5. Diagnostik und Stadieneinteilung – Harnblasenkarzinom

Leitlinie

Empfehlung

Empfehlungsgrad/LoE

AUA/ASCO/ASTRO/ SUO 2020

Multi-modal Bladder Preserving Therapy

Following completion of bladder preserving therapy, clinicians should perform regular surveillance with CT scans, cystoscopy, and urine cytology.

Laboratory Values and Urine Markers

Following therapy for muscle-invasive bladder cancer, patients should undergo laboratory assessment at three to six month intervals for two to three years and then annually thereafter. (Expert Opinion)

Strong Recommendation; LoE: Grade C

Expert Opinion 

AUA/SUO 2020

Diagnosis

In a patient with a history of NMIBC with normal cystoscopy and positive cytology, a clinician should consider prostatic urethral biopsies and upper tract imaging, as well as enhanced cystoscopic techniques (blue light cystoscopy, when available), ureteroscopy, or random bladder biopsies.

Urine Markers after Diagnosis of Bladder Cancer

In surveillance of NMIBC, a clinician should not use urinary biomarkers in place of cystoscopic evaluation.

In a patient with a history of low-risk cancer and a normal cystoscopy, a clinician should not routinely use a urinary biomarker or cytology during surveillance.

In a patient with NMIBC, a clinician may use biomarkers to assess response to intravesical BCG (UroVysion® FISH) and adjudicate equivocal cytology (UroVysion® FISH and ImmunoCyt™).

BCG Relapse and Salvage Regimens

In an intermediate- or high-risk patient with persistent or recurrent disease or positive cytology following intravesical therapy, a clinician should consider performing prostatic urethral biopsy and an upper tract evaluation prior to administration of additional intravesical therapy.

Risk Adjusted Surveillance and Follow-up Strategies

For an intermediate-risk patient whose first surveillance cystoscopy is negative for tumor, a clinician should perform subsequent cystoscopy with cytology every 3-6 months for 2 years, then 6-12 months for years 3 and 4, and then annually thereafter.

For a high-risk patient whose first surveillance cystoscopy is negative for tumor, a clinician should perform subsequent cystoscopy with cytology every three to four months for two years, then six months for years three and four, and then annually thereafter.

Expert Opinion

Strong Recommendation; Evidence Strength: Grade B

Expert Opinion

Expert Opinion

Conditional Recommendation; Evidence Strength: Grade C

Expert Opinion

Expert Opinion

EAU 2022a

Summary of evidence and guidelines for the primary assessment of non-muscle-invasive

bladder cancer

Summary of Evidence

Urinary cytology has high sensitivity in high-grade tumours including carcinoma in situ.

Recommandations

Perform cystoscopy in patients with symptoms suggestive of bladder cancer or during

surveillance. It cannot be replaced by cytology or by any other non-invasive test.

Use voided urine cytology as an adjunct to cystoscopy to detect high-grade tumour.

Perform cytology on at least 25 mL fresh urine or urine with adequate fixation. Morning

urine is not suitable because of the frequent presence of cytolysis.

Use the Paris System for cytology reporting.

Summary of evidence and guidelines for transurethral resection of the bladder,

biopsies and pathology report

Recommandations

Take biopsies from abnormal-looking urothelium. Biopsies from normal-looking mucosa

(mapping biopsies from the trigone, bladder dome, right, left, anterior and posterior bladder wall) are recommended if cytology or urinary molecular marker test is positive. If the equipment is available, perform fluorescence-guided (PDD) biopsies.

Take a biopsy of the prostatic urethra in cases of bladder neck tumour, if bladder carcinoma

in situ is present or suspected, if there is positive cytology or urinary molecular marker test

without evidence of tumour in the bladder, or if abnormalities of the prostatic urethra are

visible. If biopsy is not performed during the initial procedure, it should be completed at the

time of the second resection.

In patients with positive cytology, but negative cystoscopy, exclude an upper tract urothelial carcinoma, CIS in the bladder (by mapping biopsies or PDD-guided biopsies) and tumour in the prostatic urethra (by prostatic urethra biopsy).

