CME ARTICLE

MRI of Bladder Cancer: Local and Nodal

Staging
Iztok Caglic, MD, PhD,1* Valeria Panebianco, MD,2 Hebert A. Vargas, MD,3 Vlad Bura, MD
,4 Sungmin Woo, MD, PhD,3 Martina Pecoraro, MD,2 Stefano Cipollari, MD,2
Evis Sala, MD, PhD,1† and Tristan Barrett, MD1†

CME Information: MRI of bladder cancer - Local and nodal Authors:

staging The authors reported no conflicts of interest or financial relationships relevant
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• Define when and how to use MRI in local and nodal staging of bladder Accreditation
cancer
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View this article online at wileyonlinelibrary.com. DOI: 10.1002/jmri.27090

Received Dec 18, 2019, Accepted for publication Jan 21, 2020.

*Address reprint requests to: I.C., Department of Radiology, Addenbrooke’s Hospital and University of Cambridge, Cambridge CB2 0QQ,
UK. E-mail: iztokcaglic@gmail.com
†
Joint senior authors

From the 1Department of Radiology, Addenbrooke’s Hospital and University of Cambridge, Cambridge, UK; 2Department of Radiological, Oncological and
Anatomo-pathological sciences, "Sapienza University", Rome, Italy; 3Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York,
USA; and 4Department of Radiology, County Clinical Emergency Hospital, Cluj-Napoca, Romania
Additional supporting information may be found in the online version of this article

© 2020 International Society for Magnetic Resonance in Medicine 1

Journal of Magnetic Resonance Imaging

Accurate staging of bladder cancer (BC) is critical, with local tumor staging directly influencing management decisions and
affecting prognosis. However, clinical staging based on clinical examination, including cystoscopy and transurethral re-
section of bladder tumor (TURBT), often understages patients compared to final pathology at radical cystectomy and
lymph node (LN) dissection, mainly due to underestimation of the depth of local invasion and the presence of LN metasta-
sis. MRI has now become established as the modality of choice for the local staging of BC and can be additionally utilized
for the assessment of regional LN involvement and tumor spread to the pelvic bones and upper urinary tract (UUT). The
recent development of the Vesical Imaging-Reporting and Data System (VI-RADS) recommendations has led to further
improvements in bladder MRI, enabling standardization of image acquisition and reporting. Multiparametric magnetic res-
onance imaging (mpMRI) incorporating morphological and functional imaging has been proven to further improve the
accuracy of primary and recurrent tumor detection and local staging, and has shown promise in predicting tumor aggres-
siveness and monitoring response to therapy. These sequences can also be utilized to perform radiomics, which has shown
encouraging initial results in predicting BC grade and local stage. In this article, the current state of evidence supporting
MRI in local, regional, and distant staging in patients with BC is reviewed.
Level of Evidence: 3
Technical Efficacy Stage: 2
J. MAGN. RESON. IMAGING 2020.

B LADDER CANCER (BC) is the second most common

genitourinary malignancy after prostate cancer and the
10th commonest cancer worldwide, with an estimated over
540,000 new cases and 200,000 deaths per year.1 The inci-
dence of BC increases with age and is ~3–4 times higher in
men, with tobacco smoking being the greatest risk factor,
accounting for about 50% of cases.2 Urothelial carcinoma
accounts for ~90% of BC cases; with squamous cell carcinoma
(6–8%) and adenocarcinoma (2%) being rare subtypes.3 The
majority of patients (70%) present with nonmuscle invasive
bladder cancer (NMIBC), which has a more favorable progno-
sis than tumors that invade into the detrusor muscle of the
bladder wall: muscle invasive bladder cancer (MIBC); however,
the high rate of recurrence and disease progression requires a
robust long-term follow-up and results in the highest lifetime
treatment costs per patient compared to all cancer groups.4
The most common presenting symptoms in patients
with BC are painless hematuria and/or, less commonly, lower
urinary tract symptoms including dysuria, urgency, and fre-
quency; pelvic pain and urinary obstruction are generally lim-
ited to advanced disease.3 The traditional diagnostic workup
relies on clinical examination, cystoscopy, and transurethral
resection of bladder tumor (TURBT) to confirm the histo-
pathological diagnosis and muscle invasiveness, with com-
puted tomography (CT) typically reserved for evaluation of
locally advanced disease, N- and M-stage.5,6 Accurate staging
is critical, as prognosis and management of patients with BC
largely depends on the local tumor stage and the presence of
lymph node (LN) or distant metastases.5–7 However, there is
a substantial discrepancy between preoperative clinical staging
(combined bimanual examination, TURBT, and conven-
tional imaging) and the final pathologic staging based on radi-
cal cystectomy and LN dissection with an inaccuracy rate of
23–50%, mainly due to understaging of both the depth of
local invasion and LN metastatic involvement.8,9
Magnetic resonance imaging (MRI) is being increasingly
used for the preoperative, local staging of BC due to its high
soft-tissue contrast resolution, and the ability to assess the depth
of bladder wall invasion, with a recent meta-analyses reporting a
high diagnostic performance in differentiating NMIBC from
MIBC, as well as for predicting extravesical extension.10–14
Multiparametric (mp)MRI, which incorporates morphological
T2-weighted imaging (T2WI) alongside the functional
sequences of diffusion-weighted imaging (DWI) and dynamic
contrast-enhanced (DCE) imaging has been proven to further
improve the accuracy of primary and recurrent tumor detection
and local staging, and has shown promise in monitoring treat-
ment response.10–12,15–17 MRI can be additionally utilized for
the assessment of regional LN involvement and tumor spread
to the pelvic bones and upper urinary tract (UUT). However,
sensitivity for detecting LN metastases remains unsatisfactory
due to an overreliance on size criteria.18 Regarding UUT evalu-
ation, CT urography (CTU) is generally recommended as the
first-line investigation; however, MR urography (MRU) has
good sensitivity for depicting UUT tumors and is used when
CTU is contraindicated,6,19 or as part of an all-in-one assess-
ment of the urinary tract in high-risk disease.
In this review we describe the optimal protocols for MR
image acquisition, cover recent updates in image interpreta-
tion, describe the role of MRI in local, regional, and distal
staging of BC, and summarize the added value of bladder
mpMRI in the assessment of treatment response.
Bladder Anatomy and TNM Staging
The bladder is a hollow organ of the lower urinary tract system
located extraperitoneally in the lower anterior pelvis and sur-
rounded by perivesical fat. Its wall consists of 1) urothelium,
the innermost epithelial layer; 2) subepithelial connective tissue
(lamina propria), containing blood vessels, lymphatics, and the
thin and incomplete muscularis mucosa; 3) muscularis
propria—also known as detrusor muscle, which is composed of
inner and outer smooth muscle; and 4) loose connective tissue
of the adventitia.20 On T2WI or DWI, however, only the
muscularis propria is typically identified, either as a low signal
intensity (SI) band, or a thin line of intermediate SI intensity,
respectively. At DCE imaging, the inner layer of mucosa
(which includes the urothelium and lamina propria with

