j.1464-410x.2010.09350.x

892019 j1464-410X201009350x

httpslidepdfcomreaderfullj1464-410x201009350x 14

BJUIB J U I N T E R N A T I O N A L

UroscanNEWS AND INFORMATION RESOURCE FOR THE INTERNATIONAL UROLOGY COMMUNITY

A Fresh Approach to Prostate Cancer

983156

Has overspecialization in

prostate cancer helped or

hindered progress in its

diagnosis and treatment

Despite more elaborate

and expensive techniques

treatment is still associated

with too much toxicity It also

makes little economic sense

and is unsustainable Even the

management of prostate cancer

is filled with great uncertainty

and lacks the strategies

employed to treat other typesof cancer How can prostate

cancer be put on the same

track as breast or renal cancer

in terms of precision diagnosis

and focused therapy Such

questions are at the forefront

of research being conducted

by Mark Emberton reader in

interventional oncology at

University College London

divisional clinical director of its

hospitalrsquos Cancer Services and

clinical director of the Clinical

Effectiveness Unit at the RoyalCollege of Surgeons of England

With his research into imaging

techniques and focal therapy

Emberton is rewriting the way

prostate cancer is diagnosed

and treated by precisely

characterizing the disease and

developing targeted therapies

Recently he sat down with

ldquoUroScanrdquo to express

his frustration with

the current state of affairs in

prostate cancer and to share his

thoughts on what is needed to

redefine the way it is diagnosed

and treated

COMPARED WITH OTHER

TYPES OF CANCER HOW

DO WE DIAGNOSE AND

TREAT PROSTATE CAN-

CER DIFFERENTLY

When one thinks about pros-

tate cancer we manage it in

a strange way The prostate isthe only organ where we use

chance to make the diagnosis

Men have random biopsies It

is the only cancer where we do

not use some form of imaging

prior to biopsy For every other

organ we target the biopsy

particularly for the breast with

mammography Or we visual-

ize the tumour with things

like colonoscopy and gastro-

scopy Itrsquos odd that we donrsquot

do this with prostate cancer

Prostate cancer is the onlycancer where we insist on

removing the whole organ

when there is cancer in it We

donrsquot do that for anything

else anymore such as the

kidney or the breast Itrsquos also

the only cancer in which we

treat subclinical disease Every

other cancer has to manifest

itself in some waymdashwe feel it

or see itmdashbefore it is treated

In men with high PSA scoresand biopsy you donrsquot see any

cancer So you are treating

microscopic disease It is the

only cancer where we do this

HOW DID WE END UP ON

THIS PATH WITH PROS-

TATE CANCER IS THERE

AN EXPLANATION FOR

WHY THINGS ARE DONE

SO DIFFERENTLY

With prostate cancer being one

of the more common cancers wehave to reflect why we treat and

manage it so differently Why are

we behind the times A series

of historical occurrences may

explain this First we could feel it

with a DRE Then we were able

to stick a needle in it and take a

biopsy Finally the PSA test was

invented All of these things con-

tributed to the current situation

The two current problems

everyone agrees upon in prostate

Physicians should combine imaging studies with focal therapy

By Kevin D Blanchet

Mark Emberton

892019 j1464-410X201009350x


U R O S C A N

cancer are over-diagnosis and

over-treatment Could these

two problems be related to

our rather odd diagnostic

evaluation In other words is

there a better way to treat the

disease once we know exactly

where it is in the prostate We

need to start rethinking the way

prostate cancer is diagnosed and

challenge the current diagnostic

pathway

WHAT DO YOU SEE

AS A BETTER WAY

You can see suddenly how image

guided diagnostic strategiesmdash

maybe an imaging test to decide

who does and who doesnrsquot get

a biopsymdashwould be sensible If

we had an imaging test thatcould identify men with clini-

cally significant prostate cancer

and could be performed before

biopsy we could save a lot of

men from having unnecessary

biopsies We call this a triage test

which is what mammography is

You donrsquot biopsy every breast on

every woman that walks through

the door We offer women

