Prostate Cancer : Screening & early detection: where do we stand in 2018?

1. Prostate Cancer:Screening & early detection:where do we stand in 2018? Dr. ArunShahi MD Medical Oncology(Final)

3. Case Scenario: 1 Patient Identification: BG Age: 57 Years OldPSA: .1.4 ng/ml DRE: Bilateral Prostate Atypia/Asymmety; Non-Diagnostic for Prostate Cancer.  Ultrasound: Calcification Prominent on the Right Side but no Suspicious Areas of Hypoechogenicity  MRI (3.0 Tesla): Decreased Signal Intensity in the Right Peripheral Zone at the Base; Organ Confined. Biopsy: Negative for prostate Cancer

4. Case Scenario-2 Patient Identification: JMAge: 77 Years OldPSA: 15.5 ng/ml; Rising DRE: Non-diagnostic Ultrasound: Scattered calcification. MRI (3.0 Tesla): Decreased Signal Intensity in Left Perpheral Zone, associated with a 4.5 mm deep Apico-Mid ProstateBiopsy: Negative in 2001 with a PSA of 7.15 ng/ml (grayscale US), negative in 2002 with a (PSA of 11.5 ng/ml (Color Flow Doppler) Biopsy 2016: positive..Gleason Score 7 (4 +3) @ the Left Apex and Left Apico-Mid Prostate (PZ)

5. What is the prostate? • The prostate is a part of the male reproductive system, which includes the penis, prostate, and testicles. • The prostate is located just below the bladder and in front of the rectum. • It is about the size of a walnut and surrounds the urethra. • It produces fluid(PSA) that makes up a part of semen.

6. What is Prostate Cancer? • Cancer is a disease in which cells in the body grow out of control. • When cancer starts in the prostate, it is called prostate cancer.

8. Age Distribution of Men Diagnosedwith Prostate Cancer2016-2017 39% 40% 35% 30% 25% 20% 15% 10% 5% 0% 28% 22% 7% 3% 1% 30 40 50 60 Age 70 80 90

10. Median Age at Diagnosis andDeath 80 78 76 74 72 70 68 66 64 62 60 Diagnosis Death 13 year age gap Lung Colon All Breast Prostate

11. Lifetime Risk of Developing or Dyingof Prostate Cancer for a 50-Year-Old Man in the UnitedStates For every 100 men who develop cancer cells in their prostate during their lifetime, only 38 of them will ever be diagnosed with prostate cancer by biopsy, andonly 8.6 are at risk of dying of prostatecancer.

12. Who Gets/RISKProstate Cancer ? • Man,,Dog: onlyspecies • Both possess genes for PSA and hKZ(?related)

13. Risk Factor for Prostate Cancer? • Age • Older men are at greater risk for getting prostate cancer. • Family history • Men whose father brother or son who have had prostate cancer are two to three • T times likely to develop prostate cancer. • Race • African-American men, prostate cancer tends to starts at younger age and grow a faster then other racial or ethnic group

15. Should you screen for prostatecancer?

16. TheDebate Screening over diagnoses Prostate cancer Screening saveslives It will be keep going……

17. What is Screening for Prostate Cancer? • Cancer Screening means looking for cancer before it causes symptoms. • The goal of screening for Prostate cancer is to find cancer that may be at high risk for spreading if not treated, and to find them early before they spread. • Screening for Prostate Cancer begins with a blood test called PSA test.

18. How is the Prostate Evaluated? • Medical History • Physical Examination • Digital Rectal Examination • Urine Test and Prostate specific antigen(PSA) • Prostate Biopsy.

19. Digital Rectal Examination(DRE)

20. What is Prostate-Specific Antigen test? • PSA is a protein produced by prostate cells, which keeps semen in liquid form so that sperm can swim. • A simple blood test can measure how much PSA is present in a man’s bloodstream. • When a man has prostate cancer(Usually), his PSA level increases, which is why the PSA test is used as a screening tool.

21. What is a Normal PSA test ? • There is no specific normal or abnormal level of PSA in blood. • And level may vary over time in same person. • In the past 4.0ng/ml considered normal. • more recent studies show some men with PSA level below 4.0 ng/ml have prostate cancer:

22. Normal Range of PSA Levelsfor Men in Each AgeGroup

23. What If a screening test shows an elevated PSA level? • Patient & doctor together should explore several options if PSA is high. • 2nd PSA screening;(for better accuracy). • or DRE • and Biopsy.

24. Ruling out other causes of PSA to Rise? • Advanced age • Recent biopsy, DRE • Injury to pelvic region or prostate. • Prostatitis, BPH • Urinary tract infection, catheter in situ. • Riding a bicycle • Sex (within the past 24 hours) • Supplements that effect testosterone.

