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34 Role ofProstate MRI forPostfocal Treatment Assessment andSurveillance
423
a
c
b
d
Fig. 34.2 Multiparametric MRI in a 60-year-old man
with an elevated prostate-specic antigen level of 17.35
ng/mL who previously had a high-intensity focused ultrasound therapy. Patient has a recurrent disease located in
the left apical peripheral zone. (a) Axial T2-weighted
image shows hypointense appearance of the lesion
(arrow). (b) High–b value diffusion-weighted image
recurrence on a per-patient basis. On a per-sector
basis, the sensitivity and specicity of this interpretation system were 0.42 and 0.87, respectively. They concluded that despite the limited
sensitivity, a high level of suspicion identied
through post-HIFU MRI holds clinical signicance due to its high specicity, particularly
when acknowledging the potential for sampling
errors during biopsies.
Another study evaluated the performance of
mpMRI and prostate specic antigen (PSA) testing in follow-up after HIFU for localized PCa.
The cohort was comprised of 73 men, who underwent HIFU followed by per-protocol PSA and
mpMRI. The association between post-HIFU
mpMRI and PSA with disease persistence on
shows high signal intensity within the lesion (arrow). (c)
Apparent diffusion coefcient map showing low signal
intensity within the lesion (arrow). (d) Dynamic contrastenhanced image shows early enhancement of the lesion
(arrow). MRI/US fusion–guided biopsy revealed clinically signicant prostate cancer with an International
Society of Urological Pathology grade of 4
biopsy was studied. However, 58% of men with
persistent ≥ Gleason grade 2 disease had no visible lesions on mpMRI and the patients with false
negative mpMRI ndings had higher PSA density. The researchers concluded that mpMRI
alone may not be sufcient to rule out residual
cancer in the post-HIFU setting [19].
Focal Laser Ablation (FLA)
FLA represents a thermally induced ablation
methodology that employs high-energy laser
irradiation to induce coagulative necrosis in specied tissue regions through rapid thermal
escalation.
424
O. T. Esengur et al.
Within a cohort of 27 participants, Westin
etal. [11] documented the occurrence of a hypovascular anomaly in the zone of ablation on
mpMRI scans conducted right after FLA procedures. Subsequent imaging at a 3-month interval
post-FLA revealed the presence of a patchy or
band-like diminution in T2 signal intensity in
66.7% of the treated lesions. At the 12-month
mark, T2 scarring was noted in a similar proportion (66.7%) of the lesions. Notably, in instances
where postablation biopsies yielded positive
results, the lesions exhibited low T2 signal and
diffusion restriction on apparent diffusion coefcient (ADC) maps. Additionally, there was an
observation of focal enhancement within the
ablation region (Fig. 34.3). Furthermore, a
a
marked decrease in the forward volume transfer
constant at the ablation site was evident upon
follow-up assessments, indicating signicant
alterations postablation.
In a 2020 study, early postoperative mpMRI
observations encompassed the presence of
edema, rim enhancement surrounding the ablation area, a T2W hypointense boundary encircling the ablation zone, and the formation of a
discernible ablation cavity. Subsequent scans
delineated progressive enhancement within the
ablation zone and the development of a scar characterized by T2-hypointensity [10].
Regarding the incidence of recurrence, Chao
etal. [20] discerned in their study that the occurrence of in-eld or out-of-eld recurrence was
b
c
Fig. 34.3 Multiparametric MRI in a 73-year-old man
with an elevated prostate-specic antigen level of 7.96 ng/
mL who previously had a focal laser ablation therapy.
Patient has a recurrent disease located in the right apicalmid anterior transition zone. (a) Axial T2-weighted image
shows hypointense appearance of the lesion (arrowheads).
(b) High–b value diffusion-weighted image shows high
d
signal intensity within the lesion (arrowheads). (c)
Apparent diffusion coefcient map showing low signal
intensity within the lesion (arrowheads). (d) Dynamic
contrast-enhanced image shows early enhancement of the
lesion (arrowheads). MRI/US fusion–guided biopsy
revealed clinically signicant prostate cancer with an
International Society of Urological Pathology grade of 2
34 Role ofProstate MRI forPostfocal Treatment Assessment andSurveillance
425
prevalent, with a 40% rate of in-eld recurrence
and two instances of metastatic disease postFLA, necessitating salvage ablation interventions. In a separate analysis involving 120 patients
diagnosed with low to intermediate risk PCa, 44
individuals (constituting 36.4% of the cohort)
exhibited positive postablation MRI ndings
(with a PI-RADS score of ≥3 for out-of-eld
recurrences) or persistent PSA levels. Notably,
all recurrences were identied at the margins or
the original site of the ablation, underscoring the
localized nature of tumor recurrence [21].