2

muscularis mucosa) shows early enhancement and can thus be
differentiated from the underlying muscularis propria (outer
layer), which demonstrates delayed enhancement.13 Therefore,
from a radiological perspective there are three basic layers of
mucosa, detrusor muscle and perivesical fat which can be dis-
tinguished, all being essential for local BC staging.
The TNM system is employed for staging BC, originally
developed by the American Joint Committee on Cancer
(AJCC) and last updated in 2017 (8th ed).21 Local T-stage is
defined by the depth of tumor invasion into the deep layers of
the bladder wall and surrounding tissues. NMIBC is sub-
classified into Ta (noninvasive papillary carcinoma), Tis (non-
invasive carcinoma in situ), and T1 stage (invasion of lamina
propria). MIBC is subdivided into T2a (invasion of inner half
of the detrusor muscle) and T2b disease (invasion of the outer
half of the detrusor muscle). Of note, according to the eighth
edition of the TNM classification, there is no T2 stage when
cancer arises within bladder diverticuli, as these are classically
acquired pseudodiverticuli, and lack a muscle layer20,22
(Fig. 1). Locally advanced disease recognizes microscopic (T3a)
and macroscopic (T3b) invasion of the perivesical fat. T4 stage
indicates cancer has spread to the surrounding pelvic organs,
pelvic, or abdominal wall.21 N-stage is defined by involvement
of regional LNs (N1–N3) and is described in detail in the
corresponding section below, while M-stage constitutes either
involvement of nonregional LNs (M1a) or distant metastases
(M1b) (Table S1). In addition to TNM stage, the final treat-
ment decisions depend on the grade of cancer, which is histo-
logically stratified into low- and high-grade papillary urothelial
carcinomas according to the 2004 WHO classification.23
MRI Protocol
MRI of the urinary bladder necessitates high-resolution
images with a high signal-to-noise ratio (SNR). This may be
FIGURE 1: Tumor within bladder diverticulum. Axial T2WI (a) and diffusion weighted imaging (b) demonstrate a lesion (arrow) in
bladder diverticulum. It exhibits intermediate T2 signal (SI), has restricted diffusion and measures <1 cm, but the extent of tumor is
unlikely to be appreciated on cystoscopy alone. The lack of a true muscle layer in diverticula mean there is no T2-stage, and in this
case tumor is clearly extending into the perivesicular fat, in keeping with stage T3b.
Caglic et al.: MRI Staging in Bladder Cancer
achieved at either 1.5T or 3T, with a multichannel phase-
array surface coil with at least 16 channels being mandatory.
Localizer sequences serve to ensure correct positioning of the
surface coil and adequate bladder distension, and to plan cov-
erage for the initial high-resolution sequences.
An appropriate field-of-view (FOV) should be selected,
including the entire bladder and incorporating surrounding
structures such as pelvic LNs, the proximal urethra, pelvic
bones, the prostate and seminal vesicles (SV) in men, and
gynecological organs in female patients.24 A multiparametric
(mp) approach combining anatomical and functional
sequences is recommended for urinary BC detection and stag-
ing. The mpMRI protocol should incorporate multiplanar
T2W, DWI, dynamic contrast-enhanced images (DCE-MRI),
and T1-weighted imaging (T1WI)7 (Table 1).
Findings on T2WI, DCE, and DWI should always be
correlated and evaluated altogether, to acknowledge any inter-
sequence mismatch, that could lead to erroneously upstaging
or downstaging of tumors. Numerous studies have
highlighted the improved sensitivity, specificity, and accuracy
when two or more sequences are used for the diagnosis and
staging of BC25–27; DWI, in particular, with its limited spa-
tial resolution, should always be analyzed in conjunction with
anatomical sequences (Fig. 2).
T1WI and T2WI
T1WI spin-echo (SE) images are acquired in the axial plane
employing a large FOV, which should cover the entire pelvis
from the aortic bifurcation to the symphysis pubis. While
T1WI plays a minor role in local staging, it is useful to assess
for blood products within the bladder, lymphadenopathy, and
bone metastases; urine, bladder wall, and perivesical fat will
demonstrate, respectively, low, intermediate, and high SI
intensity.
3
Journal of Magnetic Resonance Imaging

2D fast-spin-echo (FSE) T2WI or turbo-SE thin sec- TABLE 1. Continued

tions (3–4 mm) sequences are acquired employing a small
FOV and a large matrix, in three orthogonal planes (axial, Technical Parameters Technical Parameters
coronal, and sagittal). On T2WI images, urine is of high SI at 1.5 T at 3 T
intensity, and the bladder wall demonstrates a low SI inten- Injection rate: 1.5–2 ml/s
sity (Table 2). Having high-resolution T2WI in three planes
Temporal resolution: 30s
is fundamental in order to accurately assess T-staging.
Total observation: >2min30s

Adapted from reference.7

TABLE 1. Sample Bladder MR Imaging Protocol FOV = field of view; EPI = echo planar imaging;
According to VI-RADS Recommendations (1.5 T DCE = dynamic contrast enhancement; 2D = two- dimen-
sional; 3D = three-dimensional; TR = repetition time; TE = echo
and 3 T)
time; T2WI = T2-weighted imaging; GRE = gradient echo;
SE = spin echo; NEX = number of excitations.
Technical Parameters Technical Parameters
at 1.5 T at 3 T
T2WI (axial, coronal and sagittal planes)
Selection of the most appropriate plane (the one most per-
FOV: 23 cm to encompass the entire bladder and pendicular to the wall being assessed) primarily depends on
surrounding structures the location of the tumor to accurately visualize its relation to
TR/TE: 5000 msec/80 TR/TE: 4690 msec/119 the bladder wall and perivesical fat and to minimize partial
msec msec voluming effects. For instance, for the assessment of tumors
Matrix: 256 × 189–256 Matrix: 400 × 256–320 located in the dome either coronal or sagittal images are pre-
ferred to the axial plane. An additional plane, perpendicular
Section thickens, gap: Section thickens, gap: to the tumor, may also be acquired to assess for muscle inva-
4 mm, 0–0.4 mm 3–4 mm, 0–0.4 mm
sion, or alternatively derived as a multiplanar reformatted
NEX: 1–2 NEX: 2–3 sequence when T2WI is performed using isotropic 3D acqui-
DWI: Axial plane (same orientation as for T2WI) sition.28,29 Correction of the echo time (60–80 msec) enables
a high contrast-to-noise ratio, and allows for full evaluation of
Free-breathing SE EPI sequence combined with spectral depth of muscle invasion.3
fat saturation recommended
FOV: 27–32 cm
DWI
Section thickness, gap: Section thickness, gap: DWI sequences are obtained to study the Brownian motion
4 mm, 0–0.4 mm 3–4 mm, 0.3–0.4 mm of water molecules and offer useful qualitative and quantita-
TR/TE: 4500 msec/88 TR/TE: 2500–5300 tive data on tumor cellularity and cell membrane integrity.
msec msec/61 msec Parallel imaging with short echo times, increasing the number
of excitations (NEX), and adjusting the matrix and voxel size
Matrix: 128 × 109 Matrix: 128 × 128
are strategies that can help maintain sufficient spatial resolu-
b-values: 0–800 or b-values: 0–800 or up to tion and appropriate SNR.7 DW images should generally be
1000 s/mm2 2000 s/mm2 evaluated alongside T2WI to allow visualization and direct
NEX: 10–15 NEX: 4–10 comparison of anatomical structures. DWI is acquired using
DCE: Axial plane (same orientation as for T2WI) free-breathing SE echo-planar imaging (EPI) with spectral fat
saturation in two orthogonal planes (axial and either sagittal
2D or 3D T1 GRE sequence; 3D is preferred; fat or coronal). At least two b-value sequences are required to
suppression may be used obtain an apparent diffusion coefficient (ADC) map, and
FOV: 27–35 cm should include a high b-value of 800–1000 s/mm2 to achieve
Section thickness, gap: Section thickness, gap: sufficient contrast resolution compared to surrounding tis-
2 mm, 0 mm 1 mm, 0 mm sues.25 BC shows increased SI intensity on high b-value DW
images and a reduced ADC, in contradistinction to the inter-
TR/TE: 3.3 msec/1.2 TR/TE: 3.8 msec/1.2 msec
mediate SI intensity of muscularis propria on b-value imaging
msec
and ADC. ADC measurements have been shown to correlate
Matrix: 256 × 214 Matrix: 192 × 192 with BC aggressiveness; therefore, showing promise as an
NEX: 1 NEX: 1 imaging biomarker.30–33 Acquisition of good-quality images
and adequate patient preparation can help avoid “cancer

