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metrics for sexual function. The patient-reported inventories included:
(1) the IIEF-5 questionnaire, with a maximum score of 25 indicating
maximal erectile function; and (2) a simplified three-question erectile
function scale (Supplementary material). Patients were given all
questionnaires before radiotherapy and at 2 and 5 yr after radiotherapy.
The primary endpoint of the study was to determine preservation of
sexual activity rates at 5 yr after vessel-sparing radiotherapy. Erectile
preservation was defined as a score of 1 or 2 on the three-tier patient-
reported questionnaire equating to being able to be sexually active with
or without aids.
Prespecified secondary endpoints included erectile function preser-
vation at 2 and 5 yr after radiotherapy using multiple physician- and
patient-reported inventories (Supplementary material), including the
IIEF-5 (irrespective of sexual aid use). Biochemical failure (BF) was
defined according to the Phoenix definition as a serum prostate-specific
antigen (PSA) level at least 2 ng/ml greater than the post-treatment PSA
nadir
[17]. Preplanned subset analyses included assessment of erectile
function for those receiving the addition of supplemental brachytherapy
and those receiving ADT.
To compare rates of erectile function preservation, our patient
characteristics were individually entered into validated models that
have been shown to be able to predict 2-yr post-treatment erectile
function rates after nerve-sparing prostatectomy and conventional
external beam radiotherapy (EBRT)
[18] .These models were created
from The Prostate Cancer Outcomes and Satisfaction with Treatment
Quality Assessment (PROSTQA), a prospective multicenter cohort of
men enrolled from 2003 to 2006 (similar to the years of our cohort,
including the University of Michigan) at experienced centers, and
validated in the Cancer of the Prostate Strategic Urologic Research
Endeavor (CaPSURE) registry. IIEF-5 scores were transformed into
baseline Expanded Prostate Cancer Index Composite (EPIC) sexual
health-related quality-of-life scores using the model of Schroeck
et al
[19] .2.4.
Statistical analysis
Sample size determination was based on estimated rates of erectile
preservation according to the three-tier scale. Assuming that 50% of
patients after standard IMRT report an ability to be sexually active with
or without aids 5 yr after radiotherapy
[20], we estimated that use of
vessel-sparing radiotherapy would improve this to 70%. With 90% power
for detecting a two-sided type I error rate of 5% and allowing for 5% of
patients being lost to follow-up before the 5-yr post-treatment time
point, we estimated 196 patients would be necessary. A planned interim
analysis was performed after 135 patients had 5-yr follow-up, and the
trial was closed early because of the higher than anticipated mainte-
nance of sexual activity.
Kaplan-Meier curves were generated to estimate biochemical
relapse–free survival (bRFS). Observed versus expected rates of erectile
function were compared using a paired two-sided
t
test. For all statistical
analyses, two-tailed
p
values 0 05 were considered statistically
significant. Statistical analyses were performed using R (version 3.2.2;
R Statistical Foundation, Vienna, Austria) and IBM SPSS version 22 0
(SPSS Inc., Chicago, IL USA).
3.
Results
3.1.
Cohort characteristics
The median follow-up was 8.7 yr. All patients were
followed for a minimum of 5 yr after radiotherapy.
The median age of the cohort was 63 yr (interquartile
range 57–67) and 62% were at intermediate or high risk
according to National Comprehensive Cancer Network
(NCCN) risk groupings
( Table 1). Some 61% of the cohort
received a combination of IMRT with brachytherapy, and
33% received the addition of ADT. Comorbidities are listed
in Supplementary Table 1.
Response rates were exceptionally high across all
physician- and patient-reported questionnaires (Supple-
mentary Table 2), with 97–100% of inventories completed at
baseline, 95–100% at 2 yr after treatment, and 94–100% at
5 yr after treatment.
3.2.
Primary endpoint
At 5 yr, 88% (95% confidence interval [CI] 81–92%) of
patients were able to be sexually active with or without the
use of aids
( Table 2). Some 35% (95% CI 27–43%) of patients
were able to be sexually active without the use of aids,
while 53% (95% CI 45–61%) reported they were sexually
active requiring aids. The type of sexual aid used is
summarized in Supplementary Table 3; 100%, 96%, and 93%
of the sexual aids used were phosphodiesterase-type
5 inhibitors at baseline and at 2 and 5 yr after treatment,
respectively.
3.3.
Secondary endpoints
At 5 yr, 67% of patients maintained an IIEF-5 score 16, and
67% reported moderate to very high confidence in the
ability to achieve and keep an erection during the previous
6 mo. Some 56% of the cohort reported using sexual aids at
5 yr
( Table 2 ). Of 135 patients, 13 developed biochemical
Table 1 – Baseline characteristics for the 135 patients
Variable
Result
Median age, yr (IQR)
63 (57–67)
NCCN risk group,
n
(%)
Low
52 (38.5)
Intermediate
71 (52.6)
High
12 (8.9)
Clinical T stage,
n
(%)
T1c/T2a
127 (94.1)
T2b/c
5 (3.7)
T3a
3 (2.2)
Median baseline PSA, ng/ml (IQR)
6.0 (4.7–8.7)
Grade group,
n
(%)
1 (GS 3 + 3)
60 (44.4)
2 (GS 3 + 4)
45 (33.3)
3 (GS 4 + 3)
18 (13.3)
4 (GS 8)
9 (6.7)
5 (GS 9–10)
3 (2.2)
Median percentage positive cores, % (IQR)
33.3 (16.7–50.0)
Radiotherapy type
External beam alone
53 (39.3)
External beam + brachytherapy
82 (60.7)
Androgen deprivation therapy use
Yes
44 (32.6)
No
91 (67.4)
Charlson comorbidity index
1–2
100 (74.1)
3
28 (20.7)
4–5
7 (5.2)
GS = Gleason score; IQR = interquartile range; PSA = prostate-specific antigen.
E U R O P E A N U R O L O G Y 7 2 ( 2 0 1 7 ) 6 1 7 – 6 2 4
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