Of course, there are other diagnostic options. However, all of these must remain within affordable limits (point 9). MRI and other expensive examinations would go beyond the financial scope. Even nationwide PSA screening financed by the health insurance system could easily cost the systems an additional half billion euros a year. As I said, annually, because early detection is a continuous process that involves testing at regular intervals.

Prostate cancer has a latent early phase, insofar a WHO criterion would be fulfilled. However, this gives rise to special problems, which I will discuss below. Latent early phase or latency phase means that although individual cancer cells can be detected at this stage, they remain in a kind of hibernation. Normally, cancer cells behave in such a way that they multiply unchecked, seek a connection to lymphatic or blood vessels and form daughter tumors, so-called metastases. In the case of prostate cancer, this is referred to as a clinically relevant disease. This is not the case in the latency phase. We know that there is a latency phase from autopsy studies. In this type of investigation, the prostate has been examined in deceased persons of all ages and causes of death (except prostate cancer).

Thus, cancer cells were found in 5% of cases even in those under 30 years of age. In men aged 80 and older, more than half were affected (1). What causes these changes is still largely unknown.

Heredity plays a role, that's for sure, and possibly lifestyle. Western lifestyles, which include excess meat consumption, are thought to be a risk factor. It is unclear when the latency phase begins, when it ends, and what causes it to end.

For most it ends in the 6th-7th decade of life, for others earlier, for others later, again for others never. Once the latency phase is over, the disease breaks out. Also, not all prostate cancers are the same. To all appearances, it is a cancer family, whose members have very different characters. There are the quiet, withdrawn ones, as well as the aggressive bullies and all possible types in between. In other words, we have not really understood the natural course of this disease. It is not so rare that nothing or at least not much happens, so that quite a few men do not die of their cancer, but with their cancer. This is also shown by the disproportion between diagnosis and mortality.

The lifetime risk of being diagnosed with prostate cancer is about 17%. In contrast, the lifetime risk of dying from prostate cancer is 3%. So overdiagnosis is taking place, because ideally you only want to find and save, if possible, the 3% who die from cancer. Fourteen percent receive a diagnosis and often treatment for nothing and nothing. Not only are they overdiagnosed, they are overtreated. The harder you look for prostate cancer, the more you will find latent stages with no clinical significance, and the more you will get into areas of overdiagnosis and overtreatment. Since it is not possible at the moment to properly assess the future risk to the individual, there is also no consensus on how to proceed in the case of such previously identified prostate cancer. But this is precisely what is called for in point 8 of the WHO criteria. Clinical studies are needed to find this out.

Overdiagnosis and overtreatment are important issues. To infer from this that prostate cancer is harmless would be wrong. In 2012 alone, around 92,300 men died of this disease in Europe.(2) In Western Europe, a good 200 out of every 100,000 men develop the disease each year. In a city of 3.5 million people like Berlin, with 1.6 million men and 40% of them of age for prostate cancer, that would be an extrapolated 1,300 new diagnoses each year.

Systematic errors are another source of uncertainty and complicate the interpretation of studies. They contribute to the perception of a benefit from PSA screening that may not actually be there. In the scientific community, we talk about lead time bias and length time bias. Let us assume for a moment that there is no PSA. Prostate cancer would be diagnosed as before 1991, before PSA was known. Men would eventually come to the doctor with problems and the cancer would be palpated. As stated above, we know that prostate cancer develops long before the disease breaks out. Let's continue the mind game (the numbers have nothing to do with reality, I made them up). There is no PSA, a 56-year-old man comes to the doctor with symptoms, he diagnoses prostate cancer and the man dies at 60. Now the whole thing again, but with PSA. So there is PSA and the same man goes for screening at age 52 with no symptoms. The doctor does a PSA test, which leads to a prostate cancer diagnosis. The man is unlucky and still dies of prostate cancer - eight years later. Now you could go and say: because of the PSA test, the man lived four years longer. And that is wrong! The PSA test detected the cancer four years earlier. The man lived exactly the same amount of time

In reference time bias, or length time bias, an apparent screening advantage arises from the selection of slow-growing tumors. Aggressive, fast-growing cancer does not play by the rules. It is less likely to be detected by screening because its dynamics make it more difficult to detect. Today not yet detectable, tomorrow already outgrowing early detection - or not detected at all, because hardly any PSA production would be the possibilities. Fortunately, such courses are rather rare. But actually, early detection is intended to catch precisely these cancers, because they are of the dangerous variety. Instead, more slowly growing, less dangerous tumors are found, which leads to the systematic error of reference time falsification. In purely mathematical terms, the course of the disease is prolonged on average, which could be erroneously attributed to screening.

Current guidelines (4,5) recommend PSA screening for well-informed men. For those with private health insurance, the health insurer covers the costs. In the SHI sector, the dispute about cost coverage is likely to continue. At the moment, nothing is planned in this regard.

¹ Bell KJ, Del Mar C, Wright G, et al. Prevalence of incidental prostate cancer: A systematic review of autopsy studies. Int J Cancer 2015; 137(7): 1749-57.

² Cancer Research UK, (Stand: 01.03.2016).

³ Andriole GL, Grub III RL, Buys SS, et al. Mortality Results from a Randomized Prostate-Cancer Screening Trial. NEJM 2009; 360: 1310-9.

⁴ Mottet N., Cornford P., van den Bergh R.C.N., Briers E., De Santis M., Fanti S., Gillessen S., Grummet J., Henry A., Lam T.B., Mason M.D., Van den Poel H., Van den Kwast T.H., Rouvière O., Wiegel T., Schoots I.G., Tilki D.; members of the EAU – ESTRO – ESUR –SIOG Prostate Cancer Guidelines Panel. EAU – ESTRO – ESUR – SIOG Guidelines on Prostate Cancer 2022. 978-94-92671-07-3. Publisher: EAU Guidelines Office. Place published: Arnhem, The Netherlands.

⁵ Tsodikov A, Gulati R, Heijnsdijk EHM, et al. Reconciling the effects of screening on prostate cancer mortality in the ERSPC and PLCO trials. Ann Intern Med 2017; 167: 449-455.