EURURO Vol. 72 No. 5

than patients who underwent DE-EBRT alone. Despite this

potential benefit, we found that the majority of men in this

cohort were treated without LDR-B boost, and that use of

LDR-B boost in this population declined across the study

period to a low of

15% in 2012. These findings complement

results from large randomized trials, supporting the efficacy

of LDR-B boost and suggesting that improvements in

biochemical control may translate to better OS with

additional follow-up.

The ASCENDE-RT trial recently analyzed 400 patients

with unfavorable PCa and demonstrated a 53% improve-

ment in biochemical failure in favor of LDR-B. At median

follow-up of 6.5 yr, there was no significant difference in

7-yr OS, but the trend did favor LDR-B boost (85.7% vs

81.5%). However, the study was underpowered and median

survival had not been reached, estimated to occur at

approximately 13 yr

[21]

. Other retrospective analyses

evaluating different treatment modalities and patient

populations are in agreement with the primary findings

of this study. A recent analysis by Amini et al

[25]

showed

that EBRT plus brachytherapy was associated with better

5-yr OS for both intermediate- and high-risk disease (85% vs

91%;

0.001). However, this benefit was no longer seen

on exclusion of patients who received

79.2 Gy. In the

present study, limited to LDR-B boost, using a more recent

cohort and controlling for the timing of AS, we found a

similar 7-yr OS improvement associated with brachythera-

py boost (82% vs 73%;

0.001). The benefit of which

remained regardless of dose. This is an important finding,

as doses 79.2 Gy are considered standard for modern

DE-EBRT.

In this analysis, the benefit of LDR-B boost persisted on

MVA and after adjusting for known confounders in a

propensity score–matched analysis. However, many of the

deaths seen in this study probably represent non-PCa

deaths, as demonstrated by early differences in OS. To

account for unknown confounders and in an attempt to

exclude non-PCa deaths, we created a novel analysis by

selecting only men younger than 60 yr with no comorbid-

ities. The validity of this analysis relies on the accuracy of

the comorbidity assessment in the NCDB, which has been

validated as being similar to Surveillance, Epidemiology,

and End Results (SEER)-Medicare index claims

[26]

. This

showed that the benefit of LDR-B persisted and was most

pronounced after 5 yr (7-yr OS 90% vs 85%), with an absolute

OS difference similar to that seen at 7 yr in the ASCENDE-RT

trial. Other studies have suggested PCa-specific mortality

(PCSM) of between 5% and 10% at 7 yr for patients with

unfavorable intermediate- and high-risk disease treated

with ERBT and hormone therapy

[27] .

A recent SEER

database study by Muralidhar et al

[28]

evaluated PCSM

among 45 078 patients with intermediate and high-risk PCa

who received either EBRT alone or EBRT and brachytherapy

boost at either a high-dose rate (HDR) or LDR. They found a

significant benefit in PCSM for patients receiving EBRT and

brachytherapy compared to EBRT alone (3.9% vs 5.3%;

= 0.02) for patients with high-risk disease. However, this

benefit did not persist when evaluating those with

intermediate-risk disease or favorable high-risk disease.

Of note, the median follow-up was only 3.6 yr in the

favorable high-risk cohort, which may have contributed to

the lack of a demonstrable survival benefit owing to the

long natural history of PCa. In contrast, our analysis

suggested that the associated improvement in OS for

patients selected for LDR-B boost persisted, as there was

no interaction between risk group and treatment.

Interestingly, despite improved outcomes for LDR-B

boost, our patterns of care analysis suggest a decrease in

LDR-B boost utilization between 2004 and 2012

( Fig. 1

This confirms a previous report that showed declines in the

use of combined EBRT and brachytherapy boost between

2004 and 2009

[29]

. Past investigators have proposed

multiple reasons for the decline, including an increase in the

number of prostatectomies

[29]

, increases in reimburse-

ment for other radiation modalities including intensity-

modulated radiation

[30] ,

a decrease in brachytherapy

training

[31]

, and perception of brachytherapy as a

procedure with excessive liability risk

[32]

There are several limitations to our study. First, we were

not able to compare treatment toxicity in the NCDB, and any

potential benefits of a treatment modality should be

weighed against the possibility of harm. The ASCENDE-RT

trial demonstrated that a significantly larger proportion of

patients who received LDR-B boost experienced late severe-

grade ( 3) urinary side effects compared to patients who

received EBRT alone (8% vs 2%)

[33]

. Second, given the

retrospective nature, data collection limitations are inher-

ent. Reporting bias and treatment facility selection bias may

exist, as only CoC-accredited hospitals contribute data to

the NCDB, although the NCDB still captures 70% of newly

diagnosed malignancies and has extensive quality assur-

ance mechanisms in place to ensure accurate data capture.

In addition, nonrandomized comparisons can lead to false

conclusions. It is likely that bias was introduced by

clinicians in selecting patients to undergo LDR-B that we

could not control for, despite our best efforts, which

[(Fig._3)TD$FIG]

Fig. 3 – Kaplan-Meier survival curves for men aged <60 yr with no

comorbidities and stratified by treatment type with either dose-

escalated external beam radiation therapy (DE-EBRT) or low-dose-rate

brachytherapy (LDR-B) boost (7-yr overall survival 85% vs 90%;

< 0.001).

E U R O P E A N U R O L O G Y 7 2 ( 2 0 1 7 ) 7 3 8 – 7 4 4

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