Page 138 - An Evidence Review of Active Surveillance in Men With Localized Prostate Cancer

who received active treatments. Although multivariable regression analyses or propensity score
methods were employed to control for confounding by all reviewed studies, such analyses cannot
account for unmeasured confounders of the treatment-outcome association.

Observational management strategies versus RP. Studies generally reported that men treated
with RP had lower all-cause or prostate cancer-specific mortality rates than men on WW. The
development of metastatic disease was assessed by a single study that found a significant benefit
for RP compared to WW. Morbidity of primary treatment was reported by two studies that
suggested an increased risk of urethral stricture (and procedures to treat it) were less likely
among patients managed using observational management strategies. One of these studies also
investigated cystoscopies (equally common in RP and observation groups), bladder
irrigation/cystostomy and TURP/bladder neck incision (both more common among patients
managed with observation). QoL was reported in three studies, which reported heterogeneous
results.

Observational management strategies versus RT. Studies generally reported that men treated
with RT had lower all-cause mortality rates than men on WW. One study reported prostate
cancer-specific mortality information and found no statistically significant difference between
RT and observational management. No study reported on treatment comparisons for the
development of metastatic disease. Morbidity of treatment decision was reported by only one
study which found no significant difference between observational management and BT or
EBRT. QoL measures were reported in four studies, which reported heterogeneous results.

Observational management strategies versus combined radiation modalities or active
treatments considered in aggregate. Data from one study showed that active treatments (RP,
RT, BT considered together) resulted in lower all-cause and prostate cancer-specific mortality
rates compared to WW. Morbidity of primary treatment was reported by only one study which
found that a group of patients receiving EBRT and BT (combination therapy) had a higher rate of
receiving treatments for urethral stricture compared to a group managed observationally.

Short- and long-term costs. Both short and long-term costs observed in clinical studies appear
to be higher for active treatment strategies (RP or RT) compared to WW; however evidence
originated from small studies using heterogeneous measurement methods. We did not identify
any primary study comparing the cost of AS with active treatment strategies; economic modeling
using U.S. prices suggested that within 10 to 15 years of diagnosis AS may be less costly
compared to active treatments; a study using a lifetime horizon indicated that AS may be
associated with higher costs compared to RP and BT, but lower costs compared to intensity
modulated RT (IMRT) and proton beam RT.

Key Question 5. What are the research needs regarding active surveillance
(or watchful waiting) in localized prostate cancer?
As summarized and discussed in previous sections of this report, the evidence directly
addressing the four principal Key Questions is largely incomplete. In part this is because
published studies tended to address research questions that were different in scope or focus than
the questions posed by the sponsors of the NIH State-of-the-Science Conference; in part much of
the available data are not amenable to analyses that could adequately answer the Key Questions.

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