of genetic risk factors and clinical phenotype. Endocr Relat Cancer 2010;17:R109R121.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11.

    Vasdev N, Moon A, Thorpe AC. Classification, epidemiology and therapies for testicular germ cell tumours. Int J Dev Biol 2013;57:133139.

  • 12.

    Amin MB, Edge SB, Greene F, et al.., editors. AJCC Cancer Staging Manual, 8th Ed. New York, NY: Springer International Publishing; 2017. https://doi.org/10.1007/978-3-319-40618-3

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13.

    Gilligan TD, Seidenfeld J, Basch EM, et al.. American Society of Clinical Oncology Clinical Practice Guideline on uses of serum tumor markers in adult males with germ cell tumors. J Clin Oncol 2010;28:33883404.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14.

    Ferraro S, Trevisiol C, Gion M, et al.. Human chorionic gonadotropin assays for testicular tumors: closing the gap between clinical and laboratory practice. Clin Chem 2018;64:270278.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15.

    Lempiäinen A, Hotakainen K, Blomqvist C, et al.. Increased human chorionic gonadotropin due to hypogonadism after treatment of a testicular seminoma. Clin Chem 2007;53:15601561.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16.

    Morris MJ, Bosl GJ. Recognizing abnormal marker results that do not reflect disease in patients with germ cell tumors. J Urol 2000;163:796801.

  • 17.

    Trojan A, Joller-Jemelka H, Stahel RA, et al.. False-positive human serum chorionic gonadotropin in a patient with a history of germ cell cancer. Oncology 2004;66:336338.

  • 18.

    Ballieux BE, Weijl NI, Gelderblom H, et al.. False-positive serum human chorionic gonadotropin (HCG) in a male patient with a malignant germ cell tumor of the testis: a case report and review of the literature. Oncologist 2008;13:11491154.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19.

    Nazeer T, Ro JY, Amato RJ, et al.. Histologically pure seminoma with elevated alpha-fetoprotein: a clinicopathologic study of ten cases. Oncol Rep 1998;5:14251429.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20.

    Kundu SD, Carver BS, Sheinfeld J. Retroperitoneal histologic findings of patients with elevated serum alpha-fetoprotein and pure seminoma at orchiectomy. Urology 2011;78:844847.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21.

    Salem M, Gilligan T. Serum tumor markers and their utilization in the management of germ-cell tumors in adult males. Expert Rev Anticancer Ther 2011;11:14.

  • 22.

    Kim W, Rosen MA, Langer JE, et al.. US MR imaging correlation in pathologic conditions of the scrotum. Radiographics 2007;27:12391253.

  • 23.

    Jones RH, Vasey PA. Part I: testicular cancer--management of early disease. Lancet Oncol 2003;4:730737.

  • 24.

    Dieckmann KP, Anheuser P, Schmidt S, et al.. Testicular prostheses in patients with testicular cancer - acceptance rate and patient satisfaction. BMC Urol 2015;15:16.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25.

    Robinson R, Tait CD, Clarke NW, et al.. Is it safe to insert a testicular prosthesis at the time of radical orchidectomy for testis cancer: an audit of 904 men undergoing radical orchidectomy. BJU Int 2016;117:249252.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26.

    Yossepowitch O, Aviv D, Wainchwaig L, et al.. Testicular prostheses for testis cancer survivors: patient perspectives and predictors of long-term satisfaction. J Urol 2011;186:22492252.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27.

    Fosså SD, Chen J, Schonfeld SJ, et al.. Risk of contralateral testicular cancer: a population-based study of 29,515 U.S. men. J Natl Cancer Inst 2005;97:10561066.

  • 28.

    Ragni G, Somigliana E, Restelli L, et al.. Sperm banking and rate of assisted reproduction treatment: insights from a 15-year cryopreservation program for male cancer patients. Cancer 2003;97:16241629.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29.

    Saito K, Suzuki K, Iwasaki A, et al.. Sperm cryopreservation before cancer chemotherapy helps in the emotional battle against cancer. Cancer 2005;104:521524.

  • 30.

    Brydøy M, Fosså SD, Klepp O, et al.. Paternity following treatment for testicular cancer. J Natl Cancer Inst 2005;97:15801588.

