Early detection of carcinoma in situ of the testis with a new non-invasive method.

Almost all testiculaire germ cell tumours (TGCT) have carcinoma in situ (CIS)
as common precursor. Epidemiologic data shown that 70% of the men with CIS of
the testis develop within 7 years a clinically manifest tumour. Early detection
of CIS is of large clinical value, because CIS can be threated with a low dose
of local radiotherapy. Moreover radical orchidectomy, chemotherapy and/or
radiotherapy are prevented, the treatment at a more advanced tumour stage, as
well as the long term complications of these invasive therapy.

The aim of this research is developing a non-invasive a method of early
detection of CIS using scrotal ultrasound and semen diagnostic on CIS-cells.
The results of this research will be used for the set-up of a screening study
of CIS at men with an increased risk of testicular cancer.

Primary question: Is a non-invasive method of early detection of CIS clinically
applicable in a future screening project of early detection of CIS of the
testis at men with an increased risk of testicular cancer?

Secondary questions:
- What are the sensitivity, specificity and positive predictive value of
scrotal ultrasound for early detection of testicular cancer with respect to the
testis biopsy (gold standard)?
- What are the sensitivity, specificity and positive predictive value of semen
diagnostic on CIS-cells for early detection of testicular cancer with respect
to the testis biopsy (gold standard)?
- What are the sensitivity, specificity and positive predictive value of semen
diagnostic on TGCT miRNA for early detection of testicular cancer with respect
to the testis biopsy (gold standard)?
- What are the sensitivity, specificity and positive predictive value of
bloodsamples on TGCT risico SNP's diagnostic for early detection of testicular
cancer with respect to the testis biopsy (gold standard)?
- What is the difference in the increased risk of a testicular tumor, and thus
the presence of CIS and/or positive outcomes of the non-invasive method for
early detection of testicular cancer, among oligoasthenospermic men, men with
cryptorchidism, and men with azoospermia?

Pilot study, prospective, controlled clinically diagnostic research.

The two patient groups receive the usual treatment, they underwent no extra
researches within the framework of the study. The patient groups experiences
therefore no extra risks or tax for participating to the research, however,
having them possibly the advantage of early detection of CIS.

The two control groups undergoes within the framework of the research, beside
their usual treatment, extra a blood purchase (6+7 ml), twice semendiagnostics
and a scrotal ultrasound. There are no risks linked for men from the control
groups to the additional researches which take place within the framework of
the study and these researches are just a little incriminating for the patient.
The chance on finding CIS in this group is small, but at presence of CIS in the
testis they have the advantage of early detection.

For men who in an earlier version of the current protocol (up to version 2.0,
August 26, 2009) are included and men who participated in the Crypto-study (up
to and including Amendment 2 of December 16, 2009) and/or the VASA study two
additional semen analyses and semen diagnostics will be performed and a blood
sample will be taken (6 mL). They get the results of the semen analyses
subsequent to participation in the study and may have the benefit of early
detection of CIS.

Men who are enrolled through Amendment 3 (August 30, 2012) of the Crypto-study
get an extra semen analysis. They get the results of the semen analysis
subsequent to participation in the study and may have the benefit of early
detection of CIS.