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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.

2

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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