Health and Prostate

A recent analysis of the control arm of the Prostate Cancer Prevention Trial (PCPT) has revealed that 15.2% of men with a Prostate Specific Antigen (PSA) value less than 4 ng/mL had prostate cancer detected via prostate biopsy. Current recommendations suggest PSA levels lower than 4 ng/mL do not indicate clinically significant prostate cancer; thus, the study results are groundbreaking news because no prevalence data for this group of men was previously available.

The PCPT trial enrolled men older than 55 with a prostate specific antigen (PSA) value less than 3 ng/mL and an American Urologic Society (AUS) score below 20. The men in this trial were randomly assigned to receive finasteride 5 mg or a matching placebo daily and followed for seven years with annual PSA and digital rectal exam (DRE) screening, with 9,459 men assigned to the placebo arm. After seven years of PSA and DRE screening, the men who never had a PSA higher than 4 ng/mL, an abnormal DRE, prostate surgery of any type, and had a prostate biopsy (minimum of six samples) at the end of the study were evaluated for cancer prevalence. There were 2,950 men, ages 62 to 91, who met these criteria, and in 449 (15.2%) of those men, prostate cancer was detected. Always controversial, the use of the Analysis of the patient demographics revealed that age and race did not predict those who would have prostate cancer, but a positive family history (affected brother, father, or son) did correlate with an increased risk of prostate cancer (p = 0.004). The mean prostate specific antigen (PSA) score of men with cancer was 1.78 + 0.92 ng/mL, significantly different from those without cancer at 1.34 + 0.86 ng/mL (p = 0.001). The mean annual rise in PSA (0.32 to 0.46 ng/mL) was also significantly higher in men with prostate cancer (p = 0.001).

Since prostate specific antigen (PSA) was first described in 1979, the ability of the test to predict clinically significant prostate cancer has been hotly debated. What is a normal versus an abnormal PSA value; was the test sensitive and able to reliably detect it; and what would the costs be from false-positive results in patient harm and to society in unnecessary procedures performed? — all have been questioned over the past two decades. A prostate specific antigen (PSA) level higher than 4 ng/mL is the standard indicator for a man likely to have clinically significant prostate cancer. For men with a PSA level between 4 and 10, approximately 25% will have prostate cancer. For PSAs higher than 10, this number rises to nearly 50% of patients having prostate cancer detectable by biopsy.

Even with new data on the prevalence of prostate cancer in men with a prostate specific antigen (PSA) below 4, this information does not provide any additional direction on whom to treat. The finding that 15% of men with normal PSA values have early-stage prostate cancer requires the review of prostate screening practices, more importantly because the incidence of cancer likely to be aggressive (Gleason score greater than 7), although low at 2.3%, was sprinkled throughout the PSA distribution. Not all of these patients would undergo invasive therapy, because depending on the patient’s age and life expectancy, treatment may range from watchful waiting to prostatectomy for this stage of cancer.

What to do now? It was already known, based on autopsy studies, that 15% to 60% of men ages 62 to 91 had unrecognized prostate cancer.However, none of these men diagnosed at autopsy actually died of their cancer. Thus, what patients really need to know is what the best screening method is to ensure that men who undergo biopsies and other therapies are at risk for cancer-driven effects that will affect the length and quality of their life. While a small number of the cancers found in this study were aggressive based on their Gleason score, the low prostate specific antigen (PSA) values indicate a small volume of disease that is unlikely to imminently impact a patient’s quality of life. Further limitations of this study are that its results apply only to Caucasian men older than 62. The minimum age of these patients was 62, and minorities were poorly represented in the final sample. In the otherwise asymptomatic male with a PSA of 0 to 4 ng/mL, current recommendations still continue with close follow-up of AUS score, digital rectal exam (DRE), and prostate specific antigen (PSA) to guide definitive therapy if indicated in that specific individual. The information from this study further emphasizes the critical need for patients’ annual follow-up with their oncologist or urologist to facilitate medical interventions if and when they are needed. Meanwhile, new biomarkers and stratification schema are being pursued as oncologists work to further define better diagnostics and care algorithms in the treatment of those with this challenging disease.