Irreversible Electroporation (IRE)
In IRE, electroneedle probes are positioned through
the perineum encircling the ablation target, directed
by ultrasound or MRI. Subsequently, surges of
high-voltage electric current are transmitted
through these probes, inducing the formation of
pores in the cell walls of the prostate gland, which
ultimately leads to cellular necrosis [22].
In terms of post-IRE changes on mpMRI
images, the site of ablation is observed as a
hypointense diffuse scarring area on T2W imaging, restricted water diffusion on DWI, and
decreased contrast perfusion on DCE.It is also
reported that biopsy proven actual in-eld lesions
that emerged after IRE are seen as focal hyperperfusion on DCE, restricted water diffusion on
DWI [12]. Geboers etal. [13] reported true positive in-eld lesions as hypointense on T2W imaging with restricted water diffusion on DWI and
restricted perfusion on DCE.
In the article by Scheltema etal. [12], a cohort
of 50 patients underwent IRE and subsequent
monitoring entailing a follow-up mpMRI at a sixmonth interval and a transperineal templatemapping biopsy after 12 months. For regions of
interest within the treatment eld, the sensitivity,
specicity, positive predictive values (PPV), and
negative predictive values (NPV) for detecting
clinically signicant PCa which is dened as
International Society of Urological Pathologists
grade ≥2 or ≥1 with a maximum cancer core
length of ≥4 mm, were recorded as 38%, 86%,
33%, and 88%, respectively. The PPV and NPV
for out of eld recurrence were found 50% and
80%, respectively, and for the recurrence in the
entire gland, they were found 47% and 70%,
respectively. The ndings imply that MRI may be
capable of excluding substantial disease presence. Nonetheless, considering the limited scale
of the study, it is advised to continue employing
biopsy as a conrmatory measure for the diagnosis of PCa until the outcomes are substantiated
through a more extensive trial.
Geboers etal. [13] demonstrated that the sensitivity, specicity, PPV, and NPV for mpMRI in
identifying residual clinically signicant PCa
across the entire gland were respectively 35.8%,
82.0%, 47.1%, and 74.1%. These ndings suggest that the diagnostic precision of mpMRI in
recognizing residual clinically signicant tumors
post-IRE is not optimal.
Focal Cryotherapy (FC)
In FC, PCa cells are subjected to a heat-based
ablation process which consists of successive
phases of freezing and thawing leading to their
coagulative necrosis [17].
Tokuda et al. [14] investigated the post-FC
mpMRI sequences of 16 patients for a median
follow-up period of 22 months. They reported
that, at 3 months, the T1W images, T2W images,
and DWI of most of the patients showed a hyperintense lesion with a hypointense rim. This
hyperintense area later diminished 6 months after
the therapy. However, 17 months after the procedure, every lesion became hypointense.
Furthermore, while most lesions exhibited intralesional enhancement, this nding was not found
on the rst MRI sequences taken following treatment. Most of the patients also had perilesional
enhancement as well at three months which also
disappeared in images taken 23 months after the
therapy.
The post-FC mpMRI ndings of the ablation
zone are described by Velaga etal. [15] as scarring and capsule retraction on T2W imaging,
restricted diffusion on DWI and ADC maps, and
absence of enhancement on DCE images. In-eld
recurrent disease was described as focal T2W
426
O. T. Esengur et al.
a
c
b
d
Fig. 34.4 Multiparametric MRI in a 66-year-old man
with an elevated prostate-specic antigen level of 14.61
ng/mL who previously had a cryotherapy. Patient has a
recurrent disease located in the midline mid-to-base anterior transition zone. (a) Axial T2-weighted image shows
hypointense appearance of the lesion (arrow). (b) High–b
value diffusion-weighted image shows high signal inten-
imaging hypointense lesion with early enhancement on DCE, hyperintense on DWI, and hypointense on ADC map (Fig.34.4).
