Advanced Prostate Cancer on the Attack? Genomics to the Rescue!

The most common type of prostate cancer (PCa), acinar adenocarcinoma, normally starts in the gland cells that line the prostate and make prostate fluid. If diagnosed at an early stage when it’s still localized, it can almost always be conquered. It wasn’t that long ago when treatment was designed to clobber the entire gland. This is called radical treatment (meaning attack the whole prostate) and took the form of prostatectomy, radiation, or whole-gland ablation. However, in many cases this was overkill, leaving untold thousands of patients unable to perform sexually and/or suffering with incontinence.

Thankfully, diagnosis is now earlier and more accurate than ever, allowing clinicians to design and tailor minimally invasive, non-radiation interventions that are victorious over localized tumors while preserving men’s ability to function in all ways. This more recent pathway includes

• PSA screening, followed by
• Multiparametric MRI (mpMRI) if needed, followed by
• In-bore mpMRI-guided targeted biopsy, if needed.

However, roughly 15% of PCa cell lines are aggressive yet they do not cause a rise in PSA. This means that even for men who participate in PSA screening, many will have a test result below the usual cut-off of 4.0 ng/mL — but still harbor dangerous disease.

Advanced prostate cancer is on the rise

Unfortunately, national statistics reveal an alarming situation. PCa is increasingly being diagnosed when it is no longer localized. It has already begun to leave the gland, invading the prostate bed or nearby lymph nodes, regional bones (hip, lower spine), or more distant spread (metastasis).

Why is this happening? We don’t know for sure, though professional societies like the American Urological Association have pointed fingers at the recommendations against broad PSA screening issued by the U.S. Preventive Services Task Force (less screening = late diagnosis). Or, as expressed in a Cancer Therapy Advisor article, “Another factor may also be related to the several clinical guidelines that vary in their recommendations for routine PCa screening, creating confusion among healthcare professionals questioning the usefulness of routine PSA screening and its contribution to reducing PCa morbidity or mortality.” Both of these hypotheses imply that however imperfect the PSA blood test, men who don’t annually participate in that detection starting point risk losing a treatment window.

Whatever the reason, the result of diminished screening is costly in terms of men’s lives, not to mention healthcare dollars. Statistics show that from 2010 till 2018, the rates of diagnosed metastatic PCa for men ages 45-75 grew by 41%, and from 2011-2018 by 43% among those ages 75+.^[i] Metastatic PCa is still considered uncurable at this time, though new and experimental therapies are extending life.

Using genomics to assess risk

We know that there are gene mutations linked to the development of PCa, and to the risk of more aggressive cell lines. Many of these genes can be analyzed using tissue samples from prostate biopsy. However, a needle biopsy is an invasive procedure, and the more needle samples taken, the greater the risk of infection and other side effects. While only a needle biopsy can provide a definitive PCa diagnosis, it would be great if we could assess which patients truly need to undergo a biopsy.

There are promising developments in our ability to screen more specifically for PCa than the PSA blood test, and there are now tests using blood or urine samples that can identify genetic marker or other biomarkers such as circulating tumor DNA (ctDNA), circulating tumor cells, RNA, or specific molecular proteins. For instance, there is a new urine test called the miR Sentinel™ Prostate Cancer Test. So far, it is the first and only urine test that detects and classifies prostate cancers with a high level of accuracy by picking up genetic material called small non-coding RNA (sncRNA). There is no need for rectal exam, blood test, biopsy or strict urine requirements, but it can help determine if a biopsy is warranted.

As of this writing, genetic analysis is not a universal standard of care. Although the National Comprehensive Cancer Network (NCCN) recommends that men with low, favorable intermediate, unfavorable intermediate, or high-risk disease and a life expectancy of 10 or more years consider undergoing molecular testing to further clarify risk assessment, guidelines exist that discourage broad implementation. Also, payment or reimbursement for such testing varies. For more information, check out the prostate cancer genomic testing information offered by the nonprofit organization FORCE (Facing Hereditary Cancer Empowered).

We should not have to wait until someone is diagnosed with advanced PCa to access genomic testing, but for such patients, genetic analysis should be mandatory because the information obtained can direct treatment strategy. As it is, non-white patients are less likely to be offered such analysis, a disparity that needs prompt correction. For the future, professional societies, private and public insurers, and policy makers should continue to explore the feasibility of broad screenings such as simple urine tests that are more specific for PCa risk than the PSA blood test. An annual urine screen may not only preserve life and lifestyle, it may make great economic sense in terms of avoiding biopsies, unnecessary treatment, and overtreatment with its risk of short- and long-term side effects that require ongoing clinical services. In that sense, genomic testing comes to the rescue of all of 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] Desai MM, Cacciamani GE, Gill K, et al. Trends in Incidence of Metastatic Prostate Cancer in the US. JAMA Netw Open. 2022;5(3):e222246.