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Journal of Medical Imaging and Radiation Oncology 59 (2015) 125–133
RADIATION O N C O LO GY —O R I G I N A L A RTICLE
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Is modern external beam radiotherapy with androgen
deprivation therapy still a viable alternative for prostate cancer
in an era of robotic surgery and brachytherapy: A comparison
of Australian series
Shea William Wilcox,1 Noel J. Aherne,2 Craig Steven McLachlan,3 Michael J. McKay,4 Andrew J. Last1 and
Thomas P. Shakespeare1,2,3,4
1
2
3
4
Radiation Oncology, North Coast Cancer Institute, Port Macquarie, New South Wales, Australia
Radiation Oncology, North Coast Cancer Institute, Coffs Harbour, New South Wales, Australia
Rural Clinical School, The University of New South Wales, Sydney, New South Wales, Australia
Radiation Oncology, North Coast Cancer Institute, Lismore, New South Wales, Australia
SW Wilcox MBBS, BSc; NJ Aherne MB, BCh,
BAO; CS McLachlan PhD, MPH&TM;
MJ McKay MBBS(Hons), FRANZCR, PhD, MD;
AJ Last MA, D.Phil, FRCR, FRANZCR;
TP Shakespeare MBBS, MPH, FRANZCR,
FAMS, Grad Dip Med (Clin Epi).
Correspondence
Dr Shea William Wilcox, Radiation Oncology,
North Coast Cancer Institute, Wrights Road,
Port Macquarie, NSW 2444, Australia.
Email: [email protected]
Conflict of interest: None declared.
Submitted 21 February 2014; accepted 20
November 2014.
doi:10.1111/1754-9485.12275
Abstract
Introduction: We compare the results of modern external-beam radiotherapy
(EBRT), using combined androgen deprivation and dose-escalated intensitymodulated radiotherapy with MRI-CT fusion and daily image guidance with
fiducial markers (DE-IG-IMRT), with recently published Australian series of
brachytherapy and surgery.
Methods: Five-year actuarial biochemical disease-free survival (bDFS),
metastasis-free survival (MFS) and prostate cancer-specific survival (PCaSS)
were calculated for 675 patients treated with DE-IG-IMRT and androgen
deprivation therapy (ADT). Patients had intermediate-risk (IR) and high-risk
(HR) disease. A search was conducted identifying Australian reports from
2005 onwards of IR and HR patients treated with surgery or brachytherapy,
reporting actuarial outcomes at 3 years or later.
Results: With a median follow-up of 59 months, our 5-year bDFS was 93.3%
overall: 95.5% for IR and 91.3% for HR disease. MFS was 96.9% overall
(99.0% IR, 94.9% HR), and PCaSS was 98.8% overall (100% IR, 97.7% HR).
Prevalence of Grade 2 genitourinary and gastrointestinal toxicity at 5 years
was 1.3% and 1.6%, with 0.3% Grade 3 genitourinary toxicity and no Grade
3 gastrointestinal toxicity. Eight reports of brachytherapy and surgery were
identified. The HDR brachytherapy series’ median 5-year bDFS was 82.5%,
MFS 90.0% and PCaSS 97.9%. One surgical series reported 5-year bDFS of
65.5% for HR patients. One LDR series reported 5-year bDFS of 85% for IR
patients.
Conclusions: Modern EBRT is at least as effective as modern Australian surgical
and brachytherapy techniques. All patients considering treatment for localised
prostate cancer should be referred to a radiation oncologist to discuss EBRT
as an equivalent option.
Key words: brachytherapy; external beam radiotherapy; intensity-modulated
radiotherapy prostate cancer; radical prostatectomy.
Introduction
There have been significant improvements in localised
prostate cancer treatments, with advances in surgery,
brachytherapy and external beam radiotherapy (EBRT).