4
 Caglic et al.: MRI Staging in Bladder Cancer

FIGURE 2: Higher spatial resolution of T2WI helps determine depth of invasion. Multifocal bladder tumors arising from the left lateral
bladder wall. a: The most posterior tumor (arrow) shows intermediate signal (SI) with clear extension into the low SI muscularis
propria on T2WI (inset) in keeping with T2b disease whereas the tumor above it (inset) invades only the inner half of the muscular
layer (T2a disease). Both tumors more anteriorly are confined to the mucosa. b: DWI shows corresponding high SI but the depth of
invasion is more challenging to define in such small lesions due to limited spatial resolution. Conversely, DWI readily depicts a small
tumor arising from the right lateral wall, which could be mistaken for a mucosal fold on T2Wi alone (arrowhead).

TABLE 2. Signal Characteristics on Multiparametric MRI

Structure T1W T2W DWI DCEI (early)a DCEI (late)a

Urine Low SI High SI No SI No SI High SI
Muscle Intermediate SI Low SI Mildly increased Hypo enhancing Enhancing
SI
Tumor Intermediate SI Intermediate High SI Hyper enhancing Isoenhancing
SI
Perivesical High SI High SI No SI No SI No SI
fat
T2 stage Isointense – do Low SI of High SI partly Disrupted low SI line Isointense – do not
no use for muscle within the with early use for staging
staging interrupted muscle wall enhancement
T3 stage High SI of fat High SI of fat High SI partly Disrupted low SI fat Disrupted low SI
interrupted interrupted within the fat with early fat with
enhancement enhancement

T1WI = T1-weighted imaging; T2WI = T2-weighted imaging; DWI = diffusion weighted imaging; DCEI = dynamic contract enhanced
imaging; SI = Signal.
a
DCEI with fat suppression.

mimics,” particularly relating to motion artifact and suscepti-
bility artifact induced by the presence of air (within bladder
or bowel)34 (Fig. 3).
DCE
3D gradient echo (GRE) sequences are preferred due to a
higher spatial resolution, although 2D-T1 GRE is also accept-
able; sequences can be acquired either with or without fat
suppression.35 Imaging should be obtained before and after
gadolinium-based contrast medium injection (0.1 mmol/kg at
a rate of 1.5–2.0 mL/s for standard agents), followed by a
20-mL saline flush.36 During the early injection phase
(<60 sec) the mucosa and submucosal layers (inner layer)
show enhancement and appear of high SI, compared to the
relative hypoenhancing bladder muscle (outer layer), which
appears of low SI.37 Images are acquired 30 seconds after

5
Journal of Magnetic Resonance Imaging

FIGURE 3: Susceptibility-weighted artifacts. (a) T2WI demonstrates air within the sigmoid colon, which is causing significant warping
and signal (SI) loss on DWI (arrows). (b) Postcystoscopy nondependent air within the bladder seen as an area with no SI beneath the
anterior bladder wall on T2WI, (c) with significant distortion of the bladder in the corresponding region on DWI (d, arrows).

FIGURE 4: Suboptimal bladder filling. (a) Underdistended bladder on sagittal T2WI. Collapsed mucosa may mimic tumor (arrow),
whereas wall folding may compromise detection of small lesions. (b) Overdistended bladder. Bladder wall spasm and/or patient
motion resulting in motion artifacts as shown on sagittal T2WI. In addition, thinning of the wall decreases sensitivity for flat lesions.

contrast injection, with a further 4–6 acquisitions at
30-second intervals, to detect the early enhancement of
tumor/s and mucosa and any extension of tumor into the
hypointense muscle layer, which typically enhances later
(~20 sec vs. 60 sec after contrast administration, respec-
tively).13,27,38 An alternative is to perform dynamic imaging
with a higher temporal resolution (10-sec intervals), with the
potential advantage of being able to extract pharmacokinetic
analyses.39 Delayed phase acquisitions are not required for T-
staging due to the reducing SI contrast between the different
layers of the wall and tumor7 and due to the presence of high
SI contrast agent excreted into the bladder lumen.
Patient Preparation Issues
Optimal bladder distension is essential for accurate assessment
of bladder tumors at MRI. Overdistension causes thinning of
the wall and may reduce sensitivity for detection of flat
lesions.40 In addition, overdistension induces bladder wall
spasm and is uncomfortable for patients, both of which result
in motion artifact (Fig. 4). Conversely, underdistension leads
to thickening of the detrusor muscle, which may limit the
detection of small lesions, or even lead to misinterpretation of
mucosal folding as tumor infiltration27 (Fig. 4).
There is limited evidence on the appropriate bladder
filling preparation, but consensus opinion recommends either
instructions to void 2 hours prior to the study with no further
oral intake, or drinking 500–1000 mL of water in the
30 minutes prior to MRI.27,40 In a recent prospective study,
an optimal bladder volume (140–210 mL) was achieved by
passing urine 2 hours prior to the MRI exam with no further
drinking; however, the additional fluid intake was required
for early morning appointments likely due to the presence of
relative dehydration.41
Small bowel peristalsis can induce motion artifact on
MRI, especially on T2WI, which tends to be affected more
than DWI and DCE42; some authors therefore recommend
use of antiperistaltic agents such as hyoscine butylbromide
(HBB) or glucagon to improve image quality.3,27,43,44 Addi-
tional modifications to the imaging acquisition parameters
can help mitigate motion artifact, for instance, increasing the
NEX and/or changing the phase and frequency-encoding
directions (left-to-right for axial imaging) to direct artifact
away from the bladder.45 Sampling of k-space by using a

