Page 144 - 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
United States 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. The incidence rate appears to have peaked in early-1990s. For all groups, incidence rates
declined between the early-1990s and 1999. Studies 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 from 72.2 years (1988 to
1989) to 67.2 years (2004 to 2005) for both blacks and whites. Another consistent trend over
time in studies using the SEER database has been the decrease in low (corresponding to Gleason
scores 2-4) and high grade (corresponding to Gleason score ≥7) tumors, and a concomitant
increase in intermediate grade tumors (Gleason 5-6). It has been hypothesized that this effect is
caused by changes in histopathological grading guidelines, 245 a preference towards avoiding
assigning Gleason 2-4 scores based on prostate cancer biopsy samples 99,246,247 , and the ability of
the PSA test 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 consistency among clinicians or researchers as to the definitions or
standardizations of AS. Eligibility criteria for AS based on disease and patient characteristics and
followup protocols including defining triggers for active interventions have not been
standardized. This is apparent looking at the 16 unique cohorts with formal protocols for
monitoring triggers for curative treatment of prostate cancer (AS cohorts). In all, a variety of
observational management strategies 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 clinical stage greater than T2. The strategies included
different combinations of periodic DRE, PSA testing, rebiopsy and/or imaging findings to
determine different thresholds used for seeking definitive treatments. Additional information was
provided by 13 unique cohorts of men who initially received no treatment and who were
subsequently treated only for symptomatic progression (WW cohorts). About half of these WW
cohorts were formed in the pre-PSA screening era, enrolled men with more advanced disease,
and tended to use regular prostate acid phosphatase (PAP) testing in followup.
Because of the nonstandardized usages of the terms AS and WW coupled with the fact that
the primary intents of the observational management strategies reviewed were frequently not
reported, at times it was difficult when reviewing the studies to know who had AS and who had
WW.
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

90