What are the controversies surrounding the use of Prostate-Specific Antigen (PSA) in diagnosing prostate cancer?

From the Guidelines

Using PSA to diagnose prostate cancer is controversial due to its limitations in accurately detecting clinically significant cancers, leading to overdiagnosis and overtreatment, as well as its inability to distinguish between aggressive and indolent cancers 1. The controversy surrounding PSA testing stems from its high false-positive rate, with up to 80% of positive results being false positives when the PSA cutoff is between 2.5 and 4.0 µg/L, leading to unnecessary biopsies and treatments 1. Additionally, the test's lack of specificity means that elevated PSA levels can result from non-cancerous conditions, further contributing to overdiagnosis and overtreatment 1. The ERSPC study found that 1410 men would need to be screened to prevent 1 death from prostate cancer, highlighting the small potential benefit of PSA-based screening 1. Moreover, the harms associated with prostate cancer screening and treatment, including infections, urinary incontinence, and erectile dysfunction, can have a significant impact on a patient's quality of life 1. Given these limitations and harms, the American College of Physicians recommends that clinicians inform men between the ages of 50 and 69 about the limited potential benefits and substantial harms of screening for prostate cancer, and that screening decisions should be based on a shared decision-making approach 1. Key points to consider when discussing PSA testing with patients include:

• The potential benefits of screening, including the reduction of deaths from prostate cancer
• The substantial harms associated with screening, including overdiagnosis, overtreatment, and false positives
• The importance of shared decision-making in determining whether to undergo PSA testing
• The need to weigh the potential benefits against the harms and consider individual patient preferences and values 1. Ultimately, the decision to use PSA testing should be made on a case-by-case basis, taking into account the individual patient's risk factors, preferences, and values, as well as the potential benefits and harms of screening 1.

From the Research

Controversy Surrounding PSA Diagnosis

The use of Prostate-Specific Antigen (PSA) to diagnose prostate cancer is controversial due to several reasons:

• Overdiagnosis of low-risk cancers: Studies have shown that PSA screening can lead to the diagnosis of low-risk prostate cancers that may not have caused symptoms or death during a man's lifetime 2, 3, 4.
• Lack of sensitivity and specificity: PSA testing has limited sensitivity and specificity, which can result in false positives and false negatives 4.
• Variation in clinical guidelines: There is a lack of consensus on optimal active surveillance and intervention thresholds, leading to variations in clinical practice 3, 5.
• Risk of overtreatment: The diagnosis of prostate cancer can lead to overtreatment, which can result in significant side effects and decreased quality of life 2, 3.
• Limited benefit in some studies: Some studies, such as the PLCO screening trial, have reported no benefit from PSA screening, although this may be due to flaws in the study design 6.

Limitations of PSA Screening

PSA screening has several limitations, including:

• Detection of clinically insignificant cancers: PSA screening can detect cancers that are not clinically significant and may not have caused symptoms or death during a man's lifetime 2, 4.
• False positives and false negatives: PSA testing can result in false positives and false negatives, which can lead to unnecessary anxiety and treatment 4.
• Need for additional testing: PSA screening often requires additional testing, such as biopsies and imaging studies, which can be invasive and costly 3, 5.

Need for Improved Guidelines and Research

There is a need for improved guidelines and research on PSA screening and active surveillance for prostate cancer, including:

• Development of more accurate biomarkers: Research is needed to develop more accurate biomarkers for prostate cancer, such as urinary RNA biomarkers 4.
• Standardization of clinical guidelines: Clinical guidelines for active surveillance and intervention thresholds need to be standardized to reduce variations in clinical practice 3, 5.
• Long-term studies: Long-term studies are needed to determine the effectiveness of PSA screening and active surveillance for prostate cancer 5, 6.