Page 43 - An Evidence Review of Active Surveillance in Men With Localized Prostate Cancer

For Key Question 3, we reported relevant findings from existing systematic reviews and we
also perused the reviews’ references to identify potentially eligible studies.
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For Key Question 4 we mainly relied on two AHRQ evidence reports. For treatment-
related costs, we considered economic evaluations (cost components of cost-effectiveness or
cost-utility analyses, and model-based cost-minimization or cost-consequence analyses) of AS
only. We did not include the effectiveness components of cost-effectiveness or cost-utility
analyses because they did not provide additional comparative treatment information beyond that
provided by the AHRQ reports and our own literature searches.
For all Key Questions, when necessary, the evidence summarized in previously published
systematic reviews and evidence reports was supplemented with studies identified through our
own literature searches

Primary Research Studies

Key Question 1 (Trends in Incidence, Mortality/Survival and Features
at Diagnosis)
For Key Question 1 we included studies utilizing large databases sourced from the U.S.
population (e.g., the SEER database or its component registries; the CaPSURE database; or the
National Cancer Database [NCDB]). We excluded studies conducted in other countries. We
required the reported patient data to be within the time period 1980 to 2011. Studies had to have
analyzed data from at least 1000 patients and to report numerical data informing on changes of
the parameters of interest (incidence, mortality/survival, patient-, tumor- or system-level
characteristics at diagnosis, treatment patterns).
We required that studies reported changes over time or stratified by time periods (with or
without an associated statistical test). Thus, we excluded studies of single years. We included
studies that treated time as continuous variable (e.g., year of diagnosis) or as a categorical
variable (e.g., “before 2000” versus “after 2000”). Studies reporting only qualitative descriptions
were excluded. We also excluded studies that only reported on prostate cancer patients who were
selected based on the treatment modality they received (e.g., we did not include studies where
patients had to have received radical prostatectomy or studies excluding patients receiving
AS/WW), studies enrolling patients exclusively diagnosed through transurethral resection of the
prostate performed for benign prostatic hyperplasia, and single-center studies. The latter were
excluded to maximize the applicability of the included studies to the U.S. population.
Because differences in patient selection criteria or underlying populations can confound
temporal trends, we only considered studies where trend data were obtained from within the
same database, and we avoided inferences on temporal trends across manuscripts or databases.

Key Question 2 (Definitions of Observational Management Strategies)
We considered studies reporting on observational management strategies (i.e., no immediate
active treatment with curative intent), enrolling patients based on predefined eligibility criteria,
and using prespecified protocols for followup. We considered both studies where the aim of
observational management was to offer curative treatments when disease progression meets
predefined laboratory and clinical parameters in a monitoring protocol (AS) and studies where
the aim of observational management was to offer palliative treatments when patients become
clinically symptomatic (WW). Both prospective and retrospective studies of any design were

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