Diet and Stress Reduction in Advanced Prostate Cancer

1. 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

2. Primary Research Question: • Can healthy dietary change, reinforced by stress reduction, slow or stop the progression of advanced prostate cancer?

3. 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.

4. 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.

5. 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.

6. 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.

7. 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.

8. 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.”

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

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

11. 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

12. 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 (?)

13. 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.

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

15. 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

16. 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

17. Methods • Small non-randomized pilot study • Subjects (N=10) 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

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

19. 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.

20. 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).

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

22. 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 [7.8 - 95% C.I. [3.7 - 10.1] ¥]

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

24. 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 #

25. Results • Three subjects had absolute reductions in their PSA levels.

26. 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 3 5 7 8 9 2 4 6 Subject #

27. 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 0.00 -20.00 20.00 40.00 Change in Fiber Intake (g/day) Spearman  = -.73, p=.02

28. Figure 4. Change in exercise level as a predictor of change in PSA slope 0.10 0.00 Change in -0.10 PSA Slope (log PSA) -0.20 -0.30 0.00 70.00 140.00 Change in Exercise Level (mins./ day) Spearman’s  = -.60, p=.04

29. 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) Spearman’s  = .60, p=.04

30. 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.

31. 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.

32. 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

33. Differences with Pilot Study • Randomized trial (pilot was pre-post design) • Larger sample size (N=50) • Longer intervention period (6 months vs. 4) • More funding!!

34. 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

35. 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

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

37. 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

38. Questionnaires • Identifying and demographic data • Food frequency questionnaire • Physical activity recall

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

40. 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

41. 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.

42. 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

43. 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

44. 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. (858) 622-1731, ext. 2233 Email: gsaxe@ucsd.edu

45. 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 < 40%

46. Data Analysis • PSA doubling time is defined as: PSA-DT = (ln2 [0.639]/slope)