mammography to help us decide

which ones are worth biopsying

WHY HASNrsquoT SOME-

THING LIKE THIS BEEN

DEVELOPED YET

There are societal economic

and all kinds of good and bad

reasons why we have had

intellectual laziness in this

area Some perverse incen-

tives exist At the moment

rather than point fingers we

are exploring various options

WHAT TYPE OF IMAGING

TEST WOULD BE BEST SUIT-

ED FOR PROSTATE CANCER

MRI is probably the best

contender Prostate biopsies

actually perform quite poorlythey are wrong half the time

At levels of clinically sig-

nificant disease MRI performs

with about 90ndash95 certainty

Can an imaging test such

as MRI be used to decide

who gets a biopsy This is an

important research question

with huge public health

implications In other words

rather than use chancemdashwhich

seems crazymdashyou use the

image for targeting rather

than sampling randomly

WOULDNrsquoT USING MRI TO

SCREEN FOR PROSTATE

CANCER BE QUITE COSTLY

The greatest cost in prostate

cancer therapy arises from

treating men who donrsquot need

treatment It has been estimated

in Europe that you need to treat

48 men in order to save one life

If we could get it down to 20wersquod be saving an awful lot of

money Remember it is not just

the cost of treatment but also

the costs of managing erectile

dysfunction incontinence etc

You could argue that an MRI

in a public healthcare setting

is not an expensive test and a

lot less expensive than treat-

ing someone unnecessarily

We are planning a large study

in which men will have an MRI

prior to template biopsies in

order to determine whether

MRI might serve as a triage test

for men with a high PSA level

LETrsquoS TALK ABOUT TREAT-

MENT HOW WILL IMAGING

CONTRIBUTE TO NEWER

FORMS OF THERAPY

Because our treatments involve

removing or irradiating the

whole gland we do not cur-

rently care about where the

cancer is With the advent of

active surveillance and the

possibility of focal therapy

knowing the tumourrsquos position

and topography is possibly as

important as knowing that a

man has prostate cancer Most

cancers only occupy 5 of the

tumour volume Focal therapy

is at least one strategy whereby

we can address some of the

toxicity issues associated with

treatment The treatment may

preserve function and treat the

cancer just like lumpectectomy

versus mastectomy and partial

nephrectomy versus total kid-

ney removal It may also be

able to reduce the cost

substantially with a lot

less carbon emission

WHEN IT COMES TO FO-

CAL THERAPY DO YOU

HAVE A PREFERRED

ENERGY SOURCE

983156

Last year BJUI published more than 500 peer-reviewed

papers in six sub-specialties of urology Readers are sure tohave their favourites but which ones are considered to bethe best of the best Find out at wwwbjuiorg where you

can read these contributions to the field

BJUI rsquos Editor Prof John Fitzpatrick charged his associ-ate editors (and himself) to create a list of their choices

for the best papers published in 2009 In addition to ProfFitzpatrick making these important selections were MarkEmberton Roger Kirby Alan Partin Alan Wein and Mike

Wyllie Their task wasnrsquot easy ldquoThe quality of papers wasquite impressive last yearrdquo says Prof Fitzpatrick ldquoOur bestpicks really reflect this depth and breadth of excellencerdquo

For example Prof Fitzpatrick felt the paper by Jhavar etal on gene expression (lsquoIntegration of ERG gene mappingand gene-expression profiling identifies distinct categories

of human prostate cancerrsquo) deserved one of his highestrankings ldquoNot only was the paper well written but it pre-sented important insights into the genetic basis of prostate

cancerrdquo he says ldquoThe graphical presentation of biologicalnetworks and pathways made this paper quite deserving tobe among the best published in 2009rdquo

Wein selected lsquoSignal transduction pathways of muscar-

inic receptor mediated activation in the newborn and adultmouse urinary bladderrsquo (Ekman et al) as one of his highest-ranking papers in the research category Emberton selected

the paper of fellow associate editor Wyllie titled lsquoDoes thepharmaceutical industry need urological conferences andvice-versarsquo as one of his top five selections

