In this issue of the journal Jha and colleagues (pp) report on a pilot study of the prevalence of an elevated Prostate Specific Antigen (PSA) in a population of elderly men visiting the orthopaedic outpatient clinic with low back pain. They find that the prevalence of raised PSA of more than 4 ng/ml in a cohort of 29 patients aged 50 and above was 51.7 of 100 persons, higher than in the general population, and suggest that routine PSA testing in this group of patients would help in screening for occult prostate cancer presenting with spinal metastases.
This paper offers us an opportunity to examine the worldwide changes that have taken place in screening practices for prostate cancer in the last twenty five years and the resultant epidemiological changes.
In India, prostate cancer is diagnosed late and presentation with lower urinary tract symptoms and backache has been the usual screening opportunity. However recent ICMR data seems to indicate that the incidence of prostate cancer is increasing slowly in India due to widespread availability of diagnostic ultrasound and PSA estimation. The global picture in USA, Canada, Europe, and Australia is different.
The discovery of prostate-specific antigen as a biomarker and its use as a screening tool had represented a major advance in the early diagnosis and monitoring of prostate cancer. Prompt diagnosis with prostatic biopsy and widespread adoption of radical prostatectomy or radical radiotherapy for organ confined disease led to a significant reduction in prostate cancer mortality in developed countries.
However, PSA has a lack of specificity, and an inability to differentiate indolent from life threatening disease reliably at the time of diagnosis. Indolent prostate cancer is so slow growing that it may never become life threatening.
This led to over-diagnosis and over-treatment of indolent prostate cancer, exposing patients to the harms of treatment without benefit : the harm of unnecessary biopsies, the harm of radical prostatectomy, and the harms of radiotherapy The U.S. Preventive Service Task Force (USPSTF) issued a recommendation against screening men over 75 in 2008, and against routine screening for all men in 2012, indicating that, in their interpretation, the harms of screening outweigh the benefits. This decision has been debated by urologists worldwide.
From 2012, through the end of 2016, trends in the literature indicate that there has been a decline in both PSA testing and prostate biopsy in the Western world leading to a decline in the incidence of low-, intermediate, and high-risk localized prostate cancer, and some early signs of a shift toward higher burden of disease at presentation are now apparent. These findings raise concern that there may be a reversal of the observed improvement in prostate cancer-specific mortality following institution of widespread screening.
There is now strong evidence to suggest that screening results in earlier diagnosis of prostate cancer and provides men with an oncological benefit. The ERSPC study with follow-up of more than 13 years has demonstrated a 21% relative prostate cancer mortality reduction in favour of screening, and the relative risk reduction in men screened was 27%. The SPCG-4 trial, which followed up 700 men with localised prostate cancer showed that, at 15 years, the absolute risk reduction of dying from prostate cancer was 6.1% following randomization to radical prostatectomy compared with watchful waiting. It should be noted that these findings are in variance with those of the Prostate Intervention Versus Observation Trial (PIVOT), which did not identify any statistically significant difference between the intervention and observation groups. On subgroup analysis, allcause mortality was reduced in men with PSA >10 ng/mL after radical prostatectomy. There are psychological benefits of obtaining a normal PSA test, especially those with a family history of prostate cancer. Wherever PSA testing has been introduced, mortality from prostate cancer has fallen. The benefits of PSA screening also reduces presentations of men with metastatic disease by around 70%. The morbidity reductions are impressive as are reduced costs on the healthcare system.
The way forward would then be to improve biopsy strategies and early identification of aggressive prostate cancer. Shared decision making with the patient on biopsy issues is important. Recent improvements on PSA as a biomarker include the prostate health index (phi). This is a FDA-approved blood test combining total, free and -2proPSA with greater specificity than free and total PSA for clinically-significant prostate cancer. Similarly the 4K score uses a kallikrein panel to improve the PSA test. Urine based markers like PCA3 also help the decision process. Genomic tissue based studies are now available which allow prognostication, or in the decision for rebiopsies. Multiparametric MRI is an additional tool in the diagnostic decision making process. Active surveillance for low risk cancers can avoid treatment related harm. The undoubted benefits of screening for prostate cancer in the high risk patient with a family history or a patient with aggressive high grade cancer should not be lost. Early radical therapy for the right patient will save lives.