Abstract
Cure rates of germ-cell cancer have been greater than 95% for the last decade; therefore, over the past few years there has been a greater focus on 'conservative' approaches to treatment. The increased incidence of late non-germ-cell cancers in the era of radiotherapy and the incidence of subclinical testicular deficiency and metabolic syndrome in cured patients have accelerated this trend. Taking account of the increase in cure rates of primary chemotherapy failures from 5% to 60% with intensification of chemotherapy and surgery, this Review focuses on three areas: lessons from the initial failed trials of less-intensive treatment (i.e. bleomycin withdrawal and carboplatin substitution) that emphasised the need for improved salvage therapy; successes of reducing treatment of patients with metastases classed as good-risk from four cycles(20 days) to three cycles(9 days) and using 1 day carboplatin instead of 21 day radiotherapy as adjuvant for stage 1 seminoma; and the unexpected finding at 5 years of a 72% reduction of contralateral second germ-cell cancer. This finding provides the stimulus for the next generation of conservative trials using organ preservation, aiming to reduce occurrence of metabolic syndrome and using new radiological and minimal surgery techniques to accelerate the assessment of less toxic drugs and new approaches for combined medial and surgical treatment.
Key Points
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In excess of 95% of all germ-cell cancers are cured by a combination of surgery and chemotherapy
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50% of patients who fail first line chemotherapy are cured by second line therapy, and a further 25% to 30% are cured by third line treatment
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Successful trials in low-risk non-seminoma have reduced required treatment durations from 20 days in 12 weeks to 9 days in 9 weeks, and in stage 1 seminoma: from 20 days radiation to 1 day carboplatin
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Studies of late complications from cancer treatments suggest there is still a need for future trials to be directed at further reducing the long term morbidity associated with chemotherapy and surgery
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References
Oliver RT et al. (1996) Testis conservation studies in germ cell cancer justified by improved primary chemotherapy response and reduced delay, 1978–1994. Br J Urol 78: 119–124
Robinson D et al. (2007) Mortality and incidence of second cancers following treatment for testicular cancer. Br J Cancer 96: 529–533
Heidenreich et al. (2003) Complications of primary nerve sparing retroperitoneal lymph node dissection for clinical stage I nonseminomatous germ cell tumors of the testis: experience of the German Testicular Cancer Study Group. J Urol 169: 1710–1714
Hoff Wanderas E et al. (1990) Serum follicle stimulating hormone—predictor of cancer in the remaining testis in patients with unilateral testicular cancer. Br J Urol 66: 315–317
Heidenreich A et al. (2001) The German Testicular Cancer Study G. Organ sparing surgery for malignant germ cell tumor of the testis. J Urol 166: 2161–2165
Oliver RT et al. (2003) Testis conserving chemotherapy in germ cell cancer: its potential to increase understanding of the biology and treatment of carcinoma-in-situ. APMIS 111: 86–92
Satoh M et al. (2005) Intraoperative, radio-guided sentinel lymph node mapping in laparoscopic lymph node dissection for Stage I testicular carcinoma. Cancer 103: 2067–2072
Shamash J et al. (2002) GAMEC—a novel protocol for IGCCCG poor prognosis and relapsing germ cell tumours. In Germ Cell Tumours V, 240–241 (Eds Harnden P et al.) London: Springer
Shamash J et al. (2007) A phase II study using a topoisomerase I-based approach in patients with multiply relapsed germ-cell tumours. Ann Oncol 18: 925–930
