Management of Germ Cell Tumours of the Testis in Adult Patients. German Clinical Practice Guideline Part I: Epidemiology, Classification, Diagnosis, Prognosis, Fertility Preservation, and Treatment Recommendations for Localized Stages

Introduction: This is the first German evidence- and consensus-based clinical guideline on diagnosis, treatment, and follow-up on germ cell tumours (GCTs) of the testis in adult patients. We present the guideline content in two publications. Part I covers the topic's background, methods, epidemiology, classification systems, diagnostics, prognosis, and treatment recommendations for the localized stages.

Methods: An interdisciplinary panel of 42 experts including 1 patient representative developed the guideline content. Clinical recommendations and statements were based on scientific evidence and expert consensus. For this purpose, evidence tables for several review questions, which were based on systematic literature searches (last search was in March 2018) were provided. Thirty-one experts entitled to vote, rated the final clinical recommendations and statements.

Results: We provide 161 clinical recommendations and statements. We present information on the quality of cancer care and epidemiology and give recommendations for staging and classification as well as for diagnostic procedures. The diagnostic recommendations encompass measures for assessing the primary tumour as well as procedures for the detection of metastases. One chapter addresses prognostic factors. In part I, we separately present the treatment recommendations for germ cell neoplasia in situ, and the organ-confined stages (clinical stage I) of both seminoma and nonseminoma.

Conclusion: Although GCT is a rare tumour entity with excellent survival rates for the localized stages, its management requires an interdisciplinary approach, including several clinical experts. Quality of care is highly related to institutional expertise and can be reassured by established online-based second-opinion boards. There are very few studies on diagnostics with good level of evidence. Treatment of metastatic GCTs must be tailored to the risk according to the International Germ Cell Cancer Collaboration Group classification after careful diagnostic evaluation. An interdisciplinary approach as well as the referral of selected patients to centres with proven experience can help achieve favourable clinical outcomes.

Citing Articles

Preoperative semen quality is superior to the quality shortly after orchiectomy in patients with testicular germ cell tumour - a retrospective study from two centres in Germany.

Dieckmann K, Hochmuth-Tisch J, Salzbrunn A, Matthies C, von Kopylow K, Wulfing C Basic Clin Androl. 2025; 35(1):7.

PMID: 39966729 PMC: 11837636. DOI: 10.1186/s12610-025-00252-7.

Testicular ultrasonographic features predict future risk for bilateral testicular germ cell tumour: A long-term single centre follow-up study.

Tenuta M, Mazzotta P, Sesti F, Angelini F, Gelibter A, Speranza I Andrology. 2024; 13(3):587-599.

PMID: 39078248 PMC: 11867925. DOI: 10.1111/andr.13704.

Radiomics and Clinicopathological Characteristics for Predicting Lymph Node Metastasis in Testicular Cancer.

Lisson C, Manoj S, Wolf D, Lisson C, Schmidt S, Beer M Cancers (Basel). 2023; 15(23).

PMID: 38067334 PMC: 10705534. DOI: 10.3390/cancers15235630.

MicroRNA-371a-3p-The Novel Serum Biomarker in Testicular Germ Cell Tumors.

Nestler T, Schoch J, Belge G, Dieckmann K Cancers (Basel). 2023; 15(15).

PMID: 37568759 PMC: 10417034. DOI: 10.3390/cancers15153944.

Unilateral, Small, Benign, Late-Onset, Large-Cell Calcifying Sertoli Cell Tumor: A Case Report.

Angerer M, Wulfing C, Gubitz R, Harms A, Dieckmann K Cureus. 2023; 15(7):e41614.

PMID: 37565109 PMC: 10410189. DOI: 10.7759/cureus.41614.

References

Albers P, Siener R, Krege S, Schmelz H, Dieckmann K, Heidenreich A . 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.... J Clin Oncol. 2008; 26(18):2966-72. DOI: 10.1200/JCO.2007.12.0899. View

Ruf C, Isbarn H, Wagner W, Fisch M, Matthies C, Dieckmann K . Changes in epidemiologic features of testicular germ cell cancer: age at diagnosis and relative frequency of seminoma are constantly and significantly increasing. Urol Oncol. 2013; 32(1):33.e1-6. DOI: 10.1016/j.urolonc.2012.12.002. View

Culine S, Theodore C, Terrier-Lacombe M, Droz J . Primary chemotherapy in patients with nonseminomatous germ cell tumors of the testis and biological disease only after orchiectomy. J Urol. 1996; 155(4):1296-8. View

Albany C, Adra N, Snavely A, Cary C, Masterson T, Foster R . Multidisciplinary clinic approach improves overall survival outcomes of patients with metastatic germ-cell tumors. Ann Oncol. 2017; 29(2):341-346. PMC: 6248648. DOI: 10.1093/annonc/mdx731. View

