Page 33 - An Evidence Review of Active Surveillance in Men With Localized Prostate Cancer

interpreting analyses to suggest that men with certain demographic (or other nonmodifiable)
features are more likely to accept treatment and thus other men should not be offered treatment.
Further surveys of patients, their families, and their clinicians are warranted. To improve
reliability, these should be adequately powered to ensure that sufficient numbers of men were
treated with different interventions and to allow full analyses of the tested predictors. Studies
should use established methods including standardized qualitative research designs and, ideally,
validated questionnaires to elicit preferences. Studies of this sort also need to consider the overall
adequacy of discussion with patients regarding management options—and documentation of
those discussions. Adequate documentation of these discussions will surely improve the veracity
of some of these survey data.
Future Key Questions of interest could include comparisons of interventions that improve the
likelihood that eligible men are offered AS, that improve acceptance of AS, and that improve
adherence with AS, so long as it remains the most appropriate treatment. Arguably, it is more
important to first establish how to successfully get men offered, accepting, and adhering to AS,
before determining which men are at greatest risk of failing to receive AS.

Key Question 4—Active Surveillance Versus Immediate Curative
Treatment

A randomized controlled trial with long followup would provide the best evidence to
adequately assess the differential effects between AS and immediate curative treatment. The
least biased, most reliable study design comparing two interventions is the randomized
controlled trial that adheres to modern methodological standards. Outcome assessors—
particularly those who conduct psychometric testing—should be blinded. The primary outcomes
of interest should be patient-centered outcomes, including mortality and disease-free survival,
psychometric measurements, adverse events, resource utilization, and costs. Trials need to be of
sufficiently long duration to collect data on the clinically relevant outcomes. However, limited
resources and possible difficulties recruiting patients may preclude such a study.
In lieu of randomized trials, adequate findings may possibly be extracted from long-term
databases with prospectively collected data. However, these studies, too, should use AS
protocols that are defined a priori and undergo minimal change over time or between centers.
The determination of which patients are potentially eligible for AS should also be made a priori.
These studies will need to use multivariable analyses, propensity scores, or other validated
methods to adjust for the broad range of factors that affect the decision to use AS. We do not
believe that retrospective studies are capable of providing adequate data for unbiased analyses.
Subgroup analyses of both randomized trials and prospective observational comparative
studies should be conducted to look for particular sets of men who may benefit most (or least)
from one approach or the other. Preferably, these subgroups should be considered a priori. The
factors listed in Key Questions 1 and 2 form a good starting point to consider which subgroups
may be of interest. In addition, future studies that could uncover better bio- and imaging markers
of indolent versus aggressive disease, and thus could better stage patients as having either low or
high risk disease, are necessary to better inform which patients are most likely to benefit from
observational versus active treatment.

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