Diet and Stress Reduction in Advanced Prostate Cancer

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Diet and Stress Reductionin Advanced Prostate
Cancer

• GORDON A. SAXE, MD, PhD
• UNIVERSITY OF CALIFORNIA, SAN DIEGO
• Rebecca and John Moores UCSD Cancer Center
• Dept. of Family and Preventive Medicine

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Primary Research Question

• Can healthy dietary change, reinforced by stress
  reduction, slow or stop the progression of
  advanced prostate cancer?

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Rationale

• Prostate cancer is the most commonly occurring
  cancer (other than skin cancer) among men in the
  U.S.
• In 1995, there were 244,000 new cases and 44,000
  deaths from prostate cancer in the U.S.

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Rationale

• One in six men in the U.S. will develop invasive
  prostate cancer in his lifetime.
• One in four African-American men will develop
  invasive prostate cancer.

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Rationale

• Following initial treatment, one in three
  patients will have a biochemical recurrence
  (marked by a rising PSA) within 10 years.
• Biochemical recurrence implies that there is
  microscopic evidence of cancer that has spread
  beyond the prostate.

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Rationale

• One third of those with a biochemical recurrence
  will develop clinical evidence of metastatic
  disease within the subsequent five years.
• No curative therapy exists for metastatic
  prostate cancer.

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Rationale

• Hormonal therapy can induce partial or complete
  remission and palliate symptoms.
• However, its effects are only temporary, lasting
  an average of 18 24 months.

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Rationale

• Hormone therapy is also accompanied by unpleasant
  side-effects such as hot flashes, fatigue,
  impotence, gynecomastia, osteoporosis, and muscle
  loss.
• As a result, patients with rising PSA after
  surgery tend to feel anxious and helpless in the
  face of their illness, a condition referred to as
  PSA anxiety.

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Rationale

• Risk factors for prostate cancer
• Male gender
• Age
• Heredity (genetic polymorphisms)
• Vasectomy
• Race
• Diet

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International Variation
China
1.3 per 100,000
Sweden
55.3 per 100,000
United States
102.1 per 100,000
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Rationale

• Epidemiological and laboratory evidence has
  associated specific dietary intakes with prostate
  cancer incidence, mortality, and possibly even
  disease progression
• Meat
• Dairy food
• Saturated fat

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Rationale

• Other dietary factors appear to be protective
• Whole grains
• Vegetables, especially cabbage family
• Tomatoes and other lycopene-rich foods
• Vitamin E, Selenium, and Zinc
• Green tea
• Soy foods (?)

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Rationale

• However, it is critical to promote stress
  reduction along with dietary change
• A major change in eating habits can be quite
  stressful.
• Many of these patients are already suffering from
  PSA anxiety.
• Stress reduction (such as meditation and yoga)
  may help patients to focus and make better
  dietary selections.

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Primary Research Question

• Can healthy dietary change, reinforced by stress
  reduction, slow or stop the progression of
  advanced prostate cancer?

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Definitions

• Healthy dietary change increased whole grains
  and vegetables, decreased saturated fat
• Stress reduction meditation, yoga, social
  support, mild exercise
• Advanced prostate cancer rising PSA on serial
  PSA tests after post-surgical PSA nadir

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Findings from our Pilot Study

• Can Diet in Conjunction with Stress Reduction
  Affect the Rate of Increase in Prostate Specific
  Antigen after Biochemical Recurrence of Prostate
  Cancer?
• Saxe GA, Hebert JR, Kabat-Zinn J, et al
• Journal of Urology, 166(12) 2202-7, Dec., 2001

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Methods

• Small non-randomized pilot study
• Subjects (N10) were men who had undergone
  radical prostatectomy and had subsequent rising
  PSA on serial tests
• Pre/post study design with each subject serving
  as his own control

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Methods

• Pre- vs. post-intervention rates of PSA increase
  and doubling times were compared.
• Data also gathered on diet, physical activity,
  and body weight

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Intervention

• Group-based intervention consisting of a series
  of 12 weekly classes, with each class lasting 3-4
  hours
• Subjects were asked to be accompanied by a
  support person, preferably someone with whom they
  shared meals.

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Intervention

• Each class included a cooking demonstration,
  hands-on training in prostate-healthy meal
  preparation, and a didactic presentation on diet
  and health.
• Classes also included formal instruction and
  practice in meditation and yoga (with subjects
  asked to practice daily at home).

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Results

• Signed rank test found significant reduction in
  the rate of PSA increase for the group as a whole
  (p.01).

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Results
Pre
Post
Mean Slope
0.124
0.031
95 C.I.
0.076 - 0.173
0.012 - 0.075
Median
6.5 months
17.7 months
Doubling Time
3.7 - 10.1
7.8 -
95 C.I.

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Results

• Eight out of ten subjects showed a decrease in
  their rates of PSA increase.

