When Julia Child pioneered a TV cooking show, she became the first celebrity chef. She spent years developing and testing recipes so even wannabe chefs at home could succeed at French cooking.

If only there were an easy-to-follow recipe for choosing the prostate cancer (PCa) treatment with the greatest chance for success! Decision-making is complicated by an ever-increasing menu of choices. For localized PCa, options run the gamut from Active Surveillance to partial gland to whole-gland (radical) treatments. For advanced PCa that has moved to the prostate bed or local lymph nodes, treatments like surgery, radiation, and androgen deprivation therapy (ADT) may be offered in customized combination for each case. Even for metastatic PCa, there are now immunotherapies and targeted therapies that can be combined or serialized in tailored ways.

A decision-making recipe

The guiding principle is, match the treatment to the disease. Many patients don’t realize that doctors already do have a recipe or formula for decision-making. It’s made up of the following ingredients:

• 1 part clinical factors: PSA (and PSA variants), Gleason score, number of positive biopsy needles, percent of PCa per needle sample, tumor stage
• 1 part multiparametric MRI: PI-RADS score, visual clues
• 1 part other risk factors: age, ethnicity, family history, eating habits, weight, environmental exposure to toxins, even geography

Blend all ingredients and process thoroughly to arrive at the best match. However, there’s a catch. Not all PCa cell lines are created equal.

Some are more dangerous, but until recently scientists lacked the tools to uncover the biological secrets behind cells with more aggressive behaviors. How could they detect and decode their secrets? While the time-tested recipe for treatment choice was good, it wasn’t sufficiently fine-tuned. This led to dual problems: over-treating insignificant PCa, and under-treating significant disease.

A new secret ingredient

Now there’s a new secret ingredient: biomarkers. Actually, the original biomarker PSA (prostate specific antigen) has been in use for decades, but since it wasn’t specific for cancer itself, more research into tiny PCa signatures was needed. Today, there are several types that can be picked up from blood, urine, and biopsy tissue samples. Evaluating them involves sophisticated biochemical analysis, and they vary from something as basic as the number of circulating tumor cells in a blood sample, to analysis of specific proteins found in urine, or gene expression mutations in DNA. However, they all help classify cell lines.

In fact, adding biomarkers greatly enriches treatment-to-disease matching, giving doctors the ability to help guide each patient’s choice. But constraints of time, money and knowledge still limit their availability. As recently as 2022, one author bemoaned that “… there is still a limited understanding of how to use them most effectively.”^[i] Therefore, there are increasing recommendations for doctors on when to use this secret sauce, applying which particular biomarker to which patient. Such guidelines, still in development, are like the directions that accompany a recipe’s list of ingredients.

Biomarker recommendations

One directive suggested by urologist Matthew Cooperberg is the use of genomic biomarkers with Grade Group 2 (GG2) patients who are considering Active Surveillance (AS). Dr. Cooperberg believes that all GG1 patients qualify for AS, but GG2 is somewhat ambiguous. While it is considered to be favorable-risk intermediate PCa, Cooperberg notes that GG2 “is an extremely heterogenous disease state. As such, tools to further stratify this cohort of patients is critical for the appropriate selection of active surveillance candidates.”^[ii]

On the other hand, some practitioners find them useful for almost all patients. For example, Thomas Jefferson University’s Doctor of Nursing Practice Anne Lizardi-Calvaresi uses a type of biomarker called genomic classification with most of her PCa patients:

…patients with favorable intermediate risk disease or potentially unfavorable intermediate risk disease, and for low risk disease when we’re contemplating placing them on active surveillance for newly diagnosed prostate cancer or for patients who are already on active surveillance and we’re considering whether or not we need to advance towards treatment or whether or not we
can continue with active surveillance. That’s one patient population. And then the other is patients with adverse pathologic features, post radical prostatectomy who we really are not sure do we need to radiate them or do we need to watch them? Those are the two patient populations where we really find value in genomic testing and it’s really a tool that we use when we’re determining whether or not to deliver more treatment, really is what it comes down to.^[iii]

To sum up, biomarkers supply an added ingredient that reveals underlying secrets of an individual’s PCa. As such, it is finding ever more application in the detection and diagnosis of this disease, enabling refined treatment matching as never before.

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] Farha MW, Salami SS. Biomarkers for prostate cancer detection and risk stratification. Ther Adv Urol. 2022 Jun 14;14:17562872221103988.
[ii] “How to Manage Active Surveillance in 2023 – Do We Need a Genetic Biopsy Test to Promote AS in GG2 Cancers?” Reported from the European Association of Urology meeting, Mar. 2023. https://www.urotoday.com/conference-highlights/eau-annual-congress-2023/eau-2023-prostate-cancer/143063-eau-2023-how-to-manage-active-surveillance-in-2023-do-we-need-a-genetic-biopsy-test-to-promote-as-in-gg2-cancers.html
[iii] “Integrating the Use of Prostate Genomic Classifiers into Clinical Practice – A Clinical Pathway Approach – Katie Murray and Anne Lizardi-Calvaresi.” Video lecture recorded by UroToday.com, no date. https://www.urotoday.com/video-lectures/prostate-cancer-genomic-classifier/video/mediaitem/3125-integrating-the-use-of-the-prostate-genomic-classifier-a-clinical-pathway-approach-katie-murray-and-anne-lizardi-calvaresi.html