Baskin et al. [23] found that MRI has poor
specicity in detecting residual disease after
cryotherapy. Their study showed that 91.7% of
patients with ≥Gleason grade 2 disease on follow- up biopsy had negative or low risk ndings
on corresponding imaging, leading to the conclusion that MRI is not reective of residual disease
on follow-up and making biopsy still the best
method for monitoring recurrence post-FC.
On the other hand, in the more recent study by
Velaga etal. [15], mpMRI was found to be highly
sensitive (100%) but poor specicity (14.82%) in
detecting residual PCa post-FC.The researchers
concluded that the modality may have important
sity within the lesion (arrow). (c) Apparent diffusion coefcient map showing low signal intensity within the lesion
(arrow). (d) Dynamic contrast-enhanced image shows
early enhancement of the lesion (arrow). MRI/US fusion–
guided biopsy revealed clinically signicant prostate cancer with an International Society of Urological Pathology
grade of 5
clinical applications in active surveillance postablation, helping to stratify men with high-risk
lesions requiring rebiopsy from those with lowrisk lesions who may not. Comparing their ndings to those in the article by Baskin etal. [23],
they claimed that conict between the two papers
stemmed from the fact that in Baskin etal., the
expertise of the radiologists in mpMRI was poor
and no reinterpretation was conducted by experienced radiologists leading to the poor performance of the modality in the latter paper [15].
Photodynamic Therapy (PDT)
PDT is a FT method, which rapidly destroys targeted tumors through injection of a photosensi-
34 Role ofProstate MRI forPostfocal Treatment Assessment andSurveillance
427
tizing material leading to vascular disruption.
The efcacy of PDT is often assessed using
mpMRI [16].
Following PDT using WST11 as a photosensitizer, early posttreatment mpMRI (around one
week after therapy) typically shows an increased
volume of the treated lobe and a large, homogeneous area of necrosis. At around 6-months posttreatment, mpMRI shows signicant changes in
the shape and signal of the prostate. These
changes include atrophy of the treated lobe,
irregularly shaped small uid cavities inside the
scar, disappearance of the peripheral hyperintensity of the gland. During this time, minimal areas
of necrosis (hypointense areas with no enhancement) which designate coagulative necrosis can
also be seen. Kulik etal. consider this 6-month
mpMRI as the posttreatment “baseline” appearance for further follow-up or monitoring as the
imaging ndings of the gland persist after this
timestamp [16].
For the mpMRI ndings of recurrent disease,
Kulik etal. [16] also report that the detection of
tumor recurrence in the treated area via MRI is
hindered by the diminished hyperintensity of the
peripheral prostate in T2W images and the signal
interference from scar tissue. Given the absence
of reliable recurrence features and the fact that
small lesions are often not discernible on MRI,
biopsy and post-PDT PSA levels remain the primary utilities in the diagnosis of recurrent disease. However, they state that when recurrence
was visible on MRI, T2W images showed
hypointense nodules and DCE images demonstrated early enhancement.
A 2014 study by Barrett etal. [24] indicates
that DCE-MRI holds potential as a predictive
instrument for positive outcomes post-PDT, particularly following unsuccessful external-beam
radiotherapy. Their ndings reveal that DCEMRI accurately identied recurrent disease in all
10 participants who experienced recurrence after
PDT at a one-week posttreatment evaluation. The
modality demonstrated a sensitivity of 100% and
a specicity of 60%, underscoring its capability
to guide early decisions regarding the necessity
for subsequent treatment interventions.
It is important to note that the changes induced
by PDT in the prostate are not widely reported in
the literature yet, and the specic mpMRI features in the follow-up of patients who underwent
PDT for localized PCa are still in need of being
studied.
Future Perspectives
FT is a relatively new approach in the management of localized PCa compared to prostatectomy and radiation therapy. Surveillance after FT
using imaging, mainly mpMRI, is also a relatively new concept in which traditional mpMRI
interpretation approaches (e.g., PI-RADS) utilized in treatment-naïve patients may not work.
