Underestimating Prostate Cancer Risk

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You’re cruising along the interstate with your honey, headed for a much-anticipated resort vacation. Before you hit the open road, you had your mechanic check the usual things: fluids, brake pads, tires, etc. The small oil leak he discovered was easily fixed so you now have peace of mind. However, 325 miles from home, having just tanked up and gotten back on the highway, the check engine light comes on. Dang! If you failed to tighten the gas cap, that’s one thing. But if it signals a more serious situation that will damage expensive engine components, that’s another thing altogether. What’s the risk level? Without an accurate analysis, you’re left to worry you’ll miss a window for an easy fix.

An unknown number of men diagnosed with prostate cancer (PCa) who go on Active Surveillance are in a similar situation. Their prostate cancer risk level may not have been accurately stratified as they proceed on the road of life.

The Active Surveillance trend

For decades, PCa treatment was an all-or-nothing proposition. Newly diagnosed patients either had radical (whole-gland) surgery or radiation, or they went on Watchful Waiting (WW). Sadly, radical treatments constitute “overkill” for patients with very low risk (VLR) or low risk (LR) disease but their doctors recommend a total gland treatment to “get all the cancer.” These men had very low probability of cancer-specific death, but after radical treatment they face the chance of poor quality of life due to treatment side effects of impotence and incontinence.

In recent years WW has given way to a more proactive monitoring protocol, Active Surveillance (AS). During the past decade, there has been a marked trend toward recommending AS for newly diagnosed PCa patients with low risk prostate cancer. According to a 2019 published study, the use of AS rose dramatically from 2010 to 2015. The numbers quadrupled for men age 55 or younger (from 8.61% to 34.56%); it was less steep for men age 56 and above (from 15.99% to 43.81%). In my experience, the two biggest drivers for this are a) better ability to understand and diagnose VLR and LR disease, and b) patient demand to avoid the risk of treatment side effects as long as possible.

Danger of underestimating cancer risk

At the 2017 Society of Urologic Oncology meeting, a paper on accurate risk stratification of PCa was presented by Dr. Daniel W. Lin. When it comes to qualifying patients for AS, Dr. Lin pointed out the problem of underestimating prostate cancer risk level because of inadequate information. How do we know if a patient is truly low risk, since conventional TRUS (transrectal ultrasound) guided biopsies often miss significant (Gleason grade 4) cancer? A patient whose biopsy failed to detect even one area of Gleason 3+4 or 4+3 may actually be harboring an aggressive cell line that can become life-threatening. For this individual, choosing to go on Active Surveillance is like driving with the check engine light on, believing that the problem is just a loose gas cap when in fact a worse problem is lurking under the hood.

This situation may be more prevalent than we know. Dr. Lin points out that “at least 50% of patients are reclassified to more aggressive pathology between 5-10 years after initiating AS.” The danger lies in the potential for missing a curative treatment window. While the majority of PCa cell lines behave somewhat predictably, at least 15% of PCa cases don’t signal their presence through rising PSA, and are more capable of quickly advancing beyond the gland. When this happens, hope for a successful local treatment begins to dim.

Thankfully, today’s genomic tests have the ability to identify the biomarkers of these cell lines while they are still confined within the gland.

Imaging and biomarkers

According to Dr. Lin, biomarkers from blood tests or tissue samples hold great promise for identifying specific molecular traits that flash critical warnings. In addition, he cites multiparametric MRI (mpMRI) as a modality that can be used in combination with biomarkers to paint an accurate portrait of a patient’s PCa.

These two advanced resources serve each other well. Dr. Lin states, “Combinations of imaging and biomarkers may be the key to improving the test characteristics of both modalities in the future.” However, he cautions that not all mpMRI interpreters are equally qualified, recognizing that less experienced readers may miss important imaging clues regarding disease aggressiveness. I agree. In my work, I get requests for second opinions on patients’ image CDs and radiology reports from other centers. I have seen too many “missed clues,” as Dr. Lin puts it.

When patients considering AS are correctly stratified as Very Low Risk or Low Risk through the integration of imaging and biomarkers, and they adhere to an excellent monitoring protocol, the odds are great that AS is a superb choice for them. They can confidently avoid the anxiety that often accompanies AS: “I have cancer growing in my body. What if I miss the window for an easier treatment like focal therapy?”

A safe journey on life’s road

Studies have shown that when mpMRI of the prostate is done by an experienced team with an expert reader—and integrated with biomarkers as appropriate—the accuracy of prostate cancer risk stratification is far more assured than what conventional TRUS biopsy can offer. The check engine light can safely be turned off, and the patient can confidently proceed on the trip along life’s road, free from worrying about missing an easy fix.

Copyright by Dan Sperling, MD. Reprint permission courtesy of Sperling Prostate Center (New York, Florida), the leading U.S. center for multiparametric detection, diagnosis and image-guided focal treatment of prostate cancer.

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