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. Specifically, a PSA doubling time <3 yr is no longer
used to switch to active treatment. Also, the presence of two
positive cores triggers an MRI with targeted biopsy but not
by itself a switch to active treatment. The original criteria
explain the low TFS rates, with 48% and 27% at 5 yr and
10 yr, respectively. Rates of treatment and long-term
outcomes are entirely dependent on eligibility criteria,
follow-up strategies, and thresholds for intervention
). Almost all series included in our manuscript
evaluate TFS rate which consist of the number of patients
still on AS after a certain period. The decision to submit
patients to whole-gland treatment rather than continue
with AS is mainly related to the reclassification of the tumor
with an increased risk of progression. Almost two out three
patients are still in AS after 5 yr of follow-up, although in
some series these percentages drop to 50%. Long-term
follow-up is provided by some series which indicate a 15-yr
TFS ranging from 34% to 55%. Low-risk patients on AS record
excellent long-term survival outcomes with 10-yr cancer-
specific survival ranging from 98.1% to 100%. These data
suggest that even in stringent schemes, there are a limited
number of patients who died from PCa. Based on these data,
AS should be discussed as a management option for any
man with very low-risk or low-risk PCa. Welty et al
defined factors associated with progression in patients
enrolled to AS. They found that PSA density, the number of
biopsies, and the time between biopsies were significantly
associated with biopsy reclassification or local treatment.
Current European guidelines recommend AS with a
level of evidence of 2a for patients with low-risk PCa and
>10 yr of life expectancy. Current National Comprehensive
Cancer Network guidelines distinguished very low-risk
and low-risk PCa. Very low-risk PCa should be considered to
AS when their life expectancy is between 10 yr and 20 yr. In
contrast, when life expectancy is less than 10 yr, observation
is recommended. For low-risk PCa patients, AS is an option
along with EBRT, brachytherapy, and RP for patients with
more than 10 yr of estimated life expectancy. Patients with
less than 10 yr of expected survival should be observed only.
3.6. Focal therapy for low-risk PCa
Focal therapy may represent a viable option for men with
low or intermediate-risk PCa [18_TD$DIFF] . The main purpose of
focal therapy is to selectively ablate tumors while
attempting to limit toxicity by sparing the neurovascular
bundles, sphincter, and urethra. In this regard, low volume
unifocal or unilateral tumors represent the ideal target for
this approach although at the time no high quality long-
term data exist supporting this theory and therefore should
be offered very cautiously . Several types of ablative
technologies are available: high-intensity focused ultra-
sound (HIFU), cryotherapy, photodynamic therapy, laser
interstitial thermotherapy, electroporation, radiation fre-
quency ablation, and focal brachytherapy . At this
time, focal therapy should be considered an experimental
approach that might potentially reduce toxicity compared
with whole-gland treatment. High quality prospective trials
are required to demonstrate oncologic or quality of life
benefits over other available options . A selection of
studies reporting oncological outcomes in low-risk PCa
patients treated with focal therapy are presented in .
Table 4 – Characteristics of prospective studies evaluating active surveillance in patients with low risk prostate cancer
References Design population Study
period
Patients Median
follow-up
TFS (%) Overall/disease
specific survival
[8_TD$DIFF] Randomized, population
based trial screen-detected
PCa
1995–2014 244 (51%) and
126 (27%) very
low and low risk,
respectively
96 mo TFS: 10 yr: 47% 15 yr: 34% Overall population:
CSS 10 yr: 99% CSS 15 yr: 96%
Very low risk:
CSS 10 yr: 100%
CSS 15 yr: 100%
Low risk:
CSS 10 yr: 100%
CSS 15 yr: 94%
[9_TD$DIFF] Multicentric prospective
PRIAS
2006–2012 2494 19 mo During follow-up, 527 patients
(21.1%) underwent active therapy
TFS: 2 yr 77.3%
CSS 100%
[10_TD$DIFF] Multicentric prospective
PRIAS update
2006–2015 5302 — 1768 Treated during follow
up/TFS: 5 yr: 48%, 10 yr 27%
NA
[11_TD$DIFF] European Randomized
Screening for Prostate
Cancer
1993–2007 509 patients 381
low risk
89 mo 152 (40%) Low-risk patients
treated during follow-up
TFS:10 yr 50% for low-risk patients
Low risk
OS 10 yr: 79%
CSS 10 yr: 99%
[12_TD$DIFF] Prospective randomized 1995–2014 1298 60 mo Median treatment-free survival
was 8.5 yr
OS: 10 yr 93%
OS: 15 yr 69%
CSS: 10 yr 99.9%
CSS: 15 yr 99.9%
[13_TD$DIFF] Prospective study 2002–2011 471 68 mo TFS: 5 yr 70% OS: 2 yr 99%
OS: 5 yr 96
[14_TD$DIFF] Prospective study 1995–2013 993 77 mo TFS 5 yr: 75.7%
TFS 10 yr: 63.5%
TFS 15 yr: 55.0%
CSS: 10 yr 98%
CSS: 15 yr 94%
CSS = cancer-specific survival; NA = not applicable; OS = overall survival; PCa = prostate cancer; TFS = treatment-free survival.
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