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The decreased use of brachytherapy boost for intermediate and high-risk prostate cancer despite evidence supporting its effectiveness


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The Canadian Androgen Suppression Combined with Elective Nodal and Dose Escalated Radiation Therapy (ASCENDE-RT) randomized trial showed that brachytherapy boost reduces recurrence by 50% compared to dose-escalated radiation. We examined how men with identical inclusion criteria to the ASCENDE-RT trial were being treated in the United States. We used the National Cancer Database to identify prostate cancer patients treated with radiation from 2004 through 2012 who met the inclusion criteria of the ASCENDE-RT trial (intermediate-/high-risk prostate cancer, excluding patients with prostate-specific antigen >40 or tumor stage T3b/T4). The Mantel–Haenszel test was used to investigate the trend for type of radiation modality used over the study period. A cohort of 156,411 patients was identified. Of those, 103,188 men (66%) were treated with external beam radiation therapy (EBRT) alone, 31,129 (20%) with brachytherapy alone, and 22,094 (14%) with EBRT plus brachytherapy. EBRT plus a brachytherapy boost demonstrated a significant decrease in utilization from 2004 to 2012 in both academic and nonacademic centers, declining from 15% to 8% in academic centers and from 19% to 11% in nonacademic centers (_p_-Value for trend <0.0001 for both). Academic centers were significantly less likely to use brachytherapy boost than nonacademic centers (adjusted odds ratio: 0.68; 95% confidence interval: 0.66–0.70; _p_-Value: <0.0001). Radiation oncology practices have demonstrated a significant reduction in the use of brachytherapy boost from 2004 to 2012, and the lowest utilization was in academic centers. In light of the superior results demonstrated for brachytherapy boost by the ASCENDE-RT trial, it is unclear whether academic centers are prepared to train the next generation of residents in this critical modality.
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The decreased use of brachytherapy boost for intermediate and high-risk
prostate cancer despite evidence supporting its effectiveness
Peter F. Orio III
*, Paul L. Nguyen
, Ivan Buzurovic
, Daniel W. Cail
, Yu-Wei Chen
Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women’s Hospital, Boston, MA
Harvard Medical School, Boston, MA
ABSTRACT PURPOSE: The Canadian Androgen Suppression Combined with Elective Nodal and Dose Esca-
lated Radiation Therapy (ASCENDE-RT) randomized trial showed that brachytherapy boost
reduces recurrence by 50% compared to dose-escalated radiation. We examined how men with
identical inclusion criteria to the ASCENDE-RT trial were being treated in the United States.
METHODS AND MATERIALS: We used the National Cancer Database to identify prostate can-
cer patients treated with radiation from 2004 through 2012 who met the inclusion criteria of the
ASCENDE-RT trial (intermediate-/high-risk prostate cancer, excluding patients with prostate-
specific antigen O40 or tumor stage T3b/T4). The ManteleHaenszel test was used to investigate
the trend for type of radiation modality used over the study period.
RESULTS: A cohort of 156,411 patients was identified. Of those, 103,188 men (66%) were treated
with external beam radiation therapy (EBRT) alone, 31,129 (20%) with brachytherapy alone, and
22,094 (14%) with EBRT plus brachytherapy. EBRT plus a brachytherapy boost demonstrated a
significant decrease in utilization from 2004 to 2012 in both academic and nonacademic centers,
declining from 15% to 8% in academic centers and from 19% to 11% in nonacademic centers
(p-Value for trend !0.0001 for both). Academic centers were significantly less likely to use
brachytherapy boost than nonacademic centers (adjusted odds ratio: 0.68; 95% confidence interval:
0.66e0.70; p-Value: !0.0001).
CONCLUSIONS: Radiation oncology practices have demonstrated a significant reduction in the use
of brachytherapy boost from 2004 to 2012, and the lowest utilization was in academic centers. In light
of the superior results demonstrated for brachytherapy boost by the ASCENDE-RT trial, it is unclear
whether academic centers are prepared to train the next generation of residents in this critical modality.
Ó2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.
Keywords: Prostate cancer; Brachytherapy boost; National cancer database; ASCENDE-RT; Radiation therapy
The recently reported ASCENDE-RT trial explored the
use of 1 year of androgen deprivation therapy and external
beam radiation therapy (EBRT) to the pelvis, prostate,
and seminal vesicles followed by randomization to dose-
escalated EBRT or a low-dose-rate permanent transperineal
interstitial brachytherapy boost to the prostate for
intermediate- and high-risk prostate cancer (1). The addi-
tion of a low-dose-rate prostate brachytherapy boost re-
sulted in almost a 50% reduction in prostate-specific
antigen (PSA) progression-free survival (PFS) compared
to dose-escalated EBRT and an absolute difference in
PSA PFS at 9 years of almost 20% (1). This trial has the
potential to significantly change how higher risk prostate
cancer patients are treated. The importance of biochemical
control cannot be underestimated in prostate cancer treat-
ments, as it triggers a cascade of events that reduce quality
of life and that have high economic cost (2e5).
Although the ASCENDE-RT trial is not yet published,
the abstract and multiple oral presentations are convincing.
Given the proven benefit of this brachytherapy boost trial,
we sought to examine the national practice patterns for
radiation-managed men with prostate cancer who fit the
Received 10 April 2016; received in revised form 4 May 2016;
accepted 9 May 2016.
Conflict of interest: PLN, MD, consulted for Medivation, Ferring,
Genome DX, and Nanobiotix.
* Corresponding author. Department of Radiation Oncology, Dana-
Farber Cancer Institute, Brigham and Women’s Hospital, 75 Francis St.,
Boston, MA 02115. Tel.: 781-624-4700; fax: 781-624-4710.
E-mail address: (P.F. Orio).
1538-4721/$ - see front matter Ó2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.
Brachytherapy -(2016) -
inclusion criteria of the ASCENDE-RT trial. Therefore, we
analyzed the National Cancer Database (NCDB) to
examine the use of brachytherapy boost among men with
the same inclusion criteria as patients in the ASCENDE-
RT trial from 2004 to 2012.
