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of Pages 8

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available at www.sciencedirect.com
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Platinum Priority – Prostate Cancer

Editorial by XXX on pp. x–y of this issue

Stereotactic Abative Body Radiotherapy (SABR) for Oligometastatic

Prostate Cancer: A Prospective Clinical Trial

Shankar Siva a,b,*, Mathias Bressel c, Declan G. Murphy b,d, Mark Shaw a, Sarat Chander a,
John Violet a, Keen Hun Tai a, Cristian Udovicich a, Andrew Lim a, Lisa Selbie a,
Michael S. Hofman a,b, Tomas Kron a,b, Daniel Moon a, Jeremy Goad a, Nathan Lawrentschuk a,b,
Farshad Foroudi e
a
Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; b Sir Peter MacCallum Department of Oncology,
Grattan Street University of Melbourne, VIC, Australia; c Centre for Biostatistics and Clinical Trials, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia;
d
Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; e Department of Radiation Oncology, Austin Health, Heidelberg, VIC, Australia

Article info Abstract

Article history: Background: Stereotactic ablative body radiotherapy (SABR) is an emerging treatment option
Accepted June 1, 2018 for oligometastatic prostate cancer. However, limited prospective evidence is available.
Objective: To determine the safety and feasibility of single fraction SABR for patients with
Associate Editor: oligometastatic prostate cancer. Secondary endpoints were local and distant progression-free
survival (LPFS and DPFS), toxicity, quality of life (QoL), and prostate-specific antigen response.
Giacomo Novara
Design, setting, and participants: In a prospective clinical trial, patients were screened
with computed tomography, bone scan, and sodium fluoride positron emission tomogra-
Statistical Editor: phy scan and had one to three oligometastases. Kaplan-Meier methods were used to
Andrew Vickers determine LPFS and DPFS. Toxicity was graded using Common Terminology Criteria for
Adverse Event version 4.0. QoL was assessed using European Organization for Research and
Treatment of Cancer QLQ-C30 and QLQ-BM22 at 1, 3,12, and 24 mo.
Keywords:
Intervention: A single fraction of 20-Gy SABR to each lesion.
Oligometastases Results and limitations: Between 2013 and 2014, 33 consecutive patients received SABR to
Metastasis directed therapy a total of 50 oligometastases and were followed for 2 yr. The median age was 70 yr. The
SABR Gleason score was 8 in 15 patients (45%). Twenty patients had bone only, 12 had node
only, and one had mixed disease. SABR was feasible and delivered as planned in 97% of
Quality of life
cases. There was one grade 3 adverse event (3.0%, vertebral fracture). No patient died. The
Prostate cancer 1 and 2-yr LPFS was 97% (95% confidence interval [CI]: 91–100) and 93% (95% CI: 84–100),
Positron emission tomography and DPFS was 58% (95% CI: 43–77) and 39% (95% CI: 25–60), respectively. In those not on
Clinical trial androgen deprivation therapy (ADT; n = 22), the 2-yr freedom from ADT was 48%. There
was no significant difference from baseline QoL observed. Limitations include small
Single fraction
sample size, limited duration of follow-up, and lack of a control arm.
SBRT Conclusions: A single SABR session was feasible and associated with low morbidity in this
POPSTAR cohort. Over one-third of patients did not progress and were free from ADT at 2-yr. QoL
measures were maintained with this treatment strategy.
Patient summary: This clinical trial investigated single treatment stereotactic radiother-
apy for low volume advanced prostate cancer. The approach was found to be safe with
avoidance of hormone therapy in almost half of the participants at 2 yr.
© 2018 Published by Elsevier B.V. on behalf of European Association of Urology.

* Corresponding author. Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne 3000, VIC,
Australia. Tel. +61 3 8559 5000; Fax: +61 3 8559 7371.
E-mail address: shankar.siva@petermac.org (S. Siva).

https://doi.org/10.1016/j.eururo.2018.06.004
0302-2838/© 2018 Published by Elsevier B.V. on behalf of European Association of Urology.

