Controversies of Prostate Cancer Screening: What Are Best Practices for Early Detection?

by Eli Hyams MD, Director, Prostate Cancer Program

Prostate cancer screening continues to be a challenging subject for providers and patients alike. Due to prior guidelines that discouraged screening, variation in guidelines and practice, and the high prevalence of low-risk cancer in aging men, many have opted against screening altogether. However, this neglects the tremendous strides that have been made in early detection efforts, including refined use of PSA as an “entry point” to further testing rather than a criterion for biopsy, as well as the development of diverse non-invasive tools to better understand the risk of men with elevated PSA. Understanding the benefits and limitations of PSA as a screening tool is critical, and counseling should be individualized for patients in a “shared decision-making” approach. 

PSA (“prostate specific antigen”) is an enzyme that liquifies semen. PSA is prostate-specific but not prostate-cancer specific, meaning a result can be elevated due to prostate enlargement (BPH), inflammation, or recent urinary catheter placement, urinary tract infection or prostatitis. PSA has been used as an early detection tool since the late 1980s. PSA has the benefits of ease, accessibility, low expense, and high sensitivity, which are favorable aspects of a screening tool.

DRE (“digital rectal exam”) complements PSA in the assessment of prostate cancer risk, and can reveal palpable nodules on the peripheral zone of the prostate, the most common area for cancer to occur. It can give a sense of prostate size to determine if enlargement may be contributing to a higher PSA level. A DRE is most useful for detection in the setting of an elevated PSA. 

Epidemiological data from national registry data (SEER) have shown benefits from PSA screening, specifically a decrease in mortality and presentation with metastatic disease in the screening era. There has been a decrease in prostate cancer-specific mortality from 38 to 19 per 100,000 men from 1991 to the present. Additionally, those presenting with metastatic disease decreased from 20% to 4% during the same time period. Reductions in metastatic disease in the screening era are substantial, and warrant attention when considering the benefits of screening. 

Harms of prostate cancer screening must also be considered and weighed against the benefits. These can be significant, particularly if men are not evaluated appropriately for an elevated PSA and are brought hastily to biopsy.  Indeed, psychological and physical harm can occur if men are over-tested (e.g., biopsied when they have low baseline risk), over-diagnosed (with slow growing cancer) and over-treated (for slow growing cancers, incurring unnecessary side effects). Thoughtful decision-making at each juncture is critical to ensure men are appropriately counseled on the pros and cons of testing and treatment, and only pursue interventions that are likely to benefit them.

The American Cancer Society, The US Preventive Services Task Force (USPSTF) and American Urological Association prostate cancer screening guidelines have slight variations, however they have three common themes: 

• Discuss screening with patients in a “shared decision-making” approach
• Consider a patient’s individual risk factors (age, ethnicity, family history)
• Avoid screening older men with a shortened life expectancy

Providers should discuss screening utilizing a “risk-based” approach amid shared-decision making. Below is suggested guidance:

• For average risk men, start at age 50. 
• For higher risk men, start at age 45.
• Consider individual risk factors, such as race (Black men), family history (first- or second-degree relatives with prostate cancer, multiple relatives with cancer, or history of germline mutations)
• Extend screening intervals for low risk men
  • Every 2-plus years for low baseline PSA (e.g., PSA less than 1.0 at age 45 to 50)
• Avoid screening older men who have a shortened life expectancy
  • greater than 70 years in general
  • greater than 75 years for increased risk / excellent health

We respect the trust you place in us when referring a patient. Below are suggested clinical scenarios when a referral to a urologic specialist is encouraged:

• Elevated baseline PSA confirmed on repeat PSA within 4 to 6 weeks
• Sequentially rising PSA without clear confounder
• Abnormal DRE
• High baseline risk with or without elevated PSA

It is important to understand and counsel men that risk is a continuous variable. There are no hard thresholds for “normal” versus “abnormal” PSA. PSA levels that are appropriate for a man will vary by age, prostate size, and other risk factors. If a man has an elevated and/or rising PSA, consider referring to urology for further risk assessment. Keep in mind that many men with an elevated or rising PSA will not have prostate cancer. The urologist’s job is to determine the presence or absence of significant cancer through the least invasive means. After a detailed conversation regarding risk factors and a physical exam, men will often undergo further non-invasive testing with blood or urine biomarkers or imaging such as multiparametric MRI, which can aid in risk assessment and determine the potential benefits of biopsy. Men with low risk by testing with greater specificity than PSA do not require a biopsy, which is a significant improvement in practice compared to the past. 

If men do need to have a biopsy, this can be done with image guidance (“MRI fusion biopsy”) and/or through a transperineal approach, which further lowers the risk of infection. Indeed, improving the quality and safety of biopsy, when necessary, has been a priority in urology practice. If a man is diagnosed with a low risk prostate cancer, the standard of care is “active surveillance” to safely monitor men without exposing them to the risks of treatment. This too has been a tremendous improvement in urology practice to mitigate risks of over detection.  

In conclusion, a “shared decision-making” approach with individualized risk assessment and referral to urology for further counseling and testing is the current “best practice” for early detection of prostate cancer. As discussed above, there have been great improvements in the quality of risk assessment for prostate cancer, allowing for improved selection of men for biopsy and treatment, and sparing many men unnecessary anxiety and risk.