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Psa Test in Prostate Cancer Screening

Essentials

  • The PSA test can be used to screen for prostate cancer.
  • The biggest associated problem is overdiagnosis, i.e. finding harmless cancers, leading to unnecessary treatments and complications.
  • In younger age groups (55-69 years), a screening test should always be preceded by discussing any benefits or harms with the patient.
  • Various organizations may recommend only screening men with a life expectancy of more than 10-15 years or not screening men over 70 years at all.
  • Screening tests should not be done unbeknown to the patient, as routine tests in association with health checks, for instance.
  • This text concerns screening of asymptomatic men, only. For PSA testing as part of investigation of suspected prostate symptoms, see Benign Prostatic Hyperplasia.

Prevalence of prostate cancer

  • Prostate cancer is the most common type of cancer in men. Globally, its estimated age-standardized incidence rate is about 31/100 000 and it causes about 375 000 deaths annually http://gco.iarc.fr/.
    • In Europe, the age-standardized incidence rate is about 63/100 000. Each year, more than 470 000 cases are diagnosed and more than 100 000 European men die of prostate cancer (2020). Among men over 70, the annual incidence of the disease is about 600/100 000 in Europe.
  • Prostate cancer hardly occurs in men below 45 years of age. The risk of disease increases rapidly after the age of 65.
  • The number of diagnosed cancers has increased with increasing PSA testing and longer life expectancy in men.
  • Prostate cancer detectable only histologically occurs in 30% of men over 50 and 70-80% of those over 80. One in ten cases of latent prostate cancer develops into clinical cancer.

Screening for prostate cancer

  • Prostate cancer has no specific clinical picture. Symptoms may be similar to those of benign prostatic hyperplasia. Cancer detected by screening is often asymptomatic.
  • Prostate-specific antigen (PSA) is a biomarker measured in blood that can be used to screen for early stage prostate cancer among asymptomatic men.
    • PSA levels increase with age and with increased prostatic tissue mass.
    • PSA is a quite organ-specific but not cancer-specific biomarker: increased levels may be due not only to cancer but also to benign prostatic hyperplasia, for instance.
  • In men below 50 years, 0-2.5 µg/l is considered a normal PSA level. The upper limit of the reference range rises stepwise with age: for men over 69, it is 6.5 µg/l.
    • Abnormal test results often need to be confirmed by a repeat test.
    • Men may have prostate cancer even if the PSA level is within the reference range.
    • The higher the PSA level, the more likely it is that there is cancer tissue in the prostate.
  • The free/total PSA ratio and the rate of PSA increase are significant for risk assessment.
    • If the total PSA is 2.5-10 µg/l and the share of free PSA exceeds 25%, the risk of prostate cancer is quite low and no further investigations are necessary.
    • PSA levels increasing rapidly from test to test may be a sign of prostate cancer.
    • When assessing the probability of cancer, the patient's age and the size of his prostate should also be considered.
  • In 16-year follow-up, mortality from prostate cancer was one fifth lower in the screening group, and the absolute decrease was one prevented death for 570 men invited to screening.

Problems related to screening for prostate cancer

  • The PSA test is inaccurate: it produces a lot of false positive but also false negative results. Its greatest drawback is overdiagnosis, i.e. ‘true' positive findings due to small, harmless cancers, resulting in unnecessary treatment.
  • PSA screening for prostate cancer is ethically problematic. Based on screening, asymptomatic men may be diagnosed with cancer but the course of the disease or its effect on the length of the person's life or his final cause of death cannot be predicted.
  • Invasive forms of treatment are offered for cancer that involve both immediate risks and adverse effects on quality of life.
    • All such treatments are associated with adverse effects, such as impotence, urinary incontinence and gastrointestinal symptoms affecting the quality of the patient's life.
    • One in five patients treated with radical prostatectomy develop long-term incontinence and two in three long-term erectile dysfunction. After radiotherapy, about one in two men retain erection sufficient for intercourse.
  • The older the age groups studied, the greater the probable disadvantages of screening and the lesser its benefits.
  • For the time being, setting up population-level prostate cancer screening programmes based on PSA tests is unjustified and screening needs to be targeted more precisely to maximize its benefits and to minimize its harms.
  • The U.S. Preventive Services Task Force, USPSTF, recommends screening in the 55-69-year age group only when possible advantages and disadvantages have been thoroughly discussed with the patient (shared decision making). USPSTF does not recommend screening for men over 70. In some guidelines (American Cancer Society, European Association of Urology), screening is recommended after discussion for men whose life expectancy exceeds 10-15 years 3.

