1. PROSTATE CANCER SCREENING Dan O’Connell, MD Dept of Family Medicine 2/4/05

2. MEN’S HEALTH AND DISPARITIES Higher income Dominate decision making roles in society 10 times more likely to commit DV Male MDs interupt more than female MDs Die 5-6 years sooner (74.4 vs 79.8) Do not seek out preventive medical care

3. Cancer Morbidity/Mortality, 2001 Incidence Lung 172,000 Colo-rectal 184,000 Breast214,000 Prostate232,000 Pancreas 32,200 Melanoma 60,000 Cervical10,400 Deaths Lung163,000 Colo-rectal 56,000 Breast 40,000 Prostate30,000 Pancreas31,800 Melanoma 8,000 Cervical3,700

4. Prostate CA facts 10% of men will have symptomatic disease in their lifetime 4% die from prostate cancer

9. Spectrum of disease End stage prostate CA – bone mets to lumbar spine, very painful, urine, stool incontinence, possible paralysis Benign prostate CA –Microscopic, inconsequential, found in 30% autopsies, 70% over age 80

10. PROSTATE CANCER- HETEROGENEITY Widely varying growth rates Widely varying potential to cause mortality Screening poorly differentiates clinically significant tumors from insignificant

11. Case 1 61 yo man with HTN, DJD knees heard on the radio that he should get his PSA checked What do you advise?

12. Case 2 44 yo African American notes his father died of prostate cancer at age 61 He asks if he should be checked for this

13. * For men in their 50s, about 50; for men in their 70s, about 270. † For men in their 50s, about 150; for men in their 70s, about 400. ‡ For men in their 50s, about 17; for men in their 70s, about 90. § For men in their 50s, about 30; for men in their 70s, about 100. ¦ For men in their 50s, about 12; for men in their 70s, about 63. ** For men in their 50s, about 21; for men in their 70s, about 70. Yield of PSA, Men in their 60s

14. Biopsies 4-6 biopsies obtained from different parts of glands, focusing on area of mass if found on DRE Sensitivity of biopsies (based on repeat biopsies) : 70-90%

15. Gleason Score Tumors graded 1-5 based on cells and architecture How is the Gleason score calculated?

16. Gleason Score Tumors graded 1-5 based on cells and architecture Primary and secondary Gleason 2-4 - well differentiated low grade Gleason 5-7 – Moderately Differentiated Gleason 8-10 – Poorly differentiated, high grade

17. How is prostate cancer staged?

18. Bone Scans PSA% positive bone scans <102.3% 10-195.3% 20-5016.2% Recommended for PSA >10 or Gleason 7 or more

19. CT scans For extra capsular tumors 244 men with PSA <15, Gleason 2-7, T2b or less: all had neg CT ( Lee, Int J Radiat Oncol Biol Phys, 12/00)

20. Prostate Screening Guidelines American Cancer Society - 1993 Annual DRE beginning at 40 Annual PSA –beginning at 40 for African Americans Family history of prostate cancer –beginning at 50 for all other men American Cancer Society, 1993

22. Prostate Screening Guidelines American Urological Association-1995 “Patients in these age/risk groups should be given information about these tests and should be given the option to participate”

23. Prostate Screening Guidelines American Cancer Society - 2001 PSA and Digital Rectal Examination should be offered annually, beginning at age 50 years, to men who have at least a 10-year life expectancy.... Information should be provided to patients regarding potential risks and benefits of intervention. American Cancer Society

24. An Evidence Table

25. PSA velocity For PSA between 2.5 and 4.0: “An increase of > 0.75 ng/ml per year may be 90% specific for CA (cancer) detection.”

26. Age / PSA cut-off value (ng/ml) 40 - 49 / 2.5 50 - 59 / 3.5 60 - 69 / 4.5 70 - 79 / 6.5 If there is cancer: PSA increases 2.2 for every 1 gram of cancer

27. External factors effecting PSA FALSE ELEVATION DRE Prostatitis, BPH Urinary retention Ejaculation within 48 hours FALSE DECREASE Finasteride (proscar) Saw palmetto

28. AAFP PSA Decision Aid Men in their 60s http://www.aafp.org/clinical/tools/

29. Sensitivity, Specificity, Pos Pred Value, Neg Pred Value + Prostate CA No Prostate CA PSA >43 True + 7 False + PSA <41 False - 89 True -

30. Sens, Spec PPV, NPV Sensitivity = a/ (a+c) = 3/4 = 75% Specificity = d/(b+d) = 89/96 = 93% PPV = a/ (a+b) = 3/10 = 30% NPV = d/ (c+d) = 89/90 = 99%