  • 31.

    Huyghe E, Matsuda T, Daudin M, et al.. Fertility after testicular cancer treatments: results of a large multicenter study. Cancer 2004;100:732737.

  • 32.

    Paner GP, Stadler WM, Hansel DE, et al.. Updates in the eighth edition of the tumor-node-metastasis staging classification for urologic cancers. Eur Urol 2018;73:560569.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 33.

    Yilmaz A, Cheng T, Zhang J, et al.. Testicular hilum and vascular invasion predict advanced clinical stage in nonseminomatous germ cell tumors. Mod Pathol 2013;26:579586.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 34.

    Trevino KE, Esmaeili-Shandiz A, Saeed O, et al.. Pathological risk factors for higher clinical stage in testicular seminomas. Histopathology 2018;73:741747.

  • 35.

    Tandstad T, Ståhl O, Håkansson U, et al.. One course of adjuvant BEP in clinical stage I nonseminoma mature and expanded results from the SWENOTECA group. Ann Oncol 2014;25:21672172.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 36.

    Ernst DS, Brasher P, Venner PM, et al.. Compliance and outcome of patients with stage 1 non-seminomatous germ cell tumors (NSGCT) managed with surveillance programs in seven Canadian centres. Can J Urol 2005;12:25752580.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 37.

    Lago-Hernandez CA, Feldman H, O’Donnell E, et al.. A refined risk stratification scheme for clinical stage 1 NSGCT based on evaluation of both embryonal predominance and lymphovascular invasion. Ann Oncol 2015;26:13961401.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 38.

    Kobayashi K, Saito T, Kitamura Y, et al.. Oncological outcomes in patients with stage I testicular seminoma and nonseminoma: pathological risk factors for relapse and feasibility of surveillance after orchiectomy. Diagn Pathol 2013;8:57.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 39.

    Soper MS, Hastings JR, Cosmatos HA, et al.. Observation versus adjuvant radiation or chemotherapy in the management of stage I seminoma: clinical outcomes and prognostic factors for relapse in a large US cohort. Am J Clin Oncol 2014;37:356359.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 40.

    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;59:556562.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 41.

    Leman ES, Gonzalgo ML. Prognostic features and markers for testicular cancer management. Indian J Urol 2010;26:7681.

  • 42.

    Gordetsky J, Sanfrancesco J, Epstein JI, et al.. Do nonseminomatous germ cell tumors of the testis with lymphovascular invasion of the spermatic cord merit staging as pT3? Am J Surg Pathol 2017;41:13971402.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 43.

    Nazeer T, Ro JY, Kee KH, et al.. Spermatic cord contamination in testicular cancer. Mod Pathol 1996;9:762766.

  • 44.

    Divrik RT, Akdoğan B, Ozen H, et al.. Outcomes of surveillance protocol of clinical stage I nonseminomatous germ cell tumors-is shift to risk adapted policy justified? J Urol 2006;176:14241429., discussion 1429–1430.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 45.

    Gilbert DC, Al-Saadi R, Thway K, et al.. Defining a new prognostic index for stage I nonseminomatous germ cell tumors using CXCL12 expression and proportion of embryonal carcinoma. Clin Cancer Res 2016;22:12651273.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 46.

    Vergouwe Y, Steyerberg EW, Eijkemans MJ, et al.. Predictors of occult metastasis in clinical stage I nonseminoma: a systematic review. J Clin Oncol 2003;21:40924099.

  • 47.

    Daugaard G, Gundgaard MG, Mortensen MS, et al.. Surveillance for stage I nonseminoma testicular cancer: outcomes and long-term follow-up in a population-based cohort. J Clin Oncol 2014;32:38173823.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 48.

    Heidenreich A, Sesterhenn IA, Mostofi FK, et al.. Prognostic risk factors that identify patients with clinical stage I nonseminomatous germ cell tumors at low risk and high risk for metastasis. Cancer 1998;83:10021011.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 49.

    Alexandre J, Fizazi K, Mahé C, et al.. Stage I non-seminomatous germ-cell tumours of the testis: identification of a subgroup of patients with a very low risk of relapse. Eur J Cancer 2001;37:576582.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 50.

