Slide 1

M EmbertonProfessor of Interventional OncologyDivision of Surgical and Interventional Sciences,University College London

Screening, diagnosis and management

What are the challenges?

•Over-diagnosis (over-treatment)

•Missed diagnoses (under-treatment)

•Harms of therapy

•Escalating costs

•Nihilism

•Speed of change

DIAGNOSIS

TRUS detects clinically insignificant disease

• Clinically insignificant cancers

are identified by chance

• Important cancers are incorrectly

classified as unimportant

TRUS guided biopsy misses important cancer

• TRUS biopsies are done

in a blinded manner

• They are subject to random

and systematic error

• Means that they are ‘wrong’

about half the time

A sampling strategy predicated onchance

A sampling strategy predicated onchance

2009 Apr;6(4):197-206.

MICROSCOPIC DESCRIPTION

A. Left para ant apex: Benign prostatic core with atrophy.

B. Left para ant base: Benign prostatic core with atrophy.

C. Right para ant apex: Benign prostatic core with atrophy.

D. Right para ant base: Benign prostatic core with atrophy.

E. Mid apex: Benign prostatic core with atrophy.

F. Mid base: Benign prostatic core with atrophy.

G. Left med ant apex: No specimen was received.

H. Left med ant base: No specimen was received.

I. Right med ant apex: No specimen was received.

J. Right med ant base: No specimen was received.

K. Left lateral: Benign prostatic core with atrophy.

L. Right lateral: Prostatic core with focal high grade PIN.

M. Left para post apex: Benign prostatic core with atrophy.

N. Left para post base: Benign prostatic core with atrophy.

O. Right para post apex: Benign prostatic core with atrophy.

P. Right para post base: Benign prostatic core with atrophy.

Q. Targeted anteroseptal: AdenocarcinomaGleason 3+4 in 2 of 5 cores, 1mm (10%) and 4mm(40%).

SCREENING

Welch’s screening conundrum, JAMA 2011

•‘small changes in cancer-specific mortality’

•VERSUS

•‘a boatload of hassle factors and fear, someunnecessary treatment, some resultingcomplications, and even a very few deaths (thatcan be missed in the measurement of cancer-specific mortality)’

“My value judgment is simple: It’s an awful deal. I’m happyto forgo the test and accept that I may be the one man outof 1000 who could have benefited, simply to avoid thesemuch more common harms”

Villers et al. J Urol December 2006

Tumour vol0.2cc 0.5cc

Sensitivity 77% 90%

Specificity91% 88%

PPV86% 77%

NPV85% 95%

http://www.parm-radiology.org/radiology.png

Definition 2 – ≥ Gleason 3 + 4 or any CCL ≥ 4mm

Reporter

Sensitivity

Specificity

Positive PredictiveValue (PPV)

NegativePredictive Value(NPV)

0.73 (0.63, 0.81)

0.70 (0.67, 0.73)

0.47 (0.41, 0.52)

0.88 (0.83, 0.91)

0.58 (0.49, 0.67)

0.83 (0.79, 0.86)

0.55 (0.46, 0.63)

0.85 (0.81, 0.88)

0.75 (0.63, 0.85)

0.84 (0.78, 0.89)

0.63 (0.52, 0.74)

0.90 (0.85, 0.94)

Area undercurve

0.75

0.72

0.83

$C:\Users\Hashim Uddin Ahmed\Documents\Hashim's Research\Urology Papers\Papers in Progress\Template-simulation-Definitions\Traffic-light-amber.jpg$

Sensitivity: 0.58-0.75

NPV: 0.85-0.9

Sensitivity: 0.58-0.75

NPV: 0.85-0.9

Definition 1 – ≥ Gleason 4+3 or any CCL ≥ 6mm

Reporter

Sensitivity

Specificity

Positive PredictiveValue (PPV)

Negative Predictive

Value (NPV)

0.84 (0.71, 0.92)

0.66 (0.64, 0.68)

0.30 (0.25, 0.33)

0.96 (0.93, 0.98)

0.63 (0.49, 0.76)

0.78 (0.76, 0.80)

0.33 (0.25, 0.39)

0.93 (0.90, 0.95)

0.84 (0.68, 0.93)

0.77 (0.71, 0.83)