In Australia, most of the recent published series focus on
surgical advances (e.g. robotic-assisted radical prosta-
© 2015 The Royal Australian and New Zealand College of Radiologists
tectomy or RARP)1–5 and brachytherapy.5–11 There are
few reports evaluating the results of modern EBRT.12–14
Modern EBRT has improved markedly with the now
common use of dose-escalation (DE), MRI-CT fusion,
daily image guidance with fiducial markers (IG) and
intensity-modulated radiotherapy (IMRT). In addition,
our understanding of the timing and duration of
125
SW Wilcox et al.
androgen deprivation therapy (ADT) in combination with
EBRT has improved, with multiple studies demonstrating
the additional benefits of the combination of ADT and
EBRT.15–17 These advances have improved the results of
EBRT, and are reflected in the national Australian EviQ
radiotherapy guidelines (www.EviQ.org.au), which recommend the use of DE-IG-IMRT with MRI-CT fusion and
daily image guidance using fiducial markers, combined
with ADT for intermediate-risk (IR) and high-risk (HR)
localised prostate cancer.
However, the lack of contemporary Australian series
utilising modern EBRT techniques could lead to a perception that EBRT is inferior to modern surgery or
brachytherapy,10 a view contradicting national guidelines18 and patient information booklets.19 Indeed, the
present authors occasionally receive correspondence
from other specialists regarding patients with localised
prostate cancer categorically stating the superior efficacy
of surgery or brachytherapy over EBRT.
The purpose of our report is to evaluate the long-term
efficacy of modern EBRT in treating IR and HR disease,
utilising a combination of ADT and DE-IG-IMRT, and to
compare this to contemporary Australian series of
surgery and brachytherapy.
Methods
A Medline search was conducted (1 December 2013)
using the following Boolean search: (prostate AND Australia) AND (radiotherapy OR brachytherapy OR HDR OR
LDR OR surgery OR prostatectomy), limiting the search
to studies published during or after 2005. In addition,
‘The Open Prostate Cancer Journal’, a non-Medline
indexed online open-source peer-reviewed journal, was
also searched for relevant articles. Australian surgical
and brachytherapy series including IR and/or HR prostate cancer patients were included if they reported actuarial efficacy results at 3 years or later.
Following institutional ethics approval (North Coast
New South Wales Human Research Ethics Committee,
Reference Number QA 101), the electronic medical
record (EMR) of our institution (Mosaiq, Elekta, Crawley,
UK) was interrogated to identify all patients with prostate cancer treated with our standard protocol of definitive DE-IG-IMRT and ADT. Exclusion criteria included
patients who were post-prostatectomy, node-positive,
metastatic, with histology other than adenocarcinoma,
did not receive ADT or treated from 2011 onwards.
Staging CT of the abdomen/pelvis and bone scan were
performed on all patients with HR disease.
All patients received ADT using leuprorelin or goserelin
acetate monotherapy, with 3–6 months of neoadjuvant/
concurrent ADT, and patients with HR disease receiving
adjuvant ADT for a planned 2 years. Patients underwent
trans-rectal ultrasound-guided insertion of gold fiducial
markers followed by MRI/CT fusion (as previously
reported20), unless contraindicated. Patients were
126
treated on an institutional ‘Bowel and Bladder Protocol’,
involving low-residue diet, aperients and pretreatment
oral fluid regimen to achieve a comfortably full bladder
and empty rectum. The planning CT scan (2 mm slices)
was performed with patients positioned supine and
immobilised with ankle stocks. Patients had the proximal
4−8 mm of seminal vesicles (SVs) included in their field.
Patients with HR features had distal SVs included to
either full dose (if SV positive clinically/on MRI), or to
50 Gy equivalent via simultaneous integrated boost. The
median total dose was 78 Gy (range 73.8–81 Gy) in 1.8
to 2.0 Gy fractions. Image guidance utilised either daily
online kV portal images (matched to fiducial markers) or
with daily cone beam CT (CBCT). Patients without
fiducial markers (<1% of all patients) underwent daily
CBCT matching to soft tissue and bone. Biochemical
failure was classified using the Phoenix definition (PSA
nadir + 2 ng/mL), and all patients with biochemical
failure were restaged with CT and bone scans, with
salvage androgen deprivation initiated when the PSA
reached between 10 and 20 ng/mL. Follow-up time was
calculated from the date of commencement of ADT as
recommended by Denham et al.21 Toxicity was scored
prospectively (real time) by the radiation oncologist or
radiation oncology registrar at each consultation, and
recorded in the Mosaiq EMR using common toxicity criteria (CTC): toxicity data were available for 94.1% of
patients who had reached 5 years post-treatment. Data
collection and analysis were performed independently of
the treating radiation oncologist (TPS). Kaplan–Meier
survival outcomes were calculated using SPSS v20 (IBM
Corporation, Armonk, NY, USA). Outcomes between the
DE-IG-IMRT cohort and the other Australian series were
compared at similar endpoints dictated by the published
comparison endpoint. Graph comparisons were performed after standardising the axes.
