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Testicular germ cell tumors: pathogenesis, diagnosis and treatment

Abstract

Testicular germ cell tumors represent the most common solid malignancy of young men aged 15–40 years. Histopathologically, testicular germ cell tumors are divided into two major groups: pure seminoma and nonseminoma. The pathogenesis of testicular germ cell tumors remains unknown; however, cryptorchidism is the main risk factor, and molecular studies have shown strong evidence of an association between genetic alterations and testicular germ cell tumors. In cases of suspicion for testicular germ cell tumor, a surgical exploration with orchiectomy is obligatory. After completion of diagnostic procedures, levels of serum tumor markers and the clinical stage based on the International Union Against Cancer tumor-node-metastasis classification should be defined. Patients with early-stage testicular germ cell tumors are treated by individualized risk stratification within a multidisciplinary approach. The individual management (surveillance, chemotherapy or radiotherapy) has to be balanced according to clinical features and the risk of short-term and long-term toxic effects. Treatment for metastatic tumors is based on risk stratification according to International Germ Cell Cancer Collaborative Group classification and is performed with cisplatin-based chemotherapy and residual tumor resection in cases of residual tumor lesion. High-dose chemotherapy represents a curative option for patients with second or subsequent relapses.

Key Points

  • In cases with suspicion of testicular tumor, analysis of tumor marker levels and a histological proof, usually obtained by an inguinal orchiectomy, is mandatory

  • In patients with early-stage testicular germ cell tumors, the overall disease-free survival is nearly 100%, irrespective of therapeutic strategy; surveillance remains an effective means of managing these patients

  • The therapy of advanced testicular germ cell tumors is based on risk stratification according to clinical features and International Germ Cell Cancer Collaborative Group classification (good, intermediate or poor prognosis)

  • For patients with features suggestive of a good prognosis, chemotherapy with three cycles of bleomycin, etoposide and cisplatin or four cycles of etoposide and cisplatin are the two optimal treatment regimens

  • In patients with intermediate or poor prognosis features, an intensification of treatment is necessary through four cycles of cisplatin-based chemotherapy in combination with complete resection of residual masses

  • Relapsed or refractory disease should be treated either with conventional chemotherapy or with high-dose chemotherapy; late relapsing tumors are usually chemotherapy-resistant, and surgical treatment should be the first choice

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Figure 1: Treatment of carcinoma in situ or stage I tumors.
Figure 2: Treatment of seminoma clinical stage II A or B and nonseminomatous germ cell tumors clinical stage II A or B.
Figure 3: Treatment of advanced testicular germ cell tumors.

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C. Winters researched data for the article and wrote the article. C. Winters and P. Albers both provided a substantial contribution to discussion of the content and reviewed/edited the manuscript before submission.

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Winter, C., Albers, P. Testicular germ cell tumors: pathogenesis, diagnosis and treatment. Nat Rev Endocrinol 7, 43–53 (2011). https://doi.org/10.1038/nrendo.2010.196

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