New technologies offer hope of improved diagnostic accuracy for prostate cancer
By Dr Ali Tinazli
Chief Executive Officer, Lifespin.Health
Medical diagnostics has long been an imperfect science. But new technologies are offering hope for far greater accuracy and the ability to customize treatment options to improve outcomes.
One example is prostate cancer, the second-most diagnosed cancer [1] globally after lung cancer. Each year, an estimated 186,320 prostate cancer cases will be diagnosed, and about 28,660 will die from the disease. For an American male, the lifetime risk of developing prostate cancer is one in six, with the risk of death being one in 34, or about 2.9%.
While many people believe that prostate cancer is an “older man’s” disease, an increasing number of younger men are now being tested for and diagnosed with the disease as a result of increased and earlier screening for the disease.
There is some clinical justification for doing so. A percentage of men under the age of 50 can have a genetic predisposition [2] for the disease. This is especially true among African-American males, among men who are overweight or obese, and those who have a direct family history of the disease.
Whereas the progression of the disease may be relatively slow among older men, for those who are younger or higher risk, depending on the nature of the disease, progression may be more aggressive, requiring surgery and or radiation therapy. This can present added risks of urinary incontinence and
erectile dysfunction [3]. Tumours that harbour a specific gene fusion may also be more likely to recur [4].The prognosis can be dim, including a heightened risk for rapid progression and development of metastatic disease, more adverse effects from treatment, and a higher likelihood of fatality.
For these and other reasons, the American Cancer Society and other medical associations recommend screening for certain high-risk patients beginning as early as 40, even though in many cases, elevated results from a standard prostate-specific antigen (PSA) blood test, may arise as much as 5-10 years before there is a clinical manifestation of the disease.
Challenges that need to be addressed
While increased screening is important and valuable, the method most commonly used to identify early-stage prostate cancer, the prostate-specific antigen (PSA) blood test, is not all that accurate, which leads to unnecessary and, at times, expensive follow-up testing and high anxiety for the patients as they await confirmation of their results.
PSA tests have a 70 per cent false positive rate. Infections, prostatitis, or an enlarged prostate can also elevate PSAs. They also have a 20 per cent false negative rate.
To increase accuracy, some physicians may also perform manual rectum exams to feel for potential lumps. They may also use other enhanced testing methods to reduce false positive and negative rates. These include reviewing a patient’s PSA comparing current test results to earlier results to look for
rapid changes, look at the patient’s PSA free-to-total ratio, or the prostate health index, known as PHI. Physicians may also include a urine test that examines for PCA2, which is also a marker for potential prostate cancer.
In addition, emerging genomic tests or tests carried out in in combination with MRT (Mediated Release Test) can help provide a clearer picture. However, there is a trade-off in accessibility and affordability as the 2nd generation tests are relatively expensive and can be difficult to schedule. But in all cases, having a positive result will result in more testing.
Optimizing diagnostic solutions
As such, the goal should be to optimize the effectiveness of these follow-up exams to minimize what else is needed, i.e., reducing unnecessary biopsies, and more invasive treatment, such as prostate removal, if such treatments won’t likely result in an increase in the patient’s life expectancy. Except in higher risk patient categories, this is often the case given the generally slow progression of the disease.
Fortunately, technological advancements in imaging can now deliver faster and more accurate diagnoses of prostate cancer with less ambiguity than earlier imaging systems. One example is the combination of MRI and ultrasound imaging technologies which can provide physicians with a real-time view of the prostate through a guided 3D ultrasound [5]. As a urologist moves the ultrasound probe over the prostate, advanced software moves an overlaid MRI image over the organ, allowing suspicious tissue to be digitally marked. Combining 3D ultrasound and MRI technology can also accurately map biopsy samples. Physicians are also beginning to rely more on PSMA PET-CT, which uses a radiotracer called 68Ga-PSMA-11. The radioactive targeting molecule seeks out and attaches to a protein on the surface of prostate cancer cells, which then appear brightly on a PET scan.
An Australian prospective multicentre study [6] suggests that PSMA PET-CT is more likely to detect metastases than other more conventional approaches. PSMA PET is believed to detect more prostate lesions than Fluciclovine PET in men who experienced a cancer recurrence after undergoing radical prostatectomy.
Artificial Intelligence is also coming into play as a tool to help radiologists detect, classify and characterize prostate cancer lesions without the need for segmentations or other additional measurements. With a sharper view of the lesion, radiologists are better able to not only accurately diagnose prostate cancer, but also assist oncologists in determining the best, and least invasive treatment plan.
Metabolomics in early disease detection
Researchers also need to continue to explore new ways to enhance the accuracy of early detection methods, before these follow-up tests are needed.
One possible solution may be found in the fast-developing field of metabolomics, which is showing promise to address a wide range of disease states including cancer. The study of cancer metabolism holds great interest to researchers because prostatic tissue shows high metabolic activity. As a result, researchers are exploring the opportunity of utilizing metabolic changes in the patient, by comparing them to large databases of other prostate cancer cases and using this information to supplement the static snapshot of a traditional PSA blood test.
A recent study [7] also raises the potential for identifying certain types of aggressive tumours by discovering metabolite patterns associated with a lower risk of malignant subtypes and cancer-associated death.
Published in the International Journal of Cancer, the study’s authors explain how they identified groups of related metabolites using the “treelet transform” statistical method. Researchers then used conditional logistical regression by estimating the association of metabolite patterns with prostate cancer risk. Scientific advances in metabolomics may prove useful in studying the cause of late-stage prostate cancer and identifying men at heightened risk of developing aggressive prostate tumours through metabolic phenotyping.
Understanding the metabolic profile differences between benign, low-grade, and high-grade cancer could clarify the prognosis and lead to new diagnostic testing measures.
While prostate cancer remains a significant concern, new technologies offer the promise of increasing the accuracy of early diagnosis and specificity of prognosis. This will also reduce unnecessary follow-up testing, lowering the financial burden on the patient and improve their quality of life.
About Lifespin
Germany-based Lifespin combines biology, Deep Data, artificial intelligence and cloud technologies to enable digital metabolic insights for: precision diagnostics and therapeutics for personalized disease management; precision drug monitoring for pharmaceutical, research and clinical settings; and precision nutrition for diabetes, obesity, diet and lifestyle interventions. Lifespin has standardized the metabolic baseline for human health and can detect distinct deviations caused by diseases. They are building a proprietary database, already consisting of more than 200,000 individual human metabolic profiles, to create a digital atlas of human health that provides deeper clinical insights based on metabolic information. This will enable precision diagnosis and personalized treatments.
https://lifespin.health/
References
1. https://www.wcrf.org/cancer-trends/worldwide-cancer-data/
2. https://doi.org/10.1371/journal.pgen.1006477
3. https://doi.org/10.1056/NEJMoa1209978
4. https://doi.org/10.1093/jnci/djt332
5. https://doi.org/10.1016/j.urolonc.2011.02.014
6. https://doi.org/10.2967/jnumed.117.197160
7. https://doi.org/10.1002/ijc.32314