Results
Current series using DE-IG-IMRT
There were 675 patients treated with DE-IG-IMRT and
ADT from 2006 to 2010 (Table 1). An additional 22
patients were excluded due to not receiving ADT. Three
hundred and thirty-five (49.6%) patients were IR and
340 (50.4%) were HR. Thirteen of the 675 patients
(1.9%) were classified as ‘lost to follow-up’. Median
follow-up was 59 months. Actuarial biochemical diseasefree survival (bDFS) at 5 years was 93.3% overall, and
95.5% and 91.3% respectively for IR and HR patients.
Metastasis-free survival (MFS) was 96.9% overall,
99.0% IR and 94.9% HR. Prostate cancer-specific survival (PCaSS) was 98.8% overall, 100% for IR patients
and 97.7% for HR patients.
DE-IG-IMRT treatment was associated with very low
toxicity at 5 years. Prevalence of Grade 2 genitourinary
(GU) and gastrointestinal (GI) toxicity at 5 years from
© 2015 The Royal Australian and New Zealand College of Radiologists
Is modern radiotherapy still viable?
Table 1. Patient demographics
Discussion
Parameter
Age
Median (range)
<71 years
≥71 years
PSA (ug/mL)
Median (range)
≤10
10.1–20
>20
T-stage
T1/2
T3
Gleason
6
7
8
9
10
n = 675
71 (48–85)
319
356
11 (0.6–180)
310 (45.9%)
258 (38.2%)
107 (15.9%)
549 (81.3%)
126 (18.7%)
47 (7%)
379 (56.1%)
135 (20%)
110 (16.3%)
4 (0.6%)
treatment were 1.3% and 1.6%, with 0.3% of patients
experiencing Grade 3 GU toxicity and no Grade 3 GI
toxicity reported.
Comparison
A total of 791 articles were returned by the Medline
search, of which 517 were during or after 2005. There
were eight contemporary published Australian studies
suitable for comparison, with six reporting high-dose
rate brachytherapy (HDRB) outcomes,5–10 one reporting
open prostatectomy (OP) outcomes5 and one reporting
robotic-assisted radical laparoscopic prostatectomy
(RALP) outcomes.4 One low-dose rate brachytherapy
(LDRB) series was also found in the online journal.11 The
surgical series both reported HR prostate patients only.
One dose-escalated IMRT study was found; however, it
did not report the use of daily image guidance and
patients did not appear to have fiducial markers
inserted.12 Results of HDRB studies are shown in Table 2
and Figure 1; results of surgical series are shown in
Table 3 and Figure 2. Results of the LDRB study are
shown in Table 4 and Figure 3.
For the HDRB series, the median reported actuarial
5-year bDFS was 82.5% (range 79.8–85.1%), the MFS
was 90% (reported in only one study) and the median
PCaSS was 96.5% (range 96–96.9%). For the surgical
series, only one reported 5-year bDFS,5 which was 66%.
Although prostate cancer metastases and deaths did
occur in this study, actuarial 5-year MFS and PCaSS were
not reported. The LDRB series,11 which contained predominantly low-risk patients, reported overall 5-year
bDFS of 91.9%. MFS and PCaSS were not reported.
When limited to the comparison of the IR patients,
5-year bDFS as measured from the figures was 85%.