    Sweeney CJ, Hermans BP, Heilman DK, et al.. Results and outcome of retroperitoneal lymph node dissection for clinical stage I embryonal carcinoma--predominant testis cancer. J Clin Oncol 2000;18:358362.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 51.

    Albers P, Siener R, Kliesch S, et al.. 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 2003;21:15051512.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 52.

    Sanfrancesco JM, Trevino KE, Xu H, et al.. The significance of spermatic cord involvement by testicular germ cell tumors: should we be staging discontinuous invasion from involved lymphovascular spaces differently from direct extension? Am J Surg Pathol 2018;42:306311.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 53.

    de Wit M, Brenner W, Hartmann M, et al.. [18F]-FDG-PET in clinical stage I/II non-seminomatous germ cell tumours: results of the German multicentre trial. Ann Oncol 2008;19:16191623.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 54.

    Huddart RA, O’Doherty MJ, Padhani A, et al.. 18fluorodeoxyglucose positron emission tomography in the prediction of relapse in patients with high-risk, clinical stage I nonseminomatous germ cell tumors: preliminary report of MRC Trial TE22--the NCRI Testis Tumour Clinical Study Group. J Clin Oncol 2007;25:30903095.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 55.

    Nonomura N, Nishimura K, Takaha N, et al.. Nerve-sparing retroperitoneal lymph node dissection for advanced testicular cancer after chemotherapy. Int J Urol 2002;9:539544.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 56.

    Calaway AC, Einhorn LH, Masterson TA, et al.. Adverse surgical outcomes associated with robotic retroperitoneal lymph node dissection among patients with testicular cancer. Eur Urol 2019;76:607609.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 57.

    Punjani N, Winquist E, Power N. Do retroperitoneal extragonadal germ cell tumours exist? Can Urol Assoc J 2015;9:381384.

  • 58.

    Zuniga A, Kakiashvili D, Jewett MA. Surveillance in stage I nonseminomatous germ cell tumours of the testis. BJU Int 2009; 104(9b, 9 Pt B)13511356.

  • 59.

    Oliver RT, Ong J, Shamash J, 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;63:556561.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 60.

    Stephenson AJ, Bosl GJ, Bajorin DF, et al.. Retroperitoneal lymph node dissection in patients with low stage testicular cancer with embryonal carcinoma predominance and/or lymphovascular invasion. J Urol 2005;174:557560.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 61.

    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;26:29662972.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 62.

    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;27:21222128.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 63.

    Stephenson AJ, Bosl GJ, Motzer RJ, et al.. Retroperitoneal lymph node dissection for nonseminomatous germ cell testicular cancer: impact of patient selection factors on outcome. J Clin Oncol 2005;23:27812788.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 64.

    Böhlen D, Burkhard FC, Mills R, et al.. Fertility and sexual function following orchiectomy and 2 cycles of chemotherapy for stage I high risk nonseminomatous germ cell cancer. J Urol 2001;165:441444.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 65.

    Chevreau C, Mazerolles C, Soulié M, 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;46:209215.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 66.

    De La Pena H, Sharma A, Glicksman C, et al.. No longer any role for routine follow-up chest x-rays in men with stage I germ cell cancer. Eur J Cancer 2017;84:354359.

  • 67.

    Gietema JA, Meinardi MT, Sleijfer DT, et al.. Routine chest X-rays have no additional value in the detection of relapse during routine follow-up of patients treated with chemotherapy for disseminated non-seminomatous testicular cancer. Ann Oncol 2002;13:16161620.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 68.

    Kollmannsberger C, Tandstad T, Bedard PL, et al.. Patterns of relapse in patients with clinical stage I testicular cancer managed with active surveillance. J Clin Oncol 2015;33:5157.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 69.

    Bamias A, Aravantinos G, Kastriotis I, et al.. Report of the long-term efficacy of two cycles of adjuvant bleomycin/etoposide/cisplatin in patients with stage I testicular nonseminomatous germ-cell tumors (NSGCT): a risk adapted protocol of the Hellenic Cooperative Oncology Group. Urol Oncol 2011;29:189193.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 70.