Please cite this article in press as: Siva S, et al. Stereotactic Abative Body Radiotherapy (SABR) for Oligometastatic Prostate Cancer:
A Prospective Clinical Trial. Eur Urol (2018), https://doi.org/10.1016/j.eururo.2018.06.004
EURURO-7877; No. of Pages 8
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1. Introduction
The oligometastatic disease state is an increasingly recog-
nized phenomenon in prostate cancer. Local definitive
therapies may putatively limit further seeding of metasta-
ses, with the biological mechanism of metastasis-to-
metastasis spread demonstrated in whole genome se-
quencing studies of prostate cancer patients [1,2]. Never-
theless, the optimal management of oligometastatic
prostate cancer is an ongoing area of controversy. For
example, the respondents in the 2017 Advanced Prostate
Cancer Consensus Conference, when presented with the
case of a patient with oligometastatic recurrent prostate
cancer and a previous definitively treated primary, 60%
recommended local therapy to all sites of disease with or
without systemic therapy [3]. However, there is no high-
level phase III evidence to support this approach.
Stereotactic ablative body radiotherapy (SABR) is an
appealing treatment option for metastasis-directed therapy
given its outpatient nature and short treatment duration.
However, the literature for SABR in oligometastatic prostate
cancer is largely retrospective [4,5]. Recently, outcomes
from the first prospective clinical trial were reported; the
STOMP randomized phase 2 study randomly assigned
patients to surveillance versus metastasis-directed therapy
(surgery or SABR) [6]. In 62 randomized patients, the
primary outcome measure of androgen deprivation therapy
(ADT) free survival was 21 versus 13 mo for the metastasis-
directed therapy (MDT) and surveillance arms, respectively.
We conducted a single institutional prospective clinical
trial in patients with one to three oligometastases from
prostate cancer. The primary objective of the study was to
assess the feasibility and tolerability of single fraction
treatment. Secondary objectives included the assessment of
efficacy, quality of life (QoL), and prostate-specific antigen
(PSA) change associated with treatment. Patterns of failure
were also recorded.
2. Patients and methods
2.1. Study design and participants
This prospective interventional clinical trial was approved by the Peter
MacCallum Cancer Centre institutional review board, Melbourne, Australia
(POPSTAR, ‘Pilot Study of patients with Oligometastases from Prostate
cancer treated with STereotactic Ablative Radiotherapy’, Universal Trial
Number U1111-1140-7563). All patients signed informed consent. Inclusion
criteria were pathologically confirmed prostate cancer treated with curative
intent (radical prostatectomy, primary radiotherapy, or a combination of
both); bone scan or computed tomography (CT) evidence of one to three
metastases (bone or lymph node) within 6 wk of enrolment; Eastern
Cooperative Oncology Group (ECOG) performance status of 2 or less.
Patients could be androgen sensitive or castration resistant. Patients were
considered ineligible if they had previous high dose radiotherapy to the
proposed targets (biological effective dose of >40 Gy), visceral metastases,
prior cytotoxic chemotherapy, any change in hormonal therapy regimen
within 6 wk of registration, or unstable lesions in the spine or long bones.
Patients were screened with a sodium fluoride (NaF) positron-
emission tomography (PET)/CT scan. Patients were excluded if more than
three metastases were detected after PET screening. Baseline serum PSA
Please cite this article in press as: Siva S, et al. Stereotactic Abative Body Radiotherapy (SABR) for Oligometastatic Prostate Cancer:
A Prospective Clinical Trial. Eur Urol (2018), https://doi.org/10.1016/j.eururo.2018.06.004
and testosterone levels were recorded, as well as symptoms using
Common Terminology Criteria for Adverse Events version 4.0. Pretreat-
ment spinal instability scores were recorded for spinal targets
[7]. Pretreatment QoL questionnaires (QLQ) were administered (Euro-
pean Organization for Research and Treatment of Cancer [EORTC] core
questionnaire QLQ-C30 [8] supplemented with the BM-22 [9] instru-
ment). Follow-up after SABR was every 3 mo for 2 yr with PSA testing and
CT imaging, with QoL questionnaires administered at 1, 3, 12, and 24 mo.
A second NaF PET scan was performed at 12 mo.
2.2. Interventions
Eligible patients received a single fraction SABR to all visible (1–3) sites of
disease. A margin of 5 mm was given to the gross visible tumor to define
the planning target volume. A single fraction of 20 Gy was prescribed to
the periphery at 80% of the maximal dose, covering 95% of the planning
target volume. All patients were immobilized using a commercial dual-
vacuum immobilization device (BodyFix, Stockholm, Sweden). Dose
constraints can be found in Supplementary data.
2.3. Outcome measures
The primary endpoints were feasibility and tolerability. Feasibility was
assessed for each patient and was defined as: (1) successful completion of
treatment within 3 d of intended treatment completion, and (2) image
guidance verification of treatment delivery within 5 mm of planned
delivery. Tolerability was defined as no greater than a 15% rate of grade 3+
treatment-related toxicity and no grade 5 toxicities related to SABR.
Secondary outcome measures included local and distant progression-free
survival defined on imaging (local progression-free survival [LPFS] and
distant progression-free survival [DPFS]), treatment-related adverse events,
QoL, and change in PSA. Local progression of a soft tissue metastatic lesion
was defined as an increase of 20% in the largest tumor dimension with a
minimum absolute increase of 5 mm as per Response Evaluation Criteria in
Solid Tumors [RECIST] [10]. The investigator scored local progression of
bony sclerotic metastases, with progression typically confirmed with PET.
2.4. Statistical analysis
The sample size estimate for the study was pragmatic. Based on an
estimated sample size of 30 patients, if the true underlying grade
3 toxicity rate is 10.5%, the probability of no greater than 15% of patients
in the sample (ie, maximum 4 out of 30) suffering a grade 3 or higher
acute toxicity is 80%. The final analysis was planned 2 yr after the last
patient received treatment.
All statistical analyses were performed in R (version 3.3.2; R
Development Core Team 2009, Vienna, Austria). The worst grades of
toxicities were tabulated as frequencies by grade for each toxicity type.
Time-to-event outcomes (LPFS and DPFS) were estimated using the
Kaplan-Meier method. Cumulative incidence of first failure (local,
distant, or death) was described assuming competing failures. QoL was
scaled and scored using recommended EORTC procedures [11] and were
analyzed using linear mixed models. Time (as a factor) was included as a
fixed effect while patient was included as a random effect. No within-
group correlation was assumed and the model was fitted by maximizing
the restricted log-likelihood. Mean scores and 95% confidence intervals
(CI) were estimated from the linear mixed models contrasts. No
imputation for missing values was used.
3. Results
Between April 4, 2013 and November 17, 2014, 39 patients
were enrolled and signed consent. Six patients were
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Table 1 – Baseline characteristics Table 2 – Treatment related toxicities