© 2015 The Royal Australian and New Zealand College of Radiologists
Modern EBRT has evolved rapidly due to technological
and engineering advances, resulting in higher doses of
radiation being delivered more accurately, and lower
doses to surrounding normal tissues. This has resulted in
higher cure rates with low toxicity. Many centres have
embraced modern advances in EBRT, with over 90% of
NSW centres using IMRT.22
Despite this high uptake, there has been no published
Australian series evaluating the results of DE-IMRT using
daily image guidance. A recent study investigating Australian radiation oncologist treatment practices for
patients with HR disease23 highlighted the need for Australian perspectives in light of the varied practices
throughout the country. In addition, there is a distinct
lack of published data internationally evaluating the
long-term follow-up of patients treated with DE-IG-IMRT
combined with ADT, with authors emphasising the ‘critical need’ for more data for this combination.24 The lack
of Australian data could conceivably contribute to a perception in Australia that localised prostate cancer is
better treated by surgery or brachytherapy, with at least
some Australian authors claiming the superiority of
HDRB over EBRT.10
Our series of 675 patients with IR and HR prostate
cancer treated with DE-IG-IMRT and ADT is one of
Australia’s largest contemporary institutional series of
patients treated for localised prostate cancer. Other
large Australian studies, such as the RADAR study25 and
TROG 96.01,26,27 use what would now be considered as
outdated radiotherapy techniques. These randomised
trials used doses as low as 66 Gy of radiotherapy,
without IMRT or daily image guidance. In addition, the
mainly HR patients in TROG 96.01 received a maximum
of 6 months androgen deprivation. RADAR has not yet
published efficacy results; however, TROG 96.01 has
published 5-year26 and 10-year27 results. Direct comparison to our series is difficult, given that the TROG 96.01
actuarial 5-year results are only presented in graphical
format. However, these graphs show lower PCaSS and
higher distant failure rates than in the present series.
The reasons for the better results in our series are likely
multifactorial, but may be partly due to dose escalation,
daily image guidance to reduce geographical miss and
the use of longer-term ADT for HR patients. All HR
patients in our series received adjuvant ADT, which was
used variably in the comparator studies. The use of ADT
in the setting of dose escalation is somewhat controversial. There is high-level data supporting its use in IR
and HR patients with conventional doses of radiotherapy,28 with conflicting data for its use when dose
escalating.24,29–31 However, several international series of
dose-escalated EBRT combined with ADT have excellent
results, similar to ours.24,31,32 For example, Zapatero
et al.’s series of 306 HR patients treated with 78 Gy
EBRT combined with ADT reported 89.5% 5-year bDFS.32
127
128
344
253
196
101
90
79
Khor et al.10
Izard et al.7
Zwahlen et al.8
Whalley et al.9
Savdie et al.5
Barkati et al.6
HDR + EBRT
HDR
HDR + EBRT
HDR + EBRT
PDR + EBRT
HDR + EBRT
DE-IG-IMRT
Modality
Adj 100%
Neo 9%
Neo 95%
Adj 14%
Neo 100%
Adj 21.5%
Neo 100%
Adj NR
Neo 59%
Adj 13%
Neo 100%
Adj 50.4%
ADT
HR 100%
LR and IR
(% NR)
LR 15%
IR 49%
HR 36%
LR 4.5%
IR 45.5%
HR 50.0%
IR 65%
HR 36%
IR 59%
HR 41%
IR 49.6%
HR 50.4%
Risk
groups
94.5
39.5
56
66
74
58
59
Median
follow-up
(months)
NR
(4 year overall 85%)
(4 year IR 95%, HR 66%)
79.6%
85.1%
Overall 82.5%
Overall 84%
IR 90%, HR 71%
Overall 93.3%
IR 95.5%, HR 91.3%
(4 year overall 95.7%)
(4 year IR 97.2%, HR 94.2%)
Overall 79.8%
5-year bDFS
(Phoenix)
NR
NR
NR
NR
NR
90.0%
96.9%
IR 99.0%
HR 94.9%
5-year
MFS
100%
NR
NR
96.9%
96%
NR
98.8%
IR 100%
HR 97.7%
5-year
PCaSS
11.8% stricture
GI NR
(stricture, retrospective)
6% GU
0% GI
(RTOG 6 year)
7.1% GU
0% GI
(RTOG 5 year)
2% GU
0% GI
CTCAE at 4 years
NR
>10.3% GU
0% GI
(CTCAE 3 months post RT)
0.3% GU
0% GI
(CTCAE 5 years)
Grade 3 late
toxicity
Adj, adjuvant ADT; ADT, androgen deprivation therapy; bDFS, biochemical disease-free survival; DE, dose escalation; EBRT, external-beam radiotherapy; GI, gastrointestinal; GU, genitourinary; HR, high
risk; IG, image guidance with fiducial markers; IMRT, intensity-modulated radiotherapy; IR, intermediate risk; LR, low risk; MFS, metastasis-free survival; Neo, neoadjuvant ADT; NR, not reported; PCaSS,
prostate cancer-specific survival.
