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PSA and PROSTATE CANCER

PSA and PROSTATE CANCER . Dr Kiran Hazratwala Urologist. FORMAT. PSA Refinements of PSA Prostate cancer – Natural history Investigate Localised Prostate cancer Options of treatment of localised cancer Active surveillance vs Active intervention Case studies. 1-Assessment of Risk.

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PSA and PROSTATE CANCER

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  1. PSA andPROSTATE CANCER Dr Kiran Hazratwala Urologist

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

  3. 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)

  4. 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

  5. PSA FALSE POSITIVE

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

  7. Age adjusted PSA

  8. 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.

  9. 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 Biopsy Risk 28-56% • 15-25% - consider biopsy Risk12-19% • >25% - may avoid Bx if DRE normal Risk 8%

  10. How best to use it ? • Multiple guidelines exist – NCCN guide here • NCCN

  11. 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

  12. 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

  13. 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

  14. PLCO Methods • 1993 – 2001 • 76,693 men aged 55-74 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

  15. Results -- Baseline • Screening group • 44.0% previous PSA test • Control group • 44.1% previous PSA test

  16. 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

  17. 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)

  18. 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

  19. 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

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

  21. 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)

  22. 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

  23. 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

  24. 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

  25. IF A/S is CONSIDERED Predictors of Progression • Univariateanalysisp-value. • Positive second biopsy 0.002 • PSA (baseline) 0.012 • PSAD (baseline) 0.034 • Clinical Stage >T1a 0.053 • Predicted 5 year PFP (baseline) 0.102 • Gleason score (baseline) 0.241 • PSA doubling time 0.300 • Clinical stage (baseline) 0.479 • No. of positive cores (1st biopsy) 0.590 • Proportion of cores positive (1st biopsy) 0.988

  26. 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

  27. 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

  28. 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 !!!!

  29. Case 1 cont’d • Repeat biopsy • PROSTATE TRUS BIOPSIES: • - GLEASON SCORE 3 + 4 = 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

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

  31. Case 2 cont’d • Biopsy – Prostate volume 75cc • 1 - 12. 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 3 + 3 = 6; • - NO PERINEURAL INVASION; • - NO EXTRAPROSTATIC EXTENSION • Options?? • AS • SURGERY OR LDR BRACHYTHERAPY!!!

  32. 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

  33. Case 2 cont’d • Repeat biopsy • 12 Tissue core • 2 cores 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???

  34. 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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