Embed Size (px)
Citation preview
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
