Dietary and Lifestyle Adjuncts Dietary and Lifestyle Adjuncts to Active Surveillanceto Active Surveillance

Dietary and Lifestyle Adjuncts Dietary and Lifestyle Adjuncts to Active Surveillanceto Active Surveillance

Stephen J. Freedland, M.D.Stephen J. Freedland, M.D.Assistant Professor of Urology and PathologyAssistant Professor of Urology and Pathology

Duke Prostate CenterDuke Prostate CenterDurham VA Medical CenterDurham VA Medical Center

Duke University School of MedicineDuke University School of Medicine

Stephen J. Freedland, M.D.Stephen J. Freedland, M.D.Assistant Professor of Urology and PathologyAssistant Professor of Urology and Pathology

Duke Prostate CenterDuke Prostate CenterDurham VA Medical CenterDurham VA Medical Center

Duke University School of MedicineDuke University School of Medicine

What do What do physiciansphysicians think of think of active surveillance?active surveillance?

What do What do physiciansphysicians think of think of active surveillance?active surveillance?

• Close observationClose observation– i.e. i.e. activeactive

• Prevents side effects from treatmentPrevents side effects from treatment

• Allows delayed definitive therapyAllows delayed definitive therapy

• Not right for all men, but in general Not right for all men, but in general underutilizedunderutilized

• Close observationClose observation– i.e. i.e. activeactive

• Prevents side effects from treatmentPrevents side effects from treatment

• Allows delayed definitive therapyAllows delayed definitive therapy

• Not right for all men, but in general Not right for all men, but in general underutilizedunderutilized

What do What do patientspatients think of think of active surveillance?active surveillance?

What do What do patientspatients think of think of active surveillance?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. i.e. not activenot active

• Allowing time for the tumor to growAllowing time for the tumor to grow

• Delaying the inevitableDelaying the inevitable

• Doing nothingDoing nothing– i.e. i.e. not activenot active

Active Surveillance: RationaleActive Surveillance: RationaleActive Surveillance: RationaleActive Surveillance: Rationale

Incidence: 170/100,000Incidence: 170/100,000 Mortality: 32/100,000Mortality: 32/100,000

170/100,000 get prostate cancer32/100,000 die from prostate cancer138/100,000 get prostate cancer and die from other causes

170/100,000 get prostate cancer32/100,000 die from prostate cancer138/100,000 get prostate cancer and die from other causes

What do People die from?What do People die from?What do People die from?What do People die from?

Answer: Heart Disease – number one killerAnswer: Heart Disease – number one killer

How do we prevent heart How do we prevent heart disease?disease?

How do we prevent heart How do we prevent heart disease?disease?

• Dietary modificationsDietary modifications– Weight lossWeight loss– Reduced saturated fatReduced saturated fat– Reduced refined carbohydratesReduced refined carbohydrates

• Lifestyle changesLifestyle changes– ExerciseExercise– Quit smokingQuit smoking

• Dietary modificationsDietary modifications– Weight lossWeight loss– Reduced saturated fatReduced saturated fat– Reduced refined carbohydratesReduced refined carbohydrates

• Lifestyle changesLifestyle changes– ExerciseExercise– Quit smokingQuit smoking

Why recommend the same changes Why recommend the same changes for prostate cancer patients?for prostate cancer patients?

Why recommend the same changes Why recommend the same changes for prostate cancer patients?for prostate cancer patients?

• Improves overall healthImproves overall health– Reduced risk of heart disease, diabetesReduced risk of heart disease, diabetes

• Improves quality of lifeImproves quality of life– More energyMore energy– Can improve EDCan improve ED

• Allows the patient to do “something”Allows the patient to do “something”– Patients become Patients become activeactive participants in participants in

their own caretheir own care

• May slow tumor growth?May slow tumor growth?

• Improves overall healthImproves overall health– Reduced risk of heart disease, diabetesReduced risk of heart disease, diabetes

• Improves quality of lifeImproves quality of life– More energyMore energy– Can improve EDCan improve ED

• Allows the patient to do “something”Allows the patient to do “something”– Patients become Patients become activeactive participants in participants in

their own caretheir own care

• May slow tumor growth?May slow tumor growth?

Active Surveillance +Active Surveillance +Active Surveillance +Active Surveillance +

• Active Surveillance per “protocol”Active Surveillance per “protocol”

• Aggressive dietary and lifestyle Aggressive dietary and lifestyle modificationmodification

• Goal:Goal:– Weight lossWeight loss– Specific dietary changesSpecific dietary changes– Improved physical fitnessImproved physical fitness

• Active Surveillance per “protocol”Active Surveillance per “protocol”

• Aggressive dietary and lifestyle Aggressive dietary and lifestyle modificationmodification

• Goal:Goal:– Weight lossWeight loss– Specific dietary changesSpecific dietary changes– Improved physical fitnessImproved physical fitness

DietDietDietDiet

• From the Greek word diaitaFrom the Greek word diaita

• Literally, “Literally, “way of lifeway of life””

