Page 34 - An Evidence Review of Active Surveillance in Men With Localized Prostate Cancer

Discussion

Prostate cancer epidemiology is affected by population-level trends, such as the aging of the
U.S. population, but also by changes in the application of screening and diagnostic technologies
among the population at risk. Keeping these caveats in mind, studies indicate that men in all
racial/ethnic groups experienced increases in prostate cancer incidence since the mid-1980s, with
rates peaking in the early 1990s. For all groups, incidence rates declined between the early-1990s
and 1999. Studies have consistently demonstrated that early-stage (localized and regional)
prostate cancer cases were responsible for the observed increase in prostate cancer incidence
from the mid-1980s up to the mid-1990s. Studies also demonstrated decreases in the prostate
cancer-specific mortality rate for all age groups between the early-1990s and 1999. Mean age of
diagnosis has also decreased over time for both blacks and whites. Another consistent trend in
SEER data has been the decrease in low-grade (Gleason score 2–4) and high grade (≥7) tumors,
and a concomitant increase in intermediate grade tumors (Gleason 5–6). It has been hypothesized
that this effect is due to changes in histopathological grading guidelines, a preference towards
avoiding assigning Gleason 2–4 scores based on prostate cancer biopsy samples, and PSA test’s
ability to detect moderately differentiated tumors with higher accuracy (compared to poorly-
differentiated tumors). Most studies demonstrated decreasing trends in the proportion of patients
being managed with strategies other than RP or RT throughout their respective time periods.
Studies explicitly reporting on AS/WW-type strategies indicated decreases in the proportion of
patients receiving such treatments over time; this was true even for subgroups of men with “low-
risk disease.”
There is not yet a consensus among clinicians or researchers as to the definitions of AS or of
WW, the standard protocols for the interventions, or how to manage patients whose cancers
show signs of progression. This is evidenced by the 16 unique cohorts formed in the PSA
screening era that used different formal protocols to monitor triggers for curative treatment of
prostate cancer. In all these cohorts, AS was offered to men with low-risk or clinically localized
prostate cancer although no uniform criteria were used to identify these men, with the exception
that no cohorts enrolled patients with tumors of a clinical stage greater than T2. They employed
different combinations of periodic DRE, PSA testing, rebiopsy, and/or imaging findings to
determine different thresholds used for seeking definitive treatments. The AS followup protocols
also varied across these cohorts.
Owing to the variation in usage of the terms AS and WW, and their intended and often mixed
treatment objectives (both curative and palliative), it is often difficult when reviewing the studies
to know whether patients received true AS or WW, or were simply not treated (for a variety of
reasons) or experienced delays in their treatment (and thus initially had no treatment).
Only two studies specifically examined factors related to men who were enrolled in an active
monitoring protocol with triggers for curative treatments. The first found that the free to total
PSA ratio and T stage were independent predictors of time to radical treatments in patients on the
protocol, while initial PSA, PSA density, Gleason score, number of positive cores, and prostate
volume were not independent predictors. The second study found that men with decreased
baseline anxiety and higher socioeconomic status were associated with decreased probability of
willingness to consent to randomization for AS versus definitive treatment (i.e., these men
proactively selected AS). The rest of the heterogeneous studies reported on men who did not
receive treatments or initial treatments. Therefore, whether they were on AS or WW could not be
readily discerned. The following patient and clinical variables are potentially important in
increasing the probability that a patient receives an observational management strategy: older

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