Challenges of diagnosis
Currently the early detection of prostate cancer (PCa) relies primarily on:
- digital rectal examination (DRE) of the prostate
- the serum prostate specific antigen (PSA) concentration.
The outcome of both tests can result in a prostate biopsy to confirm the diagnosis of PCa. Each of these three measures has shortfalls that contribute to an increasing number of unnecessary biopsies.
DRE is a standard procedure used in the diagnosis of PCa but:
- it has a very low positive predictive value (PPV) in identifying PCa: 10-20% in men with low PSA values (< 4.0 ng/mL).
- its reproducibility is poor and inter-examiner variability high.
DRE remains an important part of early PCa diagnosis. However, these shortcomings underscore the need for additional diagnostic measures.
Serum PSA measurement is another standard tool in the diagnosis of PCa but:
- PSA is not PCa-specific. Several other prostate conditions that are not malignant can result in elevated serum PSA levels, such as lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH) and prostatitis.
- serum PSA in a concentration up to 10 ng/mL also has a rather low PPV (approximately 20-30%).
Serum PSA remains a useful and cost-effective test. However, the lack of specificity for PCa underscores the need for additional diagnostic measures.
Transrectal ultrasound (TRUS)-guided biopsy provides the definitive diagnosis of PCa but:
- due to the low PPV of DRE and serum PSA, approximately two thirds of men will undergo an unnecessary initial biopsy. This number will grow due to the increased tendency for screening and use of lower serum PSA thresholds.
- if the biopsy is negative, this can create a false sense of security. As less than 1% of total prostate tissue is examined after biopsy, there exists a good possibility that some cancer will be missed. Approximately 10-35% of men with PCa remain undiagnosed after a single sextant biopsy. Therefore, an initial negative biopsy may trigger repeat biopsies.
- the high percentage of initial negative and subsequent repeat biopsies will increase health care costs and diminish patients’ quality of life. Biopsies induce anxiety because of the fear of having PCa and they cause discomfort, pain and complications: Table 1). Also, more rare (<1%) but severe complications, such as septicaemia, can occur.
|Complication:||% of patients|
Taking all these factors into consideration, there is obviously a need for additional diagnostic tests with improved specificity / greater PPV for PCa that, consequently, can better identify patients with a high probability of a positive biopsy. This should help in making better biopsy decisions and reducing the number of biopsies.