6

combination of rectilinear and radial trajectories has also been
shown to reduce motion artifact and increase both image
sharpness and overall image quality.46,47 This MRI technique
is known as periodically rotated overlapping parallel lines with
enhanced reconstruction (PROPELLER) and has its own
TABLE 3. VI-RADS Scoring Systems
Score Criteria
T2W—Structural category
1 Intact muscularis propria with uninterrupted low SI
line (Lesion <1 cm; papillary tumor with or
without stalk and/or thickened mucosa)
2 Intact muscularis propria with uninterrupted low SI
line (Lesion >1 cm; papillary tumor with stalk or
sessile tumor and/or high SI of the thickened
mucosa)
3 Lack of category 2 findings; either papillary tumor
without stalk or sessile tumor without high SI
thickened mucosa but no obvious disruption of
low SI muscularis propria
4 Intermediate tumor SI interrupting the baseline low
SI of muscularis propria
5 Intermediate tumor SI extending into extravesical
fat
DWI
1 Intact intermediate SI of the muscularis propria
(Lesion <1 cm; high SI on DWI and low on
ADC, with or without stalk and/or thickened
mucosa with low DWI SI)
2 Intact intermediate SI of the muscularis propria
(Lesion >1 cm; high SI on DWI and low on
ADC, with low DWI SI stalk or sessile tumor
with thickened mucosa of low/intermediate DWI
SI)
3 Lack of category 2 findings but no obvious high
DWI SI disrupting the muscularis propria
4 High DWI and low ADC SI of the tumor focally
disrupting the muscularis propria
5 High DWI and low ADC SI of the tumor
extending into the perivesical fat
DCE
1 No early enhancement of the muscularis propria
2 Early enhancement of the mucosa but not of the
muscularis propria
3 Lack of category 2 findings but no obvious early
enhancement of the muscularis propria
Caglic et al.: MRI Staging in Bladder Cancer
TABLE 3. Continued
Score Criteria
4 Focal extension of tumor early enhancement into
the muscularis propria
5 Extension of tumor early enhancement into the
perivesical fat
Adapted from reference.7
VI-RADS = Vesical Imaging-Reporting and Data System; T2WI
= T2-weighted imaging; DWI = diffusion-weighted imaging;
DCEI = dynamic contrast enhanced imaging; SI = signal
intensity.
disadvantages, including increased acquisition time and
reduced overall contrast,48,49 but may prove useful as a substi-
tute sequence for exams affected by severe motion artifact.
Allowing for an adequate time interval following previ-
ous intervention is important to enable resolution of reactive
inflammatory change within the bladder wall and perivesical
fat, which may lead to both false-negative and false-positive
findings.50 A minimum of 2 weeks is recommended after
TURBT, bladder biopsy, or intravesical therapy, while a
2–3 days interval between flexible cystoscopy or removal of
Foley catheter is sufficient for reabsorption of air in the blad-
der, which could otherwise cause susceptibility artifacts on
DWI7 (Fig. 3).
T-Staging
Accurate local staging of bladder carcinoma is key, as it has
significant prognostic implications and determines treatment
options. Nonmuscle invasive bladder carcinomas (Ta–T1) are
suitable for localized treatment, either TURBT or intravesical
chemotherapy, while radical therapy, ie, cystectomy with LN
dissection remains the gold standard for muscle invasive dis-
ease (≥T2).5–7 In addition, multimodality bladder-preserving
treatment combining TURBT, radiotherapy, and chemother-
apy can be offered to a highly selected group of patients with
MIBC (T2 stage and no CIS).6
According to the European Association of Urology
(EAU) guidelines, the current standard for diagnosis and
staging of BC is TURBT.5 However, TURBT may
understage tumors due to sampling error, particularly if
there is an absence of the detrusor layer in the specimen. In
addition, up to 25% of T1 tumors are eventually muscle
invasive on subsequent TURBT, which entirely changes
therapeutic management,51,52 and over a third of clinically
organ-confined BC have been reported to have extravesical
extension at final pathology.53 Thus, when high-grade carci-
noma is confirmed at initial histology, a repeat surveillance
cystoscopy procedure is mandated within 6 weeks of pri-
mary resection.5
7
Journal of Magnetic Resonance Imaging

chemoradiation, (unifocal, good bladder capacity) and for the

TABLE 4. Assignment of Overall VI-RADS Score
surgical planning of a radical, complete TURBT.
DWI DCE To improve acquisition and interpretation of bladder
T2WI score score score VI-RADS score MRI, the VI-RADS was developed in 2018 by a panel of
expert multidisciplinary team members. The guidelines are
1 1 1 1
aimed at accurate staging of disease, given its clinical impor-
2 2 2 2 tance, in contradistinction to PI-RADS,57 which is aimed at
3 3 3 3 detecting prostate tumors, or LI-RADS, which attempts to
characterize lesions in the cirrhotic liver.58
4 4 4
4 5 5 5
VI-RADS: Stage T1 vs. T2
5 4 4 4 According to the VI-RADS system,7 each of the three
sequences (T2WI, DWI, and DCE) is scored on a 5-point
VI-RADS scoring summary: for categories 1–3, T2WI should
be considered as the “first pass scoring.” For scores 4 and 5, the
scale, which are then combined to derive an overall VI-RADS
dominant sequences are DWI (first) and DCEI (second). score classifying the likelihood of MIBC into five categories
VI-RADS = Vesical Imaging-Reporting and Data System; T2WI (Table 3 and 4). Typically, an overall VI-RADS score 1–2
= T2-weighted imaging; DWI = diffusion weighted imaging; means MIBC is unlikely, as opposed to a score of 4–5, indicat-
DCEI = dynamic contrast enhanced imaging.
ing that MIBC is likely. To date, four retrospective14,59–61 and
one prospective study62 have validated the VI-RADS scoring
system, demonstrating good performance for identifying
MRI overcomes such limitations in local staging, with MIBC, with an area under the curve (AUC) ranging between
several studies demonstrating that mpMRI represents a reli- 0.83–0.94 and a good-to-excellent interreader agreement
able tool for differentiating NMIBC from MIBC,25,54,55 as (kappa = 0.72–0.92).
well as in diagnosing T3 disease.56 In addition, it can further Tumor morphology, size, location, and integrity of
identify MIBC suitable for bladder-sparing therapy and muscularis propria are primarily evaluated on a T2WI

FIGURE 5: VI-RADS score 2. A 76-year-old female presenting with hematuria and bladder lesion identified on ultrasound. T2WI (a:
axial plane) shows an exophytic lesion on the lower anterior bladder wall, >1 cm in greatest dimension, with preserved low SI of the
muscularis propria (VI-RADS score 2). (b) DWI with b-value = 2000 and ADC map (c), respectively, demonstrates an exophytic lesion
with restricted diffusion, with low signal (SI) stalk on DWI (arrow) and muscularis propria with continuous low SI on DWI (VI-RADS
score 2). (d) DCE imaging shows early enhancement of the lesion and inner layer, without early enhancement of the muscularis
propria (VI-RADS category 2). Overall VI-RADS score 2 was assigned and pT1 urothelial carcinoma was confirmed at histopathology
after transurethral resection of bladder tumor (TURBT).

8
 Caglic et al.: MRI Staging in Bladder Cancer

FIGURE 6: VI-RADS score 5. A 65-year-old male with hematuria and positive cytology. (a) T2WI demonstrates a lesion >1 cm in the
left lateral bladder wall, with intermediate signal (SI) that extends through the muscularis propria and to the origin of the left
seminal vesicle (VI-RADS score 5) with corresponding significant restricted diffusion on DWI (b: b-value = 2000) and on ADC map (c);
VI-RADS score 5. (d) There is early and heterogeneous enhancement of the lesion, which extends through the muscularis propria on
DCEI (VI-RADS category 4). Overall VI-RADS score 5 was assigned. Muscle involvement was proven at histopathology after
transurethral resection of bladder tumor.

