MEN'S HEALTH
ACTIVE SURVEILLANCE FOR PROSTATE CANCER
AUTHOR Ahmed Haddad, MD, MBChB, PhD
P
rostate cancer (PCa) is the most
common non-cutaneous malignancy
and the second leading cause of
cancer related death in men in the
United States. According to the
American Cancer Society, there has
been a 51% reduction in prostate
cancer mortality in the past 30 years, largely
attributable to widespread screening with serum prostate specific
antigen (PSA) (1). Not all prostate cancer detected by PSA screening
has the potential to progress or metastasize. The prevalence of
indolent prostate cancer is high, as evidenced by the findings of
autopsy studies that have shown a 40-50% prevalence of occult
prostate cancer in men over the age of 70 years who die of other
causes (2). A fundamental limitation of PSA screening is the over-
diagnosis of clinically insignificant cancers. Approximately half of
screened men diagnosed with prostate cancer on systematic biopsy
have low-risk disease defined as Gleason Score 6 (Grade Group 1)
and PSA< 10.
Several large surgical series have shown that patients with
Gleason Score 6 prostate cancer are highly unlikely to develop
metastasis or die from prostate cancer. In a study of 14,000 men
with Gleason Score 6 prostate cancer who had undergone radical
prostatectomy, Ross et al. identified only 22 men with lymph node
metastasis (3). On re-examination of the prostatectomy specimen
in these patients, they identified higher Gleason grade cancer in all
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LOUISVILLE MEDICINE
22 patients. Thus, lymph node metastasis was not identified in any
patient with true Gleason Score 6 cancer. Similarly, Eggener et al.
demonstrated that only three of 9,557 patients who had undergone
radical prostatectomy for Gleason Score 6 prostate cancer died of
prostate cancer at 15-years (4). Molecular studies underscore the
low malignant potential of Gleason 6 tumors. Gleason 6 lacks many
of the molecular hallmarks of cancer such as over-expression of
genes involved in proliferation, invasion, metastasis and evasion of
apoptosis. The term “indolent lesion of epithelial origin” has been
proposed as an alternative to Gleason 6 to minimize patient anxiety
and reduce over-treatment of these indolent cancers (5).
Historically, radical therapy with radical prostatectomy or
radiation therapy was the standard treatment for patients with
Gleason 6 cancer. We now know that this represents significant
over-treatment. Conservative management (active surveillance) has
been increasingly employed for the management of men with low-
risk prostate cancer. The National Comprehensive Cancer Network
(NCCN) guidelines state that active surveillance is preferred for
men with low-risk prostate cancer and a life expectancy of ≥ 10
years. The goal of active surveillance is to minimize toxicity from
radical treatment for men with low-risk prostate cancer with the
intention to administer curative treatment in the event of signs of
disease progression. Patients on active surveillance are monitored
with semi-annual PSA and repeat prostate biopsy every three to
five years. Progression is defined as detection of higher Gleason
grade tumor on repeat biopsy or cancer occupying a greater extent