Screening for Prostate Cancer

Mr M SaqibMRCS, MSc (Urol), FRCS (Urol)

• PROSTATE CANCER most commoncancer in men

• Survival rates have increased• Increased number of men now living with

aftermath of disease and treatment• Limited support and awareness provided

for MEN to help them cope with thedisease and its treatment

Richard J. Ablin, PhD, DSc(Hon),

PSA: The Great ProstateMistake

• Ablin, New York Times March 2010• 16% of American men diagnosed with

prostate cancer; 3% die of it• ‘I never dreamed that my discovery four

decades ago would lead to such a profit-driven public health disaster’

• 22% of men with normal (low) PSA havecancer

The Prostate Pyramid

All Men(100%)

Men with prostate cancer(50%)

Diagnosed prostate cancer(15%)

Death from prostate cancer(3%)

7 million Deaths

11 million New Cases

25 million Living with Cancer

CANCER – WORLDWIDE BURDEN (2005)

17 million Deaths

27 million New Cases

75 million Living with Cancer

CANCER – WORLDWIDE BURDEN (2030)

U.S. Health Care Spending

In 2009, the U.S. spent

$2.53 TRILLIONon Health Care

• I wonder if I should be getting my prostate

checked out?• Or, I go to pee more often?• What are my chances of cancer? Should I

be worried?

Risk Factors• Age• Family History• Ethnicity• Diet:• Cooked and processed tomatoes better than fresh• ▪European Investigation into Cancer and Nutrition (EPIC) study - positive (three other studies showed no association)• Calcium and dairy products: The EPIC study showed increased risk from dairy protein and dairy calcium.• Fat and meat: inconsistent• Fruit and vegetables: EPIC: no association with total fruit and vegetable intake Green tea (polyphenols) and

Acquired risk factors• Alcohol and smoking: Two meta-analyses: not linked• Obesity and physical activity: A recent meta-analysis

reported a small borderline increase with BMI• NSAIDs - Several meta-analyses show aspirin reduces

the risk• Statins – not in short-term!Vasectomy - marginal increase, 1.07 RR at 10 years,

selection bias.

PCPT

Efficient Health System

• Some consume too much(Unnecessary care given)

• Some consume too little(Necessary care not given)

• We could decrease the waste and improve overallhealth!

• Evidence Based Medicine

Cancer Death Rates* by Sex, US, 1975-2006

*Age-adjusted to the 2000 US standard population.Source: US Mortality Data 1960-2006, National Center for Health Statistics, Centers for Disease Control andPrevention, 2009.

Men

Both Sexes

Rate Per 100,000

Women

Breast Cancer (Taskforce Estimates)

• One year of screening women aged 40 to 49• 22,327,000 women screened• 32,000 diagnosed• 24,200 survive• 7800 deaths• 1200 lives saved by mamography

Prof. David Forman

• For many of the types of cancer that welooked at that affect both sexes, there’s noknown biological reason why men shouldbe at a greater risk than women, so wewere surprised to see such consistentdifferences…..

Men have a reputation for having a ‘stiffupper lip’ and not being as healthconscious as women.”

Professor David Forman (2009) NCIN

Treating Men

» Men are less likely than women to utilisepsychological support services

» Men are low users of cancer information

services» Current prostate support groups poorly

attended

Cont.• Voluntary groups expressed difficulty in

recruiting and retaining men on theirprogrammes

• However, men do care about their healthand want to be pro-active in collaborationwith HCPs

Consultation for PSA

• Fear of cancer• Consequences (anxiety) of living with

insignificant cancer.• Impact of Rx on QoL• Current lack of scientific proof of Rx.

Benefits of PSA

• Early detection• Could extend life if high grade cancer

detected.

Wilson and Junger Criteria 19693. Accurate diagnostic test (and acceptable, cheap)

Wilson and Junger Criteria 19691. Significant burden of particular disease in the community

30, 000 new cases/yr

10,000 deaths/ yr

Lifetime risk of 18% (doubled in PSA era)

Lifetime risk of death PCa 3%

Commonest cancer and 2nd leading cause of death in men

2. Natural history of disease should be known

Studies available on the natural history of non-screen detected PCa but we do notknow the natural history of screen detected cancer – does screening result in alead time bias?