Albers P et al. (1999) Positron emission tomography in the clinical staging of patients with Stage I and II testicular germ cell tumors. Urology 53: 808–811
Oliver RTD et al. (2004) 20 year phase 1/2 study of single agent carboplatin in metastatic seminoma:could it have been accelerated by 72 hour PET scan response? [abstract]. J Clin Oncol 22 (suppl): 4763
Powles T et al. (2007) Molecular positron emission tomography and PET/CT imaging in urological malignancies. Eur Urol 51: 1511–1521
Edmonds PM et al. (1993) Risk of a second non-testis malignancy following radiotherapy for stage 1 seminoma. In Abstracts of the BAUS Annual Meeting, 1993 June, Harrogate, 53
Zagars GK et al. (2004) Mortality after cure of testicular seminoma. J Clin Oncol 22: 640–647
Oliver RTD (1985) Testicular germ cell tumours—a model for a new approach to treatment of adult solid tumours. Postgrad Med J 61: 123–131
Williams SD et al. (1987) Treatment of disseminated germ-cell tumours with Cisplatin, Bleomycin, and either Vinblastine or Etoposide. N Engl J Med 316: 1435–1440
Mead GM and Stenning S (1997) International germ cell cancer collaborative group prognostic factor scoring system. J Clin Oncol 15: 594–603
Bajorin D et al. (1998) Metastatic germ cell tumours: modelling for response to chemotherapy. J Clin Oncol 16: 707–715
Kaye S et al. (1998) Intensive induction-sequential chemotherapy with BOP/VIP-B compared with treatment of metastatic nonseminomatous germ cell tumour. J Clin Oncol 16: 692–701
Hinton S et al. (2003) Cisplatin, etoposide and either bleomycin or ifosfamide in the treatment of disseminated germ cell tumors: final analysis of an intergroup trial. Cancer 97: 1869–1875
Boshoff CB et al. (1995) Secondary tumours following etoposide containing therapy for germ cell cancer. Ann Oncol 6: 35–40
Orchid website [www.orchid-cancer.org.uk]
Bhardwa JM et al. (2005) Assessing the size and stage of testicular germ cell tumours: 1984–2003. BJU Int 96: 819–821
Agnarsson BA et al. (2006) Testicular germ cell tumours in Iceland: a nationwide clinicopathological study. APMIS 114: 779–783
Shamash J et al. (1999) 60% salvage rate for germ cell tumours using sequential m-BOP, surgery and ifosfamide based chemotherapy. Ann Oncol 10: 685–692
Pico JL et al. (2005) 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 16: 1152–1159
Motzer RJ et al. (2000) Paclitaxel, ifosfamide, and cisplatin second-line therapy for patients with relapsed testicular germ cell cancer. J Clin Oncol 18: 2413–2418
Shamash J et al.: GAMEC—a new intensive protocol for untreated poor prognosis and relapsed or refractory germ cell tumours. Br J Cancer 97: 308–314
Ravi R et al. (1998) Surgery as salvage therapy in chemotherapy-resistant nonseminomatous germ cell tumours. Br J Urol 81: 884–888
Beck SD et al. (2005) Pathologic findings and therapeutic outcome of desperation post-chemotherapy retroperitoneal lymph node dissection in advanced germ cell cancer. Urol Oncol 23: 423–430
Zuk RJ et al. (1989) Findings in lymph nodes of patients with germ cell tumours after chemotherapy and their relation to prognosis. J Clin Pathol 42: 1049–1054
Loehrer PJ Sr et al. (1986) Teratoma following cisplatin-based combination chemotherapy for nonseminomatous germ cell tumors: a clinicopathological correlation. J Urol 135: 1183–1189
Oliver RT (2001) Testicular cancer. Curr Opin Oncol 13: 191–198
Shelley M et al. (2003) Testicular germ cell cancer. Evidence-based Oncology 34: 365–373
Horwich A et al. (1997) 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 15: 1844–1852
De Wit R et al. (2001) 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 19: 1629–1640
Fossa SD et al. (2003) Quality of life in good prognosis patients with metastatic germ cell cancer: a prospective study of the European Organization for Research and Treatment of Cancer Genitourinary Group/Medical Research Council Testicular Cancer Study Group (30941/TE20). J Clin Oncol 21: 1107–1118
