of prostate biopsy cores compared to initial biopsy. Since the initial
diagnostic 12-core systematic prostate biopsy has a 25-30% chance
of missing higher-grade cancer, an initial confirmatory biopsy
should be performed in the first six to 12 months. Young age is not
a contraindication for active surveillance and men <55 years old
can be managed safely with active surveillance especially for those
with low volume Gleason Score 6 cancer (≤2 cores positive and
no core >50% involved). However, young men with very long life
expectancy should be informed of the lack of long term data for
active surveillance beyond 15 years (8).
Several large active surveillance cohorts have underscored the
safety of this approach to the management of favorable risk prostate
cancer. In a study of 1,298 patients on active surveillance for low-risk
prostate cancer, Tosoian et al. reported only a 0.1% prostate cancer
mortality rate at 15 years (6). The investigators were selective in
their patient inclusion, including only patients with Gleason 6 with
no more than two positive cores and no core >50% involved. The
Toronto group included 993 patients and demonstrated a 5% prostate
cancer specific mortality at 15 years (7). This cohort included higher
risk patients including those with intermediate risk disease (Gleason
7 or PSA >10). Almost all the patients who developed metastasis
were in the intermediate risk subgroup.
Patient selection for active surveillance can be improved by
employing diagnostic and prognostic tools such as prostate MRI and
genomic assays. Multiparametric prostate MRI has good sensitivity
and specificity in identifying large foci of high-grade cancer which
can then be targeted during prostate biopsy (9). MRI also identifies
cancers in the anterior zone of the prostate which are usually missed
by conventional prostate biopsy. MRI will not completely replace
the need for prostate biopsy, since MRI often misses smaller foci
of cancer. However, a negative MRI increases the likelihood that
the patient does not harbor clinically significant cancer. Genomic
assays are performed on tissue from prostate biopsy and provide
an estimate of likelihood of disease progression based on tumor
biology (10). Examples of commercially available genomic tests
include the Oncotype DX test which evaluates the expression of
12 genes in four cancer related pathways; the Prolaris test which
analyzes 31 cell cycle and 15 housekeeping genes by RT-PCR; and
Confirm MDx which is an epigenetic assay. Genomic assays are
particularly useful in the patient with higher risk features such as
Gleason 6 in multiple biopsy cores or patients with low-intermediate
risk disease (Gleason 3+4=7) where a high genomic risk score may
support early treatment rather than active surveillance.
Active surveillance has gradually gained traction worldwide
as the preferred management approach for patients with low-risk
prostate cancer. However, the uptake of active surveillance is far from
universal and varies considerably amongst urologists in the United
States. Data from the US Cancer of Prostate Strategic Urologic
Research Endeavour (CAPSURE) database suggests that only 40%
of eligible low-risk patients were managed with active surveillance
MEN'S HEALTH
during 2010-2013 (11). Recent updates to the NCCN guidelines
which specify active surveillance as the preferred option for low
risk prostate cancer may lead to increased utilization of active
surveillance.
Active surveillance should be considered for all men with
low-risk prostate cancer as it limits the negative impact of over-
diagnosis and over-treatment of clinically insignificant cancer while
maintaining a window for curative treatment. The overall risk of
metastasis and prostate cancer mortality with active surveillance is
very low, approximately 3% at 15-years. Indeed, death in men on
active surveillance is most likely due to non-prostate cancer related
causes such as cardiovascular disease (10 times more likely than
prostate cancer mortality) (7). Despite the benefits, only 40% of
eligible low-risk prostate cancer patients are managed with active
surveillance and further studies are required to determine and
address the impediments to its wider adoption amongst urologists
in the United States.
Dr. Haddad is a practicing urologist at the University of Louisville.
References
1. Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA: a cancer journal
for clinicians. Jan 2017;67(1):7-30.
2. Jahn JL, Giovannucci EL, Stampfer MJ. The high prevalence of undiagnosed
prostate cancer at autopsy: implications for epidemiology and treatment of
prostate cancer in the Prostate-specific Antigen-era. International journal
of cancer. Dec 15 2015;137(12):2795-2802.
3. Ross HM, Kryvenko ON, Cowan JE, Simko JP, Wheeler TM, Epstein JI.
Do adenocarcinomas of the prostate with Gleason score (GS)