25. Probability of Finding Cancer on Biopsy According to a Man’sDRE Result and PSALevel Source: American urology association 2018

26. If Your PSA is Low?? • In general, a low PSA is a good result. • several reasons for a low PSA screening level • 1) statins to lower cholesterol, • 2) anti-inflammatory drugs and • 3) obesity.

27. Facts of Prostate Cancer Before PSA Era.

28. Prior to PSA screening test • Difficult to diagnose at earlystage. • 25% man presented with metastatic disease. • Great need for a biomarker to diagnose disease at an earlier stage

29. Prostate Cancer Incidence Peaked During theClinton Years

30. Beginning of PSA Screening Era • Approved by FDA in 1986 to monitor the progression of prostate cancer. • In 1994, FDA approved use of PSA test in conjunction with DRE for asymptomatic patient. • Mortality rate decreased 40% between 1994 and 2004 and still decreasing... • More men were diagnosed at early stage.

31. PSA screening Now in 2018 • >85% of men now present with clinically localized disease and are candidate for current therapy. • Decrease in rates of PC high risk group. • <4% of men now present with metastatic disease** • Survival rates has improved.

32. Trends in Relative 5Year SurvivalRate

33. Surprising thing ….. • Similar changes in mortality rates in other countries where PSA screening was not been routine. • Better treatment approach( radiation +/- hormone ,surgical). • Changing environment risk factor,drugs(5 alpha reductaseinhibitors,statins,metformin)

34. Research or Study on prostate cancer screening up to 2018?…..

35. European Randomized study of screening for prostate cancer(ERSPC)2009

36. ? Proven Benefit from PSA ScreeningERSPC European Randomized Screening for Prostate Cancer (ERSPC) Trial, 182,000 men age 50-74y, PSA yearly for 4 years Median follow up of 11years Conclusion: screen lowers the death rate by 21%, but you would need to screen 1,055 men and treat 37 to prevent onedeath

37. ? Proven Benefit fromPSA Screening PLCOStudy Prostate, Lung, Colorectal, Ovary US Study, n = 76,693 , annual PSA for 6 years and DRE 4 years, with 13 years followup

42. Prostate CancerScreening Mata-analysis of 6 trials ( n =387,286) • Odds of diagnosing prostatecancer • = increased by46% • Odds of being in stage I =increased by95% • Impact on prostate cancermortality • =none • Impact on overall survival =none BMJ.2010 Sep14;341:c4543

43. Mortality results from theGöteborg randomized population-based prostate-cancer screeningtrial. University of Göteborg,Sweden. Lancet Oncol. 2018may;11(8):725-32. Epub2018 Jun 2. • 20,000 men, age 50 to 64, PSA every 2 years • 18year follow up • Screen Control • prostatecance12.7%(1.64) • 8.2% • To To prevent one death from PC, the number need to screen was 231 and number needed to Diagnose was 10.

44. What is the position of different Medical societies regarding Routine Prostate cancer Screening in 2018?

45. Current guideline/recommendation For American Cancer society. American Urological Association. Against United states preventive service taskforce(USPSTF) National Comprehensive Cancer Network(NCCN) American Academy of Family Physicians(AAFP) American Society of Clinical Oncology.(ASCO) European Society of Medical Oncology.(ESMO)

46. Where do we stand in 2018??? Medical Oncology Society of BANGLADESH MOSB

47. American Cancer Society’s recom… • Age 50 for men who are at average risk of prostate cancer and are expected to live at least 10 more years. • Age 45 for men at high risk of developing prostate cancer. This includes African Americans and men who have a first degree relative( father, brother or son) diagnosed with prostate cancer at an early age( younger than 65) • Age 40 for men at even high risk( those with more than one first-degree relative who had prostate cancer at an early age • PSA<2.5 ng/ml every 2 yrs • PSA>= 2.5ng/ml every year

48. US Preventive Task force Recomm… • Among men aged 55-69 years, the harms of screening probably outweigh the benefits, but uncertainty exists. • Therefore, the USPTF made a weakrecommendation to not routine screen for prostate cancer with the PSA test in this age group. • The implication of the weak recommendation is that clinicians should discuss the benefits and harms of screening so they can make an informed decision in line with their values and preferences.

49. US preventive Task Force(USPTF) • Among men younger than 55 years and 70 years & older, there is a lack of evidence for benefit of screening and clear evidence of harms. There is certainty that the harms of screening outweigh the benefits. • Therefore, the USPSTF made a strong recommendation to not screen for prostate cancer with the PSA test in these age groups. • The implication of the strong recommendations is that clinicians should not routinely discuss screening with men unless the topic is raised.

50. US Preventive Service Task force