Diagnosing prostate cancer - Amazon Web Services · PSA at age 60 strong predictor of life-time...

The Royal Marsden

Diagnosing prostate cancer

Mr Declan Cahill Consultant Urological Surgeon The Royal Marsden

The Royal Marsden The Royal Marsden

Should I have a PSA test? Can I have a PSA test?

GP Education Day 22 February 2016 2

The Royal Marsden

prostatecanceruk.org

The Royal Marsden

83% raised PSA, Median 14ng/ml

Mean PSA Change -0.62+/- 0.75 Non significant Baseline at 12 hrs

0.4ng/ml. Clinically inconsequential

1 hour cycling 1.9+/- 1.7, 1 hr treadmill 1.0 +/- 1.0.

Both significant. Back to baseline by 48hrs.

4

The Royal Marsden

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, 60-69 >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

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

INVESTIGATIONS REQUIRED FOR REFERRAL PSA (required for urgent referrals criteria 1 & 2) First PSA: Second PSA : MSU (required for urgent referrals criteria 1 – 5): Creatinine level (request at time of referral required for all urgent referral criteria)*:

*Please tick if creatinine result to follow:

The Royal Marsden

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%

6

The Royal Marsden

2 WW Case 1

− 55 yr old − No prior LUTS − UTI symptoms. PSA at that time 7.7 − Repeat PSA 1.56. BPH o/e − Discharged

7

The Royal Marsden

2 WW Case 2

– 76 yrs old – Significant LUTS. – PSA 12.7. Repeat PSA 11.10 ng/ml – PE 2010 and 2013. Warfarinised. IHD – DRE T2 – IPSS 15. Poor flow. PVR 250/100mls – MRI T2/T3 Large lesion. Grade 5 confidence

8

The Royal Marsden

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

9

The Royal Marsden

Screening

The Royal Marsden

Lead time and Screening Interval

11

The Royal Marsden

PLCO NEJM March 2009

– 38000 screened, 38000 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.

12

The Royal Marsden

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.

13

The Royal Marsden

ERSPC NEJM March 2009

83,000 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)

14

The Royal Marsden

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.

15

The Royal Marsden

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

16

The Royal Marsden

Hugosson et al. Lancet Oncol 2010; Epub ahead of print

Göteborg study: cumulative risk of death from

PCa using Nelson-Aalen cumulative hazard

estimates

NNS 293,

NNT 12

44% mortality reduction in screened group

17

The Royal Marsden

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

18

The Royal Marsden

Example 1: PSA = 4 ng/mL

19

The Royal Marsden

Example 2: PSA = 4 ng/mL – low risk

20

The Royal Marsden

Example 3: PSA = 4 ng/mL – high risk

21

The Royal Marsden

45g

100g 150g

22

The Royal Marsden

How can we improve on PSA in the early

diagnosis of prostate cancer?

The Royal Marsden

Total PSA (ng/mL) Odds Ratio 95% CI Probability of PCa* (%)

0.00-0.50 Ref - 4

0.51-1.00 2.51 1.80-3.50 8

1.01-2.00 7.02 4.90-10.1 20

2.01-3.00 19.1 10.8-33.9 41

≥3.01 38.8 17.8-84.8 60

Lilja H et al. J ClinOncol. 2007; 25: 431-436

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

24

The Royal Marsden

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 60 0.2% risk life-threatening

cancer Vickers et al. BMJ. 2010; 341: c4521

25

The Royal Marsden

So who to screen?

55-74 year olds. 12% of screened group incurable. 70% >65 yrs. 65yrs too late

45-50 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

26

The Royal Marsden

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 55-60 yrs

Screening probably not helpful with a life expectancy <15yrs

27

The Royal Marsden

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)

28

The Royal Marsden

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

29

The Royal Marsden 30

The Royal Marsden

Life Expectancy

The Royal Marsden

70 yr old man

32

The Royal Marsden

33

The Royal Marsden

34

The Royal Marsden

-18 doctors assessing 70 clinical scenarios. Some duplicated -Underestimated by 11% on average -Inter doctor variability 0.58 -Intra doctor variability 0.74

35

The Royal Marsden

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

36

The Royal Marsden

AGE Ave. Lifespan < 25th Percentile in Health

> 75th Percentile in Health

60 years 20 years 10 years 30 years

65 17 9 26

70 14 7 21

75 10 5 15

Why 50% Surgery for 25% of 83 yr olds? How do we know who is in the top quartile of health?

www.ssa.gov/OACT/STATS/tables4c6.html

37

The Royal Marsden

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

38

The Royal Marsden 39

The Royal Marsden

40

The Royal Marsden

Integrating life expectancy with cancer risk

Gleason 6, T2b, PSA 8?

Gleason 4+3, T1c, PSA 6?

Gleason 4+4, T2b, PSA 12?

41

The Royal Marsden

www.nomograms.org

42

The Royal Marsden

43

The Royal Marsden

Life expectancy case 1

-68yrs

-DM Dx at 55yrs, asthma, hypercholeserolaemia, Hx of DVT, Ex smoker

-Gleason 3+3, T1c, PSA 5

44

The Royal Marsden

45

The Royal Marsden

Life expectancy case 2

72yrs old TIA, hypercholeserolaemia, Angina Ex smoker Gleason 4+4, T1c, PSA 8

46

The Royal Marsden

47

The Royal Marsden

dcahillurology@gmail.com

declan.cahill@rmh.nhs.uk

48