0.39 (0.29, 0.50)

0.97 (0.92, 0.99)

Area undercurve

0.80

0.71

0.85

$C:\Users\Hashim Uddin Ahmed\Documents\Hashim's Research\Urology Papers\Papers in Progress\Template-simulation-Definitions\Traffic-light-red.jpg$

Sensitivity: 0.63-0.84

NPV: 0.96-0.97

Sensitivity: 0.63-0.84

NPV: 0.96-0.97

Usefulness of prebiopsy multiparametric magneticresonance imaging and clinical variables to reduceinitial prostate biopsy in men with suspectedclinically localized prostate cancer.

Numao N, et al. J Urol. 2013 Mar 6. [Epub]

In men with a PSA </=10ug/La normal MRI was associatedwith a NPV of 93.7 - 97.5 forclinically significant disease

In men with a PSA </=10ug/La normal MRI was associatedwith a NPV of 93.7 - 97.5 forclinically significant disease

TRUS biopsy versus mp-MRI in ruling outclinically significant prostate cancer?

Negative Predictive Value

MRI - 95-97%

TRUS biopsy - 22-38%

Distribution of prostate cancer foci215 lesions / 96(104) prostates / 345 Cystoprostatectomy specimens

Nerveux, Emberton, Montrioni and Villers (J Urol 2012).

NEGATIVE

?POSITIVE?

POSITIVE

NPV for clinically significant disease is 97%

TREATMENT

Lancet Oncology on line early 17 April 2012

Max

NoGl

Max

Apex

Base

Max

Gleason 4+4

CCLmax 4mm

1 of 2 cores +ve

Targeted

(24 cores)

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UCL Trials in Focal Therapy using HIFU

Hemi-HIFU Trial

Focal-HIFU Trial

Lesion Control

HIFU Trial

http://t1.gstatic.com/images?q=tbn:ANd9GcT2cvCyt4pS9X5c55_FkZnL2kEdqVqqlpVH2IupFeRAyYwL2v-Iqw

“... 89% of men achieved the trifecta status of pad-free, leak-freecontinence, erections sufficient for intercourse and cancercontrol at 12 months.”

“... 89% of men achieved the trifecta status of pad-free, leak-freecontinence, erections sufficient for intercourse and cancercontrol at 12 months.”

Hemi-HIFU Trial

J Urol. 2011 Apr;185(4):1246-54.

Lancet Oncology on line early 17 April 2012

Eur Urol April 2012

Functional outcomes

•Pad free rate 71/71 (100%)

•Erections sufficient for penetration (n=42)

–74% at 12 months

–86% at 27 months

–7 (range 2-28) months time to recovery

Cancer control

•1/71 men in field recurrence

–Gleason 4 plus 4

–1 core positive, CCLmax 2mm

•11/71 men had out of field recurrence

–6 low risk

–3 moderate risk

–2 high risk

Vascular targeted photodynamic therapy

European Multi-centre Phase III Randomised Controlled Trial

Low risk disease

Active surveillance versus Photodynamic therapy

6 monthbiopsynegative forcancer

THE FUTURE

Commercial systems

•Eigen Artemis:

–3D TRUS-guided biopsy

–Compatible with wide range ofTRUS probes

–Non-rigid, surface-basedregistration

–MR-TRUS TRE ~3.1 +/- 1.4mm(Narayanan et al., 2009)

–4-5mm (Cool et al. 2011)

–Accounting for probe-inducedprostate deformation afterrepositioning the probe for eachbiopsy sample can lead to a time-consuming procedure

Commercial systems

•MedCom/Pi Medical BiopSee®

–3D-image-guided transperinealbiopsy and therapy

–Integrated solution

–Rigid registration

–Accuracy not fully quantified

(Zagel et al. 2011)

•PSA 6.7

•Targeted biopsies

– GLEASON 3+4 CCLmax 5mm

– 3 of 4 cores positive

•Non-targeted biopsies

–No cancer detected

Rubinsky, B., Onik G., Mikus, P. “Irreversible Electroporation: A New AblationModality - Clinical Implications.” Technology in Cancer Research andTreatment, Vol 6 No 1, pp 37-48, 2007.

NanoKnife® IrreversibleElectroporation