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Active Surveillance with Elective
Delayed Intervention. (July 2005)
These title words were followed by “walking the line
between over-treatment for indolent disease and under-treatment for
aggressive disease” in Dr. Laurence Klotz’s report of the outcome of this
management strategy for prostate cancer in 299 men (Canadian Journal of
Urology;12 (Supp 1); February 2005). The phrases “active surveillance”
(AS) or “expectant management” have replaced the older concept of
“watchful waiting”, which implied no initial treatment, but instead,
palliative intervention when symptoms developed. Serious consideration of
a strategy of deferred therapy without sacrificing curative intent is
called for as a result of the stage migration resulting from the expanding
practice of PSA screening. As cited by Klotz, “PSA screening has increased
the ratio of incidence to mortality for prostate cancer from 2.5:1 to
15:1” leading to a lifetime likelihood of a prostate cancer diagnosis in
USA males of 1:6, but only a mortality ratio of 1:40. In his editorial in
The Journal of Urology, April 2005, “Early Stage Prostate Cancer - Do We
Have A Problem With Over-Diagnosis, Over-treatment, Or Both” Peter Carroll
called for “identifying better markers of the need for treatment and
carefully constructed trials of surveillance in well selected and
monitored men”. The time is ripe for “unlinking detection and treatment”.
Two informative trials have been reported that explore
active surveillance. Both reports stress the importance of a careful
selection of men who are at low risk for recurrence, and both use the PSA
doubling time to trigger intervention. In the staging of candidates for AS
the need for a > 12 core biopsy to minimize sampling error was
emphasized, as was the importance of good communication between patient
and doctor to explain the concept.
n his article Klotz reports an 8 year follow-up of 299
Toronto men with good- or intermediate-risk cancer. Eligibility required
PSA < 15, Gleason < 7, cT < 2b. Most men, however, were PSA
< 10, Gleason < 6, cT < 2a. Rebiopsy was performed at 1.5 -
2 years. Intervention was triggered by a PSADT < 2 years or developing a
PSA >8 ng/mL. At a median of ~ 5 years 60% remained on surveillance. “Of
the patients coming off surveillance, 12% of patients came off because of
rapid biochemical progression, 8% for clinical progression, 4% for
histologic progression, and 16% due to patient preference.” At 8 years
overall survival was 85%, and disease specific survival 99%. A rapid PSA
DT of < 2 years prompted surgery in 24 of the 299. The findings: 10 were
pT2; 14, pT3a-c; and 2, N1. Interestingly, “Neither grade, stage, baseline
PSA, or age correlated significantly with PDSDT”. Reflecting on the
trial’s outcome, Klotz suggests that the threshold for intervention would
best be set at a PSA DT of “around three years”, noting that “about 20% of
patients will fall into this category.”
The Toronto group has initiated a Phase III Intergroup
Trial, “Standard Treatment Against Restricted Treatment (START), open to
good-risk patients (PSA < 10, Gleason < 6, T1c/T2a) with
randomization between active surveillance or definitive therapy with RP,
BT, or EBRT. The trial uses a PSA DT of < 3 years, or grade progression to
a predominant Gleson pattern of 4 or higher as a trigger for intervention.
The second article, “Early outcome of active surveillance
for localized prostate cancer” (BJU Int, 95, 2005) reports the
outcome of 80 men managed at the Royal Marsden Hospital whose disease
status was cT1/T2, PSA < 20 ng/mL, Gleason score < 7. Intervention
was individualized and based on the relationship of observed PSA DT and
the patient’s age, or was prompted by an upgrade in biopsy histology. At a
median F/U of 42 months, 80% remained on AS. Seven patients had RP and at
a median of 20 months all are NED. “The median PSA DT for the group was 12
years, while 25% of patients had a PDS DT of < 4.5 years.” A follow-up
clinical trial is ongoing at the Marsden in which the PSA eligibility has
been narrowed to < 15 ng/mL; and less than half of the cores may be
positive. Repeat biopsies are taken every 2 years.
In the “Men & Health” section of the New York Times, June
20, the health columnist, Gina Kolata, presents an up to date summary of
issues related to PSA screening, discusses delayed treatment, and
highlights the rate of PSA rise as important. This would be an excellent
office article for educating men.
Bottom Line:
The increasing relevance of a strategy of active surveillance brings to
mind the command of General Putnam at the Battle of Bunker Hill. “Don’t
fire until you see the whites of their eyes”; with the further advice -
unnecessary for clinicians today - “then fire low, take aim at their
waistbands” [actually a little lower].
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