The use of MRI and

PSMA PET CT to

guide salvage

therapy

Peter Black

Vancouver Prostate Centre

University of British Columbia

Financial and Other

Disclosures

I have the following financial interests or

relationships to disclose: Disclosure code

Astellas, Janssen, Merck, Roche, Bayer, Sanofi,

Lilly, Spectrum, Sitka, Cubist, BioCancell,

AbbVie, Ferring

C

New B Innovation, iProgen, GenomeDx S

Treatment of localized prostate ca

Ablative therapy

Radical

prostatectomy

External beam

radiation

Brachytherapy

Salvage

therapy

The nihilistic view of salvage

those who are likely to die of their disease will not be

rescued by salvage therapy

we don’t know where to treat because we are

treating PSA only and cannot visualize recurrence

ADT is as good as anything else we have to offer

local salvage therapy causes unacceptably high

rate of complications

major impact on quality of life

But the tides are shifting…..

More aggressive

intervention for high

risk/advanced

prostate cancer

Better imaging:

• mpMRI

• PSMA-PET

More precise

salvage therapy:

• SBRT

• ablation

Salvage after prostatectomy

1. Is PCa confined to the pelvis so that patient has

potential to respond to salvage RT?

2. Is there PCa in lymph nodes that can be surgically removed or targeted by SBRT?

3. What to do about oligometastatic recurrent PCa?

Local salvage after

radiotherapy or ablation

Some of same issues, but also:

Is the cancer localized to the prostate?

Multiparametric MRI for

identification of local recurrence

currently: local recurrence = absence of

distant recurrence based on bone scan,

CT scan and clinical risk stratification

in addition, disease in prostate post-RT determined

by systematic biopsy

can mpMRI be used to identify local

recurrence in prostatic fossa after RP

or in prostate after RT/ablation?

Multiparametric MRI post RP

88 patients with BCR after RP

median PSA 0.30 ng/mL (IQR 0.19-0.72 ng/mL)

24% had visible lesion on mpMRI

Liauw et al, Int J Radiat Oncol Biol Phys. 2013

Multiparametric MRI post RT

or ablation therapy

diffusely low T2 DCE color map ADC

UCL Experience

Kanthabalan et al Clin Oncol 2016 in press

UCL Experience

Kanthabalan et al Clin Oncol 2016 in press

UCL Trial – “FORECAST”

FOcal RECurrent Assessment and Salvage Treatment

(NCT01883128)

prior RT ± ADT; BCR according to Phoenix

plan n=177 (prospective, multicentre)

incorporates:

1. whole body MRI (compared to bone and choline PET/CT)

2. MRI-fusion biopsy

3. transperineal mapping biopsy

4. focal salvage HIFU/cryo

Study Chair: Hashim Ahmed, University College London

What about PET-CT for target

identification after BCR?

11C-choline has been superseded by 68Ga-PSMA

only ≈1300 men with PSMA PET-CT published in

the literature

suggests PPV >90%

but NPV remains unknown

need pathology or at least follow-up imaging!

information about local, nodal and distant sites

Recurrence in bone

Maurer et al Nat Rev Urology 2016

Recurrence in pelvic lymph node

Maurer et al Nat Rev Urology 2016

Heidelberg Experience

319 patients (292 with recurrence; 226 post-RP)

median serum PSA 4.6 ng/ml

≥1 suspicious lesion found in ~83% of patients

histological confirmation 42 patients:

all lesions with positive 68Ga-PSMA–PET signal had histologically

confirmed metastatic prostate cancer (n = 98)

lesion based 77% sensitivity, 100% specificity, 91% NPV and 100% PPV

29 lymph nodes missed in 3 patients (all had disease elsewhere)

one local relapse with follow-up

Afshar-Oromieh et al Eur J Nucl Med Mol Imaging 2015

Munich Experience

consecutive cohort of 248 patients with biochemical

recurrence after radical prostatectomy

mean PSA 1.99 ng/ml

89.5% patients had

suspicious lesions

33% seen only on PET

25% additional lesions

seen on PET vs. CT

Gleason score and PSA

correlated with positive scan

Eiber et al, J Nucl Med 2015; 56:668–674

Histopathologic Confirmation

Munich Experience

48 men with median PSA 1.3 underwent PLND after PET/CT or PET/MRI

performance by lymph node “fields”:

97% specificity

78% sensitivity (27% sensitivity of CT/MRI alone)

Rauscher et al, J Nucl Med 2016 in press

What is best PSA cut-off for

obtaining PSMA-PET/CT?

clinical dilemma:

salvage RT best administered at PSA < 0.5 ng/dl

but PSMA-PET/CT most sensitive at higher

Eiber et al, J Nucl Med 2015; 56:668–674

Sydney Experience PSA<1.0

n=300 PSMA-PET in

6 months in 2015!

n=70 in men with BCR post RP considering

salvage RT

PSA>0.05 but <1.0

53 lesions in 38

patients (54%)

van Leeuwen et al, BJUI 2016

van Leeuwen et al, BJUI 2016

Site n (%)*

fossa only 18 (47%)

nodes only 11 (29%)

fossa + nodes 5 (13%)

retroperitoneal N+ 2 (5%)

bone 2 (5%)

* relative to 38 with visible PET lesion

change in management

in 20(29%) of cases

PSMA “radio-guided surgery”

Maurer et al Eur Urol 2015

Conclusions

salvage therapy after failed primary treatment has

been relatively neglected up to now

advanced imaging enhances our ability to define the extent and location of recurrent disease

mpMRI enables salvage ablative therapy to the

prostate after RT

PSMA-PET facilitates salvage PLND or SBRT, although

true impact of interventions requires more study

delay systemic therapy, but improved outcomes?

clinical trials need to catch up with technology

PET-MRI and other advances (e.g. new radiotracers)

are likely to continue to improve resolution of imaging and precision of salvage therapy

Emerging frontrunner: 18F-DCFPyL-PSMA

18F has potential advantages over 68Ga:

more favorable dosimetry – can inject higher dose

lower energy of emitted protons – higher spatial

resolution

mass production (vs. local production on-site)

head-to-head comparison in BCR patients:

better tumor-to-background ratio; higher SUV values

higher rate of detection

Dietlein et al, Mol Imaging Biol 2015

PSA 4.7 after RT

CT (bone window) 18F-DCFPyL PET/CT 68Ga-PSMA-HBED-CC

PET/CT

suspicious for bone metastasis in vertebra L2

PSMA-PET/MRI

Eiber et al Eur Urol 2016 in press

Evolving paradigm

RP

Biochemical

recurrence PET-MRI EBRT/BT

Ablation

Salvage

PLND

SBRT for

oligo-

metastatic

Systemic

therapy for

widely

metastatic

Local

salvage

(prostate)