Active Surveillance of Prostate Cancer
LAURENCE KLOTZ’S RATIONAL MANAGEMENT PLAN
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.”
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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.
M.M.
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