Wilson and Junger Criteria 19694. Effective or useful treatment should be available for early stage disease

Controversy as to whether radical treatments result in longer survival

Evidence stems from Bill-Axelson A, Holmberg L et al 2005 NEJM

Prostate Cancer Screening Studies

European Randomized Study of Screening for Prostate CancerSchroeder FH et al 2009 NEJM: • 162,387 men 55-69 yrs randomised to receive PSA screening every 4 yrs or no PSAscreening in 7 European countries • Prostate cancer diagnosed in 5,990 (8.2%) of screened group and 4,307 (4.8%) of controlgroup • After median FU of 9 years there were fewer cancer deaths in screened group (214 vs 326) • 1,410 patients have to be screened to prevent 1 cancer death and 48 screened men wouldhave to be treated to prevent 1 death • Therefore although screening did reduce mortality there was high risk of overdiagnosis andscreening would not have as much effect as we would have hoped

Wilson and Junger Criteria 1969However, PSA is prostate specific but not prostate cancer specific.

Raised in many other situations

What is normal PSA?

Either absolute value 4ng/ml or age dependent:

Osterling’s age specific reference range

Age PSA(ng/ml)

40-50 2.5

50-60 3.5

60-70 4.5

70-80 6.5

Wilson and Junger Criteria 19695. Long latent period

6. Availability of health and resources

7. Economic implications

> RRP increases overall survival, relative to watchful waiting, in

men with clinically detected prostate cancer.

>For all end-points the advantages have increased over time and expected thatmay increase further with longer FU

Prostate Cancer Screening StudiesUS study - the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer ScreeningTrial Andriole GL et al NEJM 2009:

•Concluded that after 7 to 10 years of follow-up the rate of death from prostate cancer wasvery low and did not differ significantly between the two study groups

More Specificity of PSAPSA derivative Normal

PSA velocity <0.6 - 0.75ng/ml/year

*PSA doubling time More than 3 years

PSA density <0.15ng/ml/ml

PSA transitional zone density <0.35ng/ml/ml

Free to total PSA >20%

*Supersensitive PSA <0.01ng/ml

Prosdex

• Web based decision on www.Prosdex.com/index_content.htm

Shared decision making

Current attribution of prostatecancer status

Serum markerMen at risk by age

Histologicalphenotype

Men at risk by PSAor DRE

Examinationfor

extracapsulardisease

Pathologicalverification

Potential forovertreatment

Low PPVCannotexcludedisease

Random andsystematic error

(1/3 upgrade at RP)Instability of cancer

statusDetects indolent

disease

Biopsy artefactOnly applied when

TRUS positive

High NNTin screendetectedcancerCost

Morbidity

What is wrong with the currentpathway?

The prostate cancer journey... for most people

suspicion treatment follow upbiopsy

surveillance

MRI forstaging

The prostate cancer journey... new possibilities

suspicion treatment follow up

MRI todetectcancer

1

1. MRI for detecting caner: a) improve the biopsy b) eliminate post biopsy haemorrhage artefact c) eliminate biopsy in some

50%?

betterbiopsy

bettersurveillance

The prostate cancer journey... new possibilities

suspicion treatment follow up

MRI todetectcancer

1

50%?

betterbiopsy

bettersurveillance

MRI todetectchange in cancervolume orgrade

2

3. MRI to plan treatment: a) plan margins b) plan focal therapy

MRI to plantreatment

3

The prostate cancer journey... new possibilities

suspicion treatment follow up

MRI todetectcancer

1

50%?

betterbiopsy

bettersurveillance

MRI todetectchange in cancervolume orgrade

2

MRI to plantreatment

3

MRI to asesscompleteness oftreatment

MRI tomonitorforrecurrence

4 & 5MRI to asess treatment& monitor for recurrence

Transrectal Prostate biopsy

TRUS

Prostate cancer- typical appearance

0

Prostate Mapping BiopsiesApproximate 90-95% accuracy in detection ofsignificant disease (Beware: computersimulation!)