Summary of evidence and guidelines for follow-up of patients after transurethral

resection of the bladder for non-muscle-invasive bladder cancer

Recommandations

Patients with high-risk and those with very high-risk tumours treated conservatively should

undergo cystoscopy and urinary cytology at 3 months. If negative, subsequent cystoscopy

and cytology should be repeated every 3 months for a period of 2 years, and every 6

months thereafter until 5 years, and then yearly.

Perform endoscopy under anaesthesia and bladder biopsies when office cystoscopy shows

suspicious findings or if urinary cytology is positive.

During follow-up in patients with positive cytology and no visible tumour in the bladder,

mapping biopsies or PDD-guided biopsies (if equipment is available) and investigation of

extravesical locations (CT urography, prostatic urethra biopsy) are recommended.

2b

Strong

Strong

Strong

Strong

Strong

Strong

Strong

Weak

Strong

Strong

EAU 2022b

Summary of evidence and guidelines for the primary assessment of presumably invasive

bladder tumours

Summary of Evidence

Urinary cytology has high sensitivity in high-grade tumours including carcinoma in situ.

Recommandations

Take a biopsy of the prostatic urethra in cases of bladder neck tumour, when bladder

carcinoma in situ is present or suspected, when there is positive cytology without evidence of tumour in the bladder, or when abnormalities of the prostatic urethra are visible.

2b

Strong

EAU/ESMO 2019

After radical cystectomy with curative intent, follow-up of the urethra with cytology and/or cystoscopy is recommended in selected patients (e.g. multifocality, carcinoma in situ and tumour in the prostatic urethra).

Level of consensus: 88% Agree, 6% disagree, 6% equivocal

(33 voters)

JUA 2019

Follow-up strategy for NMIBC

Low risk:

·    Cystoscopy after 3 months. After that, cystoscopy every 6 months for 2 years. Then every year with cystoscope up to 5 years. After that, by clinical decision

Intermediate risk:

·    Cystoscopy + cytology 3 months later. After that, cystoscopy + cytology every 6 months for 3 years. Thereafter, cystoscopy and cytology every year until 5 years. After that, by clinical decision

High risk:

·    Cystoscopy + cytology every 3 months for 2 years. Cystoscopy + cytology every 6 months for 3–5 years. Cystoscopy + cytology every year until the 10th year. After that, by clinical decision. Urinary molecular markers are considered as appropriate. CT + CT urography every year up to 3 years, thereafter every 2 years for a total of 10 years observation

Follow-up strategy after radical cystectomy for MIBC

pT2 or less and N0

Cytology:

·    1 year: Post 3, 6, and 12 months

·    2-3 years: every 6 months

·    4 years: every 12 months

·    5 years: every 12 months

·    After 5 years (60 months): Cytology is used for urinary tract recurrence

pT3 or high or any pT N1-3

Cytology:

·    1 year: every 3 months

·    2-3 years: every 6 months

·    4 years: every 6 months

·    5 years: every 6 months

LoE and recommondation level not clearly described.

NCCN 2021

Suspicion of bladder cancer

Initial Evaluation: H&P; Office cystoscopy, enhanced if available consider cytology, Abdominal/pelvic imagingb that includes imaging of upper urinary tract collecting system before transurethral resection of bladder tumor, Screen for smoking

Recurrent or persistent disease-follow-up

Cytology positive:

·   If initial positive cytology, consider repeating cytology test within 3 months

or

If repeated positive cytology:

·   Consider selected mapping biopsies including transurethral biopsy of prostatec and

·   Cytology of upper tract and

·   Consider ureteroscopy and

·   Consider enhanced cystoscopyc (if available)

Follow-up

Intermediate Risk, Non-Muscle Invasive Bladder Cancer

·   Year 1: Urine cytology (3, 6, 12 mo)

·   Year 2: Urine cytology (every 6 mo)

·   Year 4-5: Urine tests annually

·   Year 5-10 & >10 Year: as clinicallly indicated

High-Risk, Non-Muscle Invasive Bladder Cancer

·   Year 1-2: Urine cytology (every 3 mo); Consider urinary urothelial tumor markers