As PI-RADS is compromised in the aftermath of
focal PCa therapies due to the signicant therapeutic changes to the gland, it becomes insignicant in these evaluations. Just like PI-RADS in
the pretreatment setting, a standardized system
for scoring prostate appearance on MRI after FT
would be very benecial. In order to address this
need, Giganti et al. [25] recently proposed a
three-point scale system called Prostate Imaging
after Focal Ablation (PI-FAB), for systematic
evaluation and scoring mpMRI sequences following focal ablation techniques in PCa. The
standardization of PI-FAB aims to minimize
interpretative discrepancies, leading to more
accurate and consistent assessments. The scoring
system has shown promising results in predicting
recurrent clinically signicant PCa after primary
FT.With its reasonably high sensitivity, PI-FAB
holds potential for categorizing patients who may
benet from further prostate biopsy. Nonetheless,
it is crucial to realize that the PI-FAB scoring system is in its early stages, and extensive validation
in broader patient groups is essential to thoroughly understand its efcacy and the advantages
it may offer [26].
Molecular imaging has been documented to
assist PCa diagnosis in treatment naïve and biochemically recurrent PCa. It also has the potential to further assist surveillance and management
of FT.A very commonly used target molecule for
PCa imaging is Prostate-Specic Membrane
Antigen (PSMA), which is an integral membrane
glycoprotein, markedly upregulated in the majority of PCa cells, establishing its role as a robust
428
O. T. Esengur et al.
biomarker for prostate malignancies and a prime
candidate for tumor-specic diagnostic and therapeutic interventions [27]. PSMA-targeted positron emission tomography (PET) imaging has
demonstrated superior precision in disease detection when contrasted with traditional radiological
methods like mpMRI; however, its role in FT is
quite understudied. In a 2019 study by Burger
etal. [28] with a cohort of 10 PCa patients with
negative mpMRI for recurrent disease,
68
Ga-PSMA-11 PET/MRI detected six patients as
positive with a Gleason group ≥3. This study
demonstrates that can PSMA-focused PET/MRI
techniques bare the potential for detecting local
recurrence of PCa after HIFU that was occult on
mpMRI.Future studies will help us to understand
the actual utility of molecular imaging in post-FT
surveillance.
Conclusion
mpMRI has become a crucial tool in the diagnosis, treatment planning, and posttreatment surveillance of PCa, especially with the advent of
FT techniques. In general, posttreatment changes
on T2W images often appear as brotic and signal void darker areas in the prostate, indicating
scarring. However, distinguishing between treatment effects and recurrent disease can be challenging, as both can appear hypointense. Areas of
recurrent cancer may show early enhancement
and washout, distinguishing them from treated
areas, which may have reduced or delayed
enhancement. Restricted diffusion, seen as high
signal intensity on DWI and low signal on ADC
maps, suggests high cellularity, typical of recurrent or residual cancer. On the other hand, in
posttreatment images, both DWI and ADC maps
will show hypointensity due to necrosis or
brosis.
While MRI has enhanced the detection and
delineation of PCa, it is not without its constraints. In the setting of post-FT mpMRI, these
constraints are primarily due to the distortion of
prostate anatomy following FT that leads to
treatment- related artifacts, which can complicate
the interpretation of mpMRI images. An absence
of standardized protocols for posttreatment MRI
data interpretation, and a general lack of expertise in assessing post-FT MRI images among
radiologists amplify these challenges [29].
Advancements in imaging technology, potentially through the integration of articial intelligence, radiomics, or other novel molecular
imaging techniques such as PET with PSMA and
standardized interpretation systems like PI-FAB
could benet this domain [25]. Despite these
advancements, prostate biopsy continues to be
the denitive method for the post-FT follow-up
and evaluation of local recurrence, as both PSA
kinetics and imaging interpretations present considerable interpretative challenges.
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Measuring Patient-Based
Outcomes: Setting Realistic
Expectations When Balancing
Functional Outcomes withCancer
Control
AlexanderLight, DeepikaReddy,
andSrinivasVourganti
35
Introduction
Prostate cancer is the most common male cancer,
and the majority of men will present with localized disease. Of these, most will be managed with
radical treatments, either radical prostatectomy or
radiotherapy. However, a better understanding of
this cancer’s long natural history has led to the
emergence of alternative treatment strategies.
Most recently, the ProtecT trial reported 15-year
data, concluding that radical treatments reduced
disease progression versus active monitoring but
had no additional survival benet [1].