31. What are the possible disadvantages of having a PSA test?

33. AAFP PSA Balance Sheet http://www.aafp.org/clinical/tools/

34. Cancer Morbidity/Mortality, 2001 Incidence Lung 172,000 Colo-rectal 184,000 Breast214,000 Prostate232,000 Pancreas 32,200 Melanoma 60,000 Cervical10,400 Deaths Lung163,000 Colo-rectal 56,000 Breast 40,000 Prostate30,000 Pancreas31,800 Melanoma 8,000 Cervical3,700

35. AAFP PSA Balance Sheet http://www.aafp.org/clinical/tools/

36. Prostate Screening Harms AUA Guideline www.guidelines.gov

37. Prostate Screening Harms USPSTF Guideline

38. Prostate Screening Harms ACS Guideline

39. Summary of Recommendations The U.S. Preventive Services Task Force (USPSTF) www.ahrq.gov The evidence is insufficient to recommend for or against routine screening for prostate cancer using prostate specific antigen (PSA) testing or digital rectal examination (DRE). Rating: I recommendation. I recommendation Rationale: The USPSTF found good evidence that PSA screening can detect early-stage prostate cancer but mixed and inconclusive evidence that early detection improves health outcomes. Screening is associated with important harms, including frequent false-positive results and unnecessary anxiety, biopsies, and potential complications of treatment of some cancers that may never have affected a patient's health. The USPSTF concludes that evidence is insufficient to determine whether the benefits outweigh the harms for a screened population.

40. Strength of Recommendations A. Good evidence to support B. Fair evidence to support C. No recommendation for or against. D. Fair evidence to exclude I. Insufficient Evidence to recommend for or against

41. TREATMENT – RADICAL PROSTATECTOMY Treatment in 1/3 of all cases Treatment in 1/2 of cases in men <75 10 YEAR SURVIVAL Radical prost. Radiation therapy Watchful waiting Well diff949093 Mod diff877776 Poorly dif675345 Lu-Yao GL, Yao,Lancet 1997;349:906-910.

42. HARM Men with Reduced Sexual Function Men with Urinary Problems Men with Bowel Problems Men with Other Problems Treatment Radical Prostatectomy 20%-70%15%-50% -- External Beam Radiation Therapy 20%-45%2%-16%6%-25% Brachytherapy (seeds) 36% 2 2 6%-12% 2 2 18% 2 2 Androgen Deprivation Therapy (LHRH agonists) 40%-70% Breast Swelling: 5%-25% Hot Flashes: 50%-60%

43. ANDROGEN DEPRIVATION THERAPY Bilateral Orchiectomy LHRH agonists (e.g., goserelin or leuprolide (Lupron) )

44. PSA SCREENING AT AGE 70 50% Life expectancy = 10 years Prostate CA with 90% 10 yr survival rate Less QALYs to be gained, higher harm, but also much higher number of cancers detected

46. ALTERNATIVE TO PSA early prostate cancer antigen (EPCA), a subset of PSA that appears only after the development of prostate tumors Genetic markers for Prostate CA

47. PROSTATE CANCER – ASSOCIATED FACTORS Red meat High fat diet High dairy intake Fried and charcoal grilled meat

48. PROSTATE CANCER PREVENTION Alpha-linolenic acid (ALA) (flax seed oil) (50% lower amongst lowest quintile vs top) EPA (Fish oil) – 11% less in top quintile (Leitzman Journal of Nutrition, 7/04) Selenium 0.12-0.19 ppm vs 0.06-0.09 ppm 50-70% less advanced DZ (Li, Journal of the NCI 5/04)

49. PROSTATE CANCER PREVENTION – protective factors Soy (Gronberg, Lancet, 3/03) Tomato (lycopene) (Chen, Journal of the NCI 12/01) Vitamin E (Gronberg, Lancet, 3/03) Selenium (Brooks, Journal of Urology, 12/01) Sun Exposure (Luscombe, Lancet, 8/01) Vegetable intake (>28/wk vs <14/wk- 35% less dz) (Cohen, Journal of the NCI, 1/00)

50. PROSTATE CANCER PREVENTION- NO EFFECT Smoking Alcohol Exercise Vasectomy Sexual activity

51. Testosterone exposure? Marketing of testosterone for slowing aging in men is beginning, analogous to use of estrogen replacement (HRT) in women in the 1980s Effects of disease unknown