• Should not be viewed as short-term Should not be viewed as short-term intervention to lose weightintervention to lose weight

• A proper “way of life” reduces risk of A proper “way of life” reduces risk of heart disease, #1 killer heart disease, #1 killer

• Heart healthy = prostate healthyHeart healthy = prostate healthy

• From the Greek word diaitaFrom the Greek word diaita

• Literally, “Literally, “way of lifeway of life””

• Should not be viewed as short-term Should not be viewed as short-term intervention to lose weightintervention to lose weight

• A proper “way of life” reduces risk of A proper “way of life” reduces risk of heart disease, #1 killer heart disease, #1 killer

• Heart healthy = prostate healthyHeart healthy = prostate healthy

Weight LossWeight LossWeight LossWeight Loss

• ~ 70% of men in the US are overweight ~ 70% of men in the US are overweight or obeseor obese

• Thus, ~70% of men with prostate cancer Thus, ~70% of men with prostate cancer in the US are overweight or obesein the US are overweight or obese

• Weight loss = fewer calories in than outWeight loss = fewer calories in than out– Caloric restrictionCaloric restriction– Increased energy expenditureIncreased energy expenditure– BothBoth

• ~ 70% of men in the US are overweight ~ 70% of men in the US are overweight or obeseor obese

• Thus, ~70% of men with prostate cancer Thus, ~70% of men with prostate cancer in the US are overweight or obesein the US are overweight or obese

• Weight loss = fewer calories in than outWeight loss = fewer calories in than out– Caloric restrictionCaloric restriction– Increased energy expenditureIncreased energy expenditure– BothBoth

Does Weight Loss Slow Prostate Does Weight Loss Slow Prostate Cancer Growth? Cancer Growth?

Does Weight Loss Slow Prostate Does Weight Loss Slow Prostate Cancer Growth? Cancer Growth?

• Animal Studies: YESAnimal Studies: YES• Animal Studies: YESAnimal Studies: YESDunning Rat TumorsDunning Rat TumorsDunning Rat TumorsDunning Rat Tumors LNCaP XenograftLNCaP XenograftLNCaP XenograftLNCaP Xenograft

Mukherjee et al. JNCI, 1999Mukherjee et al. JNCI, 1999Mukherjee et al. JNCI, 1999Mukherjee et al. JNCI, 1999

NOTE: Simply cutting fat perhaps not as good as cutting total or carbohydrate caloriesNOTE: Simply cutting fat perhaps not as good as cutting total or carbohydrate calories

Does Cutting Fat Slow Prostate Does Cutting Fat Slow Prostate Cancer Growth? Cancer Growth?

Does Cutting Fat Slow Prostate Does Cutting Fat Slow Prostate Cancer Growth? Cancer Growth?

• Animal studies: YESAnimal studies: YES• Animal studies: YESAnimal studies: YES

LAPC-4 XenograftLAPC-4 Xenograft

Ngo et al. Clin Can Res, 2003Ngo et al. Clin Can Res, 2003Ngo et al. Clin Can Res, 2003Ngo et al. Clin Can Res, 2003

Human Studies: Excess Calories Human Studies: Excess Calories in Prostate Cancer Riskin Prostate Cancer Risk

Human Studies: Excess Calories Human Studies: Excess Calories in Prostate Cancer Riskin Prostate Cancer Risk

• Obesity (end result of excess calories)Obesity (end result of excess calories)– 30% increased risk of fatal prostate cancer30% increased risk of fatal prostate cancer– Increased risk of cancer recurrence after Increased risk of cancer recurrence after

treatmenttreatment

• Increased energy intake increases Increased energy intake increases prostate cancer riskprostate 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 cancer30% increased risk of fatal prostate cancer– Increased risk of cancer recurrence after Increased risk of cancer recurrence after

treatmenttreatment

• Increased energy intake increases Increased energy intake increases prostate cancer riskprostate cancer risk

• Weight gain increases riskWeight gain increases risk

• Weight loss decreases riskWeight loss decreases risk

Human Studies: Lifestyle Change Human Studies: Lifestyle Change afterafter Diagnosis – Other Cancers Diagnosis – Other Cancers

Human Studies: Lifestyle Change Human Studies: Lifestyle Change afterafter Diagnosis – Other Cancers Diagnosis – Other Cancers

• WHEL study (Pierce et al, JAMA ’07)WHEL study (Pierce et al, JAMA ’07)• ~3,100 women with previously treated breast ~3,100 women with previously treated breast

cancer randomized to phone cancer randomized to phone counseling/cooking classes vs. hand-outscounseling/cooking classes vs. hand-outs

• Goal: Increase fruit and vegetable and Goal: Increase fruit and vegetable and decrease fat intakedecrease fat intake