Crawford et al, 2005; Barzell et al, 2007; Pinkstaff DM et al, 2005; Satoh et al, 2005;Merrick et al, 2007

Background - 4

Gleason Grade

Benign glands

Gleason grade3

Gleason grade5

0

MR post needle –

2 WEEKS

2 /12

6 / 12

PREBX

Incidence of nodal metastases

T1/T2 < 5% Early T3 15% T3 30% T4 >40%

Rx Options Localised Watch (AM/WW), Radical approaches, Focal approaches

Locally advanced Radical approaches, Palliative

Metastatic disease, Palliative

European Association of Urology

• Recommends for informed decision making within the physician-

patient relationship.• Recommends against mass screening.

“Men should obtain information on the risks and potential benefitsof screening and make an individual decision”

– European Urology 56(2), 2009

PCLO

PCRMP• PSA should not be added to a list of

investigations without careful consultation.• DRE is not recommended as a screening

test in asymptomatic men.• > 50 after consultation whoever asks!• High risk of over diagnosis and over

treatment.

ERCP 44/40/28%NNT 12 same as Breast

Are we more efficient?

Post Rx QoL• Quality of life declined for many men• Some men experienced limitations in their

work and social life 6 months post Rx.• Men were affected most by fatigue and

bowel symptoms.• Hot flushes, and urinary symptoms were

most difficult to deal.• Sexual Function data difficult to collect.

Coping Scale• Active coping/ planning• Self blame• Humour• Acceptance• Religion• Denial• Self distraction• Disengagement

Management Strategies

• Partner – love, support & understanding• Cancer, at back of mind, Lived with unmet questions.• Just ‘dealt’ with it best they can• Learning to live with this ‘new’ norm• Many of men’s problems were ‘managed’ by burying their

heads in the sand

Getting on with it…..

However• 28% - decline in family & social life• 33% - decline in ability to involve selves in work & hobbiesSevere symptoms persisting:Fatigue, Bowel ,Urinary, Metabolic

Raising concerns• Very pragmatic approach• However, many frustrations and limitations

voiced• Very few have shared these anxieties,

especially sexual issues

Post Rx.

• Reduced physical and emotional Sexualfunction and felt sorry for their partners(some men had discussed it with their wifebut others had not).

• and Urinary Issues• Living with uncertainty.

Consultation failure

• Men struggled with this symptom and werereluctant to discuss it with their healthcareprofessionals/partners/interviewer

• Reduced Physical and emotional desire.• Men felt ‘cheated’ of their manhood. They

had not considered that the treatmentwould have such a catastrophic affect ontheir sexuality

Contin…

• “He (the consultant) sort of dismissed thatthis can affect the sexual thing and thatwill not worry you, sure it won’t? No. It was sort of…I felt…when I look backnow, I felt he put words in my mouth. I felthe was more or less looking at my ageand making a judgement which wasn’t theright judgement for me at that timebecause I was quite active. We had anactive sexual life at that time. That hasstopped.”

LUTS

• Most common symptom pre and post-treatment

• Set pattern sometimes emerged, e.g.worse during evening or night

• Resulted in fragmented sleep.

LUTS• Always going to toilet before leaving house• Not drinking prior to leaving house• Carrying a urinal in car• Sitting in back of hall/near door• Restricted social outings

LUTS• “Well I think there are wee gaps there that

could be worked on. I think if they (wives)heard it from the doctor and they wouldhave maybe a better understanding of it asoppose to me stuttering and stammeringand trying to explain.”

• At first time point, men focused on getting through

treatment.• Following treatment, a degree of uncertainty emerged of

? recurrence• Feeling of abandonment immediately after

treatment had finished– - Professionals– - Other men

Trends in Prevalence (%) of No Leisure-Time Physical Activity, byEducational Attainment, Adults 18 and Older, US, 1992-2008

Note: Data from participating states and the District of Columbia were aggregated to represent the UnitedStates. Educational attainment is for adults 25 and older.Source: Behavioral Risk Factor Surveillance System CD-ROM (1984-1995, 1996, 1998) and Public Use Data Tape(2000 to 2008), National Center for Chronic Disease Prevention and Health Promotion, Centers for DiseaseControl and Prevention, 1997-2009.

Adults with less than a high school education

All adults

Thank You ??