675
Patients
Current NCCI series
Author
Table 2. Comparison between NCCI series and published Australian brachytherapy series
SW Wilcox et al.
© 2015 The Royal Australian and New Zealand College of Radiologists
1.0
1.0
DE-IG-IMRT (NCCI series, 2014)
0.9
Biochemical disease-free survival
Biochemical disease-free survival
Is modern radiotherapy still viable?
HDRB (Barkati et al.6)
0.8
HDRB (Khor et al.10)
0.7
0.6
0.5
HDRB (Zwahlen et al.8)
0.4
0.3
0.2
0.1
0
0
636
448
0.8
0.7
0.6
0.5
Open prostatectomy
(Savdie et al.5)
0.4
Robotic prostatectomy
(Connolly et al.4)
0.3
0.2
0.1
0
12 24 36 48 60 72 84 96 108 120
Months
Number at risk 675 675
(NCCI)
DE-IG-IMRT
(NCCI series, 2014)
0.9
0
12 24 36 48 60 72 84 96 108 120
122
Months
Fig. 1. Overall 5-year outcomes for intermediate- and high-risk patients
treated with DE-IG-IMRT and HDRB. DE, dose escalation; IG, image guidance
with fiducial markers; IMRT, intensity-modulated radiotherapy; HDRB, highdose rate brachytherapy.
It is not possible to determine individual contributions of
modern DE-EBRT techniques and ADT to these excellent
results, and this is an area requiring further research.
At 5 years, our series of modern EBRT and ADT has
results comparing very favourably with modern Australian series of brachytherapy and surgery, although
direct statistical comparison is obviously impossible for a
number of reasons. Firstly, in the absence of a prospective, randomised study, there is no way to adequately
control for bias (e.g. in patient selection) that is inherent
in institutional series (with the least favourable patients
tending to receive EBRT). Definitions of PSA failure differ
between series, but unfortunately harder endpoints,
such as MFS and PCaSS, are inconsistently reported.
However, even these endpoints are affected by how hard
one searches for metastatic failure and how (and
whether) failures were treated. In addition, the comparator series measure follow-up from different time
Number at risk 340
(NCCI)
340
318
208
Fig. 2. High-risk patients treated with DE-IG-IMRT (NCCI series, 2014), open
prostatectomy (Savdie et al.)5 and robotic-assisted radical prostatectomy
(Connolly et al.4). DE, dose escalation; IG, image guidance with fiducial markers;
IMRT, intensity-modulated radiotherapy.
points, including the start of treatment and end of radiotherapy. We have elected to use the most accurate time
point, the start of treatment, as recommended by
Denham et al. in the analysis of TROG 96.01.21 If measured from the end of radiotherapy, our 5-year bDFS was
92.5% (vs. 93.3%), and differences in survival curve
comparisons are barely discernible.
Many of the issues affecting comparisons can only be
adequately addressed by prospective randomised trials,
and strong conclusions claiming the superiority of one
treatment over another should be avoided. Although this
seems self-evident, several authors have used the
results of non-randomised, retrospective comparisons to
claim the superiority of surgery33 and brachytherapy34
over other treatments.
One example is the recent non-randomised observational study by Sooriakumaran et al.,33 which has a
Table 3. Comparison of high-risk patients treated with DE-IG-IMRT, open prostatectomy (OP), robotic-assisted laparoscopic radical prostatectomy (RALP)
Author
Patients
Technique
Risk group
Median follow-up (months)
Current NCCI series
DE-IG-IMRT
Connolly et al.4
340
IG-IMRT + ADT
High risk
59
160
High risk
26.2
Savdie et al.5
153
RALP 100%
Neo ADT 5%
Adj ADT 40%
Adj EBRT NR
OP 100%
Adj EBRT 15%
Adj ADT 16%
High risk
95.3
5-year bDFS
5-year MFS
5-year PCaSS
91.3%
(3 years, 95.8%)
NR
(3 years, 45%)
94.9%
(3 years, 97.3%)
NR
(3 years, NR)
97.7%
(3 years, 99.7%)
NR
(3 years, 100%)
65.5%
NR
NR
Adj, adjuvant; ADT, androgen deprivation therapy; bDFS, biochemical disease-free survival; EBRT, external beam radiotherapy; IG, image guidance with
fiducial markers; IMRT, intensity-modulated radiotherapy; MFS, metastasis-free survival; Neo, neoadjuvant; NR, not reported; PCaSS, prostate cancerspecific survival.
