Reports

This report is based on medical evidence presented at sanctioned medical congress, from peer reviewed literature or opinion provided by a qualified healthcare practitioner. The consumption of the information contained within this report is intended for qualified Canadian healthcare practitioners only.

62nd Annual Meeting of the Canadian Urological Association

Quebec City, Quebec / June 24-27, 2007

As discussed by Dr. Curtis Nickel, Professor of Urology, Queen’s University, Kingston, Ontario, the PROACT (Proscar and Alpha-Blocker Combination Followed by Discontinuation Trial) examined the outcomes in newly-diagnosed/watchful waiting patients with moderate-to-severe symptoms of benign prostatic hyperplasia (BPH). Patients received nine months of combination therapy with the 5-alpha reductase inhibitor (5ARI) finasteride and an alpha-blocker, followed by nine months of 5ARI monotherapy. This substudy comprised 78 men (mean age 65.6 years) who were alpha-blocker-naive prior to study entry.

Interim results from 66 patients showed that their symptoms remained stable from the end of the nine-month combination therapy phase to the end of the nine months of monotherapy. In addition, after the alpha-blocker was discontinued, they maintained their improved quality of life, experienced fewer “bothersome” symptoms, and their prostate-specific antigen (PSA) levels, which had dropped from baseline, remained stable. “The message for clinical practice is that it does seem reasonable to try a trial of alpha-blocker discontinuation after nine months in patients who have achieved a clinically beneficial response to combination therapy,” Dr. Curtis concluded.

Predictive Nomograms Using Per Cent-free PSA

Dr. Pierre Karakiewicz, Director, Cancer Prognosis and Health Outcomes Unit, and Associate Professor of Surgery, Centre hospitalier de l’Uuniversité de Montréal-Hôpital St-Luc, Montreal, Quebec, described how clinicians can use nomograms to stratify the risk of prostate cancer in men, including those with normal PSA values. His team has developed a series of predictive validated nomograms, which are available at www.nomograms.org.

As Dr. Karakiewicz explained, the PCPT (Prostate Cancer Prevention Trial) found that 26.5% of men with normal PSA values (<4 ng/mL) may actually have prostate cancer. His group recently published data on over 2300 Canadian men who volunteered to be screened for prostate cancer. Findings showed that a PSA threshold of 2.5 ng/mL would require a biopsy in 20% of the men (Chun et al. BJU Int 2007;100(1):37-41).

Citing recently published studies of results using two other nomograms, Dr. Karakiewicz presented examples of how they could be used to determine prostate cancer risk for typical patients (Chun et al. J Urol 2007;177(2) 510-5, Walz et al. Eur Urol 2006;50(3):498-505). “I hope these examples have provided you with sufficient evidence to confirm that per cent-free PSA adds information to the risk assessment of men with normal PSA values. The contribution of total PSA to risk stratification is mainly limited to values that far exceed the normal range (>10 ng/mL), and conversely, per cent-free PSA is the strongest and most important predictor of prostate cancer risk and should become a variable to quantify individual risk.”

Elevated PSA and Normal Biopsy

Dr. Armen Aprikian, Associate Professor of Surgery and Chief of Urology, McGill University Health Centre, Montreal, told the audience that cancer detection on repeat biopsy ranges from 10% to 35%. “Our goal is to ensure the detection of moderate- to high-risk prostate cancer… Conversely, we want to avoid unnecessary additional biopsies and detection of insignificant cancer. This is the dilemma we have with prostate cancer detection,” he emphasized.

Dr. Aprikian added that in the past, prostate cancer rates were elevated on repeat biopsy partly due to inadequate sampling on initial biopsy but today, standard biopsy procedure includes 10 cores. Clinicians must still determine how to manage a patient who has had two negative biopsies, whose PSA levels are elevated and who is very anxious. They can now use data from the PCPT and MTOPS (Medical Therapy of Prostatic Symptoms) trial as guidelines. The MTOPS study showed that the use of 5ARIs can significantly reduce the rate of BPH complications, and the PCPT showed that long-term finasteride use may reduce the rate of prostate cancer. Moreover, when the patient is taking the 5ARI, the performance of PSA and digital rectal exams are improved—especially in the detection of high-grade prostate cancer, “that we do not want to miss,” Dr. Aprikian stressed.

