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PSA and PROSTATE CANCER Dr Kiran Hazratwala Urologist.

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Presentation on theme: "PSA and PROSTATE CANCER Dr Kiran Hazratwala Urologist."— Presentation transcript:

1 PSA and PROSTATE CANCER Dr Kiran Hazratwala Urologist

2 FORMAT PSA PSA Refinements of PSA Refinements of PSA Prostate cancer – Natural history Prostate cancer – Natural history Investigate Localised Prostate cancer Investigate Localised Prostate cancer Options of treatment of localised cancer Options of treatment of localised cancer Active surveillance vs Active intervention Active surveillance vs Active intervention Case studies. Case studies.

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5 1-Assessment of Risk Demographic – Age, race, medical health /longevity History to rule out confounders Family History DRE – to compliment the PSA value Investigations – MSU and Ultrasound (comorbid illness will take precedence)

6 2- PSA Serum Protease – Kallikrien family of proteins Functions in semen liquefaction Half life is 3 days Prostate Specific not disease specific Very non-specific as a test Imperfect screening test BUT best we have DO NOT RELY SOLELY on it

7 PSA FALSE POSITIVE

8 PSA REFINEMENTS Aimed at decreasing unnecessary biopsies Age adjusted ranges PSA Velocity PSA density PSA free : total ratio

9 Age adjusted PSA AGE (years)Age specific reference (ng/ml) – – – – 6.5

10 PSAV and PSAD PSAV – describes rate of change slope of line of regression assumes a linear relation of PSA /TIME Traditionally was > 0.75 ng/ml/yr Now MVA > 0.5 ng/ml/yr (Loeb et al AUA 2006) PSAD – Ratio of PSA level to size on TRUS PSAD of > 0.15 warrant a biopsy !!!!! Reliability is questionable due to variation in measurements.

11 PSA FREE:TOTAL ratio Most PSA is bound to ACT or MG CaP cases have a lower free component Improves spec for CaP detection in PSA 4-10 ng/ml where risk overall is 25% Threshold is controversial BUT its use is agreed f/t ratio < 15% - warrant BiopsyRisk 28-56% 15-25% - consider biopsyRisk12-19% >25% - may avoid Bx if DRE normal Risk 8%

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13 How best to use it ? Multiple guidelines exist – NCCN guide here NCCN

14 A national recommendation Single PSA test as a predictor for the long term risk of CaP around mid 40s PSA > 0.65 ng/ml  further PSA testing should be considered as per Australasian CaP Symposium PSA level (ng/ml) Action needed < – 1 >1 Low risk repeat test in mid 50s PSA test every 2-4 yrs Annual PSA to assess PSAV

15 To test or NOT to test?? The PSA testing debate between the US and Euro Individualize the debate to patients Whats good for the economist is not always good for patient Use risk adapted approach

16 PLCO (US trial) Controversy continues over PSA testing for prostate cancer, Canada Still Confusion about the Usefulness of PSA-screening, USA. Does cancer screening save lives? Not nearly as many as you might guess

17 PLCO Methods  1993 – 2001  76,693 men aged years enrolled at 10 sites  Screened: Annual PSA for 6yrs + DRE for 4yrs  Control: “usual care”  PSA >4ng/ml “considered positive for prostate cancer”  Analysis – based on intent to screen comparison of mortality between groups

18 Results -- Baseline Screening group 44.0% previous PSA test Control group 44.1% previous PSA test

19 PLCO Screened group – 85% compliance, 15% didn’t have a PSA Control group – contamination 40% first year 52% sixth year DRE 41-46% So 85% testing vs. 52% testing Study terminated at 7 yrs – effect starts 7-9yrs

20 Concerns/explanation for results  44% of EACH group already had prior PSA  15% of “screened” group didn’t get screened  52% of “control” group were screened  Low biopsy compliance.  Too short follow up  Only 67% have reached 10year follow-up  (ERSPC: 12 year lead time)  Too few events (174 deaths from 76,693 men)

21 ERSPC: European Randomized Study of Screening for Prostate Cancer 182,000 men, 7 centres – different procedures for each site. Men 50-74years old Screened group: PSA+DRE every 4yrs (range 2-7) Any PSA >3-4 (10 in Belgium)  sextant biopsies Primary outcome death

22 Prostate Cancer Deaths 214 prostate cancer deaths in screening group 326 in control group 27% reduction for those who underwent screening (20%as intention to screen) Adjusted rate ratio 0.80 in screened group CI: 0.67 to 0.95 Rates diverged after 7-8 years

23 ERSPC Prostate Cancer Deaths 7yrs PLCO review time point ERSPC 9years median follow-up

24 Conclusions 20-27% reduction in death from prostate cancer in screened group Rate of over diagnosis estimated at 50% in screening group. Need to screen 1068 men and treat 48 men to prevent one prostate cancer death Breast cancer (781) Colorectal cancer (1250)

