Some Current Issues in the Management of Prostate Cancer

Suman Chatterjee MD

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

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

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)

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.

Active Surveillance

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

Active Surveilance

Active Surveillance

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.

Androgen Deprivation

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

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.

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

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

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

Androgen Deprivation

● Side effects:– Long term:

● Loss of bone mineral density● Altered lipid profile● Increased Cardio Vascular Events● Memory/ Cognitive effects

Androgen Deprivation

● Prevention– Vit D & Ca supplementation– Weight bearing exercise– Healthy diet– Baseline BMD at 1 year post treatment

5ARI's and Prostate Cancer

5 Alpha ReductaseInhibitors include:

Proscar (Finasteride)Avodart (Dutasteride)

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

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

5ARI's and Prostate Cancer

● Explanations:– Sampling

5ARI's and Prostate Cancer

● Other explanations:– Delay in progression– Pathologic Attributes– Induction

Thank you