© 2015 The Royal Australian and New Zealand College of Radiologists
129
SW Wilcox et al.
Table 4. Comparison of intermediate-risk patients treated with DE-IG-IMRT and LDRB
Author
Current NCCI series
DE-IG-IMRT
Yuen et al.11
Patients
Technique
Risk group
335
IG-IMRT + ADT
Intermediate risk
96
LDR
Neo ADT 43.8%
Intermediate risk
Median follow-up (months)
5-year bDFS
5-year MFS
5-year PCaSS
59
95.5%
99%
100%
66.3
85%†
NR
NR
†Estimated. ADT, androgen deprivation therapy; DE, dose escalation; IG, image guidance with fiducial markers; IMRT, intensity-modulated radiotherapy;
LDRB, low-dose rate brachytherapy; NR, not reported.
Biochemical disease-free survival
median follow-up of 5.37 years and concludes that there
may be a survival benefit for surgery over radiotherapy.
This study has been heavily criticised by urologists and
radiation oncologists alike due to selection bias putting
surgery at an advantage,35 unbalanced patient groups
favouring surgery,35,36 lack of standardised staging,36
outdated radiotherapy techniques,36 lack of optimal
ADT,36 lack of standardised (or any evaluation of)
salvage therapy36 and the paper containing major
errors.37 Not surprisingly, the comparison has been
described as ‘flawed’,38 and the conclusions as ‘scientifically untenable’.37 Unfortunately, we are unable to
compare our results to this Swedish cohort due to their
lack of actuarial reporting.
Another recent comparison34 attempts a large-scale
literature review of PSA outcomes across differing treatments, and again highlights the difficulties of comparative studies. Grimm et al.34 did not report actuarial
5-year results, instead graphically displayed standard
deviation ‘ellipses’ of published results, with no other
statistical comparisons. Grimm et al. concludes that
DE-IG-IMRT
(NCCI series, 2014)
1.0
0.8
LDR
(Yuen et al.11)
0.6
0.4
0.2
0
0
Number at risk 335
(NCCI)
12
335
24
36
Months
318
48
60
72
240
Fig. 3. Intermediate-risk patients treated with DE-IG-IMRT (NCCI series, 2014)
and LDR brachytherapy (Yuen et al.11). DE, dose escalation; IG, image guidance
with fiducial markers; IMRT, intensity-modulated radiotherapy; LDR, low-dose
rate.
130
brachytherapy (with or without EBRT) is superior to
surgery or EBRT alone. However, this paper has also
been criticised as it excluded valid studies (e.g. Zapatero
et al.’s series32), double counted some studies, used
erroneous methodology and incorrectly presented
data.39 In addition, the authors have not accounted for
selection bias, unbalanced patient groups, differences in
staging and salvage therapy, radiotherapy dose, or ADT
use. Unsurprisingly, the study has been described as
‘biased’ and failing to ‘provide evidence-based prostate
cancer treatment comparisons’.39 Although it is difficult
to directly compare, our 5-year actuarial results appear
to be better than Grimm et al.’s34 reported studies of
surgery, brachytherapy and EBRT. Zapatero et al.’s
results using DE-EBRT and ADT32 would also have been
superior to these other modalities.
There are several other limitations of our study. As
mentioned, not all published series report better endpoints, such as MFS or cancer-specific survival, and
certainly this could improve comparisons. Longer-term
data, such as 10- and 20- year outcomes, are also
required, and this has been lacking for radiotherapy
series in general. Survival curves were compared after
standardising axes. This may not be as precise as generating comparative curves from raw data; it is,
however, a reasonable means of representing published
series along with the actuarial outcomes presented in our
Tables. Toxicity outcomes are even more difficult to
compare across studies due to variations in recording
and reporting, and this issue has been noted by others.7
With regard to toxicity, although we report physicianreported toxicity, we do not report patient-reported outcomes (although we have previously done so in terms of
decision-regret40). This limitation is shared by all but
one6 of the comparator studies we identified, and highlights the need for clinicians to address this important
aspect of patient care. We also do not report ADTspecific toxicity (although we again have done so previously in terms of ADT-specific decision-regret40).