25 What is Active Surveillance? Conservative management option for localised prostate cancer Active intervention has not been ruled out whereas Watchful Waiting generally implies observation until necessary to commence hormonal therapy Men on AS may –Ultimately have active intervention –Change over to Watchful Waiting protocol –Continue on the AS protocol

26 Criteria for Offering Active Surveillance Patient Factors – Age, comorbidity PSA – Absolute levels Upper thresholds vary from <10 up to <20 ng/mL – PSA density – Pre-diagnosis PSAV and PSADT not usually addressed DRE – Clinically impalpable or at most any T2 disease Gleason Score – Gleason !6 or !7 – Absence of any high grade cancer – 3+4 vs 4+3 not generally addressed where GS 7 allowed Biopsy Core parameters – Less than 3 biopsy cores involved – No more than 50% involvement of any core

27 Criteria for Departure From AS Patient Factors – Patient request for treatment or watchful waiting – Development of co-morbidity and move to watchful waiting PSA – Absolute threshold level – PSADT/PSAV DRE – Local progression Repeat Biopsy parameters – Presence/absence of cancer in 2ndbiopsy – Increased numbers of positive cores – Increased % core involvement – Increased Gleason score – Any presence of high grade cancer

28 IF A/S is CONSIDERED Predictors of Progression Univariate analysis p-value. Positive second biopsy PSA (baseline) PSAD (baseline) Clinical Stage >T1a Predicted 5 year PFP (baseline) Gleason score (baseline) PSA doubling time Clinical stage (baseline) No. of positive cores (1st biopsy) Proportion of cores positive (1st biopsy) 0.988

29 PRIAS Study Criteria for inclusion: 1.Histologically proven carcinoma of the prostate 2.patient should be fit for curative treatment 3.PSA-level at diagnosis ! 10 ng/mL 4.PSA density (PSA D) less than 0,25.Clinical stage T1C or T2 6.Appropriate biopsy sampling (see ‘biopsy protocol’) 7.Gleason score 3+3=6 (or less) 8.One or 2 cores invaded with prostate cancer 9.Participants be willing to attend the follow-up

30 Case 1 Mr R B 58 yrs Medically well No FHx of CaP DRE = benign moderately enlarged prostate PSA 4.1 ug/l PSA repeat 4.7ug/l

31 Case 1 cont’d Biopsy PROSTATE TRUS BIOPSIES X 12: - PROSTATIC ADENOCARCINOMA, GLEASON SCORE 6 (3 + 3), PRESENT IN ONE CORE (RIGHT BASE LATERAL) - FOCAL PERINEURAL INVASION - NO EVIDENCE OF VASCULAR INVASION OR EXTRAPROSTATIC EXTENSION. Options?? AS LDR BRACHY Surgery Any other options!!!! Obviously there are 4 !!!!

32 Case 1 cont’d Repeat biopsy PROSTATE TRUS BIOPSIES: - GLEASON SCORE = 7 PROSTATIC ADENOCARCINOMA INVOLVING SEVEN BIOPSY SITES; RIGHT LOBE - PERINEURAL INVASION IDENTIFIED - NO EVIDENCE OF EXTRAPROSTATIC EXTENSION Options now?? Its easy answer now….. Ok next case

33 Case 2 Mr R S 65 yrs old Medically well Nil FHx of CaP DRE – Significantly enlarged benign prostate PSA

34 Case 2 cont’d Biopsy – Prostate volume 75cc PROSTATIC TRUS BIOPSIES: - PROSTATIC ADENOCARCINOMA OF ACINAR / USUAL TYPE; - ONE BIOPSY POSITIVE FOR CARCINOMA, SPECIMEN 8 LEFT BASE MEDIAL,MICROSCOPIC FOCUS < 5%, < 1MM; - GLEASON SCORE = 6; - NO PERINEURAL INVASION; - NO EXTRAPROSTATIC EXTENSION Options?? AS SURGERY OR LDR BRACHYTHERAPY!!!

35 Case 2 cont’d Active surveillance put in place Aug 2011 PSA Nov 2011 – 4.3 PSA Mar 2012 – 6.3 PSA June 2012 – 7.6 PSA Aug 2012 – 5.7 Time for Protocol biopsy on PRIAS study

36 Case 2 cont’d Repeat biopsy 12 Tissue core 2cores positive for Adenocarcinoma Prostate Right Apex lateral and left base medial 3+3=6 Gleason score 5 and 20% of each core +ve respectively No perineural inv or Extraprostatic extension OPTIONS now???

37 Case 2 –Yeah last slide !! Opted for continued AS PSA Dec 2012 – 4.6 PSA Mar 2013 – 5.1 Where to from here!!!!!!!!


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