FIGURE 7: T2 vs. T3 stage. (a,b) An 82-year-old man with T2 stage tumor. (a) T2WI shows left posterolateral bladder mass with
irregular border and decreased SI of the perivesicular fat (arrow). (b) DWI shows a smooth outer outline with no increased SI within the
perivesicular fat (arrow) thus confirming T2 stage. (c,d) A 68-year-old male with T3 stage tumor. (a) There is a left-sided posterolateral
bladder mass with an irregular border and decreased SI of the perivesicular fat on T2WI (arrow). (b) DWI shows an irregular outer
outline of the tumor with high SI extending into the perivesicular fat (arrow), thus confirming extravesicular extension.

sequence, while confirmation of definitive muscular invasion
depends on DWI and DCE findings. If there is discordance
between T2WI and DCE, then (high quality) DWI should
be used as the dominant sequence to improve
accuracy.12,25,27,34,55
Ta–T1 stage tumors can be either sessile or papillary
and do not show interruption of the detrusor muscle baseline
SI on any of the sequences (Fig. 5), whereas T2 tumors
should be called when focal disruption of the muscular layer
is detected on mpMRI sequences7 (Fig. 6). In addition, the
presence of a stalk in an exophytic tumor is an important
finding, as it may lead to false-positive calls; however, this is a
reassuring feature described by Takeuchi et al as an “inch-
worm” sign, which implies Ta–T1 stage.54 The stalk consists
of submucosa with a varying degree of edema and fibrous
change and its T2 SI therefore varies from hypo- to iso- to
hyperintensity; however, it does not demonstrate restricted
diffusion, appearing of low SI on DWI in contrast to the high
SI tumor that surrounds the stalk in a U-shaped configura-
tion54 (Fig. 5). Similarly, overcalling of muscle invasion can
be avoided when staging sessile tumors, which sometimes
show a thickened and inflamed and/or fibrotic submucosa.
This exhibits intermediate to low T2 SI but does not restrict
diffusion25; thus, the true tumor stands out as a C-shaped
structure with high SI on DWI.
The TNM system subdivides T2 stage by depth of
muscle invasion into T2a (<50%) and T2b stage (≥50%),
based on prognosis, with T2b disease carrying a significantly
increased risk for LN metastasis (14% vs. 30%, respectively),
resulting in decreased recurrence-free survival after
cystectomy.63 However, the therapeutic approach of T2a and
T2b disease is similar and, as this distinction is challenging
on MRI, the VI-RADS system only describes “T2 stage.”7
T2 vs. T3
T3 stage is defined as extension of the tumor into the peri-
vesical fat and is further subclassified into T3a (micro-
scopic—by definition not visualized on MRI) and T3b
(macroscopic) extravesical extension.21,25,56,64 TURBT or
biopsy specimens cannot be definitive for microscopic

9
Journal of Magnetic Resonance Imaging

FIGURE 8: T4a stage with prostate invasion. A 78-year-old man with macroscopic hematuria and urinary retention. (a) Sagittal T2WI
image shows diffuse bladder wall thickening with intermediate SI extending inferiorly and involving most of the prostate (arrows).
(b) Axial T2WI image at the level of the prostate demonstrates tumor infiltration of the gland with corresponding restricted diffusion
on ADC map (c). Note urinary catheter on sagittal image (a).

FIGURE 9: T4b stage with pelvic sidewall invasion. A 52-year-old man with advanced disease. (a) Axial T2WI shows abnormal bladder
wall thickening with intermediate to low signal (SI) tumor extending to the left pelvic sidewall (arrows) and mesorectal fat. (b,c) Axial
DWI and ADC map show associated restricted diffusion. Note two filling defects on T2WI within two bladder diverticuli consistent
with tumors (a, *) with corresponding restricted diffusion (b,c).

FIGURE 10: Postprocedural inflammation. There is diffuse bladder wall thickening with intermediate to high signal (SI) on T2WI (a)
and corresponding high SI on DWI (b). The features could be mistaken for residual diffuse infiltrative tumor; however, high SI on
ADC map (c) confirms no restricted diffusion and T2-shine-through effect. Note focal procedure-related perforation anteriorly
(arrow) with a small amount of free perivesicular fluid.

extravesical tumor extension,20,56 as adipocytes are normally
seen in between muscle bundles of the outer muscularis
propria; thus, interposition of fat with tumor cells in a biopsy
or TURBT specimen is at most suggestive of pT3 cancer and
accurate T3a categorization can only be assigned on
cystectomy specimens.20 Thus, the primary role of MRI stag-
ing is to differentiate between the T2 from T3b stage, as the
management for both T2 and T3a is the same.6,25
In T3 stage the T2WI and DWI tumor SI extends into
the perivesical fat. The outer bladder wall appears ill-defined