Tandstad T, Solberg A, Hakansson U, Stahl O, Haugnes H, Oldenburg J . Bilateral testicular germ cell tumors in patients treated for clinical stage I non-seminoma within two risk-adapted SWENOTECA protocols. Acta Oncol. 2014; 54(4):493-9. DOI: 10.3109/0284186X.2014.953256. View

Whiting P, Rutjes A, Westwood M, Mallett S, Deeks J, Reitsma J . QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med. 2011; 155(8):529-36. DOI: 10.7326/0003-4819-155-8-201110180-00009. View

Brouwers M, Kho M, Browman G, Burgers J, Cluzeau F, Feder G . AGREE II: advancing guideline development, reporting and evaluation in health care. CMAJ. 2010; 182(18):E839-42. PMC: 3001530. DOI: 10.1503/cmaj.090449. View

Sturgeon J, Moore M, Kakiashvili D, Duran I, Anson-Cartwright L, Berthold D . Non-risk-adapted surveillance in clinical stage I nonseminomatous germ cell tumors: the Princess Margaret Hospital's experience. Eur Urol. 2010; 59(4):556-62. DOI: 10.1016/j.eururo.2010.12.010. View

Chevreau C, Mazerolles C, Soulie M, Gaspard M, Mourey L, Bujan L . 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(2):209-14. DOI: 10.1016/j.eururo.2004.03.022. View

10.

Kollmannsberger C, Tandstad T, Bedard P, Cohn-Cedermark G, Chung P, Jewett M . Patterns of relapse in patients with clinical stage I testicular cancer managed with active surveillance. J Clin Oncol. 2014; 33(1):51-7. DOI: 10.1200/JCO.2014.56.2116. View

11.

Studer U, Fey M, Calderoni A, Kraft R, Mazzucchelli L, SONNTAG R . Adjuvant chemotherapy after orchiectomy in high-risk patients with clinical stage I non-seminomatous testicular cancer. Eur Urol. 1993; 23(4):444-9. DOI: 10.1159/000474650. View

12.

Zengerling F, Krege S, Schrader A, Schrader M . [National second opinion network for testicular cancer patients - transferring guidelines into practice!]. Aktuelle Urol. 2014; 45(6):454-6. DOI: 10.1055/s-0034-1395624. View

13.

Higgins J, Altman D, Gotzsche P, Juni P, Moher D, Oxman A . The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ. 2011; 343:d5928. PMC: 3196245. DOI: 10.1136/bmj.d5928. View

14.

Hayden J, van der Windt D, Cartwright J, Cote P, Bombardier C . Assessing bias in studies of prognostic factors. Ann Intern Med. 2013; 158(4):280-6. DOI: 10.7326/0003-4819-158-4-201302190-00009. View

15.

Tandstad T, Cohn-Cedermark G, Dahl O, Stierner U, Cavallin-Stahl E, Bremnes R . Long-term follow-up after risk-adapted treatment in clinical stage 1 (CS1) nonseminomatous germ-cell testicular cancer (NSGCT) implementing adjuvant CVB chemotherapy. A SWENOTECA study. Ann Oncol. 2010; 21(9):1858-1863. DOI: 10.1093/annonc/mdq026. View

16.

. 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(2):594-603. DOI: 10.1200/JCO.1997.15.2.594. View

17.

Oliver R, Ong J, Shamash J, Ravi R, Nagund V, Harper P . Long-term follow-up of Anglian Germ Cell Cancer Group surveillance versus patients with Stage 1 nonseminoma treated with adjuvant chemotherapy. Urology. 2004; 63(3):556-61. DOI: 10.1016/j.urology.2003.10.023. View

18.

Ondrus D, Kajo K, Stastna V, Ondrusova M . Controversies in the management of clinical stage I nonseminomatous germ cell testicular cancer. Klin Onkol. 2015; 28(2):112-5. View

19.

Krege S, Beyer J, Souchon R, Albers P, Albrecht W, Algaba F . European consensus conference on diagnosis and treatment of germ cell cancer: a report of the second meeting of the European Germ Cell Cancer Consensus Group (EGCCCG): part II. Eur Urol. 2008; 53(3):497-513. DOI: 10.1016/j.eururo.2007.12.025. View

20.

Daugaard G, Gundgaard M, Mortensen M, Agerbaek M, Holm N, Rorth M . Surveillance for stage I nonseminoma testicular cancer: outcomes and long-term follow-up in a population-based cohort. J Clin Oncol. 2014; 32(34):3817-23. DOI: 10.1200/JCO.2013.53.5831. View