Active surveillance of
early prostate cancer
Up to 80% of men with PSA
screen detected prostate cancer are overdiagnosed, that is, their
cancer would never have caused any symptoms  . Overdiagnosis
would not matter if treatment had no adverse effects. It would
be acceptable to treat all cases, including those destined never
to cause symptoms, if treatment was problem-free. However, while
radical treatment for prostate cancer may or may not improve a man's
longevity, it can certainly have a big impact on his lifestyle.
Ideally, such intervention should be restricted to those who
need it. Active surveillance aims to individualise the management
of early prostate cancer by selecting only those men with significant
cancers for curative treatment  .
Patients on active surveillance
are closely monitored using serum PSA levels and repeat prostate
biopsies. The choice between curative treatment and continued
observation is based on evidence of disease progression during this
monitoring. Active surveillance must be distinguished from watchful
waiting, which for decades has described a policy of observation
with the use of palliative treatment for symptomatic progression.
Put another way in order to emphasise the differences between
these two contrasting approaches, whereas watchful waiting involves
relatively lax observation with late, palliative treatment for those
who develop symptoms of progressive disease, active surveillance
involves close monitoring with early, curative treatment in those
with evidence of biochemical or histological progression.
The concept of active surveillance
was formally described for the first time in 2001 by Richard Choo
from Toronto, in a report of 'watchful observation with selective
delayed intervention for clinical, histologic, or PSA progression'
 . Eligibility was restricted to men with clinical stage T1b-T2b
disease with a Gleason Score < 7, and initial PSA <
15 ng/ml. Men were followed every 3 months for the first
2 years and then six-monthly, with digital rectal examination and
PSA testing on each visit. Repeat biopsy was performed at 18 months.
Indications for radical treatment were PSA progression, defined
as a PSA doubling time < 2 years; histologic progression, defined
as upgrading to Gleason score > 8 on re-biopsy; or clinical
progression. The latest update of this study included data on
206 men, with a median initial PSA of 6.5 ng/ml  . At a median
follow-up of 29 months, 48 had received curative treatment, 4 had
died of unrelated causes, and 154 men remained on observation.
Our own initial experience
is similarly encouraging. Between 1993 and 2001, 80 men with
early prostate cancer were managed using active surveillance at
the Marsden. To date, ten have received curative treatment, three
have died from unrelated causes, and 67 continue on observation.
No patient has developed metastatic disease, and none has died of
prostate cancer. It is interesting to note that the median PSA
doubling time in the Marsden series is as long as 12 years, suggesting
an indolent course of disease in most cases.
In the light of these encouraging
initial results, a prospective clinical trial of active surveillance
was started at the Royal Marsden Hospital in 2002. To date, over
200 men with early prostate cancer have been recruited. Men in
the trial are closely monitored with monthly PSA levels for the
first 12 months, MRI scans of the prostate, and repeat prostate
biopsies. Preliminary results suggest that approximately 80% of
men in the trial will avoid the need for curative treatment of their
Active surveillance is not
just an attractive alternative to immediate treatment, but also
an opportunity for clinical and translational research  . Active
surveillance can provide a unique insight into the natural history
of prostate cancer, and so will make it possible to identify new
markers of prostate cancer behaviour. Men on active surveillance
at the Royal Marsden are invited to give samples of blood and urine
for this type of research. The PROACTIV trial, which is under
development, will aim to study the effect of nutritional interventions
on the rate of prostate cancer progression in men with early prostate
cancer managed by active surveillance. It is hoped that this 'tertiary
prevention' approach using well-tolerated nutritional supplements
might avoid the need for conventional curative treatments in some
In summary, active surveillance
is an attractive approach to the management of early prostate cancer,
which may spare men the side effects of treatment, without compromising
survival. Active surveillance also provides an ideal setting for
research to identify new markers, which, in the future, could improve
our ability to determine which men need, and which men do not need,
treatment for their prostate cancer.
Men with early prostate
cancer (PSA less than 15, Gleason score less than or equal to 7)
aged less than 80 years who would like to find out more about the
active surveillance research program at the Institute of Cancer
Research and the Royal Marsden Hospital should contact Dr. Chris
Yao, S.L. and G. Lu-Yao, Understanding and appreciating overdiagnosis
in the PSA era. J Natl Cancer Inst, 2002. 94 (13):
Parker, C., Active surveillance: an individualized approach
to early prostate cancer. BJU Int, 2003. 92 (1):
Choo, R., et al., PSA Doubling time of prostate carcinoma
managed with watchful observation alone. Int. J. Radiat.
Oncol. Biol. Phys., 2001. 50 (3): p. 615-620.
Choo, R., et al., Feasibility study: watchful waiting for
localized low to intermediate grade prostate carcinoma with selective
delayed intervention based on prostate specific antigen, histological
and/or clinical progression. J Urol, 2002. 167 (4):
Parker, C., Active surveillance: towards a new paradigm in
the management of early prostate cancer. Lancet Oncol, 2004.
5 (2): p. 101-6.