1. Dietary and Lifestyle Adjuncts to Active Surveillance Stephen J. Freedland, M.D. Assistant Professor of Urology and Pathology Duke Prostate Center Durham VA Medical Center Duke University School of Medicine Stephen J. Freedland, M.D. Assistant Professor of Urology and Pathology Duke Prostate Center Durham VA Medical Center Duke University School of Medicine

2. What do physicians think of active surveillance? Close observationClose observation –i.e. active Prevents side effects from treatmentPrevents side effects from treatment Allows delayed definitive therapyAllows delayed definitive therapy Not right for all men, but in general underutilizedNot right for all men, but in general underutilized Close observationClose observation –i.e. active Prevents side effects from treatmentPrevents side effects from treatment Allows delayed definitive therapyAllows delayed definitive therapy Not right for all men, but in general underutilizedNot right for all men, but in general underutilized

3. What do patients think of active surveillance? Allowing time for the tumor to growAllowing time for the tumor to grow Delaying the inevitableDelaying the inevitable Doing nothingDoing nothing –i.e. not active Allowing time for the tumor to growAllowing time for the tumor to grow Delaying the inevitableDelaying the inevitable Doing nothingDoing nothing –i.e. not active

4. Active Surveillance: Rationale Incidence: 170/100,000 Mortality: 32/100,000 170/100,000 get prostate cancer 32/100,000 die from prostate cancer 138/100,000 get prostate cancer and die from other causes 170/100,000 get prostate cancer 32/100,000 die from prostate cancer 138/100,000 get prostate cancer and die from other causes

5. What do People die from? Answer: Heart Disease – number one killer

6. How do we prevent heart disease? Dietary modificationsDietary modifications –Weight loss –Reduced saturated fat –Reduced refined carbohydrates Lifestyle changesLifestyle changes –Exercise –Quit smoking Dietary modificationsDietary modifications –Weight loss –Reduced saturated fat –Reduced refined carbohydrates Lifestyle changesLifestyle changes –Exercise –Quit smoking

7. Why recommend the same changes for prostate cancer patients? Improves overall healthImproves overall health –Reduced risk of heart disease, diabetes Improves quality of lifeImproves quality of life –More energy –Can improve ED Allows the patient to do “something”Allows the patient to do “something” –Patients become active participants in their own care May slow tumor growth?May slow tumor growth? Improves overall healthImproves overall health –Reduced risk of heart disease, diabetes Improves quality of lifeImproves quality of life –More energy –Can improve ED Allows the patient to do “something”Allows the patient to do “something” –Patients become active participants in their own care May slow tumor growth?May slow tumor growth?

8. Active Surveillance + Active Surveillance per “protocol”Active Surveillance per “protocol” Aggressive dietary and lifestyle modificationAggressive dietary and lifestyle modification Goal:Goal: –Weight loss –Specific dietary changes –Improved physical fitness Active Surveillance per “protocol”Active Surveillance per “protocol” Aggressive dietary and lifestyle modificationAggressive dietary and lifestyle modification Goal:Goal: –Weight loss –Specific dietary changes –Improved physical fitness

9. DietDiet From the Greek word diaitaFrom the Greek word diaita Literally, “way of life”Literally, “way of life” Should not be viewed as short-term intervention to lose weightShould not be viewed as short-term intervention to lose weight A proper “way of life” reduces risk of heart disease, #1 killerA proper “way of life” reduces risk of heart disease, #1 killer Heart healthy = prostate healthyHeart healthy = prostate healthy From the Greek word diaitaFrom the Greek word diaita Literally, “way of life”Literally, “way of life” Should not be viewed as short-term intervention to lose weightShould not be viewed as short-term intervention to lose weight A proper “way of life” reduces risk of heart disease, #1 killerA proper “way of life” reduces risk of heart disease, #1 killer Heart healthy = prostate healthyHeart healthy = prostate healthy