Variable Statistic n (%) Adverse event Grade 1 Grade 2 Grade 3 Total

(CTCAE v4.0)
Age (yr) Median [IQR] 70 [67–75]
Gleason score (ISUP grade) 6 (1) 4 (12) Fatigue 14 14
3 + 4 = 7 (2) 7 (21) Diarrhea 5 1 6
4 + 3 = 7 (3) 7 (21) Nausea 6 6
8 (4) 10 (30) Abdominal pain 2 2
9 (5) 4 (12) Back pain 2 2
10 (5) 1 (3) Dermatitis radiation 2 2
ECOG 0 26 (79) Fracture 2 1 3
1 6 (18) Myositis 1 1 2
2 1 (3) Neuralgia 1 1
Spine Instability Score 1–2 6 (38) Pain 1 1
(n = 16 spinal metastasis) Skin hyperpigmentation 1 1
3–4 4 (25) Urinary incontinence 1 1
5–6 6 (38) Vomiting 1 1
Bone lesionsa 0 12 (36) Any AE 16 5 1 22
1 12 (36)
2 4 (12) AE = adverse events; CTCAE = Common Terminology Criteria for Adverse
3 5 (15) Events.
Lymph node lesionsa 0 20 (61)
1 12 (36)
3 1 (3)
Total lesions 1 22 (67) and all except one patient successfully completed treatment
2 5 (15) within 3 d of intended treatment completion (feasibility
3 6 (18) rate of 97% [95% CI: 84–100]). The patient who did not
PSA Median [IQR] 6.4 [1.1–12.5]
successfully completed treatment within 3 d of indent
Androgen deprivation status Castrate sensitive 22 (67)
Castrate resistant 6 (18) treatment completion had a change in rectal volume, which
ADT at time of SABR 11 (33) may have increased the risk of toxicity. This resulted in a
Primary treatment modality Surgery 18 (54) delay of treatment of 18 d. Treatment-related adverse
Radiotherapy 15 (45)
events were observed in 22 patients (67%), with one grade
ADT = androgen deprivation therapy; ECOG = Eastern Cooperative Oncology 3 toxicity (3%, vertebral fracture requiring spinal instru-
Group; IQR = interquartile range; ISUP = International Society of Urological mentation). Treatment-related adverse events within
Pathology; PSA = prostate-specific antigen; SABR = Stereotactic ablative
24 mo of SABR are described in Table 2.
body radiotherapy.
a
One patient had a mix of bone and lymph node lesions. The patient had No patient died during the study period, two had local
one bone lesion and one lymph node lesion. progression, and 20 had distant progression. The LPFS at 1 yr
was 97% (95% CI: 91–100) and at 2 yr was 93% (95% CI: 84–
100). The DPFS and at 1 yr was 58% (95% CI: 43–77) and at
excluded in the screening period. Three patients had more 2 yr was 39% (95% CI: 25–60). Kaplan-Meier survival curves
than three metastases after NaF PET/CT, one had a new are shown in Fig. 1. There were 22 patients who were
metastasis in a previous high-dose radiotherapy field, and castration sensitive and did not have ADT at the time of
two had metastases in technically unsuitable locations SABR. In this subgroup the freedom from ADT treatment at
(mandibular ramus and lymph node broadly contacting 24 mo was 48% (95% CI: 31–75). Of the 11 patients on ADT at
small bowel). In total, 33 patients with 50 oligometastases the time of SABR, five were on ADT for 2–5 mo, three were
received the trial intervention and were followed for 2 yr. on ADT for 9–12 mo, and three were on ADT for at least 2 yr.
The median age was 70 yr, and median time from treatment All 11 patients had commenced on ADT prior to referral for
of the primary was 2.9 yr. The median baseline PSA level consideration of trial enrolment, and six had castration-
was 6.4 ng/ml. The Gleason score was 8–10 in 15 patients resistant disease. The maximum change in PSA from
(45%), and 7 in 13 patients (39%). Of the 18 patients whose baseline is depicted in Fig. 2. In total, 26 patients (79%
primary treatment was prostatectomy, 15 underwent sal- [95% CI: 61–91]) had a PSA decline after SABR of whom
vage radiotherapy to prostate bed, 12 underwent lymph seven patients (27% [95% CI: 14–48]) had an undetectable
node dissection with a median of four nodes dissected PSA reading. Of the seven patients without a PSA response
(range: 1–13). No patient had lymph node involvement at (21% [95% CI: 9–39]), two had castration-resistant disease
time of surgery. Of the 33 patients, 20 had bone-only (29% [95% CI: 4–71]).
disease, 12 had node-only disease, and one had both. One, Patterns of failure based on disease location are depicted
two, and three metastases were treated in 67%, 15%, and 18% in Fig. 3. In patients with bone only disease, 2-yr LPFS and
of patients, respectively. There were 14 of the 50 metastases DPFS was 89% and 39%, respectively. Relapses after SABR to
(28%) detected by the addition of NaF PET above conven- bone (n = 12) occurred in bone only (n = 9), bone and nodes
tional CT and bone scan, at a median of one additional (n = 2), and nodes only (n = 1). For those with pelvic nodal
metastasis per patient. The baseline patient characteristics disease only the 2-yr LPFS and DPFS was 100% and 42%,
are described in Table 1. respectively. Relapses after SABR to pelvic nodes (n = 8)
All patients had image guidance verification of treatment were located in the pelvis only (n = 4) and both pelvis and
delivery during treatment within 5 mm of planned delivery extra-pelvic nodes (n = 4). Salvage radiotherapy was per-