Unfortunately, ADT toxicity has not been reported in any
of the other studies identified for our comparison despite
the use of ADT in all of them.
Although we report low levels of toxicity, we do not
believe a comparison with the other studies is valid for
several reasons. We report prevalence rates at 5 years,
© 2015 The Royal Australian and New Zealand College of Radiologists
Is modern radiotherapy still viable?
whereas the other studies variably report prevalence
and actuarial rates. The scoring systems used are different, with variation in prospective versus retrospective
scoring. It is also likely that variation in scoring will occur
depending on who scores toxicity, and this has not been
standardised in any study. In our series, toxicity was
prospectively scored by either the treating radiation
oncologist or registrars. Nonetheless, our toxicity rates
are low at 5 years, and are mirrored in the very low
levels of decision-regret reported.40 Decision-regret is a
patient-centred outcome reflecting patients’ perceptions
of outcomes, including toxicity, quality of life and cure.
Only 3.8% of our patients expressed decision-regret,
whereas regret for other modalities, such as surgery,
have been reported to be as high as 53%.41
The low levels of toxicity we report may be due to a
number of factors. Image guidance allows reduced
margins and superior organ sparing during EBRT. This
has been shown to result in lower toxicity, whether
utilising DE-IG-IMRT42 or three-dimensional conformal
radiotherapy.43 In addition, our patients received planning MRI, with MRI-CT fusion to aid volume definition.20
This has been shown to reduce the volume of the clinical
target volume by up to 31%, reducing rectal dose and
presumably reducing toxicity.44 Furthermore, the use of
ADT allows cytoreduction of prostatic volume (reducing
treatment volume), with ADT itself postulated to provide
protective effects from radiation toxicity.45,46 We also
have a policy of optimising urinary and bowel function
prior to radiotherapy through urology and gastroenterology review if baseline symptoms are present. This
ensures that functionality is maximised prior to treatment, with any symptoms appearing after radiotherapy
addressed and managed as soon as detected.47 We have
found that stringent investigation of presumed late radiotherapy toxicity often determines that radiotherapy is not
the cause of symptoms.47 The temporality of radiation
toxicity reporting may also be a significant factor, with
late radiation toxicity frequently reducing with longer
follow-up.48,49 The fact that all of the late toxicities in our
cohort were only reported at 5 years post-radiotherapy
may contribute to the excellent toxicity rates seen. The
TROG 03.04 RADAR study of radiotherapy and ADT similarly supports the reduction in radiation-related toxicity
with longer follow-up.25 Prevalence rates of urinary toxicity were low in their study, with 2.6% of patients
experiencing Grade 2 toxicity at 18 months, and reducing
to 1.7% at 36 months. Rectal toxicity levels were higher,
with greater than Grade 1 dysfunction in 15.4% at end of
radiotherapy and 18.1% at 36 months. That study was
performed prior to widespread use of image guidance,
MRI-CT fusion and IMRT, which may account for some of
the differences between series.
Despite the limitations, it is clear that modern EBRT
techniques using DE, MRI-CT fusion, daily IG with
fiducial markers and IMRT, combined with ADT, offers an
excellent alternative to surgery and brachytherapy.
© 2015 The Royal Australian and New Zealand College of Radiologists
Ongoing developments such as volumetric arc therapy
(VMAT) and intra-fraction motion compensation may
further improve results. National guidelines18 and
patient-information booklets19 are still valid when discussing EBRT as an equivalent option for localised prostate cancer. Due to the rapid engineering and
technological advances underpinning EBRT, the physician best able to discuss modern EBRT is a radiation
oncologist. This is consistent with the view expressed by
the Cancer Council Australia that ‘different specialists are
better able to explain their own treatments’.19 It seems
essential that all patients with localised prostate cancer
should be referred to a radiation oncologist.
Conclusion
Modern DE-IG-IMRT and ADT offer clinical outcomes as
efficacious as alternative treatment modalities, and
should be discussed with all patients considering definitive treatment options for localised prostate cancer.
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