Methods and materials
Study population
We used the NCDB, a joint program of the Commission
on Cancer and the American Cancer Society, to select our
study population. NCDB is a hospital-based nationwide
database which captures 70% of newly diagnosed cancer
cases and is the largest cancer registry (6). We identified pa-
tients diagnosed with nonmetastatic prostate adenocarci-
noma between 2004 and 2012, further selecting patients
who met the inclusion criteria of the ASCENDE-RT trial
(1) (i.e., patients diagnosed with NCCNs intermediate-
and high-risk disease and excluded patients whose PSA
O40 or tumor stage was T3b or higher). We further
selected patients who received radiation therapy as the
definitive treatment. Our institutional review board
approved this study.
Primary end point and covariates
We aimed to investigate the trend of radiation modalities
for the period 2004 to 2012. The treatment modalities were
categorized as EBRT alone, brachytherapy alone, or EBRT
plus brachytherapy boost. The trend analysis was stratified
by the center type (academic/research program was defined
as academic, comprehensive community cancer center,
community cancer center and others were defined as nonac-
ademic). Other covariates included in this study were socio-
demographic variables such as age ($65, !65), race,
insurance status, year of diagnosis, household income, resi-
dence type, and the percent of education level less than
high school for each patient’s area of residence; clinical
variables included tumor stage (American Joint Committee
on Cancer sixth edition), PSA (coded as!10, 10e20, O20),
Gleason score (#6, 7, 8e10), and CharlsoneDeyo comor-
bidity score (0, 1, $2). The income (7) and education (8)
information were quartiles among all the U.S. zip codes
and were based on the 2012 U.S. census data; the residence
type (9) was determined with the 2003 USDA Economic
Research Service. All the information in our analysis was
provided by the NCDB.
Statistical analysis
The baseline patients’ characteristics were presented
with descriptive statistics and compared with chi-square
test as appropriate. ManteleHaenszel test was used to
investigate the trend for radiation modalities over the study
Table 1
Patient baseline characteristics
70%) p-Value
Radiation modality (%)
EBRT alone 33,846 (72.4) 69,342 (63.2)
Brachytherapy alone 7551 (16.2) 23,578 (21.5)
EBRT þBrachy therapy 5368 (11.5) 16,726 (15.3)
Year of diagnosis !0.0001
2004e2006 14,781 (31.6) 38,292 (34.9)
2007e2009 15,524 (33.2) 37,268 (34.0)
2010e2012 16,460 (35.2) 34,086 (31.1)
Age !0.0001
!65 14,716 (31.5) 29,563 (27.0)
$65 32,049 (68.5) 80,083 (73.0)
Race !0.0001
Non-Hispanic White 32,910 (70.4) 86,025 (78.5)
Black 9309 (20.0) 15,489 (14.1)
Hispanic White 1763 (3.8) 3998 (3.7)
Other 1827 (3.9) 2949 (2.7)
Unknown 956 (2.0) 1185 (1.1)
PSA !0.0001
!10 31,878 (68.2) 73,289 (66.8)
10e20 11,139 (23.8) 27,394 (25.0)
O20 3748 (8.0) 8963 (8.2)
Gleason Score !0.0001
#6 7063 (15.1) 19,459 (17.8)
7 28,944 (61.9) 65,252 (59.5)
8e10 10,758 (23.0) 24,935 (22.7)
Tumor stage !0.0001
T1 27,464 (58.7) 63,015 (57.5)
T2 18,017 (38.5) 44,619 (40.7)
T3a 1284 (2.8) 2012 (1.8)
Charlson comorbidity score !0.0001
0 41,476 (88.7) 94,730 (86.4)
1 4,487 (9.6) 12,529 (11.4)
2þ802 (1.7) 2387 (2.2)
Insurance status !0.0001
None 955 (2.0) 1205 (1.1)
Private 16,418 (35.1) 33,848 (30.9)
Medicaid 1366 (2.9) 2340 (2.1)
Medicare 25,506 (54.5) 68,586 (62.6)
Other 1391 (3.0) 2241 (2.0)
Unknown 1129 (2.4) 1426 (1.3)
Income !0.0001
!$38,000 8007 (17.1) 19,427 (17.7)
$38,000e47,999 8781 (18.8) 27,245 (24.9)
$48,000e62,999 11,594 (24.8) 29,082 (26.5)
$63,000 17,813 (38.1) 32,074 (23.3)
Unknown 570 (1.2) 1818 (1.7)
Education !high school !0.0001
$21% 7217 (15.4) 18,059 (16.5)
13e20.9% 11,227 (24.0) 28,334 (25.8)
7e12.9% 14,304 (30.6) 36,637 (33.4)
!7% 13,471 (28.8) 24,833 (22.7)
Unknown 546 (1.2) 1747 (1.6)
Residence !0.0001
Metropolitan 40,720 (87.1) 82,208 (75.0)
Urban 4247 (9.1) 20,651 (18.8)
Rural 506 (1.1) 3150 (2.9)
Unknown 1292 (2.8) 3637 (3.3)
EBRT 5external beam radiation therapy; PSA 5prostate-specific
2P.F. Orio et al. / Brachytherapy -(2016) -
period. Multivariable logistic regression analysis was used
to identify the independent predictors for treatment with
EBRT plus brachytherapy boost vs. treatment with EBRT
alone or brachytherapy alone. All statistical analyses were
performed using SAS version 9.4. (SAS Institute Inc., Cary,
NC). We used a two-sided p-Value !0.05 in all analyses as
criteria for statistical significance.
Baseline characteristics stratified on academic vs.
nonacademic centers
Our study cohort consisted of 156,411 radiation-treated
prostate cancer patients. A total of 103,188 patients
(66%) were treated with EBRT alone, 31,129 (20%) were
treated with brachytherapy alone, and 22,049 (14%) were
treated with EBRT with brachytherapy boost. A total of
46,765 patients (30%) were treated at academic centers,
and 109,646 patients (70%) were treated at nonacademic
centers. Patient sociodemographic and clinical characteris-
tics stratified by center type are summarized in Table 1.
Trend of use of EBRT with brachytherapy boost
From 2004 to 2012, there was a steady rise in the use of
EBRT alone in both academic and nonacademic centers,
increasing from 66% to 80% and 56% to 72%, respectively;
during this same period, there was a steady decline in
brachytherapy alone being offered in academic and nonaca-
demic centers from 19% to 12% and 25% to 17%, respec-
tively. The use of EBRT and a brachytherapy boost
demonstrated the lowest utilization in this time period in
both academic and nonacademic centers from 15% to 8%
and 19% to 11%, respectively ( p-Value for trend !0.0001
for both academic and nonacademic hospitals). Academic
centers treated this patient cohort significantly more with
EBRT than with EBRT and a brachytherapy boost.