Please cite this article in press as: Siva S, et al. Stereotactic Abative Body Radiotherapy (SABR) for Oligometastatic Prostate Cancer:
A Prospective Clinical Trial. Eur Urol (2018), https://doi.org/10.1016/j.eururo.2018.06.004
EURURO-7877; No. of Pages 8
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Fig. 1 – Survival. (A) Local progression-free survival and (B) distant
progression-free survival.
formed for three of 12 patients with distant relapse after
SABR to bone metastases and two of 8 patients after SABR to
pelvic nodes.
All patients had their baseline and 1-mo QLQ-C30 and
QLQ-BM22 QoL assessment completed. Two patients have
missing QoL data at the 3-mo (one patient had a
cerebrovascular event and one patient completed the QoL
questionnaire but it was lost in transit), two at 12 mo
(patients were lost to follow-up), and 10 patients had
missing QoL at 24-mo assessment (eight patients were lost
to follow-up, one patient missed the appointment, and one
patient did not return the QoL form). Based on Cocks et al.
[12] and Ringash et al. [13], only pain subscales at 24 mo and
functional interference showed a minimal important
difference from baseline. The average change from baseline
in QoL scores for QLQ-C30 and QLQ-BM22 tools are
tabulated in Table 3, and overall QoL scores are given in
the Supplementary data.
Please cite this article in press as: Siva S, et al. Stereotactic Abative Body Radiotherapy (SABR) for Oligometastatic Prostate Cancer:
A Prospective Clinical Trial. Eur Urol (2018), https://doi.org/10.1016/j.eururo.2018.06.004
4. Discussion
To our knowledge, this is the second prospective clinical
trial to report in the context of oligometastatic prostate
cancer. The primary outcome measures of safety and
feasibility were met. A single treatment of 20 Gy was
associated with 58% and 39% of study participants being
alive and free from progression at 1 and 2 yr, respectively. Of
those with disease progression, one-quarter relapsed in an
oligometastatic pattern amenable to a further course of
salvage SABR. This is consistent with a previous report from
Decaestecker et al. [14] in which 19/50 patients (38%)
received a second course of salvage SABR after initial disease
recurrence. Similarly, in that study, the 1 and 2-yr PFS rates
were 64% and 35%, respectively. Our outcomes are consis-
tent with a systematic review of retrospective case series in
the context of patients receiving either radiotherapy or
lymph node dissection, in which 51% of patients were
progression-free between 1 and 3 yr after treatment of
oligometastases. Complicating the interpretation of this
data is that most of them received adjuvant ADT.
This study included both patients who were castration
sensitive as well as castration resistant. Therefore, some
patients received varying degrees ADT before and along
with the SABR. Of the 22/33 patients who did not have ADT
at the time of SABR, the 2-yr ADT-free survival rate was 48%.
In the recently published STOMP study, the arm receiving
local therapy for hormone castration-sensitive oligometa-
static disease had a similar outcome with a median ADT-
free survival of 21 mo for the MDT group. This was
significantly higher than the surveillance arm at 13 mo,
albeit the study was powered with an alpha of 20%. Of note,
the trigger for ADT was predefined in STOMP but was at
clinician discretion in our study. Given that there is
increasing interest in the early implementation of novel
antiandrogens [15,16] and ADT in selected patients [17], the
outcome of SABR should be taken in the context of
associated treatment-related toxicities. In the
ADT  abiraterone arms of the STAMPEDE study, 33% of
the ADT alone group reported adverse events of grade 3 or
higher during their entire time in the trial as compared with
47% in the combination group [15]. Similarly, in the
LATITUDE study, grade 3 or higher adverse events were
reported in 48% of patients in the ADT alone group versus
63% of the patients in the combination group [16]. By
comparison, the grade 3 or higher SABR-related adverse
events occurred in 3% in the present study. Given that the
majority of patients will progress after SABR for oligometa-
static disease, most patients will receive systemic therapy at
some time post SABR. An average delay of ADT of
approximately 2 yr post-SABR may be attractive for some
patients wishing to avoid or delay commencement of
lifelong systemic therapies.
Importantly, QoL was maintained with the single fraction
SABR treatment strategy in this patient cohort. The only
significant change from baseline in the EORTC QLQ-C30
was pain at 24 mo compared with baseline. Similarly,
for bone metastasis-specific module, painful sites, pain
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Fig. 2 – Waterfall plot of maximal change in prostate-specific antigen (PSA) from baseline characterized by lesion type.

Fig. 3 – Patterns of failure based on disease location of oligometastases (nodal only versus bone only). One patient was excluded from this chart due to
extra pelvic nodal disease only, and one further patient with mixed bone and nodal disease.

characteristics, and functional interference were increased 1 yr using the EORTC QLQ–C30 and QLQ-PR25 modules. By
from baseline only at the 24-mo timepoint. This is consistent comparison in the randomized phase 3 TOAD study of
with data from the STOMP study in which the overall QoL immediate versus delayed ADT in patients with PSA only
scores remained stable for both arms at baseline, 3 mo, and relapse, the immediate therapy group had worsened sexual