    Guney S, Guney N, Sonmez NC, et al.. Risk-adapted management for patients with clinical stage I non-seminomatous germ cell tumour of the testis. Med Oncol 2009;26:136142.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 71.

    Chovanec M, Hanna N, Cary KC, et al.. Management of stage I testicular germ cell tumours. Nat Rev Urol 2016;13:663673.

  • 72.

    Huddart RA, Reid AM. Adjuvant therapy for stage IB germ cell tumors: one versus two cycles of BEP. Adv Urol 2018;2018:8781698.

  • 73.

    Meinardi MT, Gietema JA, van der Graaf WT, et al.. Cardiovascular morbidity in long-term survivors of metastatic testicular cancer. J Clin Oncol 2000;18:17251732.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 74.

    Chovanec M, Abu Zaid M, Hanna N, et al.. Long-term toxicity of cisplatin in germ-cell tumor survivors. Ann Oncol 2017;28:26702679.

  • 75.

    Strumberg D, Brügge S, Korn MW, et al.. Evaluation of long-term toxicity in patients after cisplatin-based chemotherapy for non-seminomatous testicular cancer. Ann Oncol 2002;13:229236.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 76.

    Fung C, Dinh P, Jr., Ardeshir-Rouhani-Fard S, et al.. Toxicities associated with cisplatin-based chemotherapy and radiotherapy in long-term testicular cancer survivors. Adv Urol 2018;2018:8671832.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 77.

    Hartmann JT, Lipp HP. Toxicity of platinum compounds. Expert Opin Pharmacother 2003;4:889901.

  • 78.

    Kerns SL, Fung C, Monahan PO, et al.. Cumulative burden of morbidity among testicular cancer survivors after standard cisplatin-based chemotherapy: a multi-institutional study. J Clin Oncol 2018;36:15051512.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 79.

    Sprauten M, Darrah TH, Peterson DR, et al.. Impact of long-term serum platinum concentrations on neuro- and ototoxicity in cisplatin-treated survivors of testicular cancer. J Clin Oncol 2012;30:300307.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 80.

    Haugnes HS, Stenklev NC, Brydøy M, et al.. Hearing loss before and after cisplatin-based chemotherapy in testicular cancer survivors: a longitudinal study. Acta Oncol 2018;57:10751083.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 81.

    Raphael MJ, Wei X, Karim S, et al.. Neurotoxicity among survivors of testicular cancer: a population-based study. Clin Oncol (R Coll Radiol) 2019;31:653658.

  • 82.

    Lv ZJ, Wu S, Dong P, et al.. Clinical outcomes in patients with stage I non-seminomatous germ cell cancer. Asian J Androl 2013;15:558563.

  • 83.

    Mezvrishvili Z, Managadze L. Three cycles of etoposide and cisplatin chemotherapy in clinical stage IS nonseminomatous testicular cancer. Int Urol Nephrol 2006;38:621624.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 84.

    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;25:55975602.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 85.

    Weissbach L, Bussar-Maatz R, Flechtner H, et al.. RPLND or primary chemotherapy in clinical stage IIA/B nonseminomatous germ cell tumors? Results of a prospective multicenter trial including quality of life assessment. Eur Urol 2000;37:582594.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 86.

    Rabbani F, Sheinfeld J, Farivar-Mohseni H, et al.. Low-volume nodal metastases detected at retroperitoneal lymphadenectomy for testicular cancer: pattern and prognostic factors for relapse. J Clin Oncol 2001;19:20202025.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 87.

    Sheinfeld J, Motzer RJ, Rabbani F, et al.. Incidence and clinical outcome of patients with teratoma in the retroperitoneum following primary retroperitoneal lymph node dissection for clinical stages I and IIA nonseminomatous germ cell tumors. J Urol 2003;170:11591162.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 88.

    Stephenson AJ, Klein EA. Surgical management of low-stage nonseminomatous germ cell testicular cancer. BJU Int 2009; 104:13621368.

  • 89.

    Behnia M, Foster R, Einhorn LH, et al.. Adjuvant bleomycin, etoposide and cisplatin in pathological stage II non-seminomatous testicular cancer: the Indiana University experience. Eur J Cancer 2000;36:472475.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 90.

