Stereotactic body radiotherapy in the treatment of oligometastatic

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Stereotactic body radiotherapy in the treatment
of oligometastatic prostate cancer: early results
Fairleigh Reeves1, Patrick Bowden2, Anthony Costello1,2
1The
Royal Melbourne Hospital; 2Epworth Hospital Richmond, Australia
Introduction
Results
Treatment of metastatic prostate cancer with androgen deprivation therapy (ADT) is effective, but
can be associated with debilitating side effects.
•
•
•
Oligometastasis describes a state of limited metastatic capacity (Weichselbaum 2011). This may
represent an intermediate disease state that is amenable to aggressive local therapy, allowing
deferral of ADT. In practice oligometastasis usually refers to five or fewer metastases. These early
metastatic lesions may seed further metastases. Therefore, eradication of oligometastases may
alter the progression of disease and potentially offer cure in select cases.
41 treatments in 37 men
Median follow-up 5 months (6wkto 4.3y)
Metastases were detected on Bone Scan, CT, PET or MRI
Treatment details
Surgery or radiation therapy are the two treatment options in this setting. Stereotactic body
radiotherapy (SBRT) is relatively non-invasive. It delivers an ablative dose of radiotherapy to target
tissues, minimising scatter to adjacent structures. Early evidence in other cancers suggests SBRT is
a safe and effective treatment for oligometastatic disease (Tree 2013).
Lesion
Gray
Fraction
Overall
36.84 (12-70)
10 (1-35)
Lymph Node
35.5 (18-70)
5 (3-35)
Bone
40 (12-50)
10 (1-20)
Initial PSA follow-up in all patients
Aim
To evaluate the effectiveness of SBRT in oligometastatic prostate cancer.
Results
Case 1 – 62yo
March 2010 RARP (Gleason 8, PSA 6.5, staging negative)
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Post-op PSA <0.01ug/L  increased to 0.21 (Oct 2011)
December 2011 Salvage prostate bed radiotherapy
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Feb 2013 Ongoing PSA rise to 7.1 with back pain
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Bone scan  solitary lumbar vertebral metastasis
March 2013 SBRT to lumbar metastasis
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Follow-up PSA 0.35 (6wk), 0.091 (8months)
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Remains ADT free
6/52 review
Overall
7 (<0.01 – 81.51)
4.9 (<0.01 – 60)
Naïve
6.65 (0.75 – 43)
4.8 (0.217 – 60)
*Use(d)
18.7 (<0.01 – 81.51)
6.74 (<0.01 – 59.1)
CRPC
10 (4 – 72)
4.5 (0.02 – 27.5)
Case 1 2013
9.1 (2.496)
Gleason
8 (6-9)
Stage
T1c
T2a
T2c
T3a
T3b
6%
6%
17%
34%
37%
Primary Rx
RP
RP + RT
RT
32%
46%
22%
SBRT
69y (5080)
Clinical Outcomes
Time to SBRT
from 1° Rx
39months
(6wk-13y)
All patients with >1 follow-up PSA (n=31)
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42% Biochemical response
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13% Biochemical failure not requiring treatment
•
45% Biochemical failure requiring SBRT, ADT or chemotherapy
ADT status
Naïve
*Use(d)
CRPC
62%
14%
24%
ADT naïve patients (n=23)
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16 PSA response  remain ADT free
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4 started ADT (6wk – 6m post SBRT)
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3 required further SBRT
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1 started ADT (6m post SBRT)
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2 remain ADT free
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Overall 78% remain ADT free at 5 months (median)
Symptomatic
15%
Lesion type
Bone
Node
Both
59%
37%
5%
Symptomatic patients (n=6): 83% had resolution of their pain
Case 2 – 58yo
August 2007 RARP (Gleason 7, PSA 39, staging negative)
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Oct 2007 Post-op PSA 43.3ug/L, back pain
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Bone scan  solitary lumbar vertebral metastasis
December 2007 High dose RT to lumbar lesion + ADT
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August 2008 PSA <0.01  Intermittent ADT
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April 2012 PSA rise to 8.5 (HORMONE REFRACTORY)
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Bone scan  new acetabular metastasis no uptake in
previously treated lesion
May 2012 High dose RTto acetabular metastasis
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Feb 2013 ADT ceased
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Aug 2013 PSA 0.038 off ADT (S.Testosterone 7.4nmol/L)
Pre-SBRT
Primary Cancer
PSA ug/L
Age
Methods
A retrospective review was undertaken of all men with oligometastatic prostate cancer (≤5 sites of
metastasis), treated with SBRT by one clinician (PB) from Dec 2007 to Dec 2013.
Outcomes included effectiveness and safety of SBRT. Efficacy was measured by ADT use and
biochemical response (PSA). Biochemical failure was defined as two consecutive PSA rises, a
single PSA rise >50% of pre-SBRT level, or no absolute reduction in PSA.
Cases studies were also undertaken of two men with complete biochemical response to SBRT.
Results reported are median and range unless otherwise stated.
ADT status
Patient Characteristics
Acute toxicity (all patients)
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61% no toxicity
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31.7% minor side effects not requiring treatment (Grade1)
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7.3% nausea or diarrhoea requiring medication (Grade2)
Number sites
1
71%
2
22%
4 0r 5
7%
*Use(d) = current/previous ADT
excluding CRPC and
neoadjuvant/adjuvant ADT
only
Conclusions
Case 2 2007
This promising early data suggests that SBRT has the potential to safely control oligometastatic
prostate cancer in the short term, and may delay the need for ADT and its associated side effects.
Longer follow-up and prospective controlled trials are warranted.
References
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Case 3 2012
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Tree, A. et al. Stereotactic body radiotherapy for oligometastases. Lancet Oncology 2013; 14,
e28–e37
Weichselbaum, R.R. & Hellman, S. Oligometastases revisited. Nature reviews. Clinical oncology
2011; 8(6), 378–382
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