1. Preventative Care and Monitoring for Prostate Disease Joshua Broghammer, MD FACS Assistant Professor, Dept of Urology University of Kansas Medical Center

2. Disclosures I am not a urologic oncologist Reconstructive urologist Inherent bias against over treatment

3. Objectives Incidence of prostate cancer Screening guidelines Screening controversies

4. Incidence of Prostate Cancer 2010 1 – 196,038 men diagnosed with PCA – 28,560 died of PCA Excluding skin cancer, most common cancer among men Second leading cancer killer in men 1 CDC website http://www.cdc.gov/cancer/prostate/statistics/

5. Prostate Cancer Since 1992, an annual decline in prostate cancer mortality of 4% per year has been observed – Compared with decrease in breast cancer mortality of approximately 2.7%, and colorectal of 4.7% (since 2002), and lung of 2%

6. Figure 4. Trends in age-standardized death rates (log scale) for major cancers by age, 1970–2006. Jemal A, Ward E, Thun M (2010) Declining Death Rates Reflect Progress against Cancer. PLoS ONE 5(3): e9584. doi:10.1371/journal.pone.0009584 http://www.plosone.org/article/info:doi/10.1371/journal.pone.0009584

7. Prostate Cancer Screening

8. Screening-Digital Rectal Exam Detects 25% of cancers we detect today Abnormal in 6-15% of men May be the only sign of aggressive cancer 2 2. Okotie et al., Urology. 2007 Dec;70(6):1117-20.

9. Prostate Anatomy http://besthealth.bmj.com

10. Tropicana

11. PSA Prostate specific antigen Serine Protease (kallikrein like) – Semenogelin I and II Normal component of ejaculate FDA approved WITH DRE – Widespread use in 1988

12. Factors Affecting PSA Level-Size Matters

13. Other Factors UTI Prostate surgery Other instrumentation (foley, etc) Prostate inflammation – Do not treat with antibiotics and repeat – Consider rescreen in 3 months

14. Non-factors Sexual intercourse Digital rectal examination

15. Results of Cost Analysis of Screening Cost per InterventionQALY Gained Liver transplantation$237,000 Screening mammography (< age 50)$232,000 Worst case—CaP Screening$145,600 CABG—2 vessel/angina$106,000 Captopril for hypertension$ 82,600 Hydrochlorathiazide for hypertension$ 23,500 Best case—CaP Screening$ 8,700 Stop smoking MD message$ 1,300 QALY=quality-adjusted life years; CaP=prostate cancer; CABG=coronary artery bypass graft Thompson IM, Optenberg SA. Oncology (Huntingt). 1995;9:141-145.

16. Screening PSA 0-4 ng/mL classically was the normal range – Some historical evidence supports lowering limit to 0-2.5 Estimated that this would double the number of men age 40-69 with an abnormal result. 3 PSA velocity – Defined as >.75ng/ml year Age specific PSA AgeRecommended Reference (years)Range for Serum PSA (ng/mL) 40–49 0.0–2.5 50–59 0.0–3.5 60–69 0.0–4.5 70–79 0.0–6.5 3. Smith DS et al,. J Urol. 1998 Nov;160(5):1734-8.

17. Screening PSA density- PSA/volume of prostate – 0.15 ng/mL/cm3 – Prostate cancer cells produce 10x more PSA Free PSA – Ratio of free to total PSA is reduced in prostate cancer – 25%

18. Screening Controversies Economic benefits – How much screening is needed to save 1 life? 503 to save one life (updated from ERSPC trial) Quality of Life – Do risks outweigh benefits Risks associated with the test Loeb S et al., J Clin Oncol. 2011 Feb 1;29(4):464-7

19. Screening Pros 90% of prostate cancers detected are localized to the prostate (potentially curable) PSA of 4.0 ng/ml has good sensitivity – Detects over 90% of aggressive prostate cancers – 56% of non-aggressive cancers

20. Screening Cons Screening tests must satisfy the following: – Detect curable disease – Provide survival advantage – Treatment options which work Evidence is lacking to support a survival advantage, despite mortality decrease

21. Risk of a Biopsy Hospitalization rates of 0.6-4.1% – 0.3% death rate 30 days after (70% lower than aged matched controls) Era of quinolone resistance Ecoli-15% resistance rate in community High risk if your patient has gotten abx in 1 year Nam RK et al. J Urol 2010