Figure 1 graphs the utilization rates over time.
Predictors for EBRT with brachytherapy boost
In the multivariable logistic regression model, patients
diagnosed from 2007 to 2009 (adjusted odds ratio
[AOR]: 0.72; 95% confidence interval [CI]: 0.69e0.74;
p-Value!0.0001) and 2010 to 2012 (AOR: 0.52; 95% CI:
0.50e0.54; p-Value!0.0001) were less likely to receive
EBRT plus brachytherapy boost than patients from 2004
to 2006. Compared with nonacademic centers, academic
centers were less likely to offer EBRT plus brachytherapy
boost (AOR: 0.68; 95% CI: 0.66e0.70; p-Value: !0.0001).
Patients with higher Gleason score, higher tumor
stage, black, or household income$75th percentile (i.e.,
$63,000) were more likely to receive EBRT plus brachy-
therapy boost, whereas patients age $65 years, with Charl-
son comorbidity score $2, nonprivate insurance status,
living in urban or rural areas were all less likely to receive
EBRT plus brachytherapy boost (Table 2).
Analysis of the largest cancer database in the United
States found a significant decrease in the use of brachyther-
apy boost between 2004 and 2012 in the contemporary
population. Our results are consistent with earlier studies
(10, 11) and demonstrate that the United States is experi-
encing historic lows in the use of prostate brachytherapy
both as monotherapy and in the boost setting.
This finding is concerning as the randomized clinical
Phase 3 ASCENDE-RT trial (1) has shown a significant
PSA PFS benefit of adding a brachytherapy boost to EBRT
in treating intermediate- and high-risk prostate cancer
when compared to omitting brachytherapy in favor
Fig. 1. Trend of radiation modality use in 2004e2012. E, external beam radiation therapy; B, brachytherapy; E þB, external beam radiation
therapy þbrachytherapy boost.
3P.F. Orio et al. / Brachytherapy -(2016) -
of dose-escalated EBRT strategies. In addition to the
ASCENDE-RT trial, Hoskin et al. (12) also reported
improved biochemical and clinical relapse-free survivals
with the addition of a high-dose-rate brachytherapy boost
as a dose escalation strategy in higher risk patients. There
is also a large body of single institution and retrospective
data supporting dose escalation in higher risk patients
(13e16). Sylvester et al. (17) reported the 15 year biochem-
ical relapse-free survival of combined modality treatment by
risk group with excellent outcomes demonstrated in the
intermediate- and high-risk groups, 80.3% and 67.8%,
respectively. Dattoli et al. (18, 19) report similar results with
biochemical control of 82% in the intermediate-risk group
and 72% in the high-risk group at 14 years. Of grave concern
is that the rates of prostate brachytherapy utilization, both
monotherapy and in the boost setting, are decreasing in favor
of dose-escalated EBRT (10, 11), despite data suggesting
that this may not be the optimal treatment strategy, espe-
cially for higher risk patients (15, 17, 18, 20e23).
The trend toward underutilization of a brachytherapy
boost is even more prominent in academic centers, where
most of the nation’s residents are expected to receive
specialized training in these procedures. Radiation
oncology residents must emerge from their training pro-
grams comfortable and proficient in this cost-effective
and efficacious procedure while also being well versed in
this procedure as both a monotherapy and as a boost sec-
ondary to EBRT, as there are nuanced differences intrinsic
to each. The ASCENDE-RT (1) trial has reported a greater
urinary stricture rate with brachytherapy boost, which was
also seen in a CaPSURE database review (24); however,
the incidence is less than what has been reported for pros-
tatectomy and the literature suggests brachytherapy tech-
niques can be modified to further reduce this risk
(25, 26). This reinforces the critical need for academic pro-
grams to provide high case volumes and intense training in
brachytherapy techniques for their trainees.
Given the Level 1 evidence demonstrating a benefit to
the addition of a brachytherapy boost for intermediate-
and high-risk prostate cancer, current utilization trends will
need to reverse. Although an overall survival benefit has yet
to be reported, the biochemical control benefit at 9 years is
striking (1). Given the cascade of events creating a signifi-
cant quality of life reduction and economic cost that are
triggered in the event of biochemical failure, every effort
must be made to provide appropriate training opportunities
to the next generation of residents and leaders. The most
logical place to start is within residency training programs,
most often found at academic centers. Strategies are there-
fore needed to allow academic centers to bring forth the
necessary training and education required for residents to
be proficient in prostate brachytherapy in all settings. Addi-
tional training opportunities must also be brought forth to
our wider membership in the future.
In the early years of prostate brachytherapy, many resi-
dents and physicians learned the techniques of the proce-
dure first through lecture, followed by the implantation of
prostate phantoms before performing the procedure live.
MD Anderson Cancer Center published on the utilization
of a prostate brachytherapy simulator in their residency
program suggesting that it may be possible to incorporate
prostate brachytherapy simulators into academic programs
across the country (27). Surgical training programs in our
Table 2
Multivariable logistic regression for receipt of EBRT brachytherapy boost
Category AOR (95% CI) p-Value
Year of diagnosis
2004e2006 Ref
2007e2009 0.72 (0.69e0.74) !0.0001
2010e2012 0.52 (0.50e0.54) !0.0001
Hospital type
Nonacademic Ref
Academic 0.68 (0.66e0.70) !0.0001
!65 Ref
$65 0.61 (0.58e0.63) !0.0001
Non-Hispanic White Ref
Black 1.06 (1.01e1.11) 0.01
Hispanic White 0.90 (0.83e0.98) 0.01
Other 1.33 (1.23e1.44) !0.0001
!10 Ref
10e20 0.91 (0.88e0.94) !0.0001
O20 0.80 (0.75e0.84) !0.0001
Gleason Score
#6 Ref
7 1.81 (1.72e1.89) !0.0001
8e10 1.90 (1.80e2.00) !0.0001
Tumor stage
T1 Ref
T2 1.14 (1.11e1.18) !0.0001
T3a 1.54 (1.41e1.69) !0.0001
Charlson comorbidity score
0 Ref
1 1.09 (1.04e1.14) 0.0003
2þ0.79 (0.70e0.89) !0.0001
Insurance status
Private Ref
None 0.46 (0.39e0.54) !0.0001
Medicaid 0.61 (0.55e0.68) !0.0001
Medicare 0.87 (0.84e0.91) !0.0001
Other 0.44 (0.39e0.50) !0.0001
!$38,000 Ref
$38,000e47,999 1.05 (0.99e1.11) 0.055
$48,000e62,999 1.00 (0.94e1.05) 0.91
$63,000 1.26 (1.18e1.33) !0.0001
Education !high school
$21% Ref
13e20.9% 0.96 (0.92e1.01) 0.14
7e12.9% 0.98 (0.93e1.04) 0.47
!7% 0.99 (0.94e1.06) 0.86
Metropolitan Ref
Urban 0.83 (0.79e0.86) !0.0001
Rural 0.70 (0.62e0.78) !0.0001
AOR 5adjusted odds ratio; CI 5confidence interval; EBRT 5
external beam radiation therapy; PSA 5prostate-specific antigen.