·   Year 3-5: Urine cytology (every 6 mo)

·   Year 5-10: Urine tests annually

·   >10 Year: as clinicallly indicated

Post-Cystectomy Non-Muscle Invasive Bladder Cancer

·   Year 1-2: Urine cytology (every 6-12 mo), consider urethral wash cytology every 6-12 mo

·   3->10 Year: Urine cytology as clinically indicated, Urethral wash cytology as clinically indicated

Post-Cystectomy Muscle Invasive Bladder Cancer

·   Year 1-2: Urine cytology (every 6-12 mo), consider urethral wash cytology every 6-12 mo

·   3->10 Year: Urine cytology as clinically indicated, Urethral wash cytology as clinically indicated

Post-Bladder Sparing

·   Year 1-2: Urine cytology (every 6-12 mo)

·   3->10 Year: Urine cytology as clinically indicated

Metastatic Disease: Observation

·   urine cytology as clinically indicated

All recommendations are category 2A unless otherwise indicated.

NICE 2015

Do not offer routine urinary cytology or prolonged cystoscopic follow-up after 12 months for people with low-risk non-muscle-invasive bladder cancer.

After radical cystectomy consider using a follow-up protocol that consists of:

·    monitoring of the upper tracts for hydronephrosis, stones and cancer using imaging and glomerular filtration rate (GFR) estimation at least annually and

·   monitoring for local and distant recurrence using CT of the abdomen, pelvis and chest, carried out together with other planned CT imaging if possible, 6, 12 and 24 months after radical cystectomy and

·   monitoring for metabolic acidosis and B12 and folate deficiency at least annually and

·   for men with a defunctioned urethra, urethral washing for cytology and/or urethroscopy annually for 5 years to detect urethral recurrence.

The evidence was assessed as being of low to moderate quality using GRADE

The overall quality of the evidence for each outcome was low to very low as assessed with GRADE.

Referenz*

Studientyp

Evidenz-graduierung

Teilnehmer

Marker

Referenztest

Zielgrößen

Hauptergebnis

Methodische Bemerkung

Wang, 2022

·         35322590

Systematic review with meta-analysis

2-

n=12 studies

n=2456 patients diagnosed with or without bladder tumors

search period: 1999-2021

NMP22

urine cytology

diagnostic efficacy

the diagnosis of bladder cancer

Total sensitivity

·  NMP22: 0.79 (95% CI [0.73, 0.84])

·  cytology: 0.55 (95% CI [0.41, 0.69])

Total specificity

·  NMP22: 0.59 (95% CI [0.46, 0.71]

·  cytology: 0.91 (95% CI (0.81, 0.96])

Positive likelihood ratio

·  NMP22: 1.9 (95% CI [1.4, 2.6])

·  cytology: 5.9 (95% CI [3.3, 10.6])

Negative likelihood ratio

·  NMP22: 0.35 (95% CI [0.27, 0.47])

·  cytology: 0.49 (95% CI [0.38, 0.64])

Diagnostic odds ratio

·  NMP22: 5 (95% CI [3, 9])

·  cytology: 12 (95% CI [7, 21])

The area under the summary receiver operating characteristics curve

·  NMP22: 0.79 (95% CI [0.75, 0.82])

·  cytology: 0.81 (95% CI [0.77, 0.84])

At present, NMP22 cannot replace traditional cystoscopy and urine cytology, but it can be combined to detect bladder tumors. It plays a major role in screening, postoperative monitoring and follow-up.

no additional hand search, no complete search strategy reported, no information if efforts were made to minimise error in the data extraction and risk of bias assessment

There is no heterogeneity caused by the threshold effect, but there is heterogeneity caused by other reasons. The meta-regression found that the heterogeneity is mainly caused by the type of experimental research included in the study and whether the population characteristics are described in detail.

The authors declare no conflicts of interest.

No information about funding.