10

and irregular and there is associated enhancement.25,27 In
addition, another useful feature to evaluate is the outer con-
tour of the muscle invasive tumor on DWI. If the contour is
smooth and regular, this implies T2 stage, whereas an irregu-
lar and nodular surface suggests T3 disease25 (Fig. 7).
T3 vs. T4
T4 stage is defined by tumor invasion into adjacent organs,
either T4a with extension into the uterus, vagina, prostate, or
SV (Fig. 8) or T4b subcategory, incorporating either invasion
into the pelvic sidewall or abdominal wall (Fig. 9). However,
the invaded organ should be clearly stated in the report, given
the significant differences in prognosis; for instance, prostate
vs. SV involvement with 5-year survival at 38% and 10%,
respectively.65
MRI offers improved evaluation of adjacent organ inva-
sion compared to CT due to a higher soft-tissue
resolution,56,64 with a reported accuracy of 96.7%.66 A recent
meta-analysis also showed MRI to have superior accuracy
compared to clinical staging for differentiating T4b, with a
pooled sensitivity of 85% and a specificity of 98%, which is
helpful when determining the feasibility of resection vs. palli-
ative radiation.11
Involvement of adjacent structures should be suspected
when there is direct extension of the carcinoma into the adja-
cent organ, with disruption of its normal SI intensity and/or
architecture on T2WI. Reference to DCE (early enhance-
ment) and DWI (high SI on b-value imaging and low SI on
ADC map) can further increase sensitivity as well as avoid
false-positive calls.27,66
Postinterventional Appearances
When MRI is performed following intervention (postbiopsy
or TURBT), subsequent inflammatory changes with bladder
wall thickening and perivesical fat stranding may lead to
incorrect T-staging.56 A thickened and inflamed edematous
wall will show increased T2 SI intensity and an increased SI
intensity on b-value imaging may be mistaken for residual
muscle invasive tumor, requiring correlation with ADC maps
to confirm a T2 shine-through effect15 (Fig. 10). In addition,
there may be low-to-intermediate T2WI SI intensity within
the perivesicular fat due to inflammation or fibrosis,38 often
accompanied with increased enhancement on DCE, thus
mimicking extravesicular T3b disease. However, such changes
do not usually demonstrate restricted diffusion, and therefore
DWI in combination with ADC should be the primary
sequences used to differentiate procedure-related inflamma-
tory changes and fibrosis from cancerous spread into the peri-
vesical fat.15,38 Conversely, a thickened and inflamed wall
with secondarily increased enhancement may obscure a small
residual lesion.15
Caglic et al.: MRI Staging in Bladder Cancer
N-Staging
After tumor T-stage, the nodal status in BC patients is the
most significant histopathological prognostic variable.67,68 LN
involvement significantly correlates with concomitant distant
metastases and a marked decrease in 5-year disease-free sur-
vival.69,70 The incidence of nodal metastasis closely correlates
with tumor stage, with LN metastases being rare for disease
stage ≤T1, but as high as 30% for muscle invasive cancers and
60% when staging is ≥T3.64,71 Lymphadenectomy is therefore
the standard of care for cystectomy in patients with MIBC.72
Of note, tumor location has been associated with prognosis, as
there is an increased likelihood of LN involvement with
tumors located at the bladder neck or trigone of the bladder
due to increased lymphatic and vascular vessels at this site.73
BC spreads primarily to the perivesicular LNs and
regional nodal stations within the true pelvis: the obturator,
hypogastric, external iliac, and presacral nodes. The TNM
system recognizes four different stages of LN involvement
based on anatomic location rather than the size or number of
LNs. Metastasis in a single regional LN is classified as N1
stage, while involvement of >1 regional node represents N2
disease. Metastasis in common iliac nodes is defined as N3
stage, while spread to distant nonregional nodes, ie, at the
level of aortic bifurcation or higher, is considered metastatic
disease and thus classified as M1a stage. Mapping studies have
shown that there tends to be a stepwise ascending route of
nodal spread, with skipped stations above the aortic bifurca-
tion being extremely rare.70,74 In addition, primary lymphatic
landing sites vary by the location of the bladder tumor, with
superolateral carcinomas having a tendency to spread first to
external iliac LNs, whereas the anterior wall, the base, and
trigone or bladder neck carcinomas primarily metastasizing to
the internal iliac LNs.75 Although the primary tumor may be
limited to one side of the bladder wall, bilateral LN involve-
ment occurs in up to 40%.76
The standard bladder MRI protocol, which is primarily
aimed at evaluating the local T-stage, should ideally incorpo-
rate an additional sequence for the purpose of pelvic nodal
staging from at least the level of aortic bifurcation. The
knowledge of potential LN involvement above the common
iliac bifurcation will direct treatment towards extended or
superextended lymphadenectomy, wherein nodal tissue up to
the level of the aortic bifurcation or the inferior mesenteric
origin is removed, respectively.77
MRI assessment for nodal metastases relies on size
(>8 mm in short axis) and morphological criteria. Features of
LN involvement include a rounded shape (reviewed on ≥2
perpendicular planes to avoid false positives), an irregular bor-
der, loss of fat in the hilum (normal nodes show T1 high SI
intensity fatty hilum and loss of SI on DWI due to fat-satura-
tion). Additional features may include similar T1 and T2 SI
characteristics as that of primary tumor and/or central necro-
sis demonstrated by high T2 SI intensity and low T1 SI
11
Journal of Magnetic Resonance Imaging
FIGURE 11: Nodal and bone metastases. A 57-year-old man with metastatic bladder cancer. (a,b) Axial T1WI and T2WI show
enlarged left pelvic sidewall lymph nodes (LNs) and low to intermediate signal (SI) bone metastases in the sacrum (arrows); more
conspicuous as high SI on b-value DWI (c). Note the most right bone lesion is hardly seen on T1WI and T2WI.
intensity with peripheral enhancement on DCE. However,
MRI has limited accuracy in nodal assessment. A recent
meta-analysis showed the pooled specificity on a per-patient
basis to be high, at 0.94; however, the pooled sensitivity is
only 0.56.18 Similarly, Salminen et al reported a sensitivity
range of 40.7–86% and specificity 31–92% (5/6 studies
reported a specificity above 80%).78 Size criteria alone will
lack accuracy due to the inability to detect nodes involved
with micrometastases, and over 90% of normal-sized meta-
static LNs in BC have been shown to have a short axis dia-
meter ≤5 mm.79 Conversely, false-positive results are found
in nodes enlarged due to reactive hyperplasia.80
FIGURE 12: Synchronous ureteric malignancy in a patient with
high-risk bladder carcinoma. MR cholangiopancreatography-like
heavily-T2WI sequence in coronal plane readily demonstrates
duplex right kidney (proximal union of the ureters) with severe
dilatation of both moieties and severe dilatation of the common
right ureter due to obstructing distal ureteric tumor. Normal left
collecting system and ureter.
12
Functional imaging of nodes has the potential to over-
come the limitations of morphological assessment alone.79,81
ADC has been widely investigated as a biomarker for discrim-
inating benign from malignant primary lesions in several
tumor types and has shown potential to differentiate normal
from metastatic nodes in BC.82 However, the relatively small
size of nodes in relation to slice thickness of DWI means that
derived ADC values can be significantly affected by a partial
volume effect and reproducibility is further limited by differ-
ences in acquisition protocols (eg, vendor, field strength, b-
value selection).83,84 Furthermore, a number of benign condi-
tions including inflammation, sarcoidosis, lipomatosis, and
follicular hyperplasia are known to cause restricted diffusion,
leading to false-positive results.79,85–87 Thus, quantitative
ADC values for assessment of involvement cannot be reliably
applied. However, nodes display high SI on high b-value
imaging due to an inherent long T2 relaxation time, meaning
DWI can be used as a “nodal map” to identify nodal groups
prior to correlation with anatomical imaging to limit false-
positive calls (bowel mucosa, nerves, and vessels)88 (Fig. 11).
Recent studies using this nodal mapping technique have
reported improved sensitivities between 55% and 73% and
specificities of 86–90%.79,81
The most encouraging results in determining metastatic
bladder nodes have been reported using MR lymphangiography
(MRL) with ultrasmall superparamagnetic iron oxide
(USPIO).89–91 This approach, however, is complex, as it
requires expertise, prolonged reading time, and intravenous
administration of USPIO 24–36 hours prior to scanning in
order to allow time for nanoparticles to be taken up by macro-
phages, which are abundant in benign LNs but are replaced by
malignant cells in metastatic LNs.90,92 Accumulation of iron
oxide causes loss of SI in normal LNs on postcontrast T2WI,
T2W*, as well as on DWI, whereas involved LNs retain their
high SI intensity and can thus be easily depicted. Meta-analysis