4P.F. Orio et al. / Brachytherapy -(2016) -
country are increasingly using surgical simulators to train
residents in a safe environment that compensates for
varying caseloads and decreased training hours (28).By
practicing surgical procedures on a simulator, resident sur-
geons accelerate their learning curve and are more profi-
cient in their skills once they begin live surgical cases
with their attending physicians providing guidance (28).
To bring prostate brachytherapy training to a wider audi-
ence, training opportunities exist through the American
Brachytherapy Society and at the annual meeting of the
American Society for Radiation Oncology, which also pro-
vides hands on simulator training courses in conjunction
with the American Brachytherapy Society.
Since practice patterns will need to shift due to findings
of the ASCENDE-RT trial, the question becomes whether
academic centers are prepared to train the next generation
of residents in this treatment modality. A recent resident
report of brachytherapy experience in ACGME-accredited
radiation oncology training programs has demonstrated a
25% reduction in interstitial procedures from 2006 to
2011 (29). If we do not change our training environments
to align with scientific findings, one of the most effective
treatments for prostate cancer may be lost secondary to a
lack of physician training in this procedure.
Limitations of this study include that the NCDB does
not provide data for every patient treated in the United
States, but it does capture approximately 70% of patients
in this country and as such is helpful in identifying trends
in treatments over time. Second, the Charlson comorbidity
score is a summary score for comorbidity profile, and thus,
we were not able to do a more granular analysis to deter-
mine whether certain specific comorbidities were associ-
ated with brachytherapy boost omission.
Despite the ASCENDE-RT trial providing Level 1
randomized evidence for a significant improvement in
biochemical control of intermediate- and high-risk prostate
cancer with the use of EBRT plus a brachytherapy boost,
both academic and nonacademic radiation oncology prac-
tices have demonstrated a significant reduction in the use
of brachytherapy utilization from 2004 to 2012. Even more
concerning is that the lowest utilization of prostate brachy-
therapy was found in academic centers. In time, we may
lose this efficacious and cost-effective treatment from our
armamentarium if residents are deprived of appropriate
training opportunities to bring forth this procedure to the
next generation of patients.
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6P.F. Orio et al. / Brachytherapy -(2016) -
... This pattern of higher BT utilisation in patients with higher income or socioeconomic group have 232 been previously reported in the US (7,11). This may reflect patients' access to medical (Table-3). ...
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Background and purpose We aimed to evaluate utilisation of brachytherapy (BT) boost in men who had external beam radiation therapy (EBRT) for prostate cancer, and to compare patient-reported functional outcomes (PRO) following each approach in a population-based setting in Australia. Materials and methods This is a population-based cohort of men with localised prostate cancer enrolled in the Victorian Prostate Cancer Outcomes Registry, who had EBRT between 2015 and 2020. Primary outcomes were proportion who had BT-boost, and PRO (assessed using the EPIC-26 questionnaires) 12 months post-treatment. Multivariable logistic regressions were used to evaluate factors associated with BT-boost, and linear regressions were used to estimate differences in EPIC-26 domain scores between EBRT alone and EBRT+BT. Results Of the 1,626 men in the study, 88 (5.4%) had BT-boost. Factors independently associated with BT-boost were younger age, higher socioeconomic status, and treatment in public institutions. 1,555 men completed EPIC-26 questionnaires. No statistically or clinically significant differences in EPIC-26 urinary, sexual and bowel functional domain scores were observed between men who had EBRT+BT vs EBRT alone, with adjusted mean differences in urinary incontinence, urinary irritative/ obstruction, sexual, and bowel domain of 1.28 (95%CI=-3.23 to 5.79), -2.87 (95%CI=-6.46 to 0.73), 0.49 (95%CI=-4.78 to 5.76), and 2.89 (95%CI=-0.83 to 6.61) respectively. Conclusion 1-in-20 men who had EBRT for prostate cancer had BT-boost. This is the first time that PRO following EBRT+/-BT is reported at a population-based level in Australia, with no evidence to suggest worse PRO with addition of BT-boost 12 months post-treatment.
... The ASCENDE-RT trial demonstrated that compared with dose-escalated EBRT to 78 Gy, men who received a boost with LDR brachytherapy were twice as likely to be free of biochemical failure at a median follow-up of 6.5 years [7]. However, despite this category A evidence, as well as numerous prospective and retrospective studies showing improved outcomes with a brachytherapy boost, an analysis of the National Cancer Database from the years 2004-2012 reported a significant decline in the use of prostate brachytherapy at both academic and non-academic institutions, from 15% to 8%, and from 19% to 11%, respectively [8]. For this patient, we chose an LDR brachytherapy boost (instead of a high dose rate [HDR] boost) to be consistent with the ASCENDE-RT trial [7]. ...
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A 79-year-old HIV-negative Caucasian man with a medical history of smoking 20 pack-years (quit 40 years prior), early-stage non-small cell lung cancer status post-lobectomy 13 years earlier at an outside hospital without evidence of recurrence, and benign prostatic hypertrophy was diagnosed with synchronous very high-risk prostate adenocarcinoma and early-stage anal basaloid squamous cell carcinoma. He proceeded to undergo concurrent treatment for these tumors, consisting of androgen deprivation therapy, external beam radiation therapy, and a brachytherapy boost for the prostate adenocarcinoma; for the anal carcinoma, he was treated with definitive chemoradiation. Over 3.5 years since the completion of radiotherapy, he remains in clinical and biochemical remission.