Patients, therefore, need to consider carefully
the harms of treatments. Because radical treatments are applied to the whole gland, they carry
risk to surrounding structures. Accordingly, urinary incontinence is observed in 5–25%, erectile
dysfunction in 30–60%, and bowel dysfunction
A. Light · D. Reddy (*)
Imperial Prostate, Imperial College London,
London, UK
e-mail: a.light@imperial.ac.uk;
Deepika.reddy06@imperial.ac.uk
S. Vourganti
RUSH Medical College, Chicago, IL, USA
e-mail: Srinivas_vourganti@rush.edu
in 1–15%. These risks have largely persisted
despite technological innovations like robotic
surgery and three-dimensional conformal radiotherapy [2].
Driven by innovations in MRI and biopsy
strategies, focal therapy is an attractive alternative that may offer a better therapeutic ratio for
many men with an identiable index lesion.
Through ablating the tumour alone, surrounding
structures are spared, and a better functional outcome may be obtained without compromising
oncological success. The importance of preserving functional outcomes cannot be understated;
previous discrete choice experiments have identied that men are willing to trade a reduction in
cancer-specic survival for a better chance of
retaining continence and erectile function [3].
Focal therapy should be offered to eligible men,
but it is vital that clinicians discuss this treatment
strategy honestly and objectively.
The aim of this chapter is to explore the balance between oncological and functional outcomes of focal therapy in patient consultations.
Oncological Outcomes
A number of oncological outcomes are used to
assess the efcacy of prostate cancer treatments
over the short, medium, and long term. These
© The Author(s), under exclusive license to Springer Nature Switzerland AG 2024
T. J. Polascik et al. (eds.), Imaging and Focal Therapy of Early Prostate Cancer,
https://doi.org/10.1007/978-3-031-66754-1_35
431
432
A. Light et al.
should be considered both together and in isolation, as patients may weigh certain outcomes
differently. Ultimately, however, when composite
treatment failure outcomes are considered, focal
therapy and radical treatments have similar failure rates at up to 8 years follow-up [4, 5].
When discussing descriptors of success following focal treatment, it is important that these
are characterized within the context in which
they are measured. Similar to radical treatments
and active surveillance, regular post-treatment
PSA blood tests are required. MRI is also typically performed between 6 and 24 months to
assess for local recurrence. Some centers may
schedule a further surveillance MRI or may
incorporate an early post-treatment MRI to conrm complete ablation of the intended target,
particularly when treating patients early in the
learning curve. PSMA PET/CT may have high
specicity for the detection of localized recurrence but, to our knowledge, it is not routinely
used unless there is concern for extraprostatic
spread [6].
The need for post-treatment biopsies should
also be mentioned. Consensus guidelines advocate for protocol post-treatment biopsies, whilst
some centres, for example in the UK, only perform this if suspicious of localized recurrence
from PSA kinetics or imaging [7–10]. In contrast,
it is less likely that biopsy is needed after radical
prostatectomy or radiotherapy.
patients in total (2.7%) had died from their cancer. Crucially, cancer-specic mortality only
affected 3.1% of the active monitoring group,
compared to 2.2% and 2.9% in the surgery and
radiotherapy groups, respectively. Furthermore,
104/1610 (6.3%) developed metastases, of which
9.4% were noted in the active monitoring group
and 4.7% and 5.0% in the surgery and radiotherapy groups, respectively.
For focal therapy, the largest analysis and with
the longest follow-up derives from the UK HEAT
registry of HIFU cases, representing 1379 men
from 13 UK centres over 15 years [11]. Only one
patient died from their cancer in recorded follow up, only three developed metastases. The combined 7-year cancer-specic and metastasis- free
survival was 100%.
Patients should therefore, be counselled that
focal therapy has excellent medium-term outcomes with regard to metastases and survival,
which are comparable to other treatments. Given
the excellent long-term survival with active surveillance, it may be expected that focal therapy
would be at least comparable. However, considering its novelty, comment cannot yet be made
about the longer-term survival outcomes in comparison to radical treatments. Regardless, existing medium-term data are certainly reassuring.
Local Recurrence andRetreatment
Cancer-Specic Survival
andMetastases
With many cancer treatments, the most important
oncological outcome is usually cancer-specic
survival, followed by metastasis-free survival.
However, given the very long natural history of
prostate cancer, the feasibility of meaningfully
measuring these outcomes has been questioned.
