Page 64 - An Evidence Review of Active Surveillance in Men With Localized Prostate Cancer

strategies other than radical prostatectomy or radiation therapy. Studies explicitly reporting on
AS/WW, also indicated decreases over time in the proportion of patients being managed with
such observational management strategies; this was true even for subgroups of men with low-
risk disease.
There is little doubt that many of the observed trends in the presentation and natural history
of prostate cancer in the U.S. in the last 3 decades are at least in part due to the widespread use of
PSA screening. However, for many of these trends summarized in the preceding sections there
are multiple potential explanations. For example, observed trends in prostate-cancer specific
mortality may be explained by the implementation of PSA screening and its impact on
ascertaining cause of death 100 , improved treatments for localized disease (surgery or
radiotherapy), widespread use of ADT, earlier detection (and treatment) of recurrent disease, or
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changes in the underlying disease biology. Modeling studies may provide insight into the
c
underlying causes of the observed temporal changes ; modeling has been used to quantify the
impact of PSA testing on population incidence 101 , mortality 102,103 , and tumor grade at
diagnosis 104 , or to explore the potential for overdiagnosis. 96,105

Key Question 2. How are active surveillance and other observational
management strategies defined?

There are generally three scenarios in which a man with newly diagnosed prostate cancer
might not undergo immediate definitive treatments like RP or RT: 1) his disease has a low risk of
rapid progression and therefore it is felt that he could be safely monitored and still receive
definitive treatment should the need arise; 2) his disease may have a higher risk of rapid
progression but he may not be an ideal candidate for definitive treatments after careful
deliberation of the different tradeoffs (e.g., life expectancy gained versus the compromise in
quality of life living with side effects from immediate treatments), therefore, he could be
followed clinically and be offered palliative treatments should he become symptomatic; or 3) his
disease is advanced and only palliative treatments are indicated. In the literature, the first
approach (scenario 1) is generally termed “active surveillance (AS),” while the second approach
(scenario 2) is generally termed “watchful waiting (WW).” However, it is important to note that
investigators have used the terms AS and WW interchangeably. Terms like “expectant
management,” “conservative management,” and others to denote one of the two approaches have
also been used. Regardless of the actual term used, we attempt to clarify the intent of the
different approaches in summarizing the relevant studies.
AS management strategies typically use a predefined protocol to monitor triggers for
initiating curative treatments, whereas watchful waiting (WW) strategies use a somewhat passive
(compared to AS) followup and upon symptomatic disease progression palliative treatments are
instituted. A wide variety of combinations of monitoring parameters including clinical
symptoms, digital rectal examination (DRE) findings, Gleason score, PSA concentrations, PSA
doubling time and/or velocity, results from transrectal ultrasound (TRUS) guided rebiopsy, bone
scan or other imaging modalities have been used. However, the optimal monitoring strategies in
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patients choosing AS have not yet been well-characterized.
For this Key Question, we undertook a systematic review of the literature to identify studies
that followed men who were initially managed conservatively (e.g., AS and WW) and that

c For example, the Cancer Intervention and Surveillance Modeling Network (CISNET), a consortium of NCI-
sponsored investigators, uses a comparative modeling approach to explore prostate cancer trends in the US
population. Additional information is available at http://cisnet.cancer.gov/; last accessed October 31, 2011.

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