PRESENT STATUS OF PROSTATE CANCER TREATMENT AND THE ROLE OF IMAGING - PowerPoint Presentation

Slide1

PRESENT STATUS OF PROSTATE CANCER TREATMENT AND THE ROLE OF IMAGING

CÉSAR DAVID VERA-DONOSO

Department

of

Urology

Slide2

WHO IS IN THE LINE OF FIRE?

Slide3

WE NEED TO COLLABORATE IN MANY FIELDS

Slide4

WE NEED RELIABLE IMAGES TO TAKE DECISIONS

Slide5

INCIDENCE

EUROPE

In Europe,

PCa

is the most common solid neoplasm

, with an incidence rate of

214 cases per 1000 men

, outnumbering lung and colorectal cancer

PCa

is currently the second most common cause of cancer death in men

Prostate cancer affects

elderly men more often than young men

Slide6

ESTIMATED NEW CASES OF CANCER IN USA 2012: 1,638,910

UROLOGIC TUMORS

PROSTATE

BLADDER

KIDNEY AND RENAL PELVIS

URETER

TESTIS

PENIS AND OTHERS

382,880 (23,3 %)

241,740

73.510

64770

2860

8590

1570

Slide7

Slide8

250

200

150

100

0

1975

1980

1985

1990

1995

2000

New Prostate Cancer Cases and Deaths

(

per 100,000 men

)

New cases

Deaths

PSA Screening

Incidence vs. Mortality

Prostate Cancer in the U.S.

Slide9

FIRST MESSAGE

WE HAVE TO TALK A LOT AND WORK TOGETHER

Slide10

Prostate Cancer:

Natural History

P

rostate

cancer pts can have

a long history

Opportunity for multiple therapies

Toxicities and quality of life important

Issues of co-morbid disease and aging

Philosophy of

chronic

disease

management

New therapies

are identified continuously

Slide11

Natural History of Prostate Cancer

Typical patient presentation as they move through different stages

Under the care of ONCOLOGIST

Under UROLOGIST care

Nonmetastatic

Metastatic

Local

therapy

Androgen

deprivation

Therapies after LHRH agonists

and

antiandrogens

First-line

therapy

Salvage

therapy

Death

Under ONCOLOGIST care

Higano C, et al. In: Figg WD, et al. Drug management of prostate cancer; 2010.

Burden of disease

Asymptomatic

Symptomatic

Castrate sensitive

Castrate resistant

Slide12

HOW IS THE DIAGNOSTIC ITINERARY?

Slide13

Digital Rectal Examination

A –

Central zone

B –

Fibromuscular

zone

C – Transitional zone

D – Peripheral zone

E –

Periurethral

zone

Seminal Vesicles

Prostate

Slide14

In about

18% of all patients, PCa

is detected by a suspect DRE alone

, irrespective of the PSA level

A suspect DRE

is a strong indication for prostate biopsy as it is predictive for more aggressive

(Gleason score > 7) prostate cancer

Slide15

SCREENING – PSA IS ASSOCIATED:

With

an increased diagnosis of

PCa

W

ith

more localized disease and less

advanced

PCa

(T3-4, N1, M1)

From the results of five RCTs, with more than 341,000 randomized men,

no

PCa

-specific survival benefit was observed

From the results of four available RCTs,

no overall survival benefit was observed

Slide16

Molecular Images to discharge prostate cancer

To

avoid

unnecessary

biopsies

> 1,000.000 of

biopsies

are done

every

year

in USA

Just

30 % of biopsies are positive for cancer

Slide17

The role of

Imaging in Diagnosis

Multiparametric

MRI

Results

need further confirmation, and

the cost-effectiveness of

mMRI

as a triage test before the first biopsy has not been assessed

Inter-reader

variability

Slide18

Prostate cancer missed by multi-parametric MRI: Correlation with whole-mount pathology

Nelly Tan, Steven

Raman

, Los

Angeles

, CA

Systematic biopsy continues to reveal prostate cancer (

CaP

) in areas not deemed suspicious by MRI

122 patients with mp- MRI prior to radical prostatectomy

Matched each MRI lesion to its whole-mount pathology counterpart

135/283

histologically

confirmed

CaP

tumors were identified by mp-MRI (48% sensitivity).