    Kondagunta GV, Sheinfeld J, Mazumdar M, et al.. Relapse-free and overall survival in patients with pathologic stage II nonseminomatous germ cell cancer treated with etoposide and cisplatin adjuvant chemotherapy. J Clin Oncol 2004;22:464467.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 91.

    Carver BS, Shayegan B, Eggener S, et al.. Incidence of metastatic nonseminomatous germ cell tumor outside the boundaries of a modified postchemotherapy retroperitoneal lymph node dissection. J Clin Oncol 2007;25:43654369.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 92.

    Horwich A, Norman A, Fisher C, et al.. Primary chemotherapy for stage II nonseminomatous germ cell tumors of the testis. J Urol 1994;151:7278.

  • 93.

    Donohue JP, Thornhill JA, Foster RS, et al.. The role of retroperitoneal lymphadenectomy in clinical stage B testis cancer: the Indiana University experience (1965 to 1989). J Urol 1995;153:8589.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 94.

    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;15:594603.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 95.

    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;19:16291640.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 96.

    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;18:917924.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 97.

    Cary C, Jacob JM, Albany C, et al.. Long-term survival of good-risk germ cell tumor patients after postchemotherapy retroperitoneal lymph node dissection: a comparison of BEP x 3 vs EP x 4 and treating institution. Clin Genitourin Cancer 2018;16:e307e313.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 98.

    Kondagunta GV, Bacik J, Bajorin D, et al.. Etoposide and cisplatin chemotherapy for metastatic good-risk germ cell tumors. J Clin Oncol 2005;23:92909294.

  • 99.

    Jones RH, Vasey PA. Part II: testicular cancer--management of advanced disease. Lancet Oncol 2003;4:738747.

  • 100.

    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. Br J Cancer 1998;78:828832.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 101.

    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;26:421427.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 102.

    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;16:12871293.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 103.

    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;42:820826.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 104.

    Kollmannsberger C, Daneshmand S, So A, et al.. Management of disseminated nonseminomatous germ cell tumors with risk-based chemotherapy followed by response-guided postchemotherapy surgery. J Clin Oncol 2010;28:537542.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 105.

    Schmidt AH, Høyer M, Jensen BFS, et al.. Limited post-chemotherapy retroperitoneal resection of residual tumour in non-seminomatous testicular cancer: complications, outcome and quality of life. Acta Oncol 2018;57:10841093.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 106.

    Heidenreich A, Haidl F, Paffenholz P, et al.. Surgical management of complex residual masses following systemic chemotherapy for metastatic testicular germ cell tumours. Ann Oncol 2017;28:362367.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 107.

    Daneshmand S, Albers P, Fosså SD, et al.. Contemporary management of postchemotherapy testis cancer. Eur Urol 2012;62:867876.

  • 108.

    Riggs SB, Burgess EF, Gaston KE, et al.. Postchemotherapy surgery for germ cell tumors–what have we learned in 35 years? Oncologist 2014;19:498506.

  • 109.

    Loehrer PJ, Sr., Gonin R, Nichols CR, et al.. Vinblastine plus ifosfamide plus cisplatin as initial salvage therapy in recurrent germ cell tumor. J Clin Oncol 1998;16:25002504.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 110.

    Kondagunta GV, Bacik J, Donadio A, 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;23:65496555.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 111.

    Park S, Lee S, Lee J, et al.. Salvage chemotherapy with paclitaxel, ifosfamide, and cisplatin (TIP) in relapsed or cisplatin-refractory germ cell tumors. Onkologie 2011;34:416420.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 112.

    Kurobe M, Kawai K, Oikawa T, et al.. Paclitaxel, ifosfamide, and cisplatin (TIP) as salvage and consolidation chemotherapy for advanced germ cell tumor. J Cancer Res Clin Oncol 2015;141:127133.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 113.

    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;357:340348.

  • 114.

    Feldman DR, Sheinfeld J, Bajorin DF, et al.. TI-CE high-dose chemotherapy for patients with previously treated germ cell tumors: results and prognostic factor analysis. J Clin Oncol 2010;28:17061713.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 115.