Background: Patients with high-risk prostate cancer (HRPC) have multiple accepted treatment options. Because there is no overall survival benefit of one option over another, appropriate treatment must consider patient life expectancy, quality of life, and cost. Methods: The authors compared quality-adjusted life years (QALYs) and cost effectiveness among treatment options for HRPC using a Markov model with three treatment arms: (1) external-beam radiotherapy (EBRT) delivered with 20 fractions, (2) EBRT with 23 fractions followed by low-dose-rate (LDR) brachytherapy boost, or (3) radical prostatectomy alone. An exploratory analysis considered a simultaneous integrated boost according to the FLAME trial ( identifier NCT01168479). Results: Treatment strategies were compared using the incremental cost-effectiveness ratio (ICER). EBRT with LDR brachytherapy boost was a cost-effective strategy (ICER, $20,929 per QALY gained). These results were most sensitive to variations in the biochemical failure rate. However, the results still demonstrated cost effectiveness for the brachytherapy boost paradigm, regardless of any tested parameter ranges. Probabilistic sensitivity analysis demonstrated that EBRT with LDR brachytherapy was favored in 52% of 100,000 Monte Carlo iterations. In an exploratory analysis, EBRT with a simultaneous integrated boost was also a cost-effective strategy, resulting in an ICER of $62,607 per QALY gained; however, it was not cost effective compared with EBRT plus LDR brachytherapy boost. Conclusions: EBRT with LDR brachytherapy boost may be a cost-effective treatment strategy compared with EBRT alone and radical prostatectomy for HRPC, demonstrating high-value care. The current analysis suggests that a reduction in biochemical failure alone can result in cost-effective care, despite no change in overall survival.
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Introduction: To evaluate brachytherapy training experience among trainees and fellows trained through the Royal Australian and New Zealand College of Radiologists (RANZCR). Methods: All current trainees and fellows (who obtained fellowship from 2015 onwards) were sent an online anonymous questionnaire on various aspects of brachytherapy training, including number of cases observed/ performed, opinions on brachytherapy assessment during training, barriers to brachytherapy training and future role of brachytherapy. Results: The overall survey response rate was 24% (40/161 trainees, 30/126 fellows). Of the 70 respondents, 50 (71%), 38 (54%) and 43 (61%) reported to have received formal brachytherapy teaching from radiation oncologists, radiation therapists and medical physicists respectively. Most respondents had exposure to gynaecology brachytherapy - two-thirds of trainees and all fellows have performed at least one gynaecology brachytherapy procedure. Prostate brachytherapy exposure was more limited - by the end of training, 27% and 13% of fellows did not have exposure to LDR and HDR prostate brachytherapy. More than two-thirds indicated there should be a minimum number of brachytherapy case requirements during training, and half indicated that trainees should be involved in ≥6 gynaecology brachytherapy procedures. Barriers affecting training include lack of caseload (70%) and perceived decreasing role of brachytherapy (66%). Forty-three percent of respondents were concerned about the decline in brachytherapy utilisation. Conclusion: This is the first survey on brachytherapy training experience among RANZCR trainees and fellows. It highlighted limited brachytherapy exposure during RANZCR training, and the need to revisit brachytherapy training requirement in the current training programme, along with long-term brachytherapy workforce planning.
Conference Paper
High-dose-rate brachytherapy (HDR BT) is a radiation therapy that places radioactive sources at cancerous tissue using needles. HDR BT offers better dose conformality and sparing of clinical structures, lower operator dependency, and fewer acute irritative symptoms compared to the other form of BT (low-dose-rate (LDR)). However, use of HDR BT is limited for patients with pubic arch interference, where the transperineal path to the prostate is blocked. This study aims to introduce a tendon-driven needle that can bend inside tissue to reach desired positions inside prostate. Initial experiments in a phantom tissue showed the feasibility of the needle to get around the pubic arch for placement at hard-to-reach target positions.
Following adoption of moderately hypofractionated radiotherapy as a standard for localised prostate cancer, ultrahypofractioned radiotherapy delivered in five to seven fractions is rapidly being embraced by clinical practice and international guidelines. However, the question remains: how low can we go? Can radiotherapy for prostate cancer be delivered in fewer than five fractions? The current review summarises the evidence that radiotherapy for localised prostate cancer can be safely and effectively delivered in fewer than five fractions using high dose rate brachytherapy or stereotactic body radiotherapy. We also discuss important lessons learned from the single-fraction high dose rate brachytherapy experience.
Purpose Chemoradiation is considered the standard of care for locally advanced cervical cancer. While brachytherapy (BT) boost is associated with improved survival and less toxicity compared to external beam radiation therapy (EBRT) boost, it is unclear why many patients do not receive a BT boost. In this study, we compared sociodemographic and baseline patient characteristics between patients receiving EBRT boost versus BT boost. Methods We analyzed patients in the National Cancer Database diagnosed between 2004 and 2016 with FIGO stage IIB-IVA cervical cancer treated with nonpalliative doses of chemoradiation. Logistic regression analysis was utilized to evaluate BT utilization over time and by other clinicopathological and sociodemographic factors. Results Overall, 5764 patients were evaluated, of which 4937 (86%) underwent BT boost. Using multivariable logistic regression, higher FIGO stage was a significant predictor for utilization of EBRT versus BT boost, with odds ratio 2.92 (95% confidence interval [CI] 2.04–4.16; p < 0.001), 2.68 (95%CI 2.22–3.24; p < 0.001), and 4.51 (95%CI 3.05–6.67; p < 0.001) for IIIA, IIIB, and IVA, respectively, compared to IIB. Increased utilization of EBRT boost was also associated with community cancer facility types, lower income (based on zip code), earlier year of diagnosis, and higher comorbidity score. Conclusions In FIGO stage IIB-IVA cervical cancer patients treated with nonpalliative doses of chemoradiation, overall utilization of BT is 86%. Higher FIGO stage, community cancer facilities, lower income, earlier year of diagnosis, and higher comorbidity score were significant predictors of EBRT boost utilization. Future studies are needed to better understand reasons for this as higher FIGO stage patients are the mostly likely to benefit from a BT boost.