22. PLCO Cancer Screening Trial Effects of cancer screening on men 55-74 – Excluded if PSA screening in last 3 years Screening completed 2006 Data collection until 2015 76,685 enrolled – Intervention arm (38,340) Annual PSA x 6 years, DRE x 4 years – Control arm (38,345) Usual care-including opportunistic screening

23. PLCO 2012 Results Follow up – 92% at 10 years – 57% at 13 years 4250 vs. 3815 diagnosed with PCA – 12% increase in intervention arm Mortality rates from PCA – 3.7 vs. 3.4 per 10K person years (no difference) Andriole GL et al, J Natl Cancer Inst. 2012 Jan 18;104(2):125-32.

24. PLCO Controversy Control arm had many men screened PSA cutoff of 4.0 may be too high Selection bias-eligible men may be excluded due to prior screening

25. European Randomized Study of Screening for Prostate Cancer Trial Effects of PCA screening on those 50-74 182,000 enrolled – Intervention arm Screening 1 every 4 years – Control Arm No screening PSA cutoff was 3.0 ng/mL Primary outcome-death from prostate cancer Schroder FH et al., N Engl J Med. 2009 Mar 26;360(13):1320-8

26. ERSPC Results Incidence of PCA – 8.2% vs. 4.8% Rate ratio for death from PCA 0.80 PSA reduced death rate by 20%, but high over diagnosis rate – 1410 needed to screened, 48 needed to treat at 9 yrs – 503 needed to screened, 18 needed to treat at 12 yrs

27. ERSPC Controversy Shorter follow up Modest benefit in screening Several different countries (7 centers) – Sweden and Netherlands significant  PCA mortality – Other five centers showed no difference

28. To Screen or Not to Screen Need to treat 18-48 men to save a life – What if you’re “that guy” Many studies have significant flaws – Cross over of non-screened control groups Quality of life is an important factor not considered – Treatment – Death of PCA

29. Screening Guidelines No screening – US Preventative Services Task Force (Grade D) Chairman was a pediatrician – American Academy of Family Practice Selected screening – American Urological Association – American Cancer Society – National Cancer Institute – American College of Physicians

30. AUA Guidelines No PSA Screening <40 No routine screening in average risk age 40-55 Individualized screening for high risk or AA <55 55-69: Shared decision making process – Screening interval of 2 years or more No screening in men 70+ with life expectancy of <10-15 years.

31. Urinary Symptoms-LUTS Obstructive: – Decreased force – Hesitancy – Intermittency – Incomplete emptying Irritative: – Frequency – Urgency

32. Urinary Symptoms Many things can be a cause Including prostate cancer Talk to your patients

33. Screening Guidelines No Organization Supports Annual PSA Screenings in Average Risk Males

34. Where did we go wrong? Dialing down PSA Screening everyone Lack of leadership Inherent biases

35. Treatment Biases 1.Cure cancer 2.Prevent incontinence 3.Prevent erectile dysfunction

36. Treatment Modalities Watchful waiting Active Surveillance Seed Implants External radiation Radical Prostatectomy

37. Watchful Waiting Repeated PSA testing Intervention at a predetermined PSA level No real set guidelines Doesn’t sit well with patients

38. Active Surveillance T1 disease (biopsy +, negative on DRE) Gleason 6 (low grade disease) ≤ 2 out of 6+ cores positive PSA <10 No cores with >50% involvement

39. Active Surveillance Annual repeat biopsy – Combats sampling error Annual PSA – Doubling time of <2 years Consideration for MRI – Evaluate for missed tumors

40. Prostate Cancer Prevention PCPT-Prostate cancer prevention trial – Finasteride (Proscar) – 10% reduction in prostate cancer 10.5% finasteride group vs 14.9% in placebo – Increase in high grade prostate cancer 6.4% finasteride group vs 5.1% in placebo Not FDA approved for the prevention of PCA

41. Prostate Cancer Prevention SELECT-Selenium and Vitamin E Cancer Prevetion Trial Alone and in combination Selenium- Trend toward but not significant for DM Vitamin E-17% more cancers – 11 per 1000 men

42. Conclusions

43. PSA testing should exist in some form. Informed decision. Continued screening for high risk men.

44. Questions? 44