10. Weight Loss ~ 70% of men in the US are overweight or obese~ 70% of men in the US are overweight or obese Thus, ~70% of men with prostate cancer in the US are overweight or obeseThus, ~70% of men with prostate cancer in the US are overweight or obese Weight loss = fewer calories in than outWeight loss = fewer calories in than out –Caloric restriction –Increased energy expenditure –Both ~ 70% of men in the US are overweight or obese~ 70% of men in the US are overweight or obese Thus, ~70% of men with prostate cancer in the US are overweight or obeseThus, ~70% of men with prostate cancer in the US are overweight or obese Weight loss = fewer calories in than outWeight loss = fewer calories in than out –Caloric restriction –Increased energy expenditure –Both

11. Does Weight Loss Slow Prostate Cancer Growth? Animal Studies: YESAnimal Studies: YES Dunning Rat Tumors LNCaP Xenograft Mukherjee et al. JNCI, 1999 NOTE: Simply cutting fat perhaps not as good as cutting total or carbohydrate calories

12. Does Cutting Fat Slow Prostate Cancer Growth? Animal studies: YESAnimal studies: YES LAPC-4 Xenograft Ngo et al. Clin Can Res, 2003

13. Human Studies: Excess Calories in Prostate Cancer Risk Obesity (end result of excess calories)Obesity (end result of excess calories) –30% increased risk of fatal prostate cancer –Increased risk of cancer recurrence after treatment Increased energy intake increases prostate cancer riskIncreased energy intake increases prostate cancer risk Weight gain increases riskWeight gain increases risk Weight loss decreases riskWeight loss decreases risk Obesity (end result of excess calories)Obesity (end result of excess calories) –30% increased risk of fatal prostate cancer –Increased risk of cancer recurrence after treatment Increased energy intake increases prostate cancer riskIncreased energy intake increases prostate cancer risk Weight gain increases riskWeight gain increases risk Weight loss decreases riskWeight loss decreases risk

14. Human Studies: Lifestyle Change after Diagnosis – Other Cancers WHEL study (Pierce et al, JAMA ’07)WHEL study (Pierce et al, JAMA ’07) ~3,100 women with previously treated breast cancer randomized to phone counseling/cooking classes vs. hand-outs~3,100 women with previously treated breast cancer randomized to phone counseling/cooking classes vs. hand-outs Goal: Increase fruit and vegetable and decrease fat intakeGoal: Increase fruit and vegetable and decrease fat intake Intervention: Vegetables, +65%; fruit, +25%; fiber, +30%, and energy intake f/fat, -13%Intervention: Vegetables, +65%; fruit, +25%; fiber, +30%, and energy intake f/fat, -13% No change in weight in either groupNo change in weight in either group No difference in recurrence or deathNo difference in recurrence or death WHEL study (Pierce et al, JAMA ’07)WHEL study (Pierce et al, JAMA ’07) ~3,100 women with previously treated breast cancer randomized to phone counseling/cooking classes vs. hand-outs~3,100 women with previously treated breast cancer randomized to phone counseling/cooking classes vs. hand-outs Goal: Increase fruit and vegetable and decrease fat intakeGoal: Increase fruit and vegetable and decrease fat intake Intervention: Vegetables, +65%; fruit, +25%; fiber, +30%, and energy intake f/fat, -13%Intervention: Vegetables, +65%; fruit, +25%; fiber, +30%, and energy intake f/fat, -13% No change in weight in either groupNo change in weight in either group No difference in recurrence or deathNo difference in recurrence or death

