EURURO Vol. 72 No. 4

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approximately 5 yr (median), and 48% changed to WW over
a life course (approximated by 40 yr in our simulations;
). Once a transition to WW had occurred, these men
remained in this state for a median time of 9 yr ).
4. Discussion
We evaluated the change from AS to WW for men with very
low-risk PCa using a large, population-based representative
sample of men with very low-risk PCa in Sweden. Our
estimations indicate that almost half of men with very low-
risk PCa starting AS will eventually change to WW. This
proportion increased with age and with comorbidity at time
of AS initiation. Overall, the estimated median time on AS
was 5 yr. Our prevalence simulation suggests that the
number of men on WW who were previously on AS will
eventually stabilise after 30 yr.
A few studies have investigated the change from AS to
WW . For instance, van As and colleagues followed
326 men on AS for a median time of 22 mo and observed
that 20% had deferred radical treatment, 5% changed to
WW, 2% died of other causes, and 73% remained on AS. Klotz
and colleagues followed 993men over a median time of
6 yr, and observed that 267 men went on to curative
intervention and 15 died; no information on the change to
WW was available. There are currently limited guidelines
on the change from AS to WW. The treatment
pathways for men with very low-risk PCa also vary by
country and are managed differently in various health care
systems. In light of the increasing use of AS as primary
management for men with low-risk PCa in Europe and the
USA (Loeb et al, unpublished data), there is a need for
guidelines to include criteria for the change from AS to WW.
In daily clinical practise, follow-up during AS is probably not
as intense as recommended by the guidelines, and the
change from AS to WW may also not be clearly defined,
either for the patient or for the urologist, as indicated by two
recent publications based on Surveillance, Epidemiology,
and End Results data .
Our simulation, which aimed to assess the overall change
from AS to WW, suggests that in the near future there will
be a rapid increase in the number of men who will transition
from AS to WW. Our models indicate that this change from
AS to WWwill eventually become quite common. However,
it is important to note that in clinical practice the actual
transition to WW for an individual patient is not a
probabilistic entity, but is rather based on age, CCI, the
patient’s preference, and clinical practice. Thus, our model
is not intended as a tool for decision-making at an
individual level. Although the vast majority of men who
change from AS to WW will do so because of old age, some
men change to ADTwithout a previous curative intervention:
they either missed the opportunity for curative treatment or
made an active choice to not undergo curative treatment.
Our model estimates support the observation that a large
proportion of men will reach the point at which a change to
curative treatment is no longer an option. As this affects the
intensity of follow-up (eg, fewer repeat biopsies), urologists
should inform patients of this change preferably before
they start on AS.
The change from AS to WW not only affects patients and
clinicians but also has an economic impact. Currently,
protocols for AS include frequent PSA testing,
regular repeat biopsies, and in the future probably also
repeat imaging . The risk of infection after prostate
Table 3 – Median time on WW and proportion of patients reaching absorbing states as estimated from the prevalence models based on
annual inflow of 1000 patients/yr in each stratum
Age at prostate cancer diagnosis
53–57 yr 58–62 yr 63–67 yr 68–72 yr All
Median time on WW, yr (IQR) 12.6
(5.9–21.5)
10.3
(5.0–17.2)
8.8
(4.2–14.5)
8.0
(3.8–13.0)
8.7
(4.2–14.4)
Patients reaching ADT as second event (%) 28.7 27.9 27.1% 26.5 26.9
Patients reaching death as first event (%) 71.3 72.1 72.9% 73.5 73.1
ADT = androgen deprivation therapy; IQR = interquartile range; WW = watchful waiting.
Table 2 – Median time on AS and proportion transitioning to WW and absorbing states as estimated from the prevalence models based on
annual inflow of 1000 patients/yr in each stratum
Age at prostate cancer diagnosis
53–57 yr 58–62 yr 63–67 yr 68–72 yr All
Median time on AS, yr (IQR) 5.4
(2.2–10.7)
5.3
(2.2–10.4)
5.1
(2.1–9.7)
4.6
(2.1–7.7)
4.7
(2.0–8.7)
Patients reaching WW as first event (%) 29.2 34.4 45.2 62.3 48.3
Patients reaching CT as first event 61.0 54.3 42.2 24.4 39.6
Patients AS failure as first event (%) 2.2 2.1 2.0 2.2 2.3
Patients reaching death as first event (%) 7.6 9.2 10.6 11.1 9.8
AS = active surveillance; CT = curative treatment; IQR = interquartile range; WW = watchful waiting.
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