Looking into the future for recurrent cancer - CANM … Speaker Presentations/2017 PET... ·...
Transcript of Looking into the future for recurrent cancer - CANM … Speaker Presentations/2017 PET... ·...
Looking into the future for recurrent cancer
Glenn Bauman, MD
April 2017
Radical Prostatectomy
Prostate Brachytherapy
External beam RT
Image guided interventions
HIFU, Cryo, FLA, TULSA...
Prospective Phase II trial, n=56Majority intermediate risk (47/56); median PSA 7.4Index lesion defined by MRI (PiRADS 4-5 on 2 of T2W, ADC, DCE) + biopsy (TRUS or TPM)Focal ablation of the index lesion with HIFUFollow-up MRI at 2 weeks, 6mo, 12mo and biopsy at 6mo
EUROPEAN UROLOGY 68 (2015) 927–936
Focal therapy for localized prostate cancer
Biochemical Failure Post RP+ RT
RP or RP + Adjuvant RT Primary RTStephenson, J Clin Oncol. 2007
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Biologic characterization
Intra-prostatic lesion delineation
Staging
Response assessment
Therapy selection• Surveillance• RT/Sx• ADT/systemic Rx
Directed biopsyFocal therapy/boostImage guided surgery
Salvage post RT/RPHigh risk RP
SurveillancePost RTPost ADT/systemic Rx
Potential role of imaging in CaP
Imaging in Prostate Cancer
• CT/Bone Scan– staging+restaging+response
• Ultrasound – systematic biopsy guidance
• mpMRI
– Biopsy guidance for TRUS bx –ve, cancer suspicion
Potential for Image Guided Therapy in Prostate Cancer
mpMRI• DIL identification for Bx/FT/FB• Whole body MRI for metastates
Positron Emission Tomography (PET)• DIL identification for FT/FB• Identification and quantification of metastases
New PET tracers and hybrid imaging• Choline derivatives (11C, 18F)• FACBC (Fluciclovine)• PSMA (68Ga, 18F)• Acetate (18F)
PET/MRI – “One Stop Shopping” for CaP
Complete response
Partial response
Cellini et al. 2002; Int. J. Radiat. Oncol. Biol. Phys. 53:595-599
Importance of DIL in XRT
76% of cancers >0.1cm3 identified by at least 1 observers
An automated pipeline for model-based prostatecancer radiotherapy
Planned doseDose prescription
Tumor probability
Ktrans
ADC
T2
Slide courtesy of Dr. Uulke van der Heide
Systematic Review DIL boost
Bauman, Rad Onc. 2013 107(3):274• N=13, 833 patients; mainly MRI For target definition• mean boost 150% (brachy); 89 Gy (EBXRT)• significant heterogeneity • acceptable toxicity; short follow-up
Von Eyben, Clin. Genitoruinary Cancer, 2016, 14(3):189• N=11, 988 patients• significant heterogeniety• 464 patients>5 year follow-up• Low toxicity, bDFS/cDFS >80%
FeasibilityNeed for prospective studies
T2 MRI DCE-MRI DW-MRI
FLAME: focal dose escalationmulti-center phase III randomized trial
Prostate 77 Gy
Tumor 95 Gy
Number of GTVs
defined per patient
1 71%
2 21%
>3 8%
571 patients
Trial is now closed
Use of Choline PET for DIL identification
Nuc Med Comm, 2017• Biopsy and whole mount gold standards• Sensitivity: 55-90%; Specificity: 45-86%; Accuracy: 60-85% • ↑performance with ↑ tracer dose, delayed imaging, PET/MRI
What about other tracers?
Int J Radiation Oncol Biol Phys, 91(5):2015
Nat Rev Urology, Feb 2016
PSMA imaging
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Prostate Specific Membrane Antigen
• Type II trans-membrane protein• FOLH1 gene on Chromosome 11• Expressed on prostate epithelium• 100-1000x over-expression in CaPp;
increased expression with GG, AD
18F-DCFPyL• Hopkins + Canadian Consortium develop
2 stage automated synthesis
First Case – Gleason Pattern 4
Simplifying the pipeline for model-based prostatecancer radiotherapy
Planned doseDose prescription
Modified from Dr. Uulke van der Heide
PET DIL identification(PET/CT or PET/MRI)
But that’s not all you also get!
