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Some Current Issues in the Management of Prostate Cancer
Suman Chatterjee MD
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Active Surveillance
● Concept: A certain subset of prostate cancer is slow growing
● Goals:– Delay the toxic side effects of definitive treatment – Have equivalent success in outcome vs immediate
treatment
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Active Surveillance
● Vs. Watchfull waiting– An older paradigm– Slow nature of progression of prostate cancer
would only necessitate treatment after years– In the interval other comorbidities would impact
the patients life expectancy
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Active Surveilance
● The “ideal” candidate– Healthy male able to undergoe definitive treatment– Clinically confirmed INDOLENT disease– Willing and interested in continued close
observation and monitoring (including repeat biopsy)
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Active Surveillance
● INDOLENT DISEASE– Initially defined by Epstein as
● Gleason 3+3 disease● <3 cores +● < 50% of any one core
– This “classic” definition is now being expanded although our understanding of this is still limited.
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Active Surveillance
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Active Surveillance
● Important Points:– To date 7 large series are available– Longest median followup is 6.8 years– PCa mortality is <1%– ~30% progress to definitive therapy– Median time to “progression” is 2.5 years
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Active Surveilance
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Active Surveillance
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Androgen Deprivation Therapy
● Rationale– Prostate cancer was the first solid organ
malignancy which was shown to be influenced by endogenous hormones
– Removing the supply of testosterone “inactivates” the growing prostate cancer tumor for a period of time
– Invariably the effects of androgen deprivation are countered by the tumor as it becomes refractory.
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Androgen Deprivation
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Androgen Deprivation
● Effects:– Dramatic reduction in PSA and Testosterone
levels– Within 28 days most men will have become
castrate– By 3 months radiologic progression of the tumor is
halted
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Androgen Deprivation
● Durability– This is dependent on the pathology of the original
tumor– Studies seem to indicate as an average 3-5 years
of good PSA (ie tumor) control followed by another 1-2 years where the tumor progresses but symptoms are minimal
– Clinically response is quite varied.
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Androgen Deprivation
● Uses:– Local Disease
● Improved survival and control in men treated with XRBT in combination with LHRH agonists
● Occasionally in order to facilitate brachytherapy in men with large prostates
● GENERALLY NOT USED WITH SURGERY– Studies did not identify a benefit
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Androgen Deprivation
● Uses:– Metastatic Disease:
● Still considered first line therapy● Currently intermittent therapy and continous therapy are
used depending on pathology● In patients with castrate resistant disease androgen
deprivation is still given as a subset of the tumor will still show response
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Androgen Deprivation
● Side Effects:– These are divided as short and long term– Short term:
● Hot flashes● Mood/ energy effects● Weight gain● Loss of libido/ ED
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Androgen Deprivation
● Side effects:– Long term:
● Loss of bone mineral density● Altered lipid profile● Increased Cardio Vascular Events● Memory/ Cognitive effects
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Androgen Deprivation
● Prevention– Vit D & Ca supplementation– Weight bearing exercise– Healthy diet– Baseline BMD at 1 year post treatment
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5ARI's and Prostate Cancer
5 Alpha ReductaseInhibitors include:
Proscar (Finasteride)Avodart (Dutasteride)
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5 ARIs and Prostate Cancer
● 2 Large studies (PCPT and REDUCE) have shown that low risk prostate cancer is prevented with the daily use of 5ARI's over extended periods
● The relative risk reduction in both is about 25%
● There also appears to be an absolute 1.3% increase in the detection of high grade disease
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5ARI's and Prostate Cancer
● Why is this?– It's generally not “biologically plausable” that a
treatment that slows one subset of a disease increases the risk of a more advanced subset of the same disease
– As we currently understand it gleason 6 disease and gleason 8 disease are variations of the same entity so they should react the same way
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5ARI's and Prostate Cancer
● Explanations:– Sampling
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5ARI's and Prostate Cancer
● Other explanations:– Delay in progression– Pathologic Attributes– Induction
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Thank you