by Woo et al reported significantly improved pooled sensitivity
at 0.86 when using MRL compared to a conventional
approach.18 Unfortunately, USPIO is currently not licensed for
routine clinical use and is limited for research purposes in pros-
tate cancer alone (commercially known as Combidex).92
In summary, LNs should be identified on high b-value
DWI, then further assessed on anatomical sequences for size
(>8 mm), SI characteristics resembling the primary tumor, and
morphological criteria including rounded shape, an irregular con-
tour, and loss of fatty hila. However, given the limited sensitivity
of MRI in detecting metastatic LNs in BC, negative MRI cannot
obviate the need for lymphadenectomy if clinically indicated.
Conversely, given the high specificity, suspicious nodes on MRI
warrant a resection that should be extended when abnormal
nodes are identified beyond the expected pelvic stations.
MRI Urography and M-Staging
MRI Urography
EAU guidelines recommend evaluation of the upper tracts in
all patients with MIBC and in high-risk NMIBC cases (multi-
ple or high-grade tumors and tumors located at the trigone)
due to the high incidence of synchronous tumors of the upper
urinary system.6 Although CTU is currently the modality of
choice, use of MRU is recommended when there are contrain-
dications for CTU6 or in patients who need repeated imaging,
due to the lack of ionizing radiation. However, there are no
current guidelines on the optimal MRU protocol and the rela-
tively long examination time and need for expert interpretation
have limited its more widespread use.
A typical MRU protocol combines static-fluid urographic
imaging performed using T2W sequences and excretory imag-
ing performed using gadolinium-enhanced T1W sequences in
addition to morphological (T1WI and T2WI) renal imag-
ing.19,93 Premedication with a diuretic such as furosemide is
generally recommended to achieve distention of the collecting
systems and ureters and allow better visualization.19,93,94 Using
only the static-fluid technique, which relies on intrinsically
high SI intensity of urine for image contrast, is preferred in
pediatric population and in pregnant women as well as in
patients with renal impairment.94 In addition, we also find it
useful in the context of high-risk BC patients as part of an all-
in-one assessment of the urinary tract. We typically use coronal
plane with a heavily-T2WI technique, essentially the same as
for MR cholangiopancreatography. MRU is a powerful diag-
nostic tool in depicting hydronephrosis and defining the level
of obstruction93 (Fig. 12) with ureteric tumors presenting with
intermediate T2 SI and corresponding restricted diffusion.
M-Staging
At initial presentation, 10–15% of patients have metastatic
disease, the commonest sites being LNs, lungs, liver, and
bones.95 Furthermore, 50% of patients undergoing radical
Caglic et al.: MRI Staging in Bladder Cancer
cystectomy will eventually progress either locally (30%) or
with distant metastases (70%).96 In patients with MIBC,
contrast-enhanced CT of the chest, abdomen, and pelvis
remains the recommended imaging modality for assessment
of nodal status and distant metastases. Bone scintigraphy
(BS) is often used for bone assessment, particularly in symp-
tomatic patients.6,95 Despite several studies demonstrating
MRI to have a superior sensitivity and specificity for detecting
bone metastases,97–99 it has not been incorporated into cur-
rent guidelines due to its limited availability, lack of expert
knowledge, and lower cost effectiveness. However, MRI can
be especially beneficial in detecting early infiltration of bone
marrow or for characterization of incidental detected indeter-
minate lesions on BS or CT.95,99
In addition, partial M-staging of the bony pelvis and
other pelvic structures is afforded by bladder mpMRI studies.
Bone metastases in BC can be either lytic or sclerotic,100 and
will exhibit low SI on T1WI, intermediate to low SI on
T2WI, and will demonstrate restricted diffusion (high SI on
DWI and low on ADC). High b-value DWI is particularly
useful to depict high-SI intensity regions in bones, which
should subsequently be correlated with ADC and morpholog-
ical sequences to avoid pitfalls (Fig. 11). In addition, a pro-
portion of BC patients are smokers or have chronic heart
failure—conditions that tend to increase the cellularity of
bone marrow.99 This may result in high SI on b-value DWI
leading to false-positive calls, and potentially also false-
negative findings, by obscuring metastatic infiltration of bone
marrow.34 A study by Takeuchi et al including 157 BC
patients reported that only 27% of high SI intensity regions
on DWI was related to metastases, with the majority of false-
positive findings relating to hematopoietic red marrow.101
Treatment Response
Assessing treatment response is of utmost clinical importance,
in that it can help determine candidates for bladder-sparing
approaches in MIBC after neoadjuvant chemoradiation who
show complete response102 and for informing prognosis after
neoadjuvant chemotherapy (NAC) followed by radical
cystectomy, as patients with residual disease after NAC show
worse survival.103 In addition, if nonresponders can be
predicted in advance, significant chemotherapy-related toxic-
ities such as leukopenia can be avoided in these select
patients.104
There has been accumulating evidence from experimen-
tal animal studies and early human studies that MRI has the
potential to play a pivotal role in this area with its advantages
of avoiding exposure to ionizing radiation and the multi-
parametric approach utilizing anatomical and functional
sequences (eg, DWI and DCE MRI).12,105–107 For example,
Mazurchuk et al107 demonstrated using orthotopic murine
xenograft models of human bladder urothelial carcinomas
13
14
TABLE 5. Summary of the Main Studies Investigating Treatment Response
Cohort details Definition of response MRI details
First No. of Reference Response
author patients Tumor Treatment standard Response criteria rate Tesla Sequence Response assessment criteria Endpoint Conclusion
Pretreatment Yoshida S, 23 MIBC CRT (4 weeks RT RC or PC pCR 13/23 1.5 DWI (ADC) ADC < 0.74 × 10-3 mm2/s CRT-sensitive Sens/spec 92/90
2011 (T2-3aN0M0) + 2 cycles of tumors
cisplatin on
1/4th weeks)
Journal of Magnetic Resonance Imaging

Nguyen 20 MIBC pT2 GC or MVAC RC ypT1 or pT2 with 15/20 3 DWI (ADC) Not available Not available Resistant cases had
HT, 4 cycles RECIST response higher entropy,
2017 lower uniformity
(P < 0.01,=0.01)
Interim Barentsz 22 “Advanced” BC, MVAC 6 cycles Cystectomy No or “few”(<5% of 14/22 1.5 DCE, conv Tumor or LN; 50% size reduction in two Responder DCE 93/100; conv
JO, T1-4b, N1 or TUR resected specimen) (unenhanced T1 dimensions; or earliest enhancing region 79/63
1998 (n = 18) or M1 microscopic areas of and T2) changes to >10s after main artery in same
(n = 1) viable tumor plane
Schrier BP, 36 MIBC (> = T2, MVAC 6 cycles Cystectomy No or “few” microscopic 22/36 NR DCE, conv Tumor or LN; responder if >50% decrease in Responder DCE sens/spec 91/93;
2006 N1-2); or TUR areas of viable tumor (unenhanced— summed products of longest perpendicular conv 81/50
regionally met Anatomical D of all lesions with no simultaneous
or unresectable imaging—not increase in size or new lesion; CE changed
defined) to >10s
Chakiba C, 12 MIBC (T2N0M0) GC, MVAC, or Cystectomy Absence of infiltrative 6/12 1.5 DCE rSI80 (relative SI at 80 sec after injection ? 83.33/83.33
2015 HD-MVAC or TUR tumor in sample normalized to unenhanced image) > 40%
3–6 cycles
Nguyen 30 Not available Cisplatin-based RC pCR, downstaging, 23/30 3 DCE K-means clustering Responder 96/100
HT, chemotherapy or > 50% tumor
2014 volume reduction w/o
stage change
Posttreatment Choueiri 39 cT2-cT4, N0-1, ddMVAC RC Pathologic downstaging 19/39 NR DCE >50% decrease in the product of the longest Responder Sens/spec 78.9/55.0
TK, M0 to ≤pT1pN0 perpendicular diameters and delayed
2014 enhancement of residual tumor
Donaldson 21 MIBC GC 3 cycles Cystectomy “Residual” 14/24 1.5 DCE Two different DCE variables_rSI80 > 2.6; Residual 70/100 and 60/86
SB, Fp > 19.0 tumor
2013
Yoshida S, 20 MIBC (T2- CRT (4 weeks RT RC or PC pCR 13/20 1.5 T2/DCE/DWI T2WI bladder wall thickening; DCE early Residual DWI 57/92; T2 43/45;
2010 4aN0M0) + 2 cycles of intense enhancement; DWI high SI on DCE 57/18
cisplatin on b-value both 500 and 1000
1/4th weeks)

