Prostate cancer is the most common form of cancer in men in the U.S.1 As a consequence, there are currently three main methods of prostate screening: digital rectal examination (DRE), transrectal ultrasound (TRUS) and prostate specific antigen (PSA) testing. However, there is still a lot of debate over the benefits and accuracy of all three methods.
The overall aim of any screening method is to be able to detect cancer in its earliest stages to ensure the highest possible chance of successful treatment and disease management. In a bid to clear up the controversy over efficacy, work is ongoing to determine the most effective and accurate means of diagnosis and to identify new methods and techniques of spotting early prostate cancer and improving patient outcomes.
The current go-to method of screening focuses on the role of the biomarker prostate specific antigen (PSA), a blood-based protein that is elevated in the presence of a tumor as the prostate gland sheds cells into the blood.2
Unfortunately, PSA levels can also be affected by other ailments such as urinary tract infection, urinary retention or enlargement of the prostate, all of which result in the shedding of prostate gland cells into the blood and mimic tumor activity.2 This means that there is a risk men are being diagnosed with the disease when no cancer exists. This is referred to as a false positive. The opposite can also occur where prostate cancer isn’t diagnosed because of a PSA level that is too low. This is referred to as a false negative.2
This has been substantiated by the findings of the European Randomized Study of Screening for Prostate Cancer (ERSPC), which investigated the effect of PSA testing on death rates from prostate cancer in 182,000 men between 50 and 74 years of age across seven countries. The study concluded that although PSA screening does reduce deaths from prostate cancer it comes with a high risk of over-diagnosis.3
Interestingly, in the U.S., the Prostate, Lung, Colon and Ovary (PLCO) screening trial also evaluated the general effectiveness of PSA and DRE screening methods in a group of 76,693 men in 10 study centers nationwide.4 After seven to 10 years of follow-up, the death rate from prostate cancer was very low and did not differ significantly between study groups suggesting there is little difference between the two methods of detection.4
So although the effectiveness of current screening methods is still strongly disputed, there are numerous approaches being explored that are showing promise as future prostate screening techniques.
One prominent example is the screening method Stockholm3 (STHLM3), which combines data from six biomarkers (PSA, free PSA, intact PSA, hK2, MSMB, MIC1) along with specific genetic mutations and clinical variables such as age, history and previous prostate biopsy.5 In a recent study, STHLM3 was shown to be significantly better than PSA screening alone in identifying prostate cancers with a Gleason score of 7 or more (from intermediate stage cancer through to high-grade disease).5
There are also early indications that the prostate cancer gene 3 (PCA3) urine test may be useful in predicting prostate biopsy outcome. The test analyzes levels of the protein in urine samples taken from men following a prostate massage and DRE, with a recent study suggesting that PCA3 testing may be more effective at predicting early prostate cancer than the PSA screen.6
Finally, magnetic resonance-guided biopsy (MRGB) – a pre-biopsy MRI scan of the prostate in men with suspicious PSA levels – may reduce over-diagnosis and over-treatment at a similar cost to TRUS.7
Using biomarkers in screening for prostate cancer is believed to lead to faster, better, more accurate diagnosis, but controversies still persist as to the relative effectiveness of the three existing methods. A substantial body of evidence is being collated to determine which methods should be employed in the future, alongside intensive research into new biomarkers of the disease.
- Centers of Disease Control and Prevention (2015). Cancer Among Men. Available from: http://www.cdc.gov/cancer/dcpc/data/men.htm (accessed September 2016).
- National Cancer Institute (2012). Prostate-Specific Antigen (PSA) Test. Available from: https://www.cancer.gov/types/prostate/psa-fact-sheet (accessed September 2016).
- Schröder FH, et al. New England Journal of Medicine 2009; 360.13:1320-1328. Available from: http://www.nejm.org/doi/full/10.1056/NEJMoa0810084 (accessed September 2016).
- Andriole GL, et al. New England Journal of Medicine 2009; 360.13:1310-1319. Available from: http://www.nejm.org/doi/full/10.1056/NEJMoa0810696 (Accessed September 2016).
- Grönberg H, et al. The Lancet Oncology 2015; 16.16:1667-1676. Available from: http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00361-7/abstract (accessed September 2016).
- Vlaeminck-Guillem V, et al. Progrès en Urologie 2015; 25.16:1160-1168. Available from: http://www.sciencedirect.com/science/article/pii/S1166708715002407 (accessed September 2016).
- de Rooij M, et al. European Urology 2014; 66.3:430-436. Available from: http://www.sciencedirect.com/science/article/pii/S030228381301333X (accessed September 2016).