Readers of BJUI can access all of the best lists and toppapers in a special feature on the website wwwbjuiorg Ac-cess will be free until early May ldquoI think readers will find our

top picks to be provocative and interestingrdquo Prof Fitzpatricksays ldquoThey offer our readers a glimpse into how our edito-rial team and reviewers think and what they look for in a

good quality paperrdquo

The Best of 2009 Now Available Online

Additional Reading

bull Ahmed HU Moore C

Emberton M Minimally-

invasive technologies in

uro-oncology The role

of cryotherapy HIFU and

photodynamic therapy

in whole gland and focal

therapy of localized prostate

cancer Surg Oncol 2009 18

219-232

bull Ahmed HU Zacharakis E

Dudderidge T et al High-

intensity-focused ultrasound

in the treatment of primary

prostate cancer The first

UK series Br J Cancer 2009

101 19-26

bull Moore CM Pendse D

Emberton M Photodynamic

therapy for prostate cancermdash

a review of current status

and future promise Nat Clin

Pract Urol 2009 6 18-30

892019 j1464-410X201009350x


IMPORTANT PAPERS YOU MAY HAVE MISSED

bull Kupelian V Araujo AB Chiu GR et al Relative

contributions of modifiable risk factors to erectiledysfunction Results from the Boston Area CommunityHealth (BACH) Survey Prev Med 2010 50(1-2) 19-25

bull McClellan WM Resnick B Lei L et al Prevalenceand severity of chronic kidney disease and anemia inthe nursing home population J Am Med Dir Assoc2010 11 33-41

bull Boukaramab C Hannoun-Levib JM Managementof prostate cancer recurrence after definitive radiationtherapy Cancer Treat Rev 2010 January 25 [Epubahead of print]

bull Williamson SR Montironi R

Lopez-Beltran A et al Diagnosisevaluation and treatment ofcarcinoma in situ of the urinarybladder The state of the art Crit

Rev Oncol Hematol 2010 January 25 [Epub ahead of print]

bull Moses KA Paciorek AT Penson DF et al Impact ofethnicity on primary treatment choice and mortality inmen with prostate cancer Data from CaPSURE J Clin

Oncol 2010 January 25 [Epub ahead of print]