The recently reported 15-year follow-up data for
the ProtecT randomized-controlled trial provides
the best data to date for which to examine these
outcomes. The trial identied that only 45/1610
Given the targeted and nonextirpative nature of
focal therapy, recurrence within the prostate is an
inherent concern, and is thus a more pressing
medium-term outcome. Recurrence can either be
within the treated zone and its margins (in-eld
recurrence), or outside of it (out-of-eld recurrence). If identied within or close to the treatment zone, retreatment is usually feasible in the
form of a second focal therapy session without
signicant compromise to post-treatment genitourinary functional outcome [12]. Occasionally,
however, disease characteristics or patient choice
may lead to salvage whole-gland therapy being
performed. Clinicians may also utilize androgen
35 Measuring Patient-Based Outcomes: Setting Realistic Expectations When Balancing Functional…
433
deprivation therapy as standalone treatments, or
in combination with local treatments. Therefore,
the detection of local recurrence and the need for
re-retreatment are two oncological outcomes
patients should be counseled on. Whether recurrent cancers are inherently more aggressive and
ablation-resistant than primary cancers is unclear,
and the role of metrics like grade group and
tumor size is not known. However, there are data
to suggest that grade group 1 recurrent cancers
have almost no metastatic potential [13].
A 2021 72-study systematic review determined a median reported in-eld recurrence rate
of 25% (IQR 17–37%) [14]. For clinically signicant in-eld recurrent cancer as dened by
individual studies, this was 12% (IQR 5–19%).
With regard to local retreatments, a 2023 124study systematic review reported focal retreatment being performed in a range of 0–40%, and
whole-gland salvage treatments being performed
in a range of 2–54% [15]. For each outcome, a
breakdown by individual focal therapy modalities is given in Table35.1.
The largest single-study analysis derives from
the UK HEAT registry. Of 1379 men, 252 (18%)
needed at least one further focal therapy session.
26 underwent two further sessions, and 1 underwent four further sessions. Seven-year focal
retreatment-free survival was reported as 43%
(95%CI 39–49%). 132 men (10%) required
whole-gland salvage treatment. Of the 53 radical
prostatectomy patients, 9 underwent this after a
second focal HIFU session. Of 39 radiotherapy
patients, 20 had undergone a second focal HIFU.
7-year whole gland treatment- and systemic
treatment-free survival was 75% (71–80%).
Data suggest that further focal treatments are
feasible, safe, and only minorly impact sexual
and erectile function [12, 16–18]. Whole-gland
salvage treatments also appear feasible. RAFT
was two-centre UK prospective study of salvage
robotic-assisted radical prostatectomy at a
median of 2.1 years after previous focal therapy
[19]. Of 23 men, only one patient demonstrated a
Clavien-Dindo Class 1 complication, 4 (17%)
needed further treatment within a year. At 12
months, 74% had preserved urinary function, but
only 30% had preserved erectile function.
Second, a UK retrospective series compared 100
salvage radical prostatectomy patients against
100 salvage radiotherapy patients after previous
ablation; 23% and 14% needed further treatment
Table 35.1 Summary of study-reported rates for any in-eld recurrence, clinically-signicant in-eld recurrence (as
dened by individual studies), focal retreatment, and salvage whole-gland retreatment
Whole-gland
In-eld clinically-signicant
In-eld recurrence rate
No.
Range
Modality
HIFU 17 0–65 27
Cryotherapy 4 0–57 29
IRE 4 16–39 21
VTP 5 13–37 25
FLA 6 7–70 20
RFA 2 25–30 28
a
Taken from a 2021 72-study systematic review [14]
b
Taken from a 2023 124-study systematic review [15]
studies
(%)
a
Median
% (IQR)
(17–37)
(15–42)
(17–28)
(24–25)
(15–47)
(26–29)
recurrence rate
No.
studies
12 0–31 15
2 0–18 9 (5–14) 14 2–20 15 1–44
4 0–33 9 (5–16) 10 1–11 12 2–16
3 10–13 11
4 4–40 17
1 20 20 1 10 1 20
a
Range
(%)
Median
% (IQR)
(8–21)
(11–12)
(12–24)
Focal retreatment
b
rate
No.
studies
14 2–54 26 3–38
4 2–23 4 8–67
5 2–33 4 2–17
Range
(%)
salvage treatment
b
rate
No.
studies
Range
(%)