Please cite this article in press as: Siva S, et al. Stereotactic Abative Body Radiotherapy (SABR) for Oligometastatic Prostate Cancer:
A Prospective Clinical Trial. Eur Urol (2018), https://doi.org/10.1016/j.eururo.2018.06.004
EURURO-7877; No. of Pages 8

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Table 3 – Mean change from baseline (95% CI) in quality of life scores

EORTC QLQ-C30

Dimension Change at 1 mo Change at 3 mo Change at 12 mo Change at 24 mo

Global health status 0 (–6 to 6) –1 (–7 to 5) –8 (–14 to–1) –8 (–15 to–1)

Functional scales
Physical functioning –3 (–7 to 2) –3 (–7 to 2) –4 (–8 to 1) –6 (–11 to–2)
Role functioning –4 (–11 to 4) –4 (–11 to 4) –3 (–11 to 4) –8 (–17 to 0)
Emotional functioning 2 (–3 to 6) 1 (–4 to 6) –1 (–6 to 4) –2 (–8 to 3)
Cognitive functioning 1 (–4 to 6) 0 (–4 to 5) –5 (–9 to 0) –8 (–14 to–3)
Social functioning 1 (–7 to 8) 1 (–7 to 8) –8 (–16 to–1) –6 (–14 to 2)
Symptom scales/items
Fatigue 1 (–6 to 7) 4 (–3 to 11) 3 (–4 to 9) 5 (–3 to 12)
Nausea and vomiting 3 (–2 to 7) 0 (–5 to 4) –2 (–6 to 2) –1 (–5 to 4)
Pain –2 (–10 to 6) 6 (–3 to 14) 4 (–4 to 12) 11 (2 to 20)
Dyspnea 1 (–7 to 10) 5 (–4 to 14) 3 (–6 to 12) 3 (–7 to 13)
Insomnia –4 (–13 to 5) –3 (–12 to 7) 1 (–9 to 10) 1 (–10 to 11)
Appetite loss 2 (–3 to 7) –1 (–6 to 4) –2 (–7 to 3) –4 (–9 to 1)
Constipation –1 (–6 to 4) 0 (–5 to 5) 1 (–4 to 6) 3 (–2 to 8)
Diarrhea 3 (–4 to 11) 4 (–3 to 12) –3 (–11 to 5) –2 (–10 to 7)
EORTC QLQ-BM22
Painful sites 0 (–4 to 5) 4 (0 to 9) 4 (0 to 9) 10 (5 to 15)
Pain characteristics 0 (–6 to 6) 4 (–2 to 11) 4 (–2 to 10) 9 (2 to 16)
Functional interference 1 (–5 to 8) –2 (–8 to 5) –3 (–9 to 3) –10 (–17 to–3)
Psychosocial aspects 5 (–1 to 10) 9 (3 to 14) 1 (–5 to 6) –1 (–7 to 6)

CI = confidence interval; EORTC QLQ = European Organization for Research and Treatment Quality of Life Questionnaire.