J O U R N AL W AT C H

At the moment high intensity

focused ultrasound is a nice

contender Currently we are

conducting two clinical trials

Irsquom not married to it or any oth-

er energy source I suspect that

others are just as convenient

because they are non-invasive

and quick All you want is an

energy source that you can

control for pinpoint destruction

of a quantity of tissue Interest-

ingly in the US they are using

a lot of the old thermal lasers

that were thrown out in the

1990s because they didnrsquot work

for benign prostatic hyperplasia

These are now being used to

treat men with prostate cancer

in a focal manner because they

are Food and Drug Administra-tion (FDA) approved so you

donrsquot have to do any long-term

studies Cryotherapy is also

being used in the US Here in

the UK we are using vascular-

targeted photodynamic therapy

in a multicenter study

YOU ARE ALSO INTER-

ESTED IN INNOVATIVE

TRIAL DESIGN WHAT ARE

SOME OF YOUR IDEASRandomized trials are so

expensive and take so long to

mature The FDA and many

others are concerned about

the length of time it takes for

randomized trials to maturemdash

they are out of date by the time

they do maturemdashand the costs of

undertaking them You have to

ask the question why do we do

them Particularly with technical

innovation once safety is proven

you can often gain information

in a quicker way

When we do go comparative

with focal therapy one idea is

using pragmatic randomization

where the physician chooses the

control This would allow many

more patients to be recruited

more quickly The surgeon could

express his or her preference

to the control This is already

being done quite successfully in

breast cancer but as of yet not

in prostate cancer Basically you

would have three arms with

focal therapy in the middle Thesurgeon would say ldquoThis guy

I really wouldnrsquot do a radical

on him So what I will do is

randomize him to focal therapy

against active surveillancerdquo

Thatrsquos a coin toss You canrsquot

control what yoursquod get but you

can control the control The

surgeon might get another guy

and say ldquoI wouldnrsquot give this

guy active surveillance at all

Irsquom worried about him So it is

focal therapy if thatrsquos what the

guy wants But for the control

I want to make sure he gets

surgeryrdquo So you choose surgery

as the control and then you

do the coin toss The biggest

impediment to trial recruitment

is non-equipoise for the surgeon

which is overcome because they

choose the control I think it is

a nice design

U R O S C A N

TITLE

STUDY OF GLOBAL COAGULATION TESTS IN PATIENTS WITHPAROXYSMAL NOCTURNAL HAEMOGLOBINURIA

PROTOCOL ID

NCT01020188

SUMMARY

As a rare disease paroxysmal nocturnal haemaoglobinuria(PNH) results in the breakdown of red blood cells causesbone marrow failure and is associated with an increasedrisk of blood clots Treatment normally consists of bloodtransfusions and blood thinners for those with blood clotsEculizumab is now standard for patients who require reg-ular blood transfusions it prevents the breakdown of redblood cells The investigators plan to use specialised bloodtests to assess the stickiness of the blood before startingeculizumab treatment and monthly after starting treat-ment They will compare these tests with standard tests ofclotting The primary outcome measure is to establish therole of thrombin generation in assessing the prothrom-botic phenotype of PNH

ELIGIBILITY

Patients may be male or female and 18 years of age orolder All must have PNH with the presence of a PNHclone Patients on long-term anticoagulation therapy forprevious venous thrombosis are excluded The study is ex-pected to enroll 60 participants

LOCATIONS AND CONTACTS

Dupe Elebute MB MD Kingrsquos College Hospital NHS TrustLondon United Kingdom 02032995761 dupeelebutenhsnet

Clinical Trial

892019 j1464-410X201009350x


U R O S C A N

In this issue

Urological Oncology

REPEATED BIOPSYING HELPFUL IN PENILE CARCINOMA P1121

In patients with penile squamous cell carcinoma determining metastasis in inguinal

lymph nodes is an important part of clinical management Surgeons may opt to use

watchful waiting or elect to perform dissection of the nodes to assess disease spread

However a better way may be dynamic sentinel node biopsy (SNB) in patients

with clinically normal lymph nodes

Graafland et al report their experience in using SNB as a minimally invasive

staging technique since 1994 In their prospectively maintained dynamic sentinel

node database of 304 patients 12 patients with clinically node-negative

groins underwent repeat dynamic SNB for recurrent invasive penile squamous cell

carcinoma All had undergone previous penile surgery and SNB Five of the 12 patients

had undergone unilateral inguinal node dissection for metastases The median

disease-free interval was 18 months Both primary and repeat dynamic SNB were

performed in a similar fashionThe five patients with previous node dissections did not show any sentinel nodes

on preoperative lymphoscintigraphy Sentinel nodes were seen in 19 undissected

groins 15 of these had the node identified during surgery Four groins from three

patients showed metastasis on repeat SNB Median follow-up was 32 months

after the repeat SNB One patient had a groin recurrence 14 months after a tumour-

negative sentinel node procedure This individual did not have standard preoperative

ultrasonography with fine-needle aspiration cytology

MANAGING BILATERAL SYNCHRONOUS RENAL TUMOURS P1093

Several options exist for the

management of bilateralrenal masses These include

radical nephrectomy (RN) or

partial nephrectomy (PN)

ablation and observation All

of these approaches spark

considerable debate that

produces new questions for

consideration Although

masses in both kidneys

are an indication to use

nephron-sparing surgery this

approach is not used as much

as it should be Instead RN would be performed on the kidney with the larger tumourprovided a portion of the other kidney could be preserved

In their paper Lowrance et al share their experience with the surgical management

of sporadic synchronous bilateral renal tumours at a major cancer centre They detail

their preference for staged PN operating on the more involved kidney first

Specifically they report on 2777 patients who underwent PN or RN during a 19-year

period 73 of whom presented with synchronous bilateral disease

The probability of patients receiving two PNs for synchronous disease

increased over time By 2004 13 of 14 patients underwent bilateral PN Out of four

possible kidney removal combinations the most common was bilateral PN This was

conducted in 32 patients (44) A total of 45 patients (62) had their larger tumour

removed during the first operation Survival of patients with synchronous bilateral

tumours was similar to patients with unilateral disease

GOOD HYGIENE TO WARD OFF

UTI IN CYSTECTOMY PATIENTSP1107

After undergoing cystectomy for bladder

cancer patients are at risk for high levels

of bacteriuria Regardless of the urinary

diversion the majority (77 to 94) have

bacteria present in their urine Each year

about 25 of these patients experience a

symptomatic urinary tract infection (UTI)