• Intervention: Vegetables, +65%; fruit, +25%; Intervention: Vegetables, +65%; fruit, +25%; fiber, +30%, and energy intake f/fat, -13%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 ~3,100 women with previously treated breast

cancer randomized to phone cancer randomized to phone counseling/cooking classes vs. hand-outscounseling/cooking classes vs. hand-outs

• Goal: Increase fruit and vegetable and Goal: Increase fruit and vegetable and decrease fat intakedecrease fat intake

• Intervention: Vegetables, +65%; fruit, +25%; Intervention: Vegetables, +65%; fruit, +25%; fiber, +30%, and energy intake f/fat, -13%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

Human Studies: Lifestyle Change Human Studies: Lifestyle Change afterafter Diagnosis – Other Cancers Diagnosis – Other Cancers

Human Studies: Lifestyle Change Human Studies: Lifestyle Change afterafter Diagnosis – Other Cancers Diagnosis – Other Cancers

• WINS study (Chlebowski et al, JCNI ’06)WINS study (Chlebowski et al, JCNI ’06)• ~2,400 women with resected breast cancer ~2,400 women with resected breast cancer

randomized to low-fat diet vs. controlrandomized 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 ~2,400 women with resected breast cancer

randomized to low-fat diet vs. controlrandomized 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)

Human Studies: Lifestyle Change Human Studies: Lifestyle Change afterafter Diagnosis - Prostate Diagnosis - Prostate

Human Studies: Lifestyle Change Human Studies: Lifestyle Change afterafter Diagnosis - Prostate Diagnosis - Prostate

• Chan et al, JCO review ’06 on diet and Chan et al, JCO review ’06 on diet and prostate cancerprostate cancer– 5½ pages of text5½ pages of text– 1 paragraph on post-diagnosis1 paragraph on post-diagnosis– Conclusion: we don’t know muchConclusion: we don’t know much

• Chan et al, Cancer Causes Control ‘06Chan et al, Cancer Causes Control ‘06– 1,202 men with CaP1,202 men with CaP– Increased tomato sauce after diagnosis Increased tomato sauce after diagnosis

reduced progression 30-40%reduced progression 30-40%

• Chan et al, JCO review ’06 on diet and Chan et al, JCO review ’06 on diet and prostate cancerprostate cancer– 5½ pages of text5½ pages of text– 1 paragraph on post-diagnosis1 paragraph on post-diagnosis– Conclusion: we don’t know muchConclusion: we don’t know much

• Chan et al, Cancer Causes Control ‘06Chan et al, Cancer Causes Control ‘06– 1,202 men with CaP1,202 men with CaP– Increased tomato sauce after diagnosis Increased tomato sauce after diagnosis

reduced progression 30-40%reduced progression 30-40%

Human Study of Lifestyle Human Study of Lifestyle ChangeChange

Human Study of Lifestyle Human Study of Lifestyle ChangeChange

• 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 Randomized to standard diet or intensive lifestyle interventionintensive lifestyle intervention– 10% dietary fat vegan diet10% dietary fat vegan diet– Yoga, meditationYoga, 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 Randomized to standard diet or intensive lifestyle interventionintensive lifestyle intervention– 10% dietary fat vegan diet10% dietary fat vegan diet– Yoga, meditationYoga, meditation

• 4% decreased PSA in experimental arm4% decreased PSA in experimental arm

• 6% increased PSA in standard arm6% increased PSA in standard arm

SummarySummarySummarySummary

• Active surveillance chosen due to low Active surveillance chosen due to low risk of cancer progressionrisk of cancer progression– Assumption: more likely to die of causes Assumption: more likely to die of causes

other than prostate cancerother than prostate cancer– #1 killer is heart disease#1 killer is heart disease

• Heart disease is preventableHeart disease is preventable

• Active surveillance + allows patients to Active surveillance + allows patients to take active roletake active role

• Active surveillance chosen due to low Active surveillance chosen due to low risk of cancer progressionrisk of cancer progression– Assumption: more likely to die of causes Assumption: more likely to die of causes

other than prostate cancerother than prostate cancer– #1 killer is heart disease#1 killer is heart disease

• Heart disease is preventableHeart disease is preventable

• Active surveillance + allows patients to Active surveillance + allows patients to take active roletake active role

SummarySummarySummarySummary• Proper nutrition important in overall Proper nutrition important in overall

healthhealth– Reduce heart diseaseReduce heart disease– Improve quality of lifeImprove 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), meatLow: calorie, carb (glycemic index), meat– High: Exercise, vegetable and fruits, nuts, High: Exercise, vegetable and fruits, nuts,

legumes (beans and peanuts), whole grainslegumes (beans and peanuts), whole grains

• Proper nutrition important in overall Proper nutrition important in overall healthhealth– Reduce heart diseaseReduce heart disease– Improve quality of lifeImprove 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), meatLow: calorie, carb (glycemic index), meat– High: Exercise, vegetable and fruits, nuts, High: Exercise, vegetable and fruits, nuts,

legumes (beans and peanuts), whole grainslegumes (beans and peanuts), whole grains