What is the background of the HTA report?

For “ThemenCheck Medizin” (Topic Check Medicine), published by the Institute for Quality and Efficiency in Health Care (IQWiG), insured persons and other interested individuals are invited to propose topics for the assessment of medical procedures and technologies. The assessment is done in the form of a health technology assessment (HTA) report. HTA reports include an assessment of medical benefit and health economics as well as an investigation of ethical, social, legal, and organizational aspects of a technology.

In a 2-step selection procedure, which also involves the public, up to 5 topics are selected each year from among all submitted proposals. According to the legal mandate, these topics ought to be of particular relevance to patients [1]. IQWiG then commissions external teams of scientists to investigate the topics in accordance with IQWiG methods, and it publishes the HTA reports.

In 2018, IQWiG commissioned a team of scientists from universities in Hall in Tirol and Munich as well as from the Austrian National Public Health Institute in Vienna to investigate the selected topic HT18-01, testicular cancer screening. The team consisted of methodologists experienced in generating HTA reports, a urologist as well as experts with knowledge and experience in health economic, ethical, social, legal and organizational topics.

Why is the HTA report important?

Testicular cancer typically develops at an early age, between 25 and 45 years, and is the most common malignant neoplasm in young men. Representing 1.6% of all cancers, testicular cancer is one of the rarer types of cancer overall [2]. Testicular cancer is very treatable, and the odds of surviving the disease are great. Particularly when the disease is diagnosed at an advanced stage, however, late sequelae of cancer treatment such as nerve damage, infertility, hypertension, or peripheral neuropathy may develop [3]. If left untreated, the disease is fatal.

In Germany, men aged 45 years and older are eligible for one annual cancer screening. Statutory health insurance (SHI) benefits include, among other things, a specific anamnesis, including questions about any changes and complaints, inspection and palpation of the external genitals, palpation of the prostate as well as communication of findings with subsequent consultation [4].

Since testicular cancer typically develops before the 45^th year of life, a member of the general public asked the ThemenCheck Medizin team whether it might be beneficial to start routine screening in asymptomatic men as young as 16 years of age.

For testicular cancer screening in younger asymptomatic men, 2 examinations can be distinguished: (1) regular clinical palpation and scrotal ultrasound versus (2) regular testicular self-examination (TSE) (by palpation) as instructed and encouraged by healthcare staff. While the S3 guideline “Diagnostics, therapy and follow-up of testicular germ cell tumours” advises against screening the general population for testicular cancer, it recommends that particularly younger men regularly practise TSEs since they might result in earlier diagnosis [5].

It was against this backdrop that IQWiG selected the topic “testicular cancer screening” for the generation of an HTA report. From the various perspectives of an HTA report, it was investigated whether men aged 16 years and older reap health benefits from regular clinical screening by scrotal palpation and ultrasound or regular TSEs.

Demonstrating any benefit of screening – in the form of clinical screening or TSE – would require high-quality studies to show that the advantages of screening (e.g. avoided deaths) outweigh its disadvantages (e.g. unnecessary examinations possibly followed by invasive measures).

Which questions are answered – and which are not?

The commissioned team of scientists did not find any studies investigating the benefits of testicular cancer screening. Therefore, they conclude that there is no hint of benefit or harm from routine screening – whether in the form of clinical palpation and scrotal ultrasound or TSE.

In the HTA report, the external experts further sought to answer the question of how many men in Germany might theoretically benefit from screening. The authors conclude that, due to the low incidence and good treatability of testicular cancer, only a minor potential benefit of testicular screening is theoretically expected in men aged 16 years and older. However, this minor theoretical benefit would be offset by potential harm due to unnecessary examinations possibly followed by invasive measures such as testicular exploration or removal in suspicious cases.

Given that the authors were unable to find any studies on this topic, it was not possible to draw any conclusions on the cost effectiveness of testicular cancer screening.