“Perhaps in men with an elevated PSA and a negative prostate biopsy, the use of 5ARIs can help in patient management,” he suggested. Men with a negative biopsy, a large prostate gland and adequate sampling (at least 12 cores) in the initial biopsy may not need a repeat biopsy. If they also have urinary symptoms, this makes them ideal candidates to receive a 5ARI, then a decision about whether to carry out a repeat biopsy can be made depending on PSA kinetics, Dr. Aprikian summarized.

PCPT Debate

Also during the scientific sessions here this week, Dr. Laurence Klotz, Professor of Surgery, Division of Urology, University of Toronto, Ontario, described a debate that had taken place at the AUA meeting in Anaheim, California, in May 2007. Dr. Ian M. Thompson, Chair and Professor, Department of Urology, University of Texas Health Science Center, San Antonio, posited that the PCPT was a good study, while Dr. Patrick C. Walsh, University Distinguished Service Professor of Urology, Johns Hopkins University, Baltimore, Maryland, proposed that the PCPT interpretation was “a house of cards.”

Dr. Klotz strongly disagreed with Dr. Walsh and proceeded to refute his main points. Dr. Walsh had argued that testosterone, not dihydrotestosterone (DHT), is the major androgen that promotes prostate cancer, and androgen levels increase tenfold with 5ARIs. Dr. Klotz countered that testosterone is a weak androgen compared to DHT, and while intracellular testosterone levels rise, the net effect is to replace a potent androgen (i.e. DHT) with a weaker androgen (testosterone).

Dr. Walsh had stated that the PCPT was not truly a prevention trial, but Dr. Klotz countered that if the risk of cancer in patients harbouring small-volume prostate cancer is reduced, the risk of overtreatment can be avoided. Dr. Walsh had argued that the cancer reduction was really 10%, not 25%, because finasteride reduced the likelihood of patients getting a prostate biopsy, but Dr. Klotz countered that this is only true if you do not count the end-of-study biopsies.

Dr. Klotz concluded that the PCPT was “a profoundly important and positive study” funded by the National Cancer Institute involving 18,000 men, which was extremely carefully carried out and produced solid evidence of benefit. He summarized: “The criticisms are largely unfounded. I still believe men at risk, and those who are concerned, should be counselled about the benefits of 5ARIs for prevention.” There will be more data from six new studies in the next few years, he noted.

A consensus statement by the Canadian Urological Association put forth the following key points for clinical practice (CUAJ 2007;1(1):17-21). “The PCPT showed that finasteride significantly reduces the prevalence of histologically proven prostate cancer. In men who have large prostates and lower urinary tract symptoms, 5ARIs should be considered both for treatment of BPH and to reduce prostate cancer risk. For men who are concerned about prostate cancer, it is appropriate to discuss chemoprevention with finasteride. In doing the above, it is important to highlight both the benefits and the risks of long-term treatment.”

Cancer-fighting Diet

Richard Béliveau, PhD, Professor of Biochemistry, Université du Québec à Montréal, and research scientist, Hôpital Notre-Dame, informed delegates about foods that fight cancer. “It is time to focus on prevention,” he stated, defining prevention as treating a tumour while in infancy, since prostate cancer rates in North America are 25 and 35 times higher than in India and Japan, for example. He told the audience, “Seventy-five per cent of cancer cases could be prevented.” Dr. Béliveau recommended diets rich in phytochemical-containing foods that laboratory studies have identified as the most potent cancer-fighting foods: blueberries, strawberries, green tea, soy beans, tomatoes, grapes, citrus, garlic, cabbage, broccoli and turmeric.