Experts discuss prostate cancer prevention

Several experts discussed current issues related to prostate cancer prevention at the annual winter meeting of the Society for Urologic Oncology in Bethesda, MD, this week.

Fleshner talked about the ability to identify patients at specific risk for future prostate cancer. He noted that germline mutations, acquired risk, and pedigree will all contribute to future risk identification. Genome-wide associations have shown that, in certain (mostly European) populations, we can identify men with an up to 9-fold increased risk for prostate cancer, but of the 36 loci associated with increased risk, most do not have known functions.

He noted that a PSA level above an age-group median is predictive of the development of prostate cancer 15 years later, and that data from the ESPC Rotterdam group have supported this in men aged > 55 years and with a PSA > 1.5 ng/ml.

A panel chaired by Dr. Eric Klein talked about a patient with a normal DRE and a baseline PSA of 4.4 ng/ml and whether he was an appropriate candidate for prostate cancer prevention. There was consensus that, in this patient, if his PSA had risen on a re-check,then a prostate biopsy should be obtained before instituting preventive therapy. Scardino suggested that starting dutasteride would be appropriate in such a patient after re-checking his PSA. However, Klein argued that, because the risk of missing a high-risk prostate cancer in this patient is low, dutasteride could be given without a PSA re-check and that the response to the 6-month PSA could then be taken into consideration. The use of dutasteride among active surveillance patients to better stratify those at risk for disease progression was also suggested.

In the absence of Dr. Gerry Andriole, colleagues presented data regarding the ability of 5-ARIs to enhance the ability to detect prostate cancer because they decrease PSA production in the benign tissue component. They noted that in the PLESS trial, some years ago, the sensitivity of PSA increased in the finasteride group, and the “for-cause” biopsy rate decreased by about 20 percent with the use of finasteride. Finasteride therefore increased the probability of diagnosis of any cancer and of high-grade prostate cancer (Gleason score 7-10).

In the REDUCE trial, in the placebo arm, there was a total PSA increase over time with differences in initial PSA. Dutasteride brought patients to a similar PSA baseline level at 6 months, with increases after those differentiating men with prostate cancer from those without. Overall, PSA increases in dutasteride patients resulted in improved sensitivity of prostate cancer detection compared with placebo patients. It is the rise from the 6-month PSA level in men on dutasteride that identifies their risk for prostate cancer, and not the drop at 6 month from baseline, he emphasized.

Finally, Scardino discussed the use of 5-ARIs in men with an elevated PSA. He strongly emphasized that there was no longer any reason to believe that the use of 5-ARIs might result in and increased risk for high-grade prostate cancer.

He presented Lilja’s data showing that a single baseline PSA level will predict for the eventual development of prostate cancer, and specifically that, at age 60, a man with a PSA level below 1.06 ng/ml is extremely unlikely to develop prostate cancer. He also noted that the overall prostate cancer detection rate in the REDUCE trial was 21.6 percent, but that the detection rate was only 10.7 percent in the “for-cause” group, which is more representative of actual clinical practice in the “real world.” He stated that to reduce “for-cause” prostate cancer, the optimal strategy is to treat the 20-40 percent of men with the highest PSA levels. The risk of prostate cancer can be reduced from 11.7 to 9.9 percent by treating only about 40 percent of men with highest baseline PSA levels (i.e., those with a baseline > 1.3 ng/ml).

One Response

  1. As a long time proponent of the importance of dutasteride/Avodart, I am pleased to note that importance is finally being recognized by a wider range of physicians than those specialists in research and treatment of, specifically, prostate cancer who have advocated the use of 5AR inhibitors for several years.

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