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Active Surveillance of Prostate Cancer


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Laurie and Ursula Klotz

Laurence Klotz has received significant recognition in recent years because of his outstanding leadership in prostate cancer management. It has been known for many years that prostate cancer is often slow growing and may be non-lethal. This is particularly true for low grade prostate cancer. Between 1970 and 1990, transurethral resection of the prostate (TURP) for benign prostatic hypertrophy (BPH) was one of the commonest operations in men. As a resident, Laurie was taught that diagnosis of minimal, low grade prostate cancer discovered incidentally in TURP specimens should not be described to the patient as cancer, since the condition was usually not clinically significant. In 1989, the Prostate Specific Antigen (PSA) test was introduced. This led to a policy of biopsy followed by treatment, though about half the patients had low grade, or ‘low risk’ disease. Between the introduction of PSA and 2010, 95% of low risk prostate cancer patients were treated radically by surgery or radiation therapy.

A student of history, Laurie knew that accepted wisdom is often wrong. He and radiotherapists Cyril Danjoux and Richard Choo at Sunnybrook decided to watch newly diagnosed low risk patients, follow the PSA, and rebiopsy every 3-5 years. In 2002, they reviewed their first 260 patients. There were no deaths from prostate cancer. One third had been treated; the other 2/3 were spared treatment. This set off a firestorm of controversy. Laurie started proselytizing that treating these patients aggressively was ‘overtreatment’. “The PSA can be helpful, but overtreatment threatened to make the risks of early detection unacceptable, and to potentially bring an end to screening.” He was pilloried by his colleagues and others in both the radiation and surgical community. Opponents railed that “Dr. Klotz doesn’t care if patients die of prostate cancer.”

The PSA test for prostate cancer detection was described by urologist William Catalona in St. Louis. An activist, he felt every patient with localized prostate cancer should be treated radically. Catalona and Laurie were often invited to debate this contested policy. He estimates that he was in 25 debates at national and international meetings over a 5 year period. Slowly, the academic and later the community urologists caught on and “Active Surveillance”, a term coined by Laurie, is now regarded as the appropriate approach all over the world. “As predicted, both the US and Canadian Task Forces on the Public Health Exam studying this issue came out recommending against PSA testing, largely in response to concerns about overdiagnosis and overtreatment.” In Laurie’s view, early detection is worthwhile and should be encouraged, but must be married to conservative management for low risk cancer. Patients with intermediate and high risk prostate cancer benefit from early detection and treatment, and screening for prostate cancer saves lives.

These findings led to robust research on how to pick the patients who need treatment. To find those few cancers that are “wolves in sheep’s clothing” with high malignant potential, research approaches include the use of MRI, biomarkers, and sophisticated risk nomograms”. A current Google search revealed 2,000 references to Active Surveillance, 13 years after its initial description. “We recently described 1,000 of our patients followed with active surveillance. There was a 5% mortality from prostate cancer over 15 years, and the chance of dying of other causes was 10 times greater. There are large groups in Rotterdam and on the West Coast of North America accumulating patients, but they do not have the long term data that the Sunnybrook group has.

“A similar transformation is also taking place now in breast cancer, as ductal carcinoma in situ is now being followed with active surveillance. The mammogram is analogous to the PSA, and many of the controversies about risk and benefit are similar. The move towards expectant management of ductal CIS and very early low risk breast cancer is based explicitly on the success of active surveillance for prostate cancer.”

Q: How did you come to develop this management approach?

A: “I was fortunate. As a result of our early publication, I met and cultivated a cadre of people with similar interests. I had the opportunity to travel the world, persuading and building the confidence in this approach.” Laurie debated in high school at York Mills Collegiate, not far from Sunnybrook. As an undergraduate, he was President of the University of Toronto Debating Union. This was a critical skill that allowed him to excel in the discussions of PSA at the outset of Active Surveillance. The debates sparked interest at meetings, and relationships and friendships developed over the years. “I can’t emphasize enough the importance of publishing to bring about these relationships. People read your ideas, contact you, and you develop a following of likeminded people. As they get promoted, start organizing meetings, and invite you to speak, you are able to spread your ideas.”

Q: Some felt that you would never convince the Americans not to operate on patients.

A: “Doctors want to make a living, but they want to do this by practicing good medicine and doing the right thing for patients. We want to influence the grey zone of management, where multiple treatment options exist, where fee for service incentives may encourage overtreatment. My goal is to shrink the ‘grey zone’ by bringing us closer to accurate prediction so that radical intervention for most low risk patients is no longer considered a reasonable option. Currently 10-25% of eligible patients in the US are followed with Active Surveillance, compared to 75% of patients in Canada. It is less prevalent in Europe and much less prevalent in South American and Central American countries, where surgery is a competitive business. Our U.S. colleagues are getting the message, and adopting Active Surveillance, despite the fact that it has a negative impact on their surgical volumes. “The research frontier to enhance earlier identification of the patients with more aggressive disease consists of two groups: the imaging camp is trying to identify large occult cancers early, and make more precise biopsy possible by the use of MRI guided ultrasound; the biomarker camp is trying to develop genomic profiling. There is collaboration and overlap in the research. Both are extremely active, with new developments on a monthly basis.”

Q: How would you advise a surgeon in northern Ontario who has a patient with recent diagnosis of low risk prostate cancer?

A: “The first task is to ensure that the patient’s biopsy has been reviewed by a capable pathologist as low grade cancer. We do a follow-up biopsy in one year. 20% are upgraded on that follow up biopsy, and they are in most cases offered definitive therapy (surgery or radiation). The subsequent upgrading rate is about 1% per year, so after the 1 year biopsy, we biopsy infrequently - about every 5 years, unless there is a change in some other parameter. Eventually, 1/3 of patients get active treatment. There are 1% or 2% outliers who do metastasize in the Active Surveillance population despite close surveillance and intervention for those who are reclassified into a higher risk group. We believe that MRI will reduce this further. Two thirds never require treatment.”

Laurie has a hobbyist interest in politics, philosophy and economics, and he is a prodigious reader. He recently finished Barbara Tuchman’s “The Zimmerman Telegraph”, the story of a telegram that brought the United States into World War II. He is currently reading Conrad Black’s “Rise to Greatness: The History of Canada from the Vikings to the Present”. His recent election to the Order of Canada brings 3 generations of his family into the Order. His maternal grandmother Esther Volpé received the Order of Canada in 1967 for her leadership in the women’s movement in the 50s and 60s. Her son, Laurie’s uncle Bob Volpé, was the Chief of Medicine at the Wellesley Hospital and a renowned researcher of Grave’s disease. He, too, was awarded the Order of Canada.

Laurie’s wife, Ursula, is a consultant to the pharmaceutical industry. His daughter Betsy graduated from UWO and is in training as an American Sign Language translator. His son Alex is finishing his PhD in Physics at McGill. Alex was recently celebrated as the single author of a paper in the American Journal of Physics that recalculated a famous thought experiment - the transit time, if a person fell down an imaginary a tunnel through the centre of the Earth and emerged at the other side. The journal Science and then the international media picked up the story of Alex’s recalculation, which changed the transit time from 42 to 38 minutes.

Laurie was a founding editor of two urological journals. He is the Editor Emeritus of the Canadian Urology Association Journal, and Associate Editor (for prostate cancer) for the Journal of Urology. He is an editor who enjoys writing. A pianist, he formed a Canadian Urology band, ‘The Void’, which plays at national and international conferences. He plays tennis at 6 AM before work two times a week, and is still an enthusiastic member of the Urology Division hockey team.


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