Mr Declan Cahill Consultant Urological Surgeon The Royal Marsden

Transcription

1 Diagnosing prostate cancer Mr Declan Cahill Consultant Urological Surgeon

2 2 Marsden GP Education Day 22 February 2016 Should I have a PSA test? Can I have a PSA test?

3 prostatecanceruk.org

4 4 83% raised PSA, Median 14ng/ml Mean PSA Change / Non significant Baseline at 12 hrs 0.4ng/ml. Clinically inconsequential 1 hour cycling 1.9+/- 1.7, 1 hr treadmill 1.0 +/ Both significant. Back to baseline by 48hrs.

5 Urgent referrals criteria (tick category) 1.Clinically malignant prostate on rectal examination. PSA result to be sent with referral 2.Raised age related PSA (50-60 >3, >4, 70+ >6.5, 85+ >20) on 2 occasions 4 weeks apart, unless the prostate feels malignant or the PSA is over 20 when immediate referral appropriate 3.Visible haematuria in adults >18 years old 4.Non visible haematuria greater than a trace on dipstick in adults > 50 years old 5.Symptoms of UTI with persistent sterile pyuria >60 years old 6.Palpable renal mass, or renal lesion which is suspicious for malignancy identified clinically or radiologically INVESTIGATIONS REQUIRED FOR REFERRAL PSA (required for urgent referrals criteria 1 & 2) First PSA: Second PSA : MSU (required for urgent referrals criteria 1 5): 7.Testicular lump which appears to be intratesticular or solid suspicious of cancer 8.Raised/suspicious penile lesion or phimosis with discharge and/or palpable/hard area beneath prepuce Creatinine level (request at time of referral required for all urgent referral criteria)*:

6 6 2 WW continued Approximately 1/8 of total 62 day (2WW) LCA waits are prostate 62 days is tight LCA reporting 78.6% for prostate against 85% target Performance variation between 38-96%

7 7 2 WW Case 1 55 yr old No prior LUTS UTI symptoms. PSA at that time 7.7 Repeat PSA BPH o/e Discharged

8 8 2 WW Case 2 76 yrs old Significant LUTS. PSA Repeat PSA ng/ml PE 2010 and Warfarinised. IHD DRE T2 IPSS 15. Poor flow. PVR 250/100mls MRI T2/T3 Large lesion. Grade 5 confidence

9 9 How can we team up on Prostate 2WW? Don t do a PSA on men with acute LUTS If men have acute LUTS treat them and then do PSA Repeat the PSA before referring as that ll be the first thing we do with the clock ticking. MSU Is he fit for radical treatment? If in doubt repeat at 3 months and refer for a rising PSA False positives are common, false negatives are rare

10 Screening

11 11 Lead time and Screening Interval

12 12 PLCO NEJM March screened, control Annual PSA 6 yrs, DRE 4 yrs CaP incidence Screened 116/10,000 person years (2820) v 95 (2322) in control Death screened 50 v 44 control CaP death rate at 7-10 yrs low and no difference between the two groups.

13 13 Explanations Screening in control group 38% Baseline PSAs in 44% reduced CaP incidence Therapeutic advances reduced CaP mortality Inadequate follow up Await PCLO QOL study.

14 14 ERSPC NEJM March ,000 screened v 99,000 controls PSA at an average of every 4 yrs. 13 yrs f/u. Cap 8.2% (6830) screened v 4.8% (4781) control 21% reduction in CaP death in intention to screen group. 27% in those actually screened NNI = 781, NND = 27 (9yrs 48, 11 yrs 35)

15 15 ERSPC (2) Metastatic disease 0.23/1000 person years in screened group and 0.39 in control group (41% reduction in screened group) More Gleason 6 in screened group, less Gleason 7.

16 16 Cumulative rate ratios of prostate cancer mortality, Rotterdam. 29% relative risk reduction-11yrs

17 17 Göteborg study: cumulative risk of death from PCa using Nelson-Aalen cumulative hazard estimates NNS 293, NNT 12 44% mortality reduction in screened group Hugosson et al. Lancet Oncol 2010; Epub ahead of print

18 18 Conclusions ERSPC Randomized studies show that screening decreases PC mortality by 21% to 44% in the ITS analysis Overdiagnosis and treatment are a problem Active surveillance counterbalances overdiagnosis

19 19 Example 1: PSA = 4 ng/ml

20 20 Example 2: PSA = 4 ng/ml low risk

21 21 Example 3: PSA = 4 ng/ml high risk

22 22 45g 100g 150g

23 How can we improve on PSA in the early diagnosis of prostate cancer?

24 24 MPP: Marked Increased Risk of Later Diagnosis of Prostate Cancer Associated With Levels of PSA Odds of Prostate cancer diagnosis by PSA levels at Baseline Total PSA (ng/ml) Odds Ratio 95% CI Probability of PCa* (%) Ref Lilja H et al. J ClinOncol. 2007; 25:

25 25 PSA at age 60 strong predictor of life-time risk of cancer death (AUC: 0.90) 90% of prostate cancer deaths in men with PSA 2 ng/ml (top quartile) PSA 1 ng/ml at age % risk life-threatening cancer Vickers et al. BMJ. 2010; 341: c4521

26 26 So who to screen? year olds. 12% of screened group incurable. 70% >65 yrs. 65yrs too late year olds. Await PROBASE study (contamination) Able to assess risk at 45 yr but this does not obviate need for further testing Don t screen 40 yr old men

27 27 EAU Guidelines Risk adapted screening may be offered to a well informed man Risk calculators may help reduce unnecessary biopsies Early baseline testing may be helpful to identify men who need closer follow up. Optimal intervals for screening and DRE not known Risk adapted screening based on initial PSA level <1.0 in men yrs Screening probably not helpful with a life expectancy <15yrs

28 28 What s wrong with PSA screening? Too much screening of elderly men with a short life expectancy Too liberal criteria for biopsy Too aggressive treatment for low risk CaP Treatment too often administered by low volume providers (higher side effects and less cure)

29 29 How to apply screening 1. Get consent 2. Don t screen men who won t benefit 3. Don t biopsy without a compelling reason 4. Don t actively treat low risk disease 5. If you re going to treat, treat in a high volume centre

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31 Life Expectancy

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35 35-18 doctors assessing 70 clinical scenarios. Some duplicated -Underestimated by 11% on average -Inter doctor variability Intra doctor variability 0.74

36 36 Probability of survival of men at age 70 (life expectancy of 13 years)

37 37 AGE Ave. Lifespan < 25 th Percentile in Health > 75 th Percentile in Health 60 years 20 years 10 years 30 years Why 50% Surgery for 25% of 83 yr olds? How do we know who is in the top quartile of health? tml

38 38 Guarantee = about half will die before point x and about half will die after point x!!

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41 41 Integrating life expectancy with cancer risk Gleason 6, T2b, PSA 8? Gleason 4+3, T1c, PSA 6? Gleason 4+4, T2b, PSA 12?

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44 44 Life expectancy case 1-68yrs -DM Dx at 55yrs, asthma, hypercholeserolaemia, Hx of DVT, Ex smoker -Gleason 3+3, T1c, PSA 5

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46 46 Life expectancy case 2 72yrs old TIA, hypercholeserolaemia, Angina Ex smoker Gleason 4+4, T1c, PSA 8

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