Prostate Cancer Screening: the role of biopsy, PSA, PSA dynamics and isoforms

In the beginning of the past century, A. Astraldi urologist from Buenos Aires, Argentina, recognized the importance of early detection of prostate cancer and was unsatisfied with the available diagnostic tools he had to his disposal. The only diagnostic means for the urologist at that time were clinical symptoms, rectal palpation and radiographic imaging to assess bone metastases. This motivated Astraldi to study the value of eosinophilia in prostate cancer. After concluding that this blood test was not reliable for the detection of prostate cancer because of the many diseases that could cause a variation, he was the first to perform prostate biopsy following the transrectal route 1 in order to be able to differentiate between prostate cancer, prostatitis and Benign Prostate Hyperplasia (BPH). He stated that biopsy of the prostate was at that moment the most effective way to detect prostate cancer and we still believe it is. The research for a new marker of prostate cancer took a long way. Prostate Specific Antigen (PSA) was first demonstrated in prostatic tissue in 1970 2. It was purified from tissue in 1979 by Wang 3 and first measured in the serum a year later 4. This was followed by the wide use of PSA as a clinical marker for prostate cancer in 1988 5-8. The availability of a simple blood test together with improved imaging of the prostate by transrectal ultrasound (TRUS) paved the way for opportunistic screening in the clinical practice and several screening programs 9. Together with digital rectal examination (DRE), this trias prostatica (DRE, PSA and TRUS) could determine in a minimally invasive manner the need for TRUS-guided biopsy of the prostate. Nowadays prostate cancer can be detected 11-12 years 10 before giving rise to clinical symptoms and the incidence of prostate cancer increased dramatically. As autopsy studies 11, 12 show that approximately 60% of men in their sixth and seventh decade of life have prostate cancer and generally do not die of it, the health care physicians and urologists were confronted with the problem of overdetection of prostate cancer. Over-diagnosed cancers are those screen-detected cancers which would not surface clinically during a life time. Optimal screening methods should diagnose those patients with prostate cancer who need to be treated while avoiding the diagnosis in patients who will not benefit from being diagnosed.

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