Could practicing good hygiene help these

individuals decrease their risk for acquiring

such infections To test this hypothesis Thulin et al surveyed

patients who had undergone cystectomy and

urinary diversion at seven Swedish hospitals

Participants filled out a study-specific

questionnaire that inquired about various

hygienic practices such as hand washing

before catheterization or changing stoma

plates showering frequency and the use and

frequency of taking baths Out of 491 patients

contacted 452 completed the surveys

During the previous year 22 of patients

with orthotopic neobladder and cutaneous

continent reservoir had acquired asymptomatic UTI The rate was 23 for

non-continent urostomy diversion lsquoNever

washing handsrsquo before handling catheters or

stoma plates was associated with a relative

risk (RR) for UTI of 11 (05ndash25 95 CI) Those

patients with diabetes were most at risk for

developing a UTI in the past year with a RR of

21 (14ndash32) Given these results the authors

conclude that focusing on hygiene does not

significantly affect the frequency of UTIs

FIG 1 Predicted probability of receiving two PNs forsynchronous disease by year of procedure

892019 j1464-410X201009350x


U R O S C A N

cancer are over-diagnosis and

over-treatment Could these

two problems be related to

our rather odd diagnostic

evaluation In other words is

there a better way to treat the

disease once we know exactly

where it is in the prostate We

need to start rethinking the way

prostate cancer is diagnosed and

challenge the current diagnostic

pathway

WHAT DO YOU SEE

AS A BETTER WAY

You can see suddenly how image

guided diagnostic strategiesmdash

maybe an imaging test to decide

who does and who doesnrsquot get

a biopsymdashwould be sensible If

we had an imaging test thatcould identify men with clini-

cally significant prostate cancer

and could be performed before

biopsy we could save a lot of

men from having unnecessary

biopsies We call this a triage test

which is what mammography is

You donrsquot biopsy every breast on

every woman that walks through

the door We offer women

mammography to help us decide

which ones are worth biopsying

WHY HASNrsquoT SOME-

THING LIKE THIS BEEN

DEVELOPED YET

There are societal economic

and all kinds of good and bad

reasons why we have had

intellectual laziness in this

area Some perverse incen-

tives exist At the moment

rather than point fingers we

are exploring various options

WHAT TYPE OF IMAGING

TEST WOULD BE BEST SUIT-

ED FOR PROSTATE CANCER

MRI is probably the best

contender Prostate biopsies

actually perform quite poorlythey are wrong half the time

At levels of clinically sig-

nificant disease MRI performs

with about 90ndash95 certainty

Can an imaging test such

as MRI be used to decide

who gets a biopsy This is an

important research question

with huge public health

implications In other words

rather than use chancemdashwhich

seems crazymdashyou use the

image for targeting rather

than sampling randomly

WOULDNrsquoT USING MRI TO

SCREEN FOR PROSTATE

CANCER BE QUITE COSTLY

The greatest cost in prostate

cancer therapy arises from

treating men who donrsquot need

treatment It has been estimated

in Europe that you need to treat

48 men in order to save one life

If we could get it down to 20wersquod be saving an awful lot of

money Remember it is not just

the cost of treatment but also

the costs of managing erectile

dysfunction incontinence etc

You could argue that an MRI

in a public healthcare setting

is not an expensive test and a

lot less expensive than treat-

ing someone unnecessarily

We are planning a large study

in which men will have an MRI

prior to template biopsies in

order to determine whether

MRI might serve as a triage test

for men with a high PSA level

LETrsquoS TALK ABOUT TREAT-

MENT HOW WILL IMAGING

CONTRIBUTE TO NEWER

FORMS OF THERAPY

Because our treatments involve

removing or irradiating the

whole gland we do not cur-

rently care about where the

cancer is With the advent of

active surveillance and the

possibility of focal therapy

knowing the tumourrsquos position

and topography is possibly as

important as knowing that a

man has prostate cancer Most

