EURURO Vol. 72 No. 2

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Finland, and Iceland. Eligible criteria were: PSA <50 ng/ml,
clinical stage T2, negative bone scan, <75 yr of age with a
life expectancy of more than 10 yr, and no other cancer. At
18 yr, overall mortality rates were 56% versus 69% for
patients treated with RP versus watchful-waiting, respec-
tively (relative risk: 0.71, confidence interval: 0.59–0.86,
p < 0.001). The number needed to treat to prevent one
death at 18 yr was eight. At 18 yr, 17.7% died from PCa from
the RP group with 28.7% from the watchful waiting group
(relative risk: 0.56, confidence interval: 0.41–0.77,
p = 0.001). Among the 249 low-risk PCa patients, a
reduction of 15.6% in the risk of death from any cause
and 10.6% in the risk of metastases was reported
(p = 0.002 and p = 0.006, respectively). In contrast, the
reduction of 3.8% in the risk of dying from PCa was not
significant (p = 0.2). The aforementioned trials enrolled
patients between 1994–2002 and 1989–1999. Several
notable differences can be identified when compared with
contemporary low-risk patients, such as different biopsy
techniques, modifications in Gleason scoring, and differ-
ences in treatments. Aminority of patients included in these
trials had low-risk characteristics (36% and 40%), while
contemporary patients diagnosed following PSA screening
more commonly have low-risk features .
Recently, the Prostate Testing for Cancer and Treatment
trial presented 82 429 men between 50 yr and 69 yr
who received a PSA test between 1999 and 2009. Overall
2664 patients were diagnosed with localized PCa; of these,
1643 agreed to undergo randomization to active monitoring
(545), surgery (553), or radiotherapy (545). With a median
follow up of 10 yr, there were 17 deaths from PCa, eight in
the active monitoring group, five in the surgery group, and
four in the radiotherapy group. Surgery and radiotherapy
were associated with lower incidence of disease progres-
sion (112 in the AS group, 46 in the RP group, and 46 in the
RT group, p < 0.001) and metastases (33 in the AS group,
13 in the RP group, and 16 in the RT group, p = 0.004) but the
10-yr cancer specific mortality was low irrespective of the
management assigned with no differences observed among
treatments (98.8% in all groups, p = 0.5). Consequently, they
estimated 27 men would need to be treated with
prostatectomy or 33 men with radiotherapy rather than
receive active monitoring to avoid one patient having
metastatic disease. A total of nine men would need to be
treated with RP or radiotherapy to avoid one patient having
clinical progression. Although most patients had tumors
with a Gleason score of 6 (77%) or T1c stage disease (76%),
data considering only low-risk PCa were not reported. The
Prostate Testing for Cancer and Treatment trial also
investigated quality of life of 1643 patients using validated
questionnaires and patients treated with RP had the
greatest negative effect on sexual function and urinary
continence
3.4. Pathological findings at RP in patients with low-risk PCa
Many studies have evaluated pathological findings at RP in
patients with low-risk PCa ). Evaluating predictors
of upstaging or upgrading are potentially helpful in
identifying low-risk PCa patients who may benefit from
early whole-gland treatment. Dinh et al analyzed data
of 10 273 low-risk PCa patients who had RP in the
Surveillance, Epidemiology, and End Results database.
Upgrading and upstaging were identified in 44% and 9.7%,
respectively. Similar findings have been observed in other
retrospective studies suggesting that the risk of
harboring pathological Gleason score >6 ranged from 30%
to 55% and the risk of pathological Gleason 8–10 disease
was minimal (0.7–1.7%). Extraprostatic extension was
reported in 9–26% and positive surgical margin rate ranged
from 11% to 16%. Lymph node metastases at final
pathological report were exceedingly rare (range: 0.6–
0.7%). Among men with very low-risk PCa, the risk of
extraprostatic extension at RP is approximately 25% ,
while upgrading has been reported in approximately 33%
. Although upstaging and upgrading rates were
lower in very low-risk PCa when compared with low-risk
PCa, the risk of harboring adverse pathologic features is still
considerable.
Weiner et al evaluated the impact of delayed RP
(untreated for a minimum of 6 mo) in 17 943 low-risk PCa
patients and found half of patients experienced at least one
adverse pathologic outcome at RP specimen, although
delaying RP up to 12 mo did not change the risk of adverse
pathology. Auffenberg et al recently evaluated
2858 low-risk PCa patients from practices in Michigan
Urological Surgery Improvement Collaborative. Among the
group, 778 (27%) underwent immediate RP while AS was
Table 2 – Characteristics of randomized trials prospectively evaluating low-risk prostate cancer (PCa)
References Design Study
period
Population Treatment Median
follow-up (yr)
Results Conclusion
Wilt et al
2012
Prospective
trial: PIVOT
trial
1994–2002 296 Low-risk
D‘Amico patients:
148 RP vs 148 WW
WW vs RP 10.0 CSM: 12 yr: 2.7% vs 2.7%
for RP vs WW (p = 0.5),
respectively
OM: 12 yr: 37.2% vs 31.8%
for RP vs WW (p = 0.4),
respectively
RP in low-risk PCa
did not reduce
metastases, CSM, or
OM in comparison
to WW
Bill-Axelson
et al 2014
Prospective
trial: SPCG-4
1989–1999 249 Low-risk
D’Amico patients:
118 RP vs 131 WW
WW vs RP 23.2 Reductions of 15.6% OM
and 10.6% metastases;
the reduction of 3.8% CSM
was not significant
The reduction of OM
and metastases risk
for RP patients but
no difference in CSM
CSM = cancer-specific metastasis; OM = overall mortality; RP = radical prostatectomy; WW = watchful waiting.
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