Laukthina, 2021

34753702

Systematic review with network meta-analysis

2++

n=21 studies

n=7330 patients with primary detection

or were undergoing follow-up for recurrent disease

and with detected urothelial carcinoma recurrence

search up to April 2021

·  Xpert bladder cancer

·  Adxbladder

·  Bladder EpiCheck

·  Uromonitor

·  Cxbladder Monitor

cystoscopy and/or histopathology

To assess the diagnostic estimates of novel commercially available urinary biomarker tests for diagnosis and surveillance of NMIBC

Pooled sensitivity

Xpert (n=10 studies)

0.722 (95% CI 0.631; 0.798)

EpiCheck (n=3 studies)

0.736 (95% CI 0.570; 0.855)

ADXbladder (n=3 studies)

0.571 (95% CI 0.387; 0.737)

Uromonitor (n=2 studies)

0.931 (95% CI 0.788; 0.980)

Cxbladder (n=2 studies)

0.909 (95% 0.853; 0.945)

Pooled specificity

Xpert (n=10 studies)

0.763 (95% CI 0.715; 0.805)

EpiCheck (n=3 studies)

0.8444 (95% CI 0.801; 0.879)

ADXbladder (n=3 studies)

0.618 (95% CI 0.508; 0.717)

Uromonitor (n=2 studies)

0.794 (95% CI 0.615; 0.903)

Cxbladder (n=2 studies)

0.610 (95% CI 0.209; 0.902)

Pooled positive predictive value

Xpert (n=10 studies)

0.428 (95% CI 0.318; 0.544)

EpiCheck (n=3 studies)

0.479 (95% CI 0.420; 0.539)

ADXbladder (n=3 studies)

0.291 (95% CI 0.077; 0.669)

Uromonitor (n=2 studies)

0.673 (95% CI 0.355; 0.885)

Cxbladder (n=2 studies)

0.165 (95% CI 0.089; 0.284)

Pooled Negative predictive value

Xpert (n=10 studies)

0.923 (95% CI 0.901; 0.940)

EpiCheck (n=3 studies)

0.942 (95% CI 0.527; 0.969)

ADXbladder (n=3 studies)

0.820 (95% CI 0.527; 0.949)

Uromonitor (n=2 studies)

0.957 (95% CI 0.863; 0.988)

Cxbladder (n=2 studies)

0.987 (95% CI 0.817; 0.999)

Network meta-analysis

·  Sensitivity (OR 68.2, 95% CrI 7.51–1.26e + 03), specificity (OR 0.41, 95% CrI 0.04–4.34), PPV (OR 1.31, 95% CrI 0.15–10.1), and NPV (OR 14.0, 95% CrI 3.28–116) of the Uromonitor test were significantly  higher than those of any other tests for the detection of NMIBC recurrence

no additional hand search, only keyword reported

serious heterogeneity (I²≥75%) in all analysis (expect specificity EpiCheck and Uromonitor; PPV: EpiCheck, Uromonitor and Cxbladder; NPV: Xpert, Uromonitor)

Ekaterina Laukhtina

is supported by the EUSP Scholarship of the European Association of Urology (EAU). Keiichiro Mori is supported by The Uehara Memorial

Foundation.

Funding/Support and role of the sponsor: None.

Soorojebally, 2023

36592175

Systematic review

2-

patients at risk of bladder cancer and patients with risk of non-muscle invasive recurrence or progression

search period: May 2010-March 2021

·  VisioCyt® (n=2)

·  Xpert® Bladder (n=11)

·  BTA stat® (n=3)

·  BTA TRAK™ (n=0)

·  NMP22 BC® (n=4)

·  NMP22® BladderChek® Test (n=12)

·  ImmunoCyt™/uCyt1+™ (n=4)

·  UroVysion Bladder Cancer Kit® (n=29)

·  Cxbladder (n=9)

·  ADXBLADDER (n=9)

·  Urodiag® (n=2)

·  Cytology

·  Cystoscopy

clinical validity and clinical utility of eleven urinary biomarkers for bladder cancer diagnosis and for

non-muscle invasive bladder cancer

VisioCyt®

Diagnosis

vs. "classical" urinary cytology,

·  Sensitivity: 84.9% vs. 43% (any grade)

·  Sensitivity: 92.6% vs. 61.1% (high grade)

·  Sensitivity: 77.6% vs. 26.3% (low grade)

vs. Cytology/Cystoscopy

·  Specificity: 81.2% vs. 100%

Xpert® Bladder

Diagnosis

vs. cytology

·  Sensitivity: 78% vs. 44%

·  Specificity: 84% vs. 97%

NMIBC surveillance

vs. cytology

·  Sensitivity: 59-84% vs. 5-51%

·  Sensitivity: 78–100% vs. 11–85% (high grade)

·  Sensitivity: 40–77% vs. 4–13% (low grade)

·  Specificity: comparable

The test does not have any added value relative to cytology.

