PROSTATE CANCER PREVENTION - IS IT REALLY POSSIBLE

Mon, 29 Nov 2010 10:30:44 MDT

Michael D Lutz, M.D. Prostate cancer represents the most common non-skin cancer within the United States and is the second leading cause of death from cancer among men. Over 200,000 men will be diagnosed with prostate cancer in the United States this year and the incidence will continue to increase annually because of the aging male population. The risk of being diagnosed with prostate cancer now approaches one in seven in North America and Westernized nations. Although it is known the incidence of prostate cancer and the rate of death due to the disease increases with age, other risk factors for prostate cancer include a family history of prostate cancer, Afro-American race and excess dietary fat intake. Prostate cancer represents an attractive malignancy for chemo prevention due to its high incidence, prevalence, and epidemiology. Since the discovery of PSA in 1979 and the continued advancements in the technological abilities to perform outpatient prostate biopsies, the incidence of detection of prostate cancer continues to increase in the United States. Recommendations for early detection continue with support from the American Urological Association as well as the American Cancer Society and other national cancer prevention organizations. However, recently there has been some debate as to the possible role of over detection and the discovery of clinically insignificant prostate cancers. While this debate continues and we remain unable to distinguish between clinically significant and insignificant prostate cancer, continuation of this process of early detection is clinically warranted. The prospect of prostate cancer prevention was first entertained with the development of the Prostate Cancer Prevention Trial (PCPT), which was initiated in 1994, supported by the National Cancer Institute and the Southwest Oncology Group. During this time, 18,882 eligible men were studied. From 1994 to 1997 these men were placed on either Finasteride (Proscar 5 mg) or a placebo. At the seven year end point it was apparent that there was a 25% relative risk reduction of the development of low and intermediate grade prostate cancers, however, debate continues with regard to a similar 25% increase incidence of high grade prostate cancers within the Finasteride treated group. What perhaps is not truly understood by the PCPT investigators and the public at that time is that Finasteride significantly improves the sensitivity of PSA, digital rectal examination and prostate biopsy for the detection of prostate cancer. It is also important to note that 75% of the cancers detected in the PCPT were found to be clinically significant tumors as by present day criteria. A subsequent trial, the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) was initiated in 2003 and completed in 2005 with 8200 men as participants. Dutasteride (Avodart 0.5mg) like Finasteride in the PCPT, blocks the conversion of Testosterone in the bloodstream to Dihydrotestosterone (DHT) in the prostate. The difference is that Dutasteride blocks both Type 1 and 2 5Alpha Reductase receptors, whereas, Finasteride only blocks Type 2. Discussing the pharmacological and clinical differences between Dutasteride and Finasteride at this time is beyond the scope of this article, however, may be clinically important in the future. There is scientific evidence that the Type 1 5Alpha Reductase receptor is increased in high grade, locally extensive, and metastatic prostate cancers. The REDUCE trial demonstrated an approximate 25% reduction in the overall incidence of all grades of prostate cancer which may be explained by the pharmacological differences between Finasteride and Dutasteride. One of the distinguishing factors between the two prostate cancer prevention trials remains the level of PSA for inclusion and screening. Low levels of the PSA were required for the PCPT, in contradistinction to the REDUCE trial which required higher at risk levels for inclusion. It is inherently obvious that low values of PSA increase the potential for cure, but also will assuredly result in over treating men with clinically insignificantly disease. Conversely, those individuals with high PSA values will remain at higher risk for disease recurrence after definitive local curative treatment. When considering prostate cancer chemoprevention with a 5-Alpha Reductase Inhibitor (Finasteride, Dutasteride), it is likely best applied for the man who has opted for regular PSA and digital rectal examination screenings as in the population for which chemoprevention was proven effective in the previous two trials. At present, it is not possible to predict what impact a 5-Alpha Reductase Inhibitor would have on a man not undergoing regular screening studies. If one is considering chemoprevention, he should be informed of the potential benefits including delay or reduction in male pattern baldness, overall improvement in urinary function, a reduction in the risk of interventions resulting from the progression lower urinary tract symptoms and the potential for improved detection of high grade prostate cancer due to the improved efficacy of the screening tests and biopsies in men who are receiving these medications. On the other hand, they should also be informed of the reduction in ejaculatory volume, libido, erectile function, and risk of gynecomastia and the cost of the medication itself. It is with hope that the judicious application of chemoprevention for prostate cancer will achieve a long term improvement in the quality of life of those individuals, who escape the prostate cancer diagnosis. Dr. Willet Whitmore, considered by many to be Father of Urologic Oncology, once summarized this prostate cancer paradox in 1988: "If cure is possible, is it necessary, and if cure is necessary, is it possible?"