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Figure 1. Change in PSA slopes (pre-study
post-study) by subject
Change in PSA Slope
.1
Log
0
PSA
-.1
-.2
1
2
3
4
5
6
7
8
9
10
-.3
Subject
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Results

• Three subjects had absolute reductions in their
  PSA levels.

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Figure 2. PSA slopes, paired (pre-study vs.
post-study), by subject
Pre-study
Post-study
Slope
Slope
.3
Log
.2
PSA
.1
0
-.1
1
10
2
3
4
5
6
7
8
9
Subject
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Figure 3. Change in fiber intake as a predictor
of change in PSA slope
0.10
Change in
0.00
PSA Slope
-0.10
(log PSA)
-0.20
-0.30
-20.00
0.00
20.00
40.00
Change in Fiber Intake (g/day)
Spearman ? -.73, p.02
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Figure 4. Change in exercise level as a predictor
of change in PSA slope
0.10
0.00
Change in
PSA Slope
-0.10
(log PSA)
-0.20
-0.30
0.00
70.00
140.00
Change in Exercise Level (mins./ day)
Spearmans ? -.60, p.04
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Figure 5. Change in body mass index as a
predictor of change in PSA slope
0.10
0.00
Change in
PSA Slope
-0.10
(log PSA)
-0.20
-0.30
-4.00
-3.00
-2.00
-1.00
0.00
Change in Body Mass Index (kg/m2) Spearmans
? .60, p.04
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Conclusions

• In this small sample we saw a significant
  reduction in the rate of increase in PSA in men
  with biochemically recurrent prostate cancer.
• Major changes in diet and lifestyle were feasible
  in a relatively short period of time.

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Conclusions

• An intervention of this type may provide a means
  for men with recurrent prostate cancer to slow
  the progression of their disease without adverse
  side effects while simultaneously improving their
  well being and quality of life.
• These PSA results are promising and warrant
  further investigation through a larger multi-arm,
  randomized trial.

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Current Research

• Diet and Stress Reduction in Recurrent Prostate
  Cancer
• Gordon A. Saxe, MD, PhD
• Cheryl L. Rock, PhD, RD
• Dan Mercola, MD, PhD
• Carol Salem, MD

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Differences with Pilot Study

• Randomized trial (pilot was pre-post design)
• Larger sample size (N50)
• Longer intervention period (6 months vs. 4)
• More funding!!

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Study Design

• Subjects randomized to intervention or control
  status
• Intervention subjects receive program similar to
  subjects in pilot study
• Control subjects asked to maintain usual diet for
  6 months and undergo same monitoring as those in
  intervention

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Eligibility Criteria

• Biopsy-confirmed prostate cancer
• Primary therapy consisting of surgery or
  radiation treatment
• Rising PSA, documented on a minimum of three
  serial tests within a 12-month period, after
  achieving post-treatment nadir

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Eligibility Criteria

• No use of hormone therapy within the last 12
  months
• No competing health conditions that would limit
  participation
• Age 18 or older

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Monitoring

• Occurs at baseline, 3 months, and 6 months
  post-baseline
• Body weight assessment
• Blood draws for PSA, plasma carotenoids, and
  other biomarkers of tumor metastasis

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Questionnaires

• Identifying and demographic data
• Food frequency questionnaire
• Physical activity recall

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Questionnaires

• Spielberg Anxiety Scale
• Diet-related quality of life
• FACT-P
• SF-36

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Data Analysis

• Primary analysis will test the hypothesis that
  subjects in the intervention group will have a
  lower rate of increase in PSA than control
  subjects over the course of the 6-month
  intervention period
• We will also test differences in mean PSA rates
  and doubling times between intervention and
  control subjects

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Data Analysis

• We will also examine
• The effect of the intervention on quality of life
• Changes in other biomarkers of tumor metastasis
• Degree of dietary and lifestyle change by men in
  the intervention.

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Eligibility Criteria

• Biopsy-confirmed prostate cancer
• Primary therapy consisting of surgery or
  radiation treatment
• Rising PSA, documented on a minimum of three
  serial tests within a 12-month period, after
  achieving post-treatment nadir

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Eligibility Criteria

• No use of of hormone therapy within the last 12
  months
• No competing health conditions that would limit
  participation
• Age 18 or greater

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Contact Information

• GORDON A. SAXE, MD, PhD
• UNIVERSITY OF CALIFORNIA, SAN DIEGO
• Rebecca and John Moores UCSD Cancer Center
• Dept. of Family and Preventive Medicine
• Tel. [phone], ext. 2233
• Email gsaxe_at_ucsd.edu

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Sample Size Considerations

• N 50 subjects (25 intervention, 25 control)
• Based on following assumptions
• Two-sided t-test
• Mean PSA doubling time will increase by 100
  (from 245 days to 490 days) (pilot 937 days)
• Standard deviation 227 days (same as pilot)
• Alpha .05
• Study power 80
• Dropout rate

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Data Analysis

• PSA doubling time is defined as
• PSA-DT (ln2 0.639/slope)