Of 148/283 (52%) tumors in 74/122 (61%) men that missed MR detection, 110 (74%) were GS 6, 23 (16%) GS 3+4, 9 (6%) GS 4+3, 6 (4%) GS ≥8. Missed CaP foci were smaller in

size

Slide19

WHAT IS THERE ABOUT PET?

Slide20

CASE 1

57 years

old

man

2009

Systemic

Vasculitis

2002 Silicosis. bilateral

pulmonary

conglomerates

March

2011

purple

with renal, neurological compromise

PET-CT (

Nov

2013)

asked

by

his

specialist

doctor

Slide21

CASE 1

He refers a

weak

and

interrupted

urine

stream

DRE: normal.

Left

lobe

shows a

slightly

increased

size but without palpable nodules

Hypermetabolic

focus

on

posterior - inferior

left

prostatic

lobe

Slide22

Slide23

EVALUATION

PSA 0,78 ng/mL NEXT STEP

:

levofloxacin

250 mg every 12 hours 7 days

PET CT

2 months after (

Febr

2014)

Slide24

Slide25

Focus of diffusion restriction is observed in the left side periphery of the base medium-third of the gland

Slide26

06/06/2014

PROSTATIC BIOPSY Symmetrical, homogeneous prostate. Prostate Volume: 30cc TZ Volume: 16cc

Prostatic Adenocarcinoma

affecting a single core of Left Prostatic Lobe - Gleason score 6 (3 + 3)

Percentage of

GLOBAL TUMOR LOAD

: 0.5%

Slide27

Incidental prostate 18F-FDG uptake

without

calcification

indicates

the

possibility

of

prostate

cancer

ONCOLOGY REPORTS 31: 1517-1522, 2014 HIROKO et al Hirosaki Japan

3,236

male subjects

who underwent 18F-FDG PET/CT scans from 2008 to 2012 in order to identify cases of incidental prostate FDG uptake

Incidental FDG uptake of the prostate was observed in

53 cases (2%)

49 cases were included in the present study. Of the 49 cases,

8 (16%) had prostate cancer

, while 41 (84%) were benign

Urologists performed a biopsy for suspicious cases, and

12 patients underwent biopsy

Slide28

NUCLEAR MEDICAL DOCTORS

UROLOGISTS

Slide29

SECOND MESSAGE

WE HAVE TO CREATE NEW PARADIGMS

Slide30

STAGING

Slide31

LOCAL STAGING:

Multiparametric MRI

Given its low sensitivity to microscopic invasion,

MRI is not recommended in the local staging of

low-risk patients

MRI

may be useful

in selected patients with intermediate- to high-risk cancers

Slide32

CLINICAL NODAL STAGING

Since CT or MRI cannot detect microscopic lymph node invasion

, detection rates are typically < 1% in patients with a Gleason score < 8 cancer, PSA < 20

ng

/

mL

or clinically localized disease

They should therefore not be performed in low-risk patients and

reserved for patients with high-risk cancers

Slide33

TREATMENTS: ACCORDING TO RISK OF RECURRENCE

RISK

VERY LOW

RISK AND LOW RISK

(40%)

INTERMEDIATE RISK

(20 %)

HIGH

RISK

(40 %)

TREATMENT

ACTIVE SURVEILLANCE

ACTIVE

SURVEILLANCE, RADICAL PROSTATECTOMY, RADIOTHERAPY ( EBRT +/- BRACHYTHERAPY

)

EBRT

, RADICAL PROSTATECTOMY, HORMONAL TREATMENT

Slide34

TREATMENT: WATCHFUL WAITING/ACTIVE MONITORING

In patients with the

lowest risk of cancer progression:

cT1-2a

PSA < 10

ng

/

mL

biopsy Gleason score< 6 ( 10 cores)

< 2 positive biopsies

minimal biopsy core involvement (< 50% cancer per

biopsy

).

Slide35

ACTIVE SURVEILLANCE might mean

NO TREATMENT at all for patients older than 70 yearsin younger patients, it might mean a possible treatment delayed for years PRESERVING QUALITY OF LIFE AND AVOIDING REPEATED BIOPSIES

WHY IS IMPORTANT ACTIVE SURVEILLANCE?