Freedman L et al. (1985) Prognostic factors in advanced non-seminomatous germ cell testicular tumours: results of a multicentre study. Lancet 1: 8–11
Freedman LS et al. (1987) Histopathology in the prediction of relapse of patients with stage 1 testicular teratoma treated by orchidectomy alone. On behalf of MRC Testicular Tumour Subgroup (Urological Working Party). Lancet 2: 294–298
Leiter E and Brendler H (1967) Loss of ejaculation following bilateral retroperitoneal lymphadenectomy. J Urol 98: 375–378
Williams SD et al. (1987) Immediate adjuvant chemotherapy versus observation with treatment at relapse in pathological stage II testicular cancer. N Engl J Med 317: 1433
Oliver R et al. (2004) Long term follow up of Anglian Germ Cell Cancer Group surveillance versus adjuvant chemotherapy treated stage 1 non-seminoma patients. Urology 63: 556–561
Albers P (2007) Management of stage I testis cancer. Eur Urol 51: 34–43
Steiner H et al. (2004) Long-term results of laparoscopic retroperitoneal lymph node dissection: a single-center 10-year experience. Urology 63: 550–555
Rassweiler J et al. (2006) Laparoscopic and robotic assisted radical prostatectomy—critical analysis of the results. Eur Urol 49: 612–624
Stephenson AJ et al. (2005) Retroperitoneal lymph node dissection for nonseminomatous germ cell testicular cancer: impact of patient selection factors on outcome. J Clin Oncol 23: 2781–2788
Donohue JP et al. (1987) Correlation of computerized tomographic changes and histological findings in 80 patients having radical retroperitoneal lymph node dissection after chemotherapy for testis cancer. J Urol 137: 1176–1179
Albers P et al. (2006) One course adjuvant PEB chemotherapy versus retroperitoneal lymph node dissection in patients with stage I non-seminoma [abstract]. J Clin Oncol 24: 4512
Tyrrell CJ and Peckham MJ (1976) The response of lymph node metastases of testicular teratoma to radiation therapy. Br J Urol 48: 363–370
Williams C (1977) Current dilemmas in the management of non-seminomatous germ cell tumors of the testis. Cancer Treat Rev 4: 275–297
Oliver RTD et al. (1984) Possible new approaches to the management of seminoma of the testis. Br J Urol 56: 729–733
Logothetis CJ et al. (1987) Cyclophosphamide and sequential cisplatin for advanced seminoma: long term follow up 52 patients. J Urol 138: 789–794
Bokemeyer C et al. (2004) Metastatic seminoma treated with either single agent carboplatin or cisplatin-based combination chemotherapy: a pooled analysis of two randomised trials. Br J Cancer 91: 683–687
Travis LB et al. (2005) Second cancers among 40,576 testicular cancer patients: focus on long-term survivors. J Natl Cancer Inst 97: 1354–1365
Warde P et al. (2002) Prognostic factors for relapse in stage I seminoma managed by surveillance: a pooled analysis. J Clin Oncol 20: 4448–4452
Oliver RTD (2005) One-dose carboplatin in seminoma. Lancet 366: 1526
Fossa SD et al. (1999) 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 17: 1146
Jones WG et al. (2005) 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 (ISRCTN18525328). J Clin Oncol 23: 1200–1208
Logue JP et al. (2003) Short course para-aortic radiation for stage I seminoma of the testis. Int J Radiat Oncol Biol Phys 57: 1304–1309
Classen J et al. (2004) Para-aortic irradiation for stage I testicular seminoma: results of a prospective study in 675 patients. A trial of the German testicular cancer study group (GTCSG). Br J Cancer 90: 2305–2311
Oliver RT et al. (1994) Pilot studies of 2 and 1 course carboplatin as adjuvant for stage I seminoma: should it be tested in a randomized trial against radiotherapy? Int J Radiat Oncol Biol Phys 29: 3–8
Dieckmann K et al. (2000) Adjuvant treatment of clinical stage 1 seminoma: is a single course of carboplatin sufficient? Urology 55: 102–106