cancers only occupy 5 of the

tumour volume Focal therapy

is at least one strategy whereby

we can address some of the

toxicity issues associated with

treatment The treatment may

preserve function and treat the

cancer just like lumpectectomy

versus mastectomy and partial

nephrectomy versus total kid-

ney removal It may also be

able to reduce the cost

substantially with a lot

less carbon emission

WHEN IT COMES TO FO-

CAL THERAPY DO YOU

HAVE A PREFERRED

ENERGY SOURCE

983156

Last year BJUI published more than 500 peer-reviewed

papers in six sub-specialties of urology Readers are sure tohave their favourites but which ones are considered to bethe best of the best Find out at wwwbjuiorg where you

can read these contributions to the field

BJUI rsquos Editor Prof John Fitzpatrick charged his associ-ate editors (and himself) to create a list of their choices

for the best papers published in 2009 In addition to ProfFitzpatrick making these important selections were MarkEmberton Roger Kirby Alan Partin Alan Wein and Mike

Wyllie Their task wasnrsquot easy ldquoThe quality of papers wasquite impressive last yearrdquo says Prof Fitzpatrick ldquoOur bestpicks really reflect this depth and breadth of excellencerdquo

For example Prof Fitzpatrick felt the paper by Jhavar etal on gene expression (lsquoIntegration of ERG gene mappingand gene-expression profiling identifies distinct categories

of human prostate cancerrsquo) deserved one of his highestrankings ldquoNot only was the paper well written but it pre-sented important insights into the genetic basis of prostate

cancerrdquo he says ldquoThe graphical presentation of biologicalnetworks and pathways made this paper quite deserving tobe among the best published in 2009rdquo

Wein selected lsquoSignal transduction pathways of muscar-

inic receptor mediated activation in the newborn and adultmouse urinary bladderrsquo (Ekman et al) as one of his highest-ranking papers in the research category Emberton selected

the paper of fellow associate editor Wyllie titled lsquoDoes thepharmaceutical industry need urological conferences andvice-versarsquo as one of his top five selections

Readers of BJUI can access all of the best lists and toppapers in a special feature on the website wwwbjuiorg Ac-cess will be free until early May ldquoI think readers will find our

top picks to be provocative and interestingrdquo Prof Fitzpatricksays ldquoThey offer our readers a glimpse into how our edito-rial team and reviewers think and what they look for in a

good quality paperrdquo

The Best of 2009 Now Available Online

Additional Reading

bull Ahmed HU Moore C

Emberton M Minimally-

invasive technologies in

uro-oncology The role

of cryotherapy HIFU and

photodynamic therapy

in whole gland and focal

therapy of localized prostate

cancer Surg Oncol 2009 18

219-232

bull Ahmed HU Zacharakis E

Dudderidge T et al High-

intensity-focused ultrasound

in the treatment of primary

prostate cancer The first

UK series Br J Cancer 2009

101 19-26

bull Moore CM Pendse D

Emberton M Photodynamic

therapy for prostate cancermdash

a review of current status

and future promise Nat Clin

Pract Urol 2009 6 18-30

892019 j1464-410X201009350x








































YOU ARE ALSO INTER-

ESTED IN INNOVATIVE















in a quicker way




































a nice design

U R O S C A N

TITLE


PROTOCOL ID

NCT01020188

SUMMARY


ELIGIBILITY




Clinical Trial

892019 j1464-410X201009350x


U R O S C A N

In this issue

Urological Oncology

















































































892019 j1464-410X201009350x








































YOU ARE ALSO INTER-

ESTED IN INNOVATIVE















in a quicker way




































a nice design

U R O S C A N

TITLE


PROTOCOL ID

NCT01020188

SUMMARY


ELIGIBILITY




Clinical Trial

892019 j1464-410X201009350x


U R O S C A N

In this issue

Urological Oncology

















































































892019 j1464-410X201009350x


U R O S C A N

In this issue

Urological Oncology

















































































j.1464-410x.2010.09350.x

Documents