EURURO Vol. 72 No. 6

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were 6.01% and 7.10% with PRIAS, 5.40% and 6.39% with
the MRI-based, and 6.93% and 8.19% with the 5-yr biopsy
strategies, respectively. Lifetime risks of receiving radical
treatment were 46% with PRIAS, 50% with the MRI-based,
and 43% with 5-yr biopsy strategies. AS using the PRIAS
(33.79 QALYs), MRI-based (33.89 QALYs), and 5-yr biopsy
(33.63 QALYs) strategies yielded higher QALYs than WW
(33.36 QALYs). Supplementary shows the 10-yr
and lifetime risks of receiving radical treatment,
metastasis, and PCa death for cohorts starting at different
ages.
3.3. Sensitivity analyses
In one-way sensitivity analysis for the end point of LYs
), the risk of metastasis for untreated grade
reclassification, age at initiation, proportion with initial
misclassification, and ratio of reduction in metastasis with
treatment versus WW had the greatest overall impact on
remaining life expectancy. However, only age >77.6 yr at
initiation led to a switch in preferred strategy from AS to
WW based on the outcome of LYs. To test whether this age
sensitivity was an artifact of discontinuing biopsies at 75 yr
in the base case scenario, we generated a separate model
and performed an analysis starting at age 70 and 75 yr with
biopsies extending until 85 yr, and AS yielded slightly more
LYs (+0.14 and +0.07, respectively).
Given the variability in reported rates of treatment-related
complications and difficulties in estimating joint-state utili-
ties for side effects, sensitivity analyses were also performed
for the outcome QALYs B). The discount rate, risk of
metastasis for untreated grade reclassification, duration of
treatment complications, and age at initiation all had a
substantial impact on expected QALY. However, the only
parameters leading to a shift in the preferred management
strategy were discount rate (0.0018), risk of metastasis (2.4%
at 10 y), duration of treatment-related complications (>27 y)
and age (63).
In two-way sensitivity analyses ), AS was preferred
with a shorter duration and lower decrement in utility from
treatment-related complications, whereas WW was associat-
ed with more QALYs with long-term larger utility decrement
from treatment complications. AS was also associated with
more QALYs across the range of utilities, except at a very low
Table 1 – Parameters of the Markov model comparing watchful waiting and active surveillance
Variable Point estimate Range for sensitivity analysis
Epidemiologic variables
Proportion with initial grade misclassi fication 35% low risk
31% very low risk
0–42%
Probability of grade reclassification Low risk: 1.2%/yr
Very low risk: 1%/yr
0–2.7%/yr
Probability of metastasis with untreated grade reclassi fication MFS 99% at 5 yr,
91% at 10 yr,
82% at 15 yr,
then stabilizes
1.2–21.3% at 10 yr
Relative risk of metastasis with treatment versus watchful waiting 0.57 0.38–0.75
Probability of PCa death given metastasis Median overall
survival 60 mo,
85% PCa death
20–80 mo
Test performance variables
PSA sensitivity 49.5% 40.2–58.8%
PSA speci ficity 50.8% 44.2–78.7%
MRI sensitivity 69% 44–86%
MRI specificity 78% 53–91%
Biopsy sensitivity with normal MRI 53% 43–63%
Increase in biopsy sensitivity with an abnormal MRI 32% 23–38%
Biopsy specificity 1 Fixed at 1 (assumption)
Complications variables
Probability of infection after biopsy 4.0% 0–6.3%
Probability of death from treatment 0.2% 0–0.88%
Utilities
Utility for no treatment 0.97 0.5–1
Decrement in utility for patients having complication after biopsy 0.07 0.06–0.43
Utility during treatment 0.67 0.65–0.90
Decrement in utility from complications after treatment 0.02 0–0.29
Duration of utility decrement from complications after treatment 10 yr 1–40 yr
Decrement in utility with metastasis 0.21 0.10–0.50
Discount rate 0 0–0.03
MFS = metastasis-free survival; MRI = magnetic resonance imaging; PCa = prostate cancer; PSA = prostate-specific antigen.
a The range for sensitivity analysis was drawn from the literature.
b Utility decrements were used to preserve the rank order of utilities for different states. For example, the utility for “no treatment, biopsy” is defined by
subtracting the decrement of utility for the “no treatment, biopsy” state from the utility of the “no treatment” state. By setting the upper bound of the decrement
to be less than the utility of the “no treatment ” state, we can assure that the utility for the “no treatment, biopsy” state is always lower than that for the “no
treatment” state.
c The decrement in utility for biopsy complications was applied for 1 mo.
d A decrement of 0.11 was applied to men undergoing treatment at age 70 to account for more frequent complications in this age group.
E U R O P E A N U R O L O GY 7 2 ( 2 0 17 ) 8 9 9 – 9 0 7 901