“Out of all the stars labeled Box Office Poison by the Independent Theater Owners Association in 1938, Katharine Hepburn is one who maintains a high degree of name recognition today…”

This is the opening sentence of a January 2023 article in Hollywood Revue, explaining how the Great Kate was dealt a blow to her reputation—a blow that put the kibosh on her trajectory into stardom. However, the intrepid actress eventually transcended being blackballed to become The First Lady of Cinema.

A parallel situation occurred in prostate cancer screening after the PSA had gained national prominence as a way to detect prostate cancer (PCa). In 2012, the US Preventive Services Task Force (USPSTF) put the kibosh on PSA’s promise by demoting it to a Grade D recommendation against its use as a screening test. By then, the test had risen to stardom as a lifesaver. “The introduction of prostate-specific antigen (PSA)–based screening for prostate cancer in the early 1990s was followed by a nearly 2-decade long decline in prostate cancer metastasis and mortality.”^[i] However, just as some unfortunate Hepburn films had made a deep cut in ticket sales, the PSA test had led to unfortunate harms that cut deeply into men’s quality of life. Since its big flaw was that it lacked specificity for PCa, suspicious PSA results rushed untold numbers of men to negative TRUS biopsies—with their risks of infection and other side effects— or biopsies positive for insignificant prostate cancer (PCA). As a result, countless men were then overtreated with aggressive surgery or radiation that left them unable to hold pee or attain erections.

Since the 2012 downgrade, three trends are serving to restore PSA’s reputation as an important step in saving men’s lives:

1. Longer term, higher quality studies support the health and economic benefits of screening,
2. The previous harms associated with PSA (overbiopsy and overdiagnosis) are avoidable thanks to a combination of better imaging using MRI, less invasive MRI-targeted biopsies, promotion of Active Surveillance for qualified patients, and focal therapies for qualified patients.
3. A shift in scientific understanding of PCa (its natural history, variety of cell lines, genetic mutations, etc.) now recognizes the difference between insignificant PCa (does not need immediate treatment) vs. significant PCa (needs immediate treatment).

Since a suspicious PSA blood test acts as a preliminary alert that this individual may have PCa, it has the potential to preserve the natural course of his life by eliminating a possibly deadly disease. In fact, a 2024 randomized study of over 24,000 men found that just “a single invitation for PSA screening compared with standard practice without routine screening reduced prostate cancer deaths at a median follow-up of 15 years.”^[ii] One would think the USPSTF would sit up and take notice.

Restoring the value of PSA

Just as Katharine Hepburn restored her reputation and went on to Hollywood glory, it’s time to restore the good name of inexpensive, broad PSA screening and bring back its luster as a lifesaver. How do we go about this? First, let’s say how we DON’T do this. If a man’s PSA test comes back abnormally high or rising, we DON’T rush him into a conventional TRUS-guided biopsy that randomly samples a minimum 12 areas of his prostate gland. This practice simply perpetuates the PSA problem recognized back in 2012. Instead, to avoid the possible harms of such a biopsy method, that same man has a multiparametric MRI (mpMRI) scan of his prostate done on a powerful 3 T (Tesla) magnet—preferably by an experienced radiologist. Under those conditions, mpMRI consistently predicts the presence of clinically significant PCa that should be biopsied. Without recognition of significant disease, the man can safely avoid a biopsy and continue to monitor with PSA.

A recent high-quality study by Tauvinen, et al. (2024) also suggests that an intermediate step called a biomarker analysis can be done between mpMRI and biopsy.^[iii] The intent is to further identify men with genomic red flags for PCa aggressiveness, a step that offers “…promise of aiming detection efforts specifically at more aggressive, potentially lethal cancers,”^[iv] while ruling out the need for biopsy if imaging and biomarkers together indicate it’s safe to continue to monitor by PSA/mpMRI for progression. Thus, a simple PSA test followed up with noninvasive measures rules biopsy need in or out. For those didn’t need a biopsy, the PSA test led them to additional baseline information (MRI and biomarkers) with future value. They’ve lost nothing and gained clinical knowledge.

On the other hand, if the additional step(s) after an abnormal PSA yield detection of significant PCa, the final step toward a confirmatory diagnosis should be a real-time MRI-guided targeted biopsy. Not only does this selectively sample the suspicious area most likely to harbor aggressive PCa cells, it only requires a few needles. “In this technique, direct visualization of the needle, needle guide, and needle trajectory during the procedure provides a precise and versatile strategy to accurately sample suspicious lesions, improving detection of clinically significant cancers.”^[v] This approach minimizes biopsy risks while providing the most accurate diagnosis—again eliminating the earlier harms associated with PSA.

The PSA test as a screening tool should be brought back as a routine part of every man’s annual wellness visit. Its history of collateral harm has been redeemed. Following a PSA alert, mpMRI quickly and painlessly identifies if a) PCa is present, b) it is still localized, and c) it is insignificant or significant. If it is significant, an extra step may be used to test for high-risk biomarkers. All of that should occur before a biopsy. Then if needed, a real-time MRI targeted biopsy diagnosis is so accurate that treatment (or Active Surveillance, if appropriate) can be tailored to the individual. All this, thanks to a humble annual blood draw! If Oscars were given for early detection, PSA would win the Best Starting Point Award.

NOTE: This content is solely for purposes of information and does not substitute for diagnostic or medical advice. Talk to your doctor if you are experiencing pelvic pain, or have any other health concerns or questions of a personal medical nature.

References

[i] Tosoian JJ, PensonDF, Chinnaiyan AM. A Pragmatic Approach to Prostate Cancer Screening. JAMA. Published online April 06, 2024. doi:10.1001/jama.2024.4089
[ii] Martin RM, Turner EL, Young GJ, Metcalfe C et al. Prostate-Specific Antigen Screening and 15-Year Prostate Cancer Mortality: A Secondary Analysis of the CAP Randomized Clinical Trial. JAMA. 2024 Apr 6:e244011.
[iii] Auvinen A, Tammela TLJ, Mirtti T, et al. Prostate Cancer Screening With PSA, Kallikrein Panel, and MRI: The ProScreen Randomized Trial. JAMA. Published online April 06, 2024.
[iv] Tosoian et al., ibid.
[v] Recchimuzzi DZ, Diaz de Leon A, Pedrosa I, Travalini D et al. Direct MRI-guided In-Bore Targeted Biopsy of the
Prostate: A Step-by-Step How To and Lessons Learned. Radiographics. 2024 Feb;44(2):e230142.