Biologic characterization
Intra-prostatic lesion delineation
Staging
Response assessment
Therapy selection• Surveillance• RT/Sx• ADT/systemic Rx
Directed biopsyFocal therapyImage guided surgery
Salvage post RT/RPHigh risk RP
SurveillancePost RTPost ADT/systemic Rx
Potential role of imaging in CaP
Biochemical Failure Post RP
RP or RP + Adjuvant RT Primary RTStephenson, J Clin Oncol. 2007
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Sites of recurrent disease at BF
Local failure
• Prostate/prostate bed
Regional failure
• Pelvic nodes
Distant failures
• Extra-pelvic nodes
• Bone
Restaging CT and bone scan have poor sensitivity if PSA <10 and low PSA velocity (when recurrence is most likely to be localized or limited)
UROLOGY 61: 607–611, 2003.29
Challenges in Recurrent Disease
• Routine hormone therapy at the time of BF exposes men who have limited disease to morbidity of ADT
• Observation until symptomatic metastases denies men a potential therapeutic window for treatment and exposes them to morbidity from recurrence
• Lack of a well established post-RT salvage pathways also influences upstream treatment decisions (RP vs. RT). Variable use of adjuvant and salvage RT post RP
• Conventional restaging is relatively insensitive with early BF thus limiting ability to detect isolated local recurrence vs. oligometastatic vs. extensive metastatic disease
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IGPC-003 Trial
Post RP (n=10)6 none/bed3 pelvic nodes1 extra-pelvic
Post RT (n=10)2 none6 prostate2 pelvic nodes1 extra-pelvic
Improving the treatment of recurrent CaPRestaging with 18F-Fluorocholine PET/MRI
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Movember GAP-2
N=96; 10 sites worldwide• London• UHN• Laval University
Accrual completeAnalysis underway
Improving outcomes of post RP salvage RT
Modality 3-5 yr bDFS Toxicities
Salvage RP 47-71% Incontinence: 50%Rectal injury: 5-15%Stricture: 30-30% RSRP
Salvage Cryotherapy 34-77% Incontinence: 11-40%Fistula: 1-3%Obstruction: 11-73% With focal Cryo
Salvage HIFU 46-61% Incontinence: 7-50%Fistula: 3-7%Obstruction: 9-36% With focal HIFU
Salvage Brachytherapy 34-89% Incontinence: 0-30%Gr 3/4 GU: 14-47%Gr 3/4 GI: 0-24% With focal Brachy
Management of Local Recurrence post RT
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HDR Salvage Brachytherapy
• MRI with mapping biopsies
• Directed to tumour only
• 2 brachytherapy implants (13 Gy x 2) separated 7-10 days apart
Slide courtesy of Dr. Peter Chung
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Biochemical profile
Salvage HDR brachytherapy
Post treatment biopsy
Time41
Slide courtesy of Dr. Peter Chung
Composite PTV defined on PSMA-PET+MRI18Gy/single HDR treatment
6mo PSA 5.65 -> 0.67; CR on mpMRI and PET/CT
Annals of Oncology 24: 2881–2886, 2013
N=140, biochemical recurrence post RPSurvival from time of detection of metastases
Improving the treatment of recurrent CaPManagement of Oligometastatic Disease
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Patterns of salvage:• Nodal – 78%• Bone – 21%• Visceral – 1%
Staging• 98% choline PET/CT
Heterogeneity of Rx• 61% adjuvant ADT• 49% elective nodal Rx
“For MDT to be successful, three main prerequisites should be fulfilled: (1) accurate imaging to detect early metastases, (2) complete eradication of all oligometastaticsites, and (3) acceptable toxicity”
Improving the treatment of recurrent CaPMx of Oligometastatic Disease – Systematic Review
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Treatment of oligometastatic disease
0 0.03 0.09 0.16 0.08 0.17
0.58
1.07
1.65
2.48 2.39
3.99
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PSA Salvage
radiotherapy
Re-staged
