SBRT (SABR) in prostate cancer
Transcript of SBRT (SABR) in prostate cancer
The Royal Marsden
SBRT (SABR) in prostate cancer
Dr Alison Tree, Consultant Clinical Oncologist
Royal Marsden Hospital/ Institute of Cancer
Research
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Conflicts of interest
– Honoraria, travel grants and research grants from Elekta
– Research funding from Accuray
– Research funding from MSD
– Honoraria from Astellas, Bayer, Janssen and Ferring.
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SBRT for localised prostate cancer
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Why might SBRT work in localised prostate cancer?
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Biologically effective dose of 36.25 Gy in 5 fractions
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CHHiP trial
T1b-T3a N0 M0
Estimated risk of SV involvement ≤ 30%
PSA ≤ 30ng/ml
Randomise
74Gy / 37f
(standard)
60Gy / 20f
(hypofractionated)
57Gy / 19f
(hypofractionated)
Hormone treatment
(3-6 months)
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Moderate hypofractionation is non-inferior
Dearnaley et al, Lancet Oncology 2016
a/b estimate
1.8 Gy
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Can we go below 3 Gy/fraction?
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Ahead of their time
Lloyd-Davies et al, Urology, 1990
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Freeman and King Radiat Oncol (2011) 6:3
41 patients
5 year PFS 92.7%
GI 2.5% G2, 0% G3
GU 7% G2, 2.5% G3
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v
Until 2013, state of the evidence base…
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Cohort studies
Head of an Old Man with a White Beard, van Dyck, courtesy of the Met museum New York
Freeimages.com
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Two papers – Green journal and red journal
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Limitations
– Not randomised
– “phase II study”
– Variable definitions of follow-up schedule (although no physician-
reported toxicity outcomes in this paper)
– Median follow-up 36 months
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PSA outcomes
King et al, Rad Oncol, 2013
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QOL in GU, GI and sexual domains over time
Bowel functionBladder function Sexual function
King et al, IJROBP, 2013
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Bottom line
– SBRT causes a QOL ‘dip’ in urinary and bowel domains at 3 months
post-treatment
– QOL nearly back to baseline by 6 months.
– Patients with poorer urinary and bowel QOL at baseline actually have an
QOL better than baseline after 6/12
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The data from these two papers caused ASTRO to change their position on prostate SBRT..
“It is ASTRO’s opinion that data supporting the use of
SBRT for prostate cancer have matured to a point
where SBRT could be considered an appropriate
alternative for select patients with low to intermediate
risk disease.”
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Canadian ProCaRS database
– 7974 patients, contemporaneous
– Treated with EBRT (74-79.8 Gy), LDR (144-145 Gy),
HDR or SBRT (35 Gy in 5)
– Propensity score matching
Loblaw et al, Clin Oncol 2017
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LDR
EBRT
Loblaw et al, Clin Oncol 2017
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Rob Meier data – abstract only
– 309 patients, prospective, multicentre Phase II
– 40 Gy in 5 to CTV, 36.25 Gy in 5 to PTV
– 5 year PFS 97.1%
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The PACE trial
Low/Intermediate risk prostate cancer
Candidate for surgery?
NoYes
RandomiseeRandomisee
SBRT 36.25 Gy in 5 fractions
EBRT 60 Gy in 20 fractions
SBRT 36.25 Gy in 5 fractions
Prostatectomy
CI Dr Nick van As
Funded by Accuray
PACE B858 patients
PACE A234 patients
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Skeptics say…
– Highly selected, mostly low risk patients, most of whom may not have
needed treatment
– No surprise they do well oncologically
– Toxicity appears manageable, but not measured robustly in many cases
– Until we have Level one evidence (PACE, HYPO), should not be
standard of care in UK.
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SBRT in prostate oligometastases
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The concept of oligometastases - can we shift the therapeutic paradigm?
• Intermediary state of metastatic disease
• ≤ 3 metastatic sites
Slide courtesy of Dr Aitken
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Number of metastases depends on how hard you look
– 117 patients scanned for BCR
– 100 had at least one PSMA-avid lesion
– In 67% these were missed on CT or MRI
– In 42% of people scanned, PSMA changed management
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Are oligometastatic patients going to do well anyway?
Localised prostate cancer, treated radically, ADT and bisphosphonate
randomisation
1071 men, median follow up 7.4 years
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Sridaran et al
– 176 relapsed in the bone, 26% single met, 28% 2-3 mets,
47% more than 3
– Gleason at presentation did not predict oligometastatic
vs polymetastatic
– Those relapsing with more mets had a higher PCSM
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What can SBRT achieve in prostate oligomets? Local control
Aitken et al, 88% LC at (mixed histologies)
Ost et al, 99% LC at 3 years if BED >100 Gy (<100 Gy LC 79%)
Habl et al 100% LC at 2 years
Jereczek-fossa et al 90.3% LC
Bhattacharya et al 89% LC (mixed histologies)
Aitken et al, Clin Onc (2015) 27: 7Ost et al, Eur Urol (2016) 69:1Habl et al. BMC Cancer (2017) 17:361 Jereczek-fossa et al Clin Genitour Can (2017) 15:4Bhattacharya et al, BJR (2015) 88:1048
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The converse argument
Murphy et al, European Urology 2017
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Murphy et al, European Urology 2017
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Mixed histologies, mixed scenarios
Tree et al, Lancet Oncol (2013) 14:1
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Cohort studies
Head of an Old Man with a White Beard, van Dyck, courtesy of the Met museum New York
Selection bias
Measurement bias
Reporting bias
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Deferal of ADT – a worthwhile endpoint
– Side effects of ADT….
– Ost et al LN mets – ADT-FS 44 months
– Decaestecker et al median ADT-FS 25 months
Ost et al Clin Onc, 2016Decaestecker et al Radiat Oncol, 2014
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What clinical trial data is coming?
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SABR-COMET: SABR vs SOC
PI: Dr. David Palma
& Prof Suresh Sunan
NCT01446744
Primary
Endpoint:
Overall
Survival
306 patients
recruited
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CORE: SBRT vs SOC
PI: Dr. Vincent Khoo
NSCLC, Breast or Prostate Cancer Patients
Completed radical treatment
≤3 Extra-cranial metachronous oligo-
metastases
Suitable for SBRT
Randomise (1:1)
Standard of CareSBRT+
Standard of Care
Standard of Care
defined prior to randomisation including:
Chemotherapy, hormone therapy,
palliative radiotherapy or observation
Primary Endpoint:
Progression Free Survival
Target :
206 patients
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STOMP CI Piet Ost, Ghent
– 58 patients
– SBRT vs surveillance in oligometastatic metachronous relapse
– Manuscript accepted by JCO…
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What’s coming?
ORIOLE
CI Phuoc Tran,
Johns Hopkins
54 men
Non-CRPC PCa
SBRT vs SOC
Biomarkers+++
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All patients get SBRT to
1-2 sites of
oligoprogression
CI Dr Alison Tree
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The wisdom of Twitter
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Our mission, should you choose to accept it
– Randomised trials as much as possible
– Good quality prospective evidence otherwise
– Work together – ART-NET, MR-Linac consortium, SABR consortium,
UCH/Christie Proton research
– To avoid fake news
– And lets make radiotherapy (even) great(er) again
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Thank you for your attention
@alison_tree