Life may be viewed as an accumulation of lessons learned through experience. Some lessons are learned almost with the speed of lightning because the evidence is simple, clear and immediate. For example, touching a hot stove quickly teaches the victim to either avoid the stove, or gently test it by holding a hand above the surface to feel for heat. On the other hand, more problematic lessons take years or even decades to gain the necessary experience and create tools to solve the problem. Such is the case with overtreating prostate cancer (PCa).

When the PSA test was introduced about 30 years ago, it was seen as a blessing. The medical world didn’t have to wait for PCa symptoms to appear at a point where the disease was incurable. Instead, suspicion of silent PCa was obtained through an abnormally high blood test result. Great! However, it led to unintended consequences. Soon, millions of men were being sent for biopsies. At first, they were sextant biopsies using 6 needles, three on each side of the gland, to sample for cancer—which was assumed to be a multifocal disease. Since 6 proved to often miss PCa, over the next decade or so the number expanded to 12, followed by a trend to do saturation biopsies with 20+ needles, since prostatectomy specimens revealed cancer missed by a lower number of needles.

For these and other reasons, patients whose biopsies were positive for even a small amount of low-risk PCa were encouraged to have their entire gland (plus a few lymph nodes) surgically removed by radical prostatectomy, or treated with radiation. Back then, evidence was lacking that many cases did not need immediate treatment—or possibly, any treatment at all! Thus, untold thousands of patients had their prostate glands clobbered, which is called overtreatment. We just didn’t realize it at the time. And, even if we had, there weren’t less aggressive treatment options available. Given the lack of sufficient evidence and the scarcity of precision diagnostic tools, many patients who were overtreated were left with urinary or bowel incontinence, and erectile dysfunction as the price they paid for the chance to eradicate their cancer. This was the PCa landscape as we entered the New Millennium.

New tools, new evidence

Thankfully, since 2000 there has been a virtual revolution in detecting, diagnosing and treatment PCa. New tools like more refined targeted biopsy methods, improved scientific analysis, powerful multiparametric MRI scans, and the development of ablation technologies to immediately destroy tumors in the body have accomplished three goals:

• We can now identify which patients need a biopsy and which don’t,
• Of the patients whose biopsy is positive to PCa, which need immediate treatment, and
• Of those who need immediate treatment, which need a whole-gland treatment and which can buy time with a repeatable focal treatment.

There’s one group of patients, however, for which we still need more evidence. These are men whose PCa appears suitable for holding off on treatment to see if it progresses to the point where intervention must occur. Today’s guidelines urge doctors and low-risk patients to avoid overtreatment through an Active Surveillance (AS) protocol in order to monitor their disease.

But AS may need to be more intensive for some patients than others. As a news announcement from the Fred Hutch Cancer Center quotes genetic epidemiologist Burcu Darst, PhD, “ ‘The guidelines recommend they go on active surveillance rather than getting treated. For many of them, it’s really unlikely they’ll later be diagnosed with aggressive disease.’ The problem — for patients, clinicians and researchers — is figuring out who will develop an aggressive form of the disease and who will not.”

How intense should AS monitoring be?

The standard protocol for AS according to the National Comprehensive Cancer Network (NCCN) is:

• PSA testing: Every 6 months or less, unless clinically indicated
• Digital rectal exam (DRE): Every 12 months or less, unless clinically indicated
• Repeat prostate biopsy: Every 12 months or less, unless clinically indicated
• Multiparametric MRI (mpMRI): Every 12 months or less, unless clinically indicated

This is fairly intensive, especially when it’s time for a repeat biopsy. However, Darst and others are working on a new tool that may help identify patients unlikely to experience progression of their PCa into more life-threatening cancer. The tool is called a polygenic risk score, or PRS. A person’s blood or saliva can be used for analysis of potentially dangerous gene mutations. Based on the findings, a numeric score is assigned. Those with lower scores may qualify for less intensive AS.

A large-scale research study was conducted with 1200 PCa patients from Jan. 2023 – April 2024. All patients were on AS for localized PCa. Each patient was given a PRS based on the presence of 451 multi ancestry PCa risk variants and 400 PCa specific risk variants. The patients were monitored for any upgrading, which was then correlated with their PRS. The study authors found that “high PRS was associated with risk of upgrading and possibly tumor multifocality,” suggesting clinical decision-making in favor of closer, more intensive AS protocols.^[i]

This work is promising, but not yet ready for prime time. The authors caution that PRS has the potential to inform AS protocols, but more research is needed to see if the new tool improves clinical decisions. Until that occurs, the Sperling Prostate Center offers advanced diagnosis through our multiparametric MRI (mpMRI) and real-time MRI-guided targeted biopsy in which a minimal number of needles provides maximum diagnostic accuracy. When indicated, our Center can provide genomic analysis. All of our services are designed to inform treatment matching, so each patient receives customized treatment according to his PCa and his lifestyle preferences. For more information, contact us.

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] Goss LB, Liu M, Zheng Y, Guo B et al. Polygenic Risk Score and Upgrading in Patients With Prostate Cancer Receiving Active Surveillance. JAMA Oncol. 2024 Dec 12.