Page 32 - An Evidence Review of Active Surveillance in Men With Localized Prostate Cancer

Key Question 2—Definition of Active Surveillance

Little new research is needed to address how active surveillance has been defined by
researchers. However, interpretation of future studies would be best served if there were a
standard, agreed-upon definition of AS that clearly distinguished it from WW and other forms of
withheld or noncurative treatments. A consensus conference may be the most appropriate forum
to define AS. Features of the definition will need to include (1) the goal or intent of the
intervention; (2) the “eligibility criteria,” a determination of which patients should be offered AS
based on disease and patient characteristics; (3) the “followup protocol,” the minimum set of
tests that should be followed and their timing; and (4) the criteria or triggers for stopping AS to
seek definitive treatments.
Assuming that AS is an intervention plan that many patients may select (if offered) in order
to avoid the side effects from immediate invasive treatment for a potentially nonlethal disease, it
would be desirable to determine the best AS protocol that would minimize prostate-cancer
specific morbidity and mortality, and that patients and caregivers would adhere to. This best AS
protocol should be investigated by randomized or other prospective comparative studies that
directly compare different protocols. Examples of comparisons for future trials could include use
of different combinations of followup testing, different timing for the tests, and different
definitions of progression that would determine when curative treatment is offered. The
outcomes of greatest clinical importance are those that are most pertinent to patients’ health,
well-being, and longevity. Examples include all-cause mortality, prostate-cancer-specific
mortality, symptomatic disease, urological and other complications (from testing, treatment, or
deferring treatment), quality of life, anxiety, and family dynamics. Also of interest would be
overall costs, use of resources, and numbers of negative invasive tests (i.e., biopsies showing no
progression, thus arguing they were unnecessary).
At a minimum, future study reports should be very explicit and clear as to their definitions of
AS (or WW), the goals of the intervention, the exact protocols, the exact definitions of
progression, how and when protocols or standards changed during their study (and why), and
how often and why patients and clinicians chose not to follow the protocols.

Key Question 3—Factors That Affect Offer of, Acceptance of, and
Adherence to Active Surveillance

Current databases tend to have data only about what treatment patients received and when.
Therefore, whether different treatment options were offered to them, whether they accepted those
options, and whether they adhered to their initial choices could only be inferred. Even the best
analysis of predictors of initial treatment cannot adequately address this Key Question. Thus, full
statistical analyses of predictors will require the prospective collection of data specifically about
what interventions were offered to each patient, which treatments the patients accepted, and
when they chose to receive curative treatment despite lack of evidence of progression. These
datasets will need to be sufficiently large to allow for testing of multiple predictor variables. In
addition, future studies should only perform complete analyses of all treatment options without
arbitrarily grouping treatments or selectively excluding treatments. This will minimize bias and
increase clarity about what is being tested.
Future database analyses and prospective observational studies should focus on those
predictors that are amenable to change or that can be acted upon. Researchers should avoid

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