When did prostate cancer screening start?

Prostate Cancer Early Detection 2017: New Data, New Strategies

In 2016, the data on the early detection of prostate cancer changed due to current publications. The dilemma regarding prostate cancer screening began with the simultaneous publication of two studies in the New England Journal of Medicine in 2009. The larger European study (ERSPC study) with a total of 160,000 participants compared a randomized control group with no PSA determinations should, with a screening group in which PSA was determined every two years. A significant reduction in prostate cancer mortality in the screening group was shown over the course of eleven years. In contrast, the result in the American study (PLCO study) with a total of 80,000 participants, distributed 1: 1 between the screening and control arms and with a median follow-up interval of 6.3 years, was negative [1, 2]. In the years that followed, this led to a detailed discussion of the benefits and risks of a screening program, as the reduction in prostate cancer mortality was balanced against the associated overtreatment - with the result of incontinence and impotence. Ultimately, the discussion in 2011 led to the recommendation by the US health authorities to discourage general screening using PPE.
Five years after the recommendation was published by the health authorities, the American colleagues reported on the effects of this general recommendation at last year's American Urologist Congress. Over the period from 2008 to 2013, a continuous decrease in PSA regulations by 15–20% was observed in all parts of the US population [3]. In addition, a prostate punch biopsy showed an overall decreasing clarification in the case of elevated PSA values, and if a diagnosis was carried out, this was done with higher PSA values ​​overall. Overall, therefore, fewer prostate biopsies were performed and, as a result, more positive biopsies and more carcinomas with a Gleason score of 8 and metastatic diseases were diagnosed. In addition to the decrease in diagnostic measures for the detection of prostate cancer, there was also a change in the treatment of prostate cancer. Overall, fewer radical prostatectomies were performed and more aggressive carcinomas and a clear increase in pT3 and organ-transcending stages were found [4, 5].

High PSA contamination in the control arm of the PLCO study

This negative development is due not least to the incorrect interpretation or presentation of the PLCO study from 2009. The high PSA contamination in the control group had already been blamed for the negative outcome of the study in 2009. PSA contamination means that for men in the control group, in whom no PSA determinations should be carried out, the value was determined anyway and, if the values ​​were elevated, consequences were taken if necessary. In the statistical plan, a maximum PSA contamination in the control group of 20% was assumed. In the primary publication of 2009, the actually measured PSA contamination was given as 38% [2], almost twice as high as assumed. Last year, the colleagues again evaluated all questionnaires regarding the PSA determination in the control group of the PLCO study and showed that over 90% of all men in the control group carry out a PSA determination in the three years before and / or during the study let. Overall, more PSA determinations were carried out in the control group than in the screening group, so that two identical groups were compared with one another and thus no differences could be found [6].
For this reason, the American study for assessing the effect of PSA screening is worthless. This contrasts with the European screening study as the only meaningful study on PSA screening, which in a follow-up publication from 2014 after 13 years of follow-up observed a relative reduction in prostate cancer mortality in the screening group compared to the control group of 29% Has. According to this, a total of 27 prostate carcinomas must be diagnosed in order to save a man from death from prostate carcinoma [7].

Use the PSA test more intelligently!

The PSA test should, however, be used much more intelligently. It can be used as a prognostic factor for the individual assessment of the risk of developing prostate cancer in the course of his life. There is convincing data on this from the Malmö study from the 1970s and 1980s. 21,277 men were followed up over a period of 27 years. Of these, 1,408 developed clinically manifest prostate cancer. The level of the initial PSA value from the 1970s was correlated with the probability of developing clinically manifest prostate cancer after 25 years. With a baseline PSA value of <0.7 ng / ml at the age of 45–49 years, the probability of dying from prostate cancer within 25 years is 0.5%. If the PSA value in this age group is 1.6 ng / ml, the risk of dying from prostate cancer within 25 years is 5%. The PLCO study also showed comparable data [8, 9].
In a cohort study, the Swedish colleagues compared the unscreened population from the Malmö study with the screened population from the Gothenburg study, which was part of the ERSPC study, with regard to prostate cancer detection and the reduction in mortality from prostate cancer. Over a period of 17 years, the probability of discovering prostate cancer in the screened compared to the unscreened population increased from 6% to 15%. At the same time, the mortality from prostate cancer in the screened compared to the unscreened group was reduced from 0.8% to 0.2%, i.e. H. In the screened population, seven men died of prostate cancer, in the non-screened population, however, 29 men died in the same period. From this, the colleagues calculated a “Number Needed to Diagnosis” of 16, i. H. In order to save a man from prostate cancer death, 16 men must be diagnosed with prostate cancer [10].
A screening program is cost-effective if it starts well before the age of 63. If you start at the age of 55 and measure the PSA value every two to three years, a qualitatively adequate year of life obtained through the screening costs around 50,000 dollars. This amount per year of life gained is considered reasonable in Anglo-American literature. If screening is started after the age of 63, the costs increase to 200,000–300,000 dollars per qualitatively adequate year of life gained [11].