PURPOSE While brachytherapy is an effective treatment for localized prostate cancer, there has been a noticeable decline in its use. Training opportunity for prostate brachytherapy has been in steady decline, with some residents receiving little to no hands-on training. This work was developed to design a training environment that uses a phantom-based simulator to teach the process of TRUS-based prostate brachytherapy METHODS AND MATERIALS A prostate phantom was fabricated from a representative prostate patient TRUS scan. Three materials were used: gelatin powder, graphite powder, and water. The prostate was developed using 9% gelatin and 0.3% graphite per 100 ml water. Five radiation oncologists were asked to qualitatively score the phantom according to image quality, haptic feedback, needle insertion quality, and its compatibility with operative tools. The contrast-to-noise ratio (CNR) was estimated using different concentrations of graphite. The elasticity of the phantom was evaluated based on ultrasound elastography measurements RESULTS The prostate phantom had an average CNR of 3.94 ± 1.09 compared to real prostate images with a CNR of 2 ± 1.8. The average Young's modulus was computed to be 58.03 ± 6.24 kPa compared to real prostate tissue (58.8 ± 8.2 kPa). Oncologists ranked the phantom as “very good” for overall quality of the phantom. They reported that needle insertion quality was “very good” during a simulated brachytherapy procedure. CONCLUSION We have developed a 3D printing prostate phantom to be used for training purposes during prostate brachytherapy. The phantom has been evaluated for image quality and elasticity. The reconstructed phantom could be used as an anthropomorphic surrogate to train residents on prostate brachytherapy procedures.
BACKGROUND AND PURPOSE Despite the excellent clinical outcomes from brachytherapy treatments compared with other modalities and the low associated costs, there have been reports of a decline in utilization of brachytherapy. The aim of this study was to investigate in detail the trend in utilization of brachytherapy in the province of Québec, Canada, from 2011 to 2019. MATERIALS AND METHODS All radiotherapy clinics in the province of Quebec, and among these the clinics that provide brachytherapy treatments, were identified. This observational retrospective cohort study involved analysis of data compiled by the Ministère de la Santé et des Services Sociaux du Québec for the period of 2011 to end of 2019 on all brachytherapy procedures performed in the province of Quebec. Time series graphs were used to describe the number of high dose rate (HDR) and low dose rate (LDR) brachytherapy treatments during the studied time period. Statistical analysis was conducted using R statistical software. RESULTS Between 2011 and 2019, 12 hospitals in the province of Québec provided radiotherapy treatments, and all of them offered brachytherapy services. The median annual number of brachytherapy sessions was 4413 (range 3930-4829). HDR brachytherapy represented over 90% of all brachytherapy treatments throughout the study period. Significant changes over time were observed in the number of treatments: at least 5% change was seen only for the two most common subtypes of brachytherapy, HDR interstitial and HDR intracavitary, with an increase of 9.6% and a decrease of 9.2%, respectively. The use of other subtypes of brachytherapy (HDR-plesiotherapy, LDR-interstitial, LDR-intracavitary, LDR-eye plaque) was stable between 2011 and 2019, with ≤ 2.5% variation. CONCLUSION This study demonstrates an overall steady use of brachytherapy between 2011 and 2019 in Quebec. Brachytherapy offers numerous advantages for the treatment of diverse cancer sites. Although more sophisticated external beam radiotherapy treatments have emerged in the last decades, the precision and cost-effectiveness of brachytherapy remain unbeaten. To ensure the continued use and availability of brachytherapy, governments must put in place policies and regulations to that effect. Training and exposure of future health care professionals to brachytherapy within Quebec and Canada is essential to provide all patients the same access to this life saving modality.
Background and Purpose Long-term toxicity of high dose-rate brachytherapy as monotherapy for prostate cancer is not well defined. We report late toxicity and health related quality of life (HRQOL) changes from a randomized phase II clinical trial of two different fractionation schemes. Materials and Methods Eligible patients had NCCN low or intermediate risk prostate cancer. 170 patients were randomized to receive either a single 19 Gy or two-fractions of 13.5 Gy one week apart. Toxicity was measured using Common Terminology for Adverse Events (CTCAE) v4.0, and HRQOL was measured using the Expanded Prostate Index Composite (EPIC). Results Median follow-up was 63 months. The 5-year cumulative incidence of Grade 2 or higher genitourinary (GU) and gastrointestinal (GI) toxicity was 62% and 12% in the single-fraction arm, and 47% and 9% in the two-fraction arm, respectively. Grade 3 GU toxicity was only seen in the single fraction arm with a cumulative incidence of 2%. The 5-year prevalence of Grade 2 GU toxicity was 29% and 21%, in the single- and two-fraction arms, respectively, with Grade 2 GI toxicity of 1% and 2%. Beyond the first year, no significant differences in mean urinary HRQOL were seen compared to baseline in the two-fraction arm, in contrast to the single-fraction arm where a decline in urinary HRQOL was seen at 4 and 5 years. Sexual HRQOL was significantly reduced in both treatment arms at all timepoints, with no changes in the bowel domain. Conclusions HDR monotherapy is well tolerated with minimal impact on HRQOL.
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Background: Serious adverse events have been associated with androgen deprivation therapy (adt) for prostate cancer (pca), but few studies address the costs of those events. Methods: All pca patients (ICD-9-CM 185) in Ontario who started 90 days or more of adt or had orchiectomy at the age of 66 or older during 1995-2005 (n = 26,809) were identified using the Ontario Cancer Registry and drug and hospital data. Diagnosis dates of adverse events-myocardial infarction, acute coronary syndrome, congestive heart failure, stroke, deep vein thrombosis or pulmonary embolism, any diabetes, and fracture or osteoporosis-before and after adt initiation were determined from administrative data. We excluded patients with the same diagnosis before and after adt, and we allocated each patient's time from adt initiation to death or December 31, 2007, into health states: adt (no adverse event), adt-ae (specified single adverse event), Multiple (>1 event), and Final (≤180 days before death). We used methods for Canadian health administrative data to estimate annual total health care costs during each state, and we examined monthly trends. Results: Approximately 50% of 21,811 patients with no pre-adt adverse event developed 1 or more events after adt. The costliest adverse event state was stroke ($26,432/year). Multiple was the most frequent (n = 2,336) and the second most costly health state ($24,374/year). Costs were highest in the first month after diagnosis (from $1,714 for diabetes to $14,068 for myocardial infarction). Costs declined within 18 months, ranging from $784 per 30 days (diabetes) to $1,852 per 30 days (stroke). Adverse events increased the costs of adt by 100% to 265%. Conclusions: The economic burden of adverse events is relevant to programs and policies from clinic to government, and that burden merits consideration in the risks and benefits of adt.