activity at most timepoints up to 2 yr, with the divergence
greatest at 6 mo. The immediate therapy group also
experienced significantly more hormone treatment-related
symptoms than the delayed group at 6 and 12 mo.
It is acknowledged that MDT remains an investigational
area [4] and there are conflicting views on whether ablation
or resection of metastatic disease, even in the oligometa-
static setting, provides meaningful benefits to patients
[18,19]. This is the first clinical trial to report outcomes of
single fraction SABR for oligometastatic prostate cancer.
This approach has advantages with respect of patient
convenience and resource utilization, although potential
theoretical disadvantages with respect to increased treat-
ment-related toxicity. With only five (15%) grade 2 and one
grade 3 (3%) adverse events were recorded in this patient
cohort, we observed that the side effect profile of a single
fraction 20-Gy SABR appears very tolerable in short to
medium term. Long-term adverse events, whilst reportedly
low in retrospective reports [4,14,20–22], require confirma-
tion through additional prospective datasets with longer
follow-up. Importantly, using a single fraction approach,
local tumor control was typically achieved with a 2-yr LPFS
of 93%. This is concordant with a multi-institutional
retrospective study that found a 3-yr LPFS of 93% with
multi-fraction SABR [23]. Similarly, a systematic review of
retrospective studies investigating SABR for oligometas-
tases to lymph nodes, for which the crude control was 98.1%
of patients at a median time of 22.5 mo [20], although in the
context of approximately 40% receiving concurrent ADT. It is
as yet unclear whether the addition of ADT with SABR will
improve outcomes through eradication of micrometastatic
disease or whether it will simply delay progression after
local ablative therapy. Regardless, prostate cancer may be
particularly appropriate for treatment with large dose per
fraction SABR from a radiobiological perspective due to a
higher proportion of tumor cell kill at doses that are
typically delivered with conventional fractionation [24–
26]. Thus, it may be that single doses in the range of 20 Gy is
as effective as more fractionated SABR treatments delivered
with a slightly higher total dose, although this hypothesis is
yet to be formally tested.
There are several important limitations of the present
study that should be acknowledged. This is a selected
patient cohort of small sample size and limited duration of
follow-up. Additional studies are required to confirm
findings, especially secondary outcomes of the study. NaF
PET/CT scanning was used in the screening process and
response assessment outcomes may have been different
using more modern PET imaging such as prostate specific
membrane antigen PET/CT [27]. In particular Na-F PET,
whilst superior than conventional imaging for bone
metastases, has low sensitivity and specificity for nodal
metastases, thereby decreasing the likelihood of identifying
a truly oligometastatic cohort of patients. Local progression
was investigator defined due to difficulty scoring responses
in bony sclerotic metastases. As this was a feasibility and
safety study, castration-sensitive and castration-resistant
disease were accepted. This resulted in a limited patient
subset in which to assess duration of ADT delay.
5. Conclusions
Single fraction SABR for oligometastatic prostate cancer is
both safe and feasible. Local tumor control is typically
achieved. In selected patients with one to three oligome-
tastases, a proportion of patients do not progress at 2 yr, and
QoL is maintained with this approach. As the majority of
patients are destined to fail this approach, the addition of

Please cite this article in press as: Siva S, et al. Stereotactic Abative Body Radiotherapy (SABR) for Oligometastatic Prostate Cancer:
A Prospective Clinical Trial. Eur Urol (2018), https://doi.org/10.1016/j.eururo.2018.06.004
EURURO-7877; No. of Pages 8
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novel systemic therapy combinations and/or methodologies
for better selection of patients should be further investi-
gated in future clinical trials.
Author contributions: Shankar Siva had full access to all the data in the
study and takes responsibility for the integrity of the data and the accuracy
of the data analysis.
Study concept and design: Siva, Bressel, Murphy, Shaw, Chander, Hofman,
Kron, Foroudi.
Acquisition of data: Siva, Bressel, Murphy, Shaw, Chander, Violet, Tai,
Udovicich, Lim, Selbie, Hofman, Kron, Moon, Goad, Lawrentschuk,
Foroudi.
Analysis and interpretation of data: Siva, Bressel, Foroudi.
Drafting of the manuscript: Siva, Bressel, Murphy, Shaw, Chander, Violet,
Tai, Udovicich, Lim, Hofman, Kron, Moon, Goad, Lawrentschuk, Foroudi.
Critical revision of the manuscript for important intellectual content: Siva,
Bressel, Murphy, Shaw, Chander, Violet, Tai, Udovicich, Lim, Hofman,
Kron, Moon, Goad, Lawrentschuk, Foroudi.
Statistical analysis: Bressel.
Obtaining funding: Foroudi, Siva.
Administrative, technical, or material support: Selbie, Lim, Udovicich.
Supervision: None.
Other: None.
Financial disclosures: Shankar Siva certifies that all conflicts of interest,
including specific financial interests and relationships and affiliations
relevant to the subject matter or materials discussed in the manuscript
(eg, employment/affiliation, grants or funding, consultancies, honoraria,
stock ownership or options, expert testimony, royalties, or patents filed,
received, or pending), are the following: None.
Funding/Support and role of the sponsor: The Prostate Cancer Foundation
of Australia and the Movember Foundation provided funding for the
study. The Peter MacCallum Cancer Centre acted as trial sponsor and
assisted with conduct of the study.
Appendix A. Supplementary data
Supplementary material related to this article can be
found, in the online version, at https://doi.org/10.1016/j.
eururo.2018.06.004.
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Please cite this article in press as: Siva S, et al. Stereotactic Abative Body Radiotherapy (SABR) for Oligometastatic Prostate Cancer:
A Prospective Clinical Trial. Eur Urol (2018), https://doi.org/10.1016/j.eururo.2018.06.004