Informing the patient about screening

  • The patient should be provided with information on possible consequences of a PSA test.
    • A PSA test may reveal prostate cancer that has spread outside the capsule or shows an otherwise high risk of progression that could be cured by radical surgery or radiotherapy, thus saving the patient's life.
    • However, it is more probable that the PSA test and biopsy will reveal an early, local tumour best treated by active surveillance. Invasive treatment with its adverse effects would be unnecessary but the patient would remain constantly worried about the development of his PSA levels.
  • A PSA test must not be performed unbeknown to an asymptomatic patient. It must not be included as a screening test in health checks.
  • Routine screening must be distinguished from using a PSA test as part of the clinical examination of a patient when prostate cancer is suspected as a possibility.
  • From the viewpoint of a single patient, a negative PSA test combined with a physician's assessment of the patient's situation may calm the patient significantly, but cancer, however, can never be definitely excluded.

Examples of topics to be discussed in shared decision making

  • Screening may be both beneficial and harmful.
    • Prostate cancer is one of the most common types of cancer and one of the most common causes of death among menhttp://gco.iarc.fr/today/online-analysis-multi-bars.
    • Many men with prostate cancer are never diagnosed and die of another cause unaware of the disease and asymptomatic.
  • Screening is done with the PSA test, which can be repeated every few years.
    • The test is inaccurate. The result may be positive in the absence of cancer or negative despite cancer.
    • The test may need to be repeated frequently in case of uncertainty because rising levels may suggest cancer even if the results are within the normal range.
  • The diagnosis cannot be based on the PSA test alone but must always be confirmed by biopsy. MRI can be used as a supplementary diagnostic investigation, and it will help to target the biopsy.
    • Biopsy may involve complications, such as infections or bleeding.
    • There are sources of error associated with biopsy, too, such as missing the area with cancer when taking the biopsy.
  • A cancer diagnosis is a lot more probable among men participating in screening than among those not participating.
    • However, a large share of diagnosed cancers will not cause any problems within the patient's lifetime.
    • No test can prove with certainty whether the diagnosed cancer is indolent or will spread rapidly and cause problems. Treatment decisions must be made individually, and treatment may consist of active surveillance, surgery or radiotherapy.
    • Treatments may be associated with adverse effects, such as urinary incontinence or erectile dysfunction. When choosing the treatment, the level of harm caused by any adverse effects should be discussed with the patient. Erectile dysfunction, for instance, will be a bigger problem for a person with an active sexual life than for a sexually inactive person. The development of incontinence is usually unwelcome for anyone.

    References

    • European Association of Urology. Guidelines: Protate cancer. http://uroweb.org/guideline/prostate-cancer/
    • Hugosson J, Roobol MJ, Månsson M et al. A 16-yr Follow-up of the European Randomized study of Screening for Prostate Cancer. Eur Urol 2019;76(1):43-51. [PubMed]
    • US Preventive Services Task Force., Grossman DC, Curry SJ et al. Screening for Prostate Cancer: US Preventive Services Task Force Recommendation Statement. JAMA 2018;319(18):1901-1913. [PubMed]
    • Gandaglia G, Albers P, Abrahamsson PA et al. Structured Population-based Prostate-specific Antigen Screening for Prostate Cancer: The European Association of Urology Position in 2019. Eur Urol 2019;76(2):142-150. [PubMed]
    • Hoffman R. Screening for prostate cancer. UpToDate referred 24.1.2022
    • SWOP - The Prostate Cancer Research Foundation: Prostate cancer risk calculator http://www.prostatecancer-riskcalculator.com/