    Albers P, Ganz A, Hannig E, et al.. Salvage surgery of chemorefractory germ cell tumors with elevated tumor markers. J Urol 2000;164:381384.

  • 116.

    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;21:113122.

  • 117.

    Lipphardt ME, Albers P. Late relapse of testicular cancer. World J Urol 2004;22:4754.

  • 118.

    Oing C, Lorch A, Bokemeyer C. Ongoing clinical trials in testicular cancer: the TIGER trial. Oncol Res Treat 2016;39:553556.

  • 119.

    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;29:21782184.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 120.

    McHugh DJ, Feldman DR. Conventional-dose versus high-dose chemotherapy for relapsed germ cell tumors. Adv Urol 2018;2018:7272541.

  • 121.

    Bokemeyer C, Oechsle K, Honecker F, et al.. Combination chemotherapy with gemcitabine, oxaliplatin, and paclitaxel in patients with cisplatin-refractory or multiply relapsed germ-cell tumors: a study of the German Testicular Cancer Study Group. Ann Oncol 2008;19:448453.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 122.

    De Giorgi U, Rosti G, Aieta M, et al.. Phase II study of oxaliplatin and gemcitabine salvage chemotherapy in patients with cisplatin-refractory nonseminomatous germ cell tumor. Eur Urol 2006;50:10321039.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 123.

    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;25:513516.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 124.

    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;22:108114.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 125.

    Mulherin BP, Brames MJ, Einhorn LH. Long-term survival with paclitaxel and gemcitabine for germ cell tumors after progression following high-dose chemotherapy with tandem transplant. Am J Clin Oncol 2015;38:373376.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 126.

    Pectasides D, Pectasides M, Farmakis D, et al.. Gemcitabine and oxaliplatin (GEMOX) in patients with cisplatin-refractory germ cell tumors: a phase II study. Ann Oncol 2004;15:493497.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 127.

    Seidel C, Oechsle K, Lorch A, et al.. Efficacy and safety of gemcitabine, oxaliplatin, and paclitaxel in cisplatin-refractory germ cell cancer in routine care–registry data from an outcomes research project of the German Testicular Cancer Study Group. Urol Oncol 2016;34:167.e21167.e28.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 128.

    Miller JC, Einhorn LH. Phase II study of daily oral etoposide in refractory germ cell tumors. Semin Oncol 1990; 17(1, Suppl 2)3639.

  • 129.

    U.S. Food and Drug Administration. FDA grants accelerated approval to pembrolizumab for first tissue/site agnostic indication. 2017. Available at: https://www.fda.gov/drugs/informationondrugs/approveddrugs/ucm560040.htm. Accessed October 7, 2019.

    • PubMed
    • Export Citation
  • 130.

    Le DT, Durham JN, Smith KN, et al.. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science 2017;357:409413.

  • 131.

    Le DT, Uram JN, Wang H, et al.. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med 2015;372:25092520.

  • 132.

    Adra N, Einhorn LH, Althouse SK, et al.. Phase II trial of pembrolizumab in patients with platinum refractory germ-cell tumors: a Hoosier Cancer Research Network Study GU14-206. Ann Oncol 2018;29:209214.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 133.

    Feldman DR, Lorch A, Kramar A, et al.. Brain metastases in patients with germ cell tumors: prognostic factors and treatment options-an analysis from the global germ cell cancer group. J Clin Oncol 2016;34:345351.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 134.

    Schmoll HJ, Souchon R, 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;15:13771399.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 135.

    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;24:878888.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 136.

    Boyle HJ, Jouanneau E, Droz JP, et al.. Management of brain metastases from germ cell tumors: a single center experience. Oncology 2013;85:2126.

  • 137.

    Loriot Y, Pagliaro L, Fléchon A, et al.. Patterns of relapse in poor-prognosis germ-cell tumours in the GETUG 13 trial: Implications for assessment of brain metastases. Eur J Cancer 2017;87:140146.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 138.

    Kollmannsberger C, Nichols C, Bamberg M, et al.. First-line high-dose chemotherapy +/- radiation therapy in patients with metastatic germ-cell cancer and brain metastases. Ann Oncol 2000;11:553559.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation

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