With regard to ethical, legal, social, and organizational aspects, the authors of the HTA report emphasize that the male general population tends to know little about testicular cancer or TSE. Studies have also shown that, where requisite information and training is provided, TSE is practised more frequently. All things considered, however, the report concludes that general testicular cancer screening – not only in terms of benefits, but also from an ethical perspective – cannot be recommended.

These conclusions of the report apply to general testicular cancer screening in young men. A different conclusion on the benefit of screening might be reached when analysing routine screening in men with specific risk factors for testicular cancer (e.g. undescended testicle in childhood, family history or personal history of testicular cancer, infertility). In this population, the benefit of testicular cancer screening might be greater than in the general population since the probability of diseases being identified through screening is, of course, higher in high-risk groups.

In principle, men with testicular abnormalities should always promptly see a physician.

What’s the next step?

The HTA report has underscored that there is no empirical or theoretical basis for recommending a population-based screening for testicular cancer in men 16 to 45 years of age. The situation might be different for men at higher risk of testicular cancer. A comment on the HTA report suggested conducting studies on this question. IQWiG welcomes this suggestion and offers constructive support for the development of relevant study concepts.

Furthermore, specific tumour markers for testicular cancer screening are currently being developed [6]. If successful, the future role of tumour markers with reliable test characteristics should be explored for testicular cancer screening in high-risk groups.

Testicular cancer is very treatable. Nevertheless, impairments can develop due to late sequelae of cancer therapy in some cases, for instance in patients starting therapy in the advanced stage of disease. The S3 guideline “Diagnostics, therapy and follow-up of testicular germ cell tumours” therefore recommends, for instance, that affected men with metastatic germ cell tumour be treated in centres with proven experience [5]. In this context, it might be worth examining whether an improvement in care might be achieved by further quality assurance measures, such as the centralized provision of services.

References

1.

Bundesgesetzblatt 2015; Teil 1(30): 1211-1244.

2.

Kaatsch P, Spix C, Katalinic A, Hentschel C, Luttmann S, Stegmaier C, et al. Krebs in Deutschland für 2013/2014. Berlin: Robert Koch-Institut; 2017. URL: https://www​.krebsdaten​.de/Krebs/DE/Content​/Publikationen/Krebs_in_Deutschland​/kid_2017​/krebs_in_deutschland_2017​.pdf?__blob=publicationFile.

3.

Pottek TS, Hartmann M, Bokemeyer C. Aftercare and delayed toxicity of testicular cancer. Dtsch Arztebl 2005; 102(48): A3342-A3348.

4.

Gemeinsamer Bundesausschuss. Richtlinie des Gemeinsamen Bundesausschusses über die Früherkennung von Krebserkrankungen (Krebsfrüherkennungs-Richtlinie/KFE-RL) [online]. 05.12.2019 [Accessed: 07.02.2020]. URL: https://www​.g-ba.de/downloads​/62-492-2002​/KFE-RL_2019-12-05_iK-2020-01-01.pdf.

5.

Leitlinienprogramm Onkologie (Deutsche Krebsgesellschaft, Deutsche Krebshilfe, AWMF). S3-Leitlinie Diagnostik, Therapie und Nachsorge der Keimzelltumoren des Hodens: Langversion 1.0 [online]. 05.2019 [Accessed: 07.02.2020]. URL: https://www​.leitlinienprogramm-onkologie​.de/fileadmin/user_upload​/Downloads/Leitlinien​/Hodentumoren/LL​_Hodentumoren_Langversion_1.0.pdf.

6.

Dieckmann KP, Radtke A, Geczi L, Matthies C, Anheuser P, Eckardt U, et al. Serum levels of microRNA-371a-3p (M371 test) as a new biomarker of testicular germ cell tumors: results of a prospective multicentric study. J Clin Oncol 2019; 37(16): 1412-1423. [PMC free article: PMC6544462] [PubMed: 30875280]