Intelligent screening with PPE, ...

The latest German S3 guideline for the treatment of prostate cancer gives the recommendations for early detection (comprehensive screening is not recommended) as follows:
First PSA determination from the age of 45 and a life expectancy over 10 years; If the PSA value is <1 ng / ml, the interval between the PSA determinations should be four years, if the PSA value is 1–2 ng / ml two years and if the PSA value is over 2 ng / ml take place annually [12].

... multiparametric MRI and ...

An additional multiparametric MRI (mpMRI) can v. a. be used in the re-biopsy. The combination of multiparametric MRT-ultrasound fusion biopsy and random biopsy seems to have the highest detection rate of prostate carcinomas (see article by Tiemeyer and Peters, p. 98). Despite the high detection rate of mpMRI, the rate of false positive results for PI-RADS-IV and PI-RADS-V grades is between 30% and 50% [13].

... risk calculators

In addition to the use of the mpMRI, risk calculators can also improve the intelligent use of the PSA determination. For this purpose z. B. the ProstateCheck app to estimate the likelihood of the patient developing prostate cancer in the following years. This probability can be calculated from the parameters PSA value, the ratio of free / total PSA and the age of the patient. Depending on their height, this results in the control intervals or the indication for a punch biopsy. With the help of such risk calculators, 20–30% of biopsies can be saved, with a simultaneous detection rate of high-risk prostate carcinomas of 89% [14].
The Swiss working group around Franz Recker has developed proposals for intelligent preventive care as an individual, risk-adapted prostate PSA screening from the available resources. She suggests determining a baseline PSA value from the age of 45 and, if there is a family history, from the age of 40. According to the risk assessment using the prostate app, the prevention interval should then be fixed at intervals of one to a maximum of eight years. If the PSA value is> 3 ng / ml, the prostate app should be used diagnostically. If the calculated risk of finding prostate cancer in the punch biopsy is below 11%, a PSA follow-up check is carried out after one year. If the risk of prostate cancer is between 11% and 20%, an additional mpMRI should be performed. If this is noticeable, an MRI-ultrasound fusion biopsy should be attempted. If the MRI is negative, it must be discussed with the patient whether a biopsy should be performed or whether a check-up can be carried out after one year. If the risk of prostate cancer is greater than 20%, a systematic random biopsy should be performed, possibly in combination with an mpMRI [15]. Overall, this leads to significantly fewer biopsies and an increased detection of aggressive prostate carcinomas, which can then be actively treated.

literature
1. Schröder FH et al. Screening and prostate-cancer mortality in a randomized European study. N Engl J Med 2009; 360: 1320-8.
2. Andriole GL et al. Mortality results from a randomized prostate-cancer screening trial. N Engl J Med 2009; 360: 1310-9.
3. Fleshner K et al. The effect of the USPSTF PSA screening recommendation on prostate cancer incidence patterns in the USA. Nat Rev Urol 2017; 14: 26-37.
4. Jemal A et al. Prostate cancer incidence and PSA testing patterns in relation to USPSTF screening recommendations. J Am Med Ass 2015; 314: 2054-61.
5. Misra-Hebert AD et al. Prostate cancer screening practices in a large, integrated health system: 2007-2014. BJU Int 2017, Jan 31 [Epub ahead of print, DOI 10.1111 / bju.13793].
6. Shoag JE et al. Reevaluating PSA testing rates in the PLCO trial. N Engl J Med 2016; 374: 1795-6.
7. Schröder FH et al. Screening and prostate cancer mortality: Results of the European Randomized Study of Screening for Prostate Cancer (ERSPC) at 13 years of follow-up. Lancet 2014; 384: 2027-35.
8. Vickers AJ et al. Strategy for detection of prostate cancer based on relation between prostate specific antigen at age 40-55 and long term risk of metastasis: Case-control study. Br Med J 2013; 346: f2023.
9. Shoag J et al. Lethal prostate cancer in the PLCO cancer screening trial. Eur Urol 2016; 70: 2-5.
10. Carlsson S et al. Screening for prostate cancer starting at age 50-54 years. A population-based cohort study. Eur Urol 2017; 71: 46-52.
11. Heijnsdijk EA et al. Cost-effectiveness of prostate cancer screening: A simulation study based on ERSPC data. J Natl Cancer Inst 2014; 107: 366.
12. Interdisciplinary guideline of quality S3 for the early detection, diagnosis and therapy of the different stages of prostate cancer. Long version 4.0 - December 2016: 31-43. AWMF register number 043 / 0220L.
13. Filson CP et al. Prostate cancer detection with magnetic resonance-ultrasound fusion biopsy: The role of systematic and targeted biopsies. Cancer 2016; 122: 884-92.
14. Randazzo M et al. A "PSA pyramid" for men with initial prostate-specific antigen ≤ 3 ng / ml: A plea for individualized prostate cancer screening. Eur Urol 2015; 68: 591-7.
15. Kwiatkowski M et al. Prostate cancer screening: And yet it moves! Asian J Androl 2015; 17: 437-8.