DCE = dynamic contrast enhanced; DWI = diffusion weighted imaging; MIBC = muscle invasive bladder cancer.

that longitudinal MRI measurements were able to construct
tumor growth curves and accurately measure a reduction in
tumor volume compared to necropsy specimens, providing a
basis for MRI to be used in assessment/prediction of treat-
ment response.
Pretreatment MRI for Prediction of Treatment
Response
The literature is sparse when it comes to the value of pre-
treatment MRI for predicting treatment response (Table 5).
In a retrospective study by Yoshida et al,108 DWI was used to
predict pathologic complete response (pCR) in 23 patients
with MIBC undergoing cisplatin-based low-dose
chemoradiotherapy followed by partial or radical cystectomy.
Using a cutoff of ADC values <0.74 × 10−3 mm2/s yielded a
sensitivity and specificity of 92% and 90%, respectively. In
addition, in a study by Nguyen et al,17 DWI was used to pre-
dict response, which was defined as either downstaging
(to ypT1 or ypT2 with RECIST response) in a cohort of
20 patients with MIBC receiving cisplatin-based NAC
followed by radical cystectomy. Patients with tumors resistant
to NAC demonstrated higher entropy and lower uniformity
on ADC maps, or, in other words, showed a more heteroge-
neous spatial distribution of ADC values within the tumor
compared with those that were sensitive. Overall, due to lim-
ited evidence, there is currently no recommended imaging
modality to predict NAC response.109
Interim MRI for Prediction of Treatment Response
MRI performed in the setting of interim evaluation of tumor
response after the first few cycles of chemotherapy is poten-
tially very useful, as earlier prediction of treatment failure can
help decide to stop treatment to reduce unnecessary morbid-
ity and costs (Table 5). In an early prospective study of
MIBC or node-positive BC by Barentz et al,110 DCE was
shown to be superior to anatomical sequences (T1WI) in
predicting response during a methotrexate/vinblastine/
adriamycin/cisplatin (MVAC) regimen (after the 4th cycle out
of a total of 6 cycles), showing sensitivity and specificity of
93% and 100% for DCE-MRI and 79% and 63% for
T1WI, respectively. Following studies by several investigators
also demonstrated that DCE-MRI using various criteria (eg,
relative SI intensity, size reduction, or K-means clustering) at
mid-cycle of cisplatin-based chemotherapy in patients with
MIBC or node-positive disease was useful in predicting
responders with sensitivities and specificities of 83–96% and
83–100%, respectively.16,111,112
Assessment of Treatment Response After Therapy
Few studies have evaluated the role of MRI after completion
of cisplatin-based chemotherapy or chemoradiation (Table 5).
Choueiri et al113 found that DCE-MRI after completion of
treatment in patients with MIBC who received chemotherapy
Caglic et al.: MRI Staging in Bladder Cancer
showed sensitivity and specificity of 79% and 55%, respec-
tively, for determining responders. In addition, the MRI-
based response was predictive of superior 1-year disease-free
survival rates: radiological responders, 86% (95% confidence
interval, 63–95) vs. nonresponders, 62% (95% confidence
interval, 31–82%). In addition, Donaldson et al35 showed
that DCE-MRI was able to detect residual tumor after che-
motherapy with a sensitivity and specificity of 70% and
100%, respectively. It has also been observed that DWI
(92%) is superior to DCE-MRI or T2WI (18% and 45%,
respectively) in terms of specificity for detecting residual
tumor after chemoradiation in patients with MIBC albeit
similar sensitivities (43–57%).
Limitation and Further Directions
Despite the above promising results, several limitations
should be noted regarding the use of MRI in assessing and
predicting treatment response in BC. First, the published lit-
erature in this area is still small, with most studies based on a
small number of patients (N = 12–40). Second, not only were
the patient populations different (mostly MIBC, but some
studies also including node-positive disease or distant metasta-
sis), the definitions of response were quite heterogeneous
among the studies (ie, pCR, downgrading, or tumor size
reduction). Third, the methodology in assessing MRI
response, including the type of MRI sequence (DCE-MRI,
DWI, or T1WI/T2WI) and interpretation criteria (ie, relative
SI, tumor size, or histogram analysis) used were not uniform.
Such heterogeneity should be resolved and methods tested by
previous investigators should be validated in order for MRI to
be used in clinical trials or even routine clinical practice.
Radiomics
Radiomics analysis of medical images has developed exponentially
over the past decade, in particular in the field of oncological
imaging, including for BC.32,114–117 Radiomics can be performed
on either anatomical and functional mpMRI sequences.
Radiomic analyses of bladder mpMRI have shown
promising results not only in estimating tumor grade and dis-
ease aggressiveness, but also in predicting the local stage of
BC.32,114–116 Several quantitative features have been identi-
fied on T2WI that have proven useful in predicting both
muscle invasive disease114 and extravesical extension.116 A
recent study by Xu et al reported good performance
(AUC = 0.861) in the preoperative prediction of muscular
invasiveness by utilizing 13 T2WI radiomic signatures in
68 patients with clinicopathologically confirmed BC.114
Another study by Tong et al included 65 patients undergoing
radical cystectomy and identified nine features that predicted
T3 disease at a patient level with a sensitivity, specificity, and
AUC at 0.742, 0.824, and 0.806, respectively.116
Despite this early promise, further radiomic studies
including DWI and DCE analysis and larger, multicenter
15
Journal of Magnetic Resonance Imaging
datasets are required before radiomics can be employed in
routine clinical practice to support and enhance local staging
of BC and help optimize therapeutic management.
Conclusion
Accurate staging of BC is essential for determining both prog-
nosis and optimal treatment. Current clinical staging lacks
accuracy, whereas bladder mpMRI has shown high diagnostic
performance in determining the local stage of BC and has the
additional advantage of assessing tumor spread to LNs, bones,
and involvement of the UUT. MRI also shows promise for
predicting tumor aggressiveness and detecting therapeutic
response to chemotherapy or radiotherapy, and thus could be
used to guide radical intervention and treatment of recurrence.
Acknowledgments
Authors I.C., T.B., and E.S. acknowledge research support
from Cancer Research UK, National Institute of Health
Research Cambridge Biomedical Research Centre, Cancer
Research UK, and the Engineering and Physical Sciences
Research Council Imaging Centre in Cambridge and Man-
chester and the Cambridge Experimental Cancer Medicine
Centre.
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