A new paper on PSA screening for prostate cancer (PCa) begins by pointing out that screening reduces PCa deaths; however, PSA followed by immediate biopsy increases cases of low-risk patients who have overly aggressive treatments that leave them with impaired urinary or sexual function—up to 12 years or more!^[i] The authors propose more refined screening steps to better identify PSA false alarms before more invasive tests occur. The next steps should determine who needs a biopsy, and in turn, who can delay treatment or have a minimalist therapy vs. those who need immediate aggressive treatment.

The article made me think of the expression, “separating sheep from goats.” While it may sound like weeding out the bad from the good, its origins come from the practical side of herding. About 10,000 years ago, people discovered that sheep and goats had common benefits for humans: easy to domesticate, economical to feed even in desert locations, milk for drinking or cheese production, meat, and hair or wool for weaving. No wonder ancestral cultures developed the art of herding animals!

Sheep and goats were grazed together on available pasturage, each with slightly different feeding habits that complement each other. With enough space to roam, they are compatible. But, when herded in for the night, it’s not wise to pen them together. Sheep tend to be docile, but goats can become aggressive and butt the sheep. This cranks up unruly flock behavior. Wise shepherds recognized it was in the best health interests of both species to separate the sheep from the goats in two different pens.

In the paper I mentioned above, the authors are getting at is this: It’s very important to recognize that suspicious PSA results should not be herded together. You have to answer two questions as efficiently, accurately and harmlessly as possible:

1. Whose PSA means PCa, and whose doesn’t?
2. For those with PCa, whose cancer is docile (sheep) and whose can become aggressive (goat)?

Getting answers efficiently, accurately, harmlessly

PSA screening has merit as a warning system, but not as a diagnostic system. An abnormally high PSA test result—or a result that rises over several years—raises a red flag. However, it does not necessarily mean PCa is present. Many noncancerous conditions also raise PSA, so more information is needed. The methods for obtaining it should be efficient, accurate, and harmless.

In the traditional screening pathway, a needle biopsy is the next step to gain information. While this is efficient, it is not always accurate or harmless (see my blog on the human pincushion). A more accurate and harmless pathway is suggested by the authors: “After a positive prostate-specific antigen test result (more than 4 ng/mL), the test should be repeated.”^[ii] This is definitely efficient and harmless. Then, if the result is still high, they recommend multiparametric MRI (mpMRI) and urine or blood biomarkers before biopsy. While having a prostate mpMRI may feel less efficient than a blood or urine test, a noninvasive picture is worth a thousand inefficient words and invasive tests. Up to this point, these steps accurately and harmlessly distinguish who does or does not need a biopsy. For those who end up in the need-a biopsy group, the latest research shows that an in-bore MRI-guided targeted biopsy is the most accurate with the least potential for harm. Sure, a randomized TRUS biopsy in a urologist’s office may take less time, but the trade-off in diagnostic accuracy and reducing harm by using minimum needles is evident.

If your own screening pathway has brought you to the point of a biopsy, the biopsy itself is the definitive way of separating the sheep (insignificant PCa) from the goats (significant PCa). It reveals the Gleason score and Grade Group (GG) scores that define whether the cancer is insignificant or significant, according to accepted definitions:

Gleason score	Grade Group (GG)	Definition	Risk level
Gleason 3+3=6	Grade Group 1	Insignificant	Very low/low
Gleason 3+4=7	Grade Group 2	Significant	Intermediate (favorable)
Gleason 4+3=7	Grade Group 3	Significant	Intermediate (unfavorable)
Gleason 4+4=8	Grade Group 4	Significant	High
Gleason 4+5=9, 5+4=9, 5+5=10	Grade Group 5	Significant	Very high

Separating those who don’t need immediate treatment from those who do

Back to the article, the authors state, “The primary intent of screening is to identify patients with clinically significant prostate cancer who may benefit from curative treatment while minimizing the detection of clinically insignificant cancer.”^[iii] A more refined pathway clarifies that:

1. Not every man with an unusual PSA needs a biopsy. Get more information by repeat PSA test, mpMRI, urine or blood biomarkers to rule out biopsy need.
2. Not every biopsy will be positive for PCa. If negative, follow up with annual PSAs and same steps as in A.
3. If the biopsy is positive for PCa, is it insignificant or significant?
1. If insignificant, the patient may be a candidate for Active Surveillance or focal therapy. b. If significant, match the aggressiveness of the treatment to the Grade Group plus clinical factors from the biopsy, mpMRI, etc.

Following logical steps in a screening pathway is the most accurate, efficient, and harmless way to identify patient needs. Or, to put it another way, it’s the best way to separate the sheep (insignificant PCa) from the goats (significant PCa).

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] Unger JM, Till C, Tangen CM, Hershman DL et al. Long-Term Adverse Effects and Complications After Prostate Cancer Treatment. JAMA Oncol. 2024 Nov 7:e244397.
[ii] Ibid.
[iii] Xu J, McPharlin S, Mulhem E. Prostate Cancer Screening: Common Questions and Answers. Am Fam Physician. 2024 Nov;110(5):493-499.