46Slide courtesy of Dr. Hans Chung
Metastatic Workup (3/2014)
47Slide courtesy of Dr. Hans Chung
SBRT to Pelvic Nodes (5/2014)
• Prophylactic pelvic nodes to 25Gy/5#
• Grossly visible pelvic node boost to 30Gy/5#
48Slide courtesy of Dr. Hans Chung
PSA Trend
0 0.03 0.08 0.08 0.17
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PSA
Pelvic nodal SBRT
49Slide courtesy of Dr. Hans Chung
Routine Scans (6/2015)
50Slide courtesy of Dr. Hans Chung
Improving the treatment of recurrent CaPComparison of PET restaging (meta-analysis)
Am J Nucl Med Mol Imaging 2014;4(6):580-601
RT
RP
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N=532 men with BF post RP (452) or RT (107) imaged with 68Ga-PSMA PET/CTIncreasing lesion detection with increasing PSA:
Post RP failures: 52% overall detection; 35% nodal; 13% local; 11% bone
Post RT failures: 95% overall detection; 71% local; 34% nodal; 17% bone
Didn’t track outcomes
Mainly post RP BF failures (80%) +/-prior salvage prostate bed RT (50%)
N=131, median PSA 2.2 ng/ml
76% management impact (99/131)
ADT to lesion directed therapy (44)Switch to surveillance (29)Switch from to ADT (14)Therapy modification (8)
68Ga
DCFPyL
Mol Imaging Biol (2015) 17:575
[18F]-DCFPyl advantages: availability, production amount, and image resolution
N=14 biochemical recurrence post RT or RP
All Ga68 lesions detected by DCFPyLDFCPyL detected additional lesions vs. Ga68DFCPyL had higher SUVmax to background
“Our results indicate that the [18F]-labeled compound [18F]DCFPyL is a highly promising alternative to [68Ga]- Ga-PSMA-HBED-CC for PSMA-PET/CT imaging in relapsed prostate cancer. Based on significantly higher SUVvalues in the PSMA-avid lesions, [18F]DCFPyLPET/CT may represent a valuable tool to detect small prostate cancer lesions with high sensitivity.”
Improving the treatment of recurrent CaP[18F]-DCFPyL vs. [68Ga] PSMA Imaging for restaging
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Biochemical failure after primary RT (n=80)
[18F]DFCPyL PET/CT (optional PET/MRI)
Number of men with extra-prostatic recurrenceNumber and sites of recurrence
Impact on proposed management plan
CT Thorax + abdomen + bone scan + mpMRI pelvis
Number of men with extra-prostatic recurrenceNumber and sites of recurrence
Proposed management plan
Actual management at 6,12,24,26 months• Biopsy • Salvage therapies• HROQOL and Toxicity
Canadian trials of 18F-DCFPyL
PICsLondon, Hamilton, PMCC, OCC• N=80, BF post RT
PSMA PET/CT for Prostate CancerBC Cancer agency• N=200, BF post RP or RT
First PICs Patient
Biologic characterization
Intra-prostatic lesion delineation
Staging
Response assessment
Therapy selection• Surveillance• RT/Sx• ADT/systemic Rx
Directed biopsyFocal therapyImage guided surgery
Salvage post RT/RPHigh risk RP
SurveillancePost RTPost ADT/systemic Rx
Potential role of imaging in CaP
Imaging systemic disease
Kwee et al, J Nuc Med, 2014
• MATV = SUV>3.0; 40%
Castration Resistant Prostate Cancer (CRPC)18F-FCH pre and post chemotherapy
18F-Choline 3mo 18F-Choline
Now Open
MISTR N=40, Hamilton + London
18F-DCFPyL PET/CT vs. 18F-FDG PET/CT pre and post CTX
Imaging-based response evaluation. Clemens Kratochwil et al. J Nucl Med 2016;57:1170-1176
(c) Copyright 2014 SNMMI; all rights reserved
PSMA-Targeted Radionuclide Therapy of Metastatic Castration-Resistant Prostate Cancer with 177Lu-Labeled PSMA-617
Conclusions
Increasing role for imaging in directing therapy in prostate cancer:
• DIL directed focal therapy or boost
• Selection of patients for local salvage
• Treatment of oligo-metastatic disease
• Prognosis and response in CRPC
mpMRI: early/localized CaP
PET/CT: advanced/recurrent/metastatic CaP
PET/MRI: “one stop shopping”
Lu177-PSMA: treatment
THANK YOU