Slide36

Slide37

TREATMENT: RADICAL PROSTATECTOMY

COMPLICATIONS

Slide38

COMPLICATIONS DEFINITIVE RADIOTHERAPY

Any

significant

toxicity

(> grade 2)

22,8 %

Erectile

Disfunction

52 %

Increased

risk of developing

secondary rectum cancer 1.7 -fold

in comparison with the surgery group

Bladder cancer increased by 2.34-fold in comparison with a healthy control population

Slide39

Active Surveillance for Low-Risk Prostate Cancer Worldwide:

The PRIAS Study

More

than

4500

patients

right

now

Prostatic

Biopsy

is

necessary at years 1,4,7 At 2 years

81% of

patients

stay

on

AS

WE NEED A RELIABLE IMAGE TO REPLACE BIOPSY IN THE FOLLOW UP

THIRD MESSAGE

Slide40

SENTINEL NODE IN RADICAL PROSTATECTOMY

TREATMENT

Slide41

Lymphadenectomy

It is the gold standard for N-staging

lymph node dissection limited to the

obturator

fossa

will miss about 50% of lymph node metastases

The primary removal of the so-called

sentinel lymph node (SLN),

has the main aim of reducing the eventual morbidity associated with an extended pelvic node dissection

It remains experimental in 2014

Slide42

Different reports mention that 19-35% of positive lymph nodes are found exclusively outside the area of the traditionally limited LND

Besides being a staging procedure, pelvic eLND

can be curative, or at least beneficial,

in a subset of patients with limited lymph node metastases

A recent prospective study randomized

360 consecutive patients to receive extended LND versus standard LND

. After a median follow-up of 74 months, this study confirmed that an

extended LND positively affected BPFS in intermediate and high-risk

PCa

GUIDELINES EAU 2014

Slide43

Distribution

of SLNs (percentage)

Slide44

Slide45

Slide46

The

Optimal Tracer

H

ybrid

radioactive

+

fluorescent

radiocolloid

+ PSMA

antibody

Slide47

LAST NEWS

Slide48

38 patients prior to planned RP with intermediate or high-risk

After injection of 122±17 MBq

68Ga-HBED-PSMA

a fully-diagnostic PET/MRI including

multiparametric

prostate MRI

Results

Despite

unremarkable

conventional

imaging

68Ga-HBED-PSMA PET/MRI

revealed

metastasized disease in two patientsTumor involvement of the prostate could be visualized by 68Ga-HBED-PSMA PET in 95% of patients (36/38)68Ga-HBEDPSMA PET/MRI detected 6 out of 11 patients with histological lymph node involvement (sensitivity: 55%)

and correctly classified 24 out of 25 patients without histological evidence of lymph node metastases (specificity: 96%).

Slide49

A comparison

of 111In-J591 SPECT with 89Zr-J591 PET imaging

for

Prostate

Cancer

patients

.

Sandhya

Chalasani

*, Douglas

Scherr

,

Cornell

University ,New York, NY To compare pilot cohorts of men scheduled for radical prostatectomy imaged with novel antibody conjugates: Cohort 1

Eight

patients

(111In-J591) (SPECT) or Cohort 2

Eleven

patients

(89Zr-J591/

PSMA

) PET

Slide50

Conclusions

111In-J591 demonstrated targeting in localized disease in prostatectomy specimen, but pathologic validation was only inferred by quadrant due to

low soft tissue contrast and the inherent resolution limits

89Zr-J591/PSMA-PET

can

identify discrete intra-prostatic tumor foci

, and in our cohort,

visualized most of the index lesions

. Additionally, high-grade tumors are generally better visualized with this novel imaging agent

There is a relationship between SUV on the 89Zr-J591-PET of tumor foci and their aggressiveness as defined by Gleason score

Slide51

New imaging

modalities: USPIO

Ultra-small particles of iron oxide (USPIO)

can dramatically improve the detection of microscopic lymph node metastases on MRI

MR sensitivity improved

from 35.4% to 90.5% with the use of USPIO

This approach may be cost-effective, but is limited by the lack of availability of USPIO in Europe

Slide52

CONCLUSIONS: MI for

Treatment

Treatment of prostate cancer is

a moving target

Most patients die with prostate cancer not from prostate cancer

Side effects of treatments:

sexual dysfunction and incontinence

Active surveillance or watchful waiting

 You can help us to

select the correct patient for this treatment providing us

an image that identifies any perceptible change

Slide53

FUNCTIONAL IMAGES ARE THE FUTURE!