15. Human Studies: Lifestyle Change after Diagnosis – Other Cancers WINS study (Chlebowski et al, JCNI ’06)WINS study (Chlebowski et al, JCNI ’06) ~2,400 women with resected breast cancer randomized to low-fat diet vs. control~2,400 women with resected breast cancer randomized to low-fat diet vs. control Goal: Decrease fat intakeGoal: Decrease fat intake Intervention: energy intake f/fat, -19%Intervention: energy intake f/fat, -19% 2.7 kg drop in weight in intervention2.7 kg drop in weight in intervention Overall, 24% reduction in recurrence riskOverall, 24% reduction in recurrence risk ER+: 15% reduction (p=0.28)ER+: 15% reduction (p=0.28) ER-: 42% reduction (p=0.02)ER-: 42% reduction (p=0.02) WINS study (Chlebowski et al, JCNI ’06)WINS study (Chlebowski et al, JCNI ’06) ~2,400 women with resected breast cancer randomized to low-fat diet vs. control~2,400 women with resected breast cancer randomized to low-fat diet vs. control Goal: Decrease fat intakeGoal: Decrease fat intake Intervention: energy intake f/fat, -19%Intervention: energy intake f/fat, -19% 2.7 kg drop in weight in intervention2.7 kg drop in weight in intervention Overall, 24% reduction in recurrence riskOverall, 24% reduction in recurrence risk ER+: 15% reduction (p=0.28)ER+: 15% reduction (p=0.28) ER-: 42% reduction (p=0.02)ER-: 42% reduction (p=0.02)

16. Human Studies: Lifestyle Change after Diagnosis - Prostate Chan et al, JCO review ’06 on diet and prostate cancerChan et al, JCO review ’06 on diet and prostate cancer –5½ pages of text –1 paragraph on post-diagnosis –Conclusion: we don’t know much Chan et al, Cancer Causes Control ‘06Chan et al, Cancer Causes Control ‘06 –1,202 men with CaP –Increased tomato sauce after diagnosis reduced progression 30-40% Chan et al, JCO review ’06 on diet and prostate cancerChan et al, JCO review ’06 on diet and prostate cancer –5½ pages of text –1 paragraph on post-diagnosis –Conclusion: we don’t know much Chan et al, Cancer Causes Control ‘06Chan et al, Cancer Causes Control ‘06 –1,202 men with CaP –Increased tomato sauce after diagnosis reduced progression 30-40%

17. Human Study of Lifestyle Change Ornish et al, J. Urology 2005Ornish et al, J. Urology 2005 93 men on AS for PSA<10, Gleason <793 men on AS for PSA<10, Gleason <7 Randomized to standard diet or intensive lifestyle interventionRandomized to standard diet or intensive lifestyle intervention –10% dietary fat vegan diet –Yoga, meditation 4% decreased PSA in experimental arm4% decreased PSA in experimental arm 6% increased PSA in standard arm6% increased PSA in standard arm Ornish et al, J. Urology 2005Ornish et al, J. Urology 2005 93 men on AS for PSA<10, Gleason <793 men on AS for PSA<10, Gleason <7 Randomized to standard diet or intensive lifestyle interventionRandomized to standard diet or intensive lifestyle intervention –10% dietary fat vegan diet –Yoga, meditation 4% decreased PSA in experimental arm4% decreased PSA in experimental arm 6% increased PSA in standard arm6% increased PSA in standard arm

18. SummarySummary Active surveillance chosen due to low risk of cancer progressionActive surveillance chosen due to low risk of cancer progression –Assumption: more likely to die of causes other than prostate cancer –#1 killer is heart disease Heart disease is preventableHeart disease is preventable Active surveillance + allows patients to take active roleActive surveillance + allows patients to take active role Active surveillance chosen due to low risk of cancer progressionActive surveillance chosen due to low risk of cancer progression –Assumption: more likely to die of causes other than prostate cancer –#1 killer is heart disease Heart disease is preventableHeart disease is preventable Active surveillance + allows patients to take active roleActive surveillance + allows patients to take active role

19. SummarySummary Proper nutrition important in overall healthProper nutrition important in overall health –Reduce heart disease –Improve quality of life Slow tumor growth?Slow tumor growth? Ideal way of life not knownIdeal way of life not known My recommendation:My recommendation: –Low: calorie, carb (glycemic index), meat –High: Exercise, vegetable and fruits, nuts, legumes (beans and peanuts), whole grains Proper nutrition important in overall healthProper nutrition important in overall health –Reduce heart disease –Improve quality of life Slow tumor growth?Slow tumor growth? Ideal way of life not knownIdeal way of life not known My recommendation:My recommendation: –Low: calorie, carb (glycemic index), meat –High: Exercise, vegetable and fruits, nuts, legumes (beans and peanuts), whole grains