3 Background: This trial compared the efficacy of DE-EBRT and LDR-B for National Comprehensive Cancer Network (NCCN) high and intermediate-risk disease. Methods: A planned sample size of 400 patients were randomized to one of two treatment arms and stratified by risk group. Both arms received 12 months of androgen deprivation therapy (ADT) with luteinizing hormone releasing hormone (LHRH) agonist plus a non-steroidal anti-androgen for at least 1 month. After 8 months of neo-adjuvant ADT, both arms received whole pelvis EBRT (46Gy/23#). Patients assigned to DE-EBRT (standard arm) then received a conformal EBRT boost (32Gy/16#). Patients assigned to LDR-B (experimental arm) received an Iodine-125 LDR boost prescribed to a minimum peripheral dose of 115Gy. The primary endpoint was relapse free survival (RFS) defined by biochemical criteria using the nadir+2 ng/mL threshold. Time zero was the date of the first LHRH injection. Results: Between Dec 2002 and Sep 2011, 276 high-risk and 122 intermediate-risk pati...
Purpose: To determine whether a previously reported substratification system can be extrapolated to patients with high-risk prostate cancer treated with permanent interstitial brachytherapy. Methods and materials: Four hundred six National Comprehensive Cancer Network patients with high-risk prostate cancer treated with permanent prostate brachytherapy with or without supplemental external beam radiotherapy were stratified into good (prostate-specific antigen >20 or Gleason score ≥8 or ≥T3), intermediate (prostate-specific antigen >20 and ≥T3), and poor (Gleason score ≥8 with ≥1 additional high-risk feature) prognostic cohorts. Because of only 1 patient with intermediate high-risk disease, the analysis was performed on patients in the good and poor cohorts. Biochemical failure (BF), prostate cancer-specific mortality (PCSM), distant metastasis, and overall mortality were assessed as function of prognostic group. Multiple parameters were evaluated for impact on outcome. Results: With a median followup time of 7.9 years, 10- and 14-year rates of BF and PCSM for the entire cohort were 7.8% and 3.7%, respectively. The BF rate was significantly greater in the poor prognostic category (16.8% vs. 7.8%, p = 0.041). The poor prognostic category was the strongest predictor of BF in univariate and multivariate analyses. No statistically significant differences in PCSM, distant metastasis, or overall mortality were identified between the good and poor prognostic categories. Conclusions: Patients with high-risk prostate cancer treated with a brachytherapy approach have excellent long-term biochemical control and cancer-specific survival. The poor prognostic high-risk category had a higher rate of BF compared with the good prognostic category without a higher rate of PCSM or distant metastasis.
Primary androgen deprivation therapy (pADT) is commonly used to treat elderly men diagnosed with localized prostate cancer (CaP), despite the lack of evidence supporting its use. To examine the effect of pADT on mortality and to assess contemporary trends of pADT use in elderly men with CaP. Men older than 65 yr residing in Surveillance, Epidemiology, and End Results (SEER) registry areas diagnosed with localized or locally advanced CaP between 1992 and 2009 and not receiving definitive therapy. Propensity score (PS)-weighted Cox proportional hazards models were used to estimate the effect of pADT use on overall survival among patients receiving pADT. The interaction between comorbidity-adjusted life expectancy (LE) and pADT use was assessed within the Cox and PS-weighted models. Contemporary (2004-2009) trends for pADT use were analyzed by linear regression. The primary cohort included 46 376 men, of whom 17 873 received pADT (39%). Patients with >10 yr LE had lower pADT utilization rates than patients with short LE. Between 2004 and 2009, the use of pADT in men with localized CaP decreased by 14% (from 36% to 22%). Relative to observation, pADT was associated with a survival disadvantage, with a hazard ratio for all-cause mortality of 1.37 (95% confidence interval 1.20-1.56). Limitations included biases not accounted for by the PS-weighted model, changes in CaP staging over the study period, the absence of prostate-specific antigen (PSA) data prior to 2004, and the limits of retrospective analysis to demonstrate causality. The use of pADT in elderly men with localized CaP has decreased over time. For men forgoing primary definitive therapy, the use of pADT is not associated with a survival benefit compared to observation, and denies men an opportunity for cure with definitive therapy. The deleterious effect of pADT is most pronounced in men with prolonged LE. In this report, we assessed the effect of primary androgen deprivation (pADT) on prostate cancer mortality and determined current trends in the use of pADT. We showed that use of pADT in men aged >65 yr with localized prostate cancer has decreased over time. We also found that pADT is detrimental to men with localized prostate cancer, and particularly men with longer life expectancy. Therefore, we conclude that ADT should not be used as a primary treatment for men with prostate cancer that has not spread beyond the prostate. Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.
Purpose To design and implement a unique training program that uses a phantom-based simulator to teach the process of prostate brachytherapy (PB) quality assurance and improve the quality of education. Methods and Materials Trainees in our simulator program were practicing radiation oncologists, radiation oncology residents, and fellows of the American Brachytherapy Society. The program emphasized 6 core areas of quality assurance: patient selection, simulation, treatment planning, implant technique, treatment evaluation, and outcome assessment. Using the Iodine 125 (125I) preoperative treatment planning technique, trainees implanted their ultrasound phantoms with dummy seeds (ie, seeds with no activity). Pre- and postimplant dosimetric parameters were compared and correlated using regression analysis. Results Thirty-one trainees successfully completed the simulator program during the period under study. The mean phantom prostate size, number of seeds used, and total activity were generally consistent between trainees. All trainees met the V100 >95% objective both before and after implantation. Regardless of the initial volume of the prostate phantom, trainees' ability to cover the target volume with at least 100% of the dose (V100) was not compromised (R=0.99 pre- and postimplant). However, the V150 had lower concordance (R=0.37) and may better reflect heterogeneity control of the implant process. Conclusions Analysis of implants from this phantom-based simulator shows a high degree of consistency between trainees and uniformly high-quality implants with respect to parameters used in clinical practice. This training program provides a valuable educational opportunity that improves the quality of PB training and likely accelerates the learning curve inherent in PB. Prostate phantom implantation can be a valuable first step in the acquisition of the required skills to safely perform PB.