Krege S et al. (2006) Single agent carboplatin for CS IIA/B testicular seminoma. A phase II study of the German Testicular Cancer Study Group (GTCSG). Ann Oncol 17: 276–280
Sant M et al. (2007) Ten-year survival and risk of relapse for testicular cancer: a EUROCARE high resolution study. Eur J Cancer 43: 585–592
Oliver TD et al. (2005) Pooled analysis of phase II reports of 2 vs 1 course of carboplatin as adjuvant for stage 1 seminoma [abstract]. J Clin Oncol 23: 4572
Oliver RTD et al. (2005) Radiotherapy versus single-dose carboplatin in adjuvant treatment of stage 1 seminoma: a randomised trial. Lancet 366: 293–300
Warde P (2006) Are carboplatin and radiotherapy equally effective for the adjuvant treatment of stage I seminoma? Nat Clin Pract Oncol 3: 18–19
Loehrer PJ Sr and Bosl GJ (2005) Carboplatin for stage I seminoma and the sword of Damocles. J Clin Oncol 23: 8566–8569
Motzer RJ et al. (2006) Testicular cancer. Clinical practice guidelines in oncology. J Natl Compr Canc Netw 4: 1038–1058
Huddart RA and Joffe JK (2006) Preferred treatment for stage I seminoma: a survey of Canadian radiation oncologists. Clin Oncol (R Coll Radiol) 18: 693–695
Sternswald J et al. (1978) Lymphopenia and change in distribution of human B and T lymphocyte in peripheral blood induced by irradiation for mammary carcinoma. Lancet 1: 1352–1356
Fossa S et al. (1989) Long term mobidity after infradiaphragmatic radiotherapy in young men with testicular cancer. Cancer 64: 404–408
Nuver J et al. (2005) The metabolic syndrome and disturbances in hormone levels in long-term survivors of disseminated testicular cancer. J Clin Oncol 23: 3718–3725
Mardiak J et al. (2007) Damage of bone metabolism and osteoporosis in testicular cancer patients[abstract]. J Clin Oncol 25 (suppl): 5052
Willemse P-PM (2007) Bone abnormalities in male germ-cell cancer survivors [abstract]. J Clin Oncol 25 (suppl): 5053
Oliver R (2006) Epidemiology of testis cancer. In Comprehensive Textbook of Genitourinary Oncology, edn 3, 547–558 (Eds Vogelzang N et al.) Philadephia: Lippincott Williams & Wilkins
Oliver RTD (1990) Atrophy, hormones, genes and viruses in aetiology of germ cell tumours. Cancer Surv 9: 263–268
Skakkebaek NE et al. (2001) Testicular dysgenesis syndrome: an increasingly common developmental disorder with environmental aspects. Hum Reprod 16: 972–978
Sharpe RM (2003) The 'oestrogen hypothesis'—where do we stand now? Int J Androl 26: 2–15
Mahood IK et al. (2006) Cellular origins of testicular dysgenesis in rats exposed in utero to di(n-butyl) phthalate. Int J Androl 29: 148–154
Rajpert-De Meyts E (2006) Developmental model for the pathogenesis of testicular carcinoma in situ: genetic and environmental aspects. Hum Reprod Update 12: 303–323
Petersen PM et al. (1999) Semen quality and reproductive hormones before orchiectomy in men with testicular cancer. J Clin Oncol 17: 941–947
Hoei-Hansen CE et al. (2007) Towards a non-invasive method for early detection of testicular neoplasia in semen samples by identification of fetal germ cell-specific markers. Hum Reprod 22: 167–173
Harisinghani MG et al. (2005) A pilot study of lymphotrophic nanoparticle-enhanced magnetic resonance imaging technique in early stage testicular cancer: a new method for noninvasive lymph node evaluation. Urology 66: 1066–1071
Eggener SE et al. (2007) Incidence of disease outside modified retroperitoneal lymph node dissection templates in clinical stage I or IIA nonseminomatous germ cell testicular cancer. J Urol 177: 937–942
Powles T et al. (2003) Novel in-vitro approaches to the treatment of cisplatin resistant germ cell tumours [abstract]. Proc Am Soc Clin Oncol 22: 547
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Oliver, T. Conservative management of testicular germ-cell tumors. Nat Rev Urol 4, 550–560 (2007). https://doi.org/10.1038/ncpuro0905
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DOI: https://doi.org/10.1038/ncpuro0905
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