PSA and Prostate Cancer Mortality: What’s the Link?

The dramatic decline in prostate cancer mortality started soon after the increase in the use of PSA as a screening tool, although the major randomized clinical trials did not replicate many of these results — even those trials including surgery and radiation. The authors proposed that the introduction of adjuvant hormonal therapy in the 1990s — especially luteinizing hormone-releasing hormone (LHRH) agonists — substantially contributed to this decline in mortality.

The introduction of routine PSA screening has also been associated with a decrease in the incidence of metastatic prostate cancer. Again, this was not replicated in European trials, where the protocol was repeat PSA testing every 2 to 4 years compared with testing annually in the United States. This type of protocol could also be associated with earlier introduction of adjuvant hormonal therapy based on more frequent testing.

The authors argued that PSA screening has led to overdiagnosis and overtreatment of a condition that may not actually cause symptoms or death. Therefore, they agree with the US Preventive Services Task Force to not recommend routine PSA testing without an individualized discussion of all the potential risks and benefits. Treatments for prostate cancer can frequently impact morbidity and patient quality of life, especially when the patient is older. And this is not uncommon, as the median age at death due to prostate cancer — 80 years — is relatively high.⁷ When a primary care physician is considering recommending PSA testing for a patient, there is also a concern that it could distract from other medical issues, along with raising certain medicolegal concerns.

If providers continue to proceed with PSA testing despite the issues raised by the study authors, the authors recommend that there be a higher PSA threshold for biopsies, such as 10 nanograms per milliliter. In addition to an absolute increase in the threshold, the authors also propose that other strategies be considered, such as a complex algorithm to factor in a patient’s age and rate of PSA increase over time, adjusting for prostate volume, and utilizing magnetic resonance imaging to identify lesions to biopsy.

In conclusion, the authors stated that routine PSA screening provides a substantial benefit for few patients, while exposing other patients to potentially significant physical and mental morbidity with biopsies, surgeries, treatments, and financial obligations.

It may be “easy” to find certain cancers using PSA, however, it is significantly more challenging to find those specific types of cancers that if left untreated, can lead to negative patient outcomes. More thorough screening trials will be challenging to complete in the future based on the number of patients needed for those trials and the hurdles surrounding tracking the long-term follow-up data.

References

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5. Thompson IM, Goodman PJ, Tangen CM, et al. The influence of finasteride on the development of prostate cancer. N Engl J Med. 2003;349(3):215-224.
6. Mahal BA, Yang DD, Sweeney C, Trinh QD, Feng FY, Nguyen PL. Identification of low prostate-specific antigen, high Gleason prostate cancer as a unique hormone-resistant entity with poor survival: a contemporary analysis of over 600,000 patients. Int J Radiat Oncol Biol Phys. 2017;99(Suppl 2):S133.
7. Surveillance, Epidemiology, and End Results Program (SEER). SEER Cancer Statistics Review (CSR) 1975-2016. Updated April 9, 2020. Accessed April 26, 2020.