Page 36 - An Evidence Review of Active Surveillance in Men With Localized Prostate Cancer

Introduction

In 2011, more than 240,000 men are projected to be diagnosed with prostate cancer and
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33,000 to die from the disease in the United States. In the United States, most cases of prostate
cancer are detected via prostate-specific antigen (PSA) screening. The cancer is usually
localized, and most tumors have low histological grades and low Gleason scores. Indeed, more
than half of prostate cancers detected by PSA screening are expected to be early-stage, low-risk
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tumors. Such cancers are an infrequent cause of death, and those affected are more likely to die
of unrelated causes.
A number of immediate active treatment options are available for localized prostate cancer.
Most commonly, radical prostatectomy (RP) or radiation therapy (RT), with or without androgen
deprivation therapy (ADT) are offered with curative intent. However, the clinical benefit of
immediate therapy with curative intent has not yet been demonstrated for localized prostate
cancer in a PSA-screened population. It is likely that a large number of men are receiving
treatment with curative intent without clinical benefit due to the slow progression of many
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prostate tumors. Both surgical and radiation treatments result in significant short- and long-term
adverse events, including impotence, urinary dysfunction, and other complications. Thus,
determination of the appropriate management strategy for early-stage, low-risk prostate cancer is
an important public health concern.
Active surveillance (AS) and watchful waiting (WW) are two observational followup
strategies that forego immediate therapy in patients with prostate cancer. AS is curative in intent,
while WW palliative. AS is appropriate in men with disease believed to be indolent and therefore
may not require therapy. Because prediction tools are imperfect, these men are monitored closely
and treated with curative intent at signs of progression or at patients’ discretion. In this way, the
considerable adverse effects of treatment are at best avoided and at least deferred. This approach
is to be distinguished from men for whom treatment is deemed inappropriate due to comorbidity;
for these men, WW is generally considered, as it offers the option of palliative therapy upon
symptomatic disease progression. AS often entails a multifactorial followup of patients—
monitoring of PSA values, digital rectal examinations (DRE), prostate imaging, and periodic
prostate biopsies—while WW is commonly a relatively passive strategy, with interventions
triggered by symptoms. However, there is a continuum of aggressiveness of followup for both
AS and WW, as currently practiced. Even though the two terms are used commonly in the
scientific literature, the underlying intent (curative vs. palliative) is not always made clear.
Furthermore, many analyses or databases combine AS, WW, and noncurative treatments like
primary ADT in their analyses, making it impossible to ferret out issues specifically related to
AS.
The choice of immediate active treatment requires the careful consideration of a number of
tradeoffs, such as balancing the harms of short- and long-term complications from curative
treatments against the benefits of potential reductions in long-term morbidity and mortality. AS
and other observational management strategies may, therefore, be considered by men who are
more interested in avoiding the risks of curative treatment. Thus, it is important to clarify
appropriate eligibility criteria and followup protocols for observational strategies that could
minimize both unnecessary early curative treatments and avoidable prostate cancer symptoms
and deaths. Of course, this strategy depends on the supposition that AS is as effective as (or no
worse than) immediate curative treatments in an appropriate subgroup of men diagnosed with
prostate cancer; this, however, remains to be proven. Furthermore, some men may be
uncomfortable with observational management and feel a strong need to “do something,” and

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