Did you ever watch a murder mystery in which all the clues appear to point to an easy solution—but there’s a late breaking twist when the killer turns out to have “hiding in plain sight” all along? Here’s a similar situation: all the usual clinical factors seem to indicate that a prostate cancer patient has low risk disease. At the doctor’s recommendation, the patient may choose a focal therapy or Active Surveillance, and the initial strategy looks like it has succeeded. However, as expressed in a Harvard Medicine newsletter, 10-15% of prostate cancer (PCa) cases appear low risk, but they’re not. In a surprising and unpleasant twist, the strategy doesn’t go as planned. It becomes apparent that the patient was actually harboring a more aggressive PCa.

Low-risk PCa is usually diagnosed based on several clinical factors (patient age, PSA, Gleason grade or Grade Group, stage, and family history). If a patient’s diagnostic workup ends there, how can the doctor know if a potential killer cell line is “hiding in plain sight”? Thankfully, for men with low-risk PCa there is a growing array of new risk assessment methods. In addition to the usual factors, the following shed more specific light on the situation:

• Total volume of cancer
• PSA density
• PSA kinetics (rate of increase)
• PI-RADS score of 4-5 for suspicious lesions seen on multiparametric MRI
• Circulating tumor cells for germline profiling
• Genomic analysis.^[i]

Integrating any or all of the above factors provides additional information to help tailor a treatment plan for low-risk patients. Unfortunately, these evaluations are often not done when the usual clinical factors appear favorable. However, there is an emerging movement to change that situation:

There are many factors which should be routinely integrated into the initial management decision as well as determining intensity and frequency of active surveillance. Development of comprehensive multivariable instruments to guide clinical decisions is encouraged.^[ii]

As of this writing, the newer diagnostic tools are primarily reserved for cases of patients clearly at risk for advanced or metastatic disease.^[iii] On the other hand, grass roots patient awareness of the value of deeper analysis is increasing. For instance, a national patient advocacy organization, ZERO Prostate Cancer, advises newly diagnosed men:

Genomic testing is useful for helping prostate cancer patients and their doctors decide on a treatment. These tests are most helpful for those who are newly diagnosed with prostate cancer that is still confined to the prostate. … By looking at the genetic makeup of the prostate cancer, genomic tests may help predict whether a person’s prostate cancer will grow slowly or aggressively.

The Sperling Prostate Center suggests that patients newly diagnosed with low-risk, localized PCa discuss with their doctor the merits of additional analysis of their situation. The best way to tailor a treatment strategy to an individual’s needs is to have as complete a profile of his PCa as possible. The American Society of Clinical Oncology advises patients and their doctors to seek preauthorization: “Most health insurance plans will cover the cost of genetic testing when recommended by a physician. However, all coverage and reimbursement is subject to Medicare, Medicaid, and third-party payer benefit plans.”

Finally, here’s a gentle reminder that 3T multiparametric MRI (mpMRI) done by an expert specialist is like engaging Sherlock Holmes to consult to your mystery-solving team. Don’t wait for an unexpected twist. When it comes to detecting and identifying a patient’s disease and need for further testing, mpMRI excels at identifying abnormalities that may not have been picked up by other clinical factors. If you are diagnosed with low-risk disease, make sure you leave no clues overlooked. Then you can confidently choose the treatment plan that matches the true nature of your disease.

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.

[i] Ho MD, Ross AE, Eggener SE. Risk Stratification of Low-risk Prostate Cancer: Individualizing Care in the Era of Active Surveillance. J Urol. 2023 Jul;210(1):38-45.
[ii] Ibid.
[iii] Genetic and Genomic Testing for Prostate Cancer: Beyond DNA Repair. Cameron Herberts, Alexander W. Wyatt, Paul L. Nguyen, and Heather H. Cheng. American Society of Clinical Oncology Educational Book 2023 :43