Cxbladder

Diagnosis

vs. cytology

·  Sensitivity: 81% vs. 56%

·  Specificity: 85% vs. 94%

NMIBC surveillance

vs. cytology

·  Cxbladder test was superior to cytology

Test seems clinically useful for the follow-up because it can reduce by about 39% the mean number of annual cystoscopies.

ADXBLADDER

No study compared this test

directly to cystoscopy.

Diagnosis

·  Sensitivity: 73%

·  Specificity: 68.4%

Surveillance

vs. cytology

·  Sensitivity: 75.6% vs. 44.9% (low grade)

·  Sensitivity: Se: 100% vs 81.8% (MIBC recurrence)

Test specificity was lower than that of cytology for the detection of all recurrence types.

·  The combination of cytology and ADXBLADDER test increases the test value.

·  It is currently impossible to recommend this test instead of cystoscopy.

Urodiag®

We note the absence of comparison with urinary cytology.

Diagnosis

·  Sensitivity: 97.6%

·  Specificity: 84.8%

Recurrence detection

·  Sensitivity: 94.5%

·  Specificity: 75.9%

Among the 68/72 cancer recurrences, were correctly predicted (93.3% in the low risk, 92.9% in the intermediate risk, and 96.6% in the high-risk group).

Overall

·  sensitivity of the evaluated biomarkers was high, but at the cost of lower specificity compared with urinary cytology

·  any increase in the false positive rate results in an increase of unnecessary cystoscopies/other tests

·  no biomarker can replace urinary cystoscopy or urinary cytology

·  they might be interesting for the initial diagnosis

·  Some biomarkers may have a clinical utility in NMIBC surveillance in patients with negative or equivocal cystoscopy or negative or atypical urinary cytology, and also in recurrence prediction, thus contributing to the decision of active surveillance in these patients.

inclusion and exclusion criteria not clearly described (e. g. reference status, publication types, outcomes), short search period, only one database used, no information if efforts were made to minimise error in the study selection, data extraction and risk of bias assessment, included study numbers and characteristics not completely reported, no funnel plot

The authors declare that they have no conflict of

interest.

No information about funding.

Aalami, 2021

33997007

Systematic review with meta-analysis

2-

n=4 studies

n=656 participants (417 bladder cancer patients, 239 controls)

search up to October 2020

angiogenin

diagnostic role of the angiogenin

Pooled sensitivity

0.71 (95% CI: 0.66–0.75)

Pooled specificity

0.78 (95% CI: 0.73–0.81)

Positive likelihood ratio

3.34 (95% CI: 2.02–5.53)

Negative likelihood ratio

0.37 (95% CI: 0.32–0.44)

DOR

9.99 (95% CI: 4.69–21.28)

„gold standard“ of the included studies not reported, no complete search strategy reported, no information if efforts were made to minimise error in the data extraction, risk of bias in the included studies not addressed

The I2 heterogeneity of sensitivity, specificity, likelihood ratio +, likelihood ratio - , and DOR were 20.8%, 92.1%, 82.7%, 0%, and 77.4%.

The authors declare that they have no conflicts of interest.

No information about funding.

Soputro, 2022

35950042

Systematic review with meta-analysis

2-

n=17 studies

patients who presented with primary

macroscopic haematuria without prior diagnosis of bladder cancer

Median age: 59-69 y

search up to September 2020

·  AssureMDx (n=1)

·  CxBladder (n=2)

·  Bladder Tumour Antigen (n=4)

·  Immunocyt/uCyt+ (n=4)

·  NMP22 (n=8)

·  UroVysion (n=