BACKGROUND Brachytherapy has been shown to be an efficacious and cost-effective treatment among patients with localized prostate cancer. In this study, the authors examined trends in brachytherapy use for localized prostate cancer using a large national cancer registry.METHODS In the National Cancer Data Base (NCDB), a total of 1,547,941 patients with localized prostate cancer were identified from 1998 through 2010. Excluding patients with lymph node-positive or metastatic disease, the authors examined primary treatment trends focusing on the use of brachytherapy over time. Patients with available data (2004-2009) were stratified by National Comprehensive Cancer Network risk criteria. Controlling for year of diagnosis and demographic, clinical, and pathologic characteristics, multivariate analyses were performed examining the association between patient characteristics and receipt of brachytherapy.RESULTSIn the study cohort, brachytherapy use reached a peak of 16.7% in 2002, and then steadily declined to a low of 8% in 2010. Of the 719,789 patients with available data for risk stratification, 41.1%, 35.3%, and 23.6%, respectively, met low, intermediate, and high National Comprehensive Cancer Network risk criteria. After adjustment, patients of increasing age and those with Medicare insurance were more likely to receive brachytherapy. In contrast, patients with intermediate-risk or high-risk disease, Medicaid insurance, increasing comorbidity count, and increasing year of diagnosis were less likely to receive brachytherapy.CONCLUSIONS For patients with localized prostate cancer who are treated at National Cancer Data Base institutions, there has been a steady decline in brachytherapy use since 2003. For low-risk patients, the declining use of brachytherapy monotherapy compared with more costly emerging therapies has significant health policy implications. Cancer 2014. © 2014 American Cancer Society.
OBJECTIVES: To identify and review the currently available simulators and explore the evidence supporting their efficacy for training in prostate surgery. MATERIALS AND METHODS: A review of the current literature was performed between 1999 and 2013. The search terms included a combination of urology, prostate surgery, robotic prostatectomy, laparoscopic prostatectomy, TURP, simulation, virtual reality, animal model, human cadavers, training, assessment, technical skills, validation and learning curves. Furthermore, relevant abstracts from the AUA, EAU, BAUS and WCE meetings, between 1999 and 2013, were included. Only studies related to prostate surgery simulators were included and studies regarding other urological simulators were excluded. RESULTS: A total of 22 studies were identified, which carried out a validation study. Five validated models and/or simulators were identified for transurethral resection of the prostate (TURP), one for GreenLight laser therapy, three for laparoscopic radical prostatectomy (LRP) and four for robotic surgery. Of the TURP simulators, all five demonstrated content validity, three demonstrated face validity and four construct validity. The GreenLight laser simulator demonstrated face, content and construct validities. All three animal models for LRP demonstrated construct validity whilst The Chicken Skin Model was also content valid. Only two robotic simulators were identified with relevance to robot-assisted laparoscopic prostatectomy (RALP), both of which demonstrated construct validity. CONCLUSIONS: A wide range of different simulators are available for prostate surgery including synthetic bench models, virtual-reality platforms, animal models, human cadavers, distributed simulation and advanced training programmes and modules. The currently validated simulators may be used by healthcare organisations to provide supplementary training sessions for trainee surgeons. Further research should be conducted to validate simulated environments, determine which simulators have greater efficacy than others, assess the cost effectiveness of the simulators and the transferability of skills learnt. However, with surgeons investigating new possibilities for easily reproducible and valid methods of training, simulation offers a great scope to be implemented alongside traditional methods of training.
SEER and the NCDB are continually evolving registries which have a number of important similarities. While the major strength of SEER is in its population-based sampling approach to accurately study cancer incidence, the NCDB captures more cancer cases, offers several unique variables for research, and most importantly, has feedback mechanisms to directly assist hospitals in quality improvement. Bagaria and colleagues study is an example of how such databases can be used to evaluate variation in a particular treatment pattern as well as adherence to an established cancer care quality measure. Fundamentally, SEER and the NCDB are ideally positioned to study trends in cancer care over time, patterns of care, and rare cancers. By themselves and also via linkages with tertiary data sources, they also allow researchers and policy makers to recognize and understand particular areas of cancer need to decide on resource allocation, identify high-risk groups, and evaluate cancer control programs and adherence to quality measures. Finally, as examples of highly coordinated and standardized methods of data collection and reporting, the two tell remarkably similar stories of cancer incidence and care over the last several decades.
To analyze the recent trends in the utilization of external beam radiation therapy (EBRT) and brachytherapy (BT) for the treatment of prostate cancer. Using the Surveillance, Epidemiology, and End Results (SEER) database, information was obtained for all patients diagnosed with localized prostate adenocarcinoma between 2004 and 2009 who were treated with radiation as local therapy. We evaluated the utilization of BT, EBRT, and combination BT+EBRT by the year of diagnosis and performed a multivariable analysis to determine the predictors of BT as treatment choice. Between 2004 and 2009, EBRT monotherapy use increased from 55.8% to 62.0%, whereas all BT use correspondingly decreased from 44.2% to 38.0% (BT-only use decreased from 30.4% to 25.6%, whereas BT+EBRT use decreased from 13.8% to 12.3%). The decline of BT utilization differed by patient race, SEER registry, median county income, and National Comprehensive Cancer Network risk categorization (all p<0.001), but not by patient age (p=0.763) or marital status (p=0.193). Multivariable analysis found that age, race, marital status, SEER registry, median county income, and National Comprehensive Cancer Network risk category were independent predictors of BT as treatment choice (all p<0.001). Moreover, after controlling for all available patient and tumor characteristics, there was decreasing utilization of BT with increasing year of diagnosis (odds ratio for BT=0.920, 95% confidence interval: 0.911-0.929, p<0.001). Our analysis reveals decreasing utilization of BT for prostate cancer. This finding has significant implications in terms of national health care expenditure.