1. Some Current Issues in the Management of Prostate Cancer Suman Chatterjee MD

2. 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

3. 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

4. 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)

5. 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.

6. Active Surveillance

7. ● 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

8. Active Surveilance

9. Active Surveillance

10. 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.

11. Androgen Deprivation

12. ● 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

13. 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.

14. 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

15. 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

16. 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

17. Androgen Deprivation ● Side effects: – Long term: ● Loss of bone mineral density ● Altered lipid profile ● Increased Cardio Vascular Events ● Memory/ Cognitive effects

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

19. 5ARI's and Prostate Cancer 5 Alpha Reductase Inhibitors include: Proscar (Finasteride) Avodart (Dutasteride)

20. 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

21. 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

22. 5ARI's and Prostate Cancer ● Explanations: – Sampling

23. 5ARI's and Prostate Cancer ● Other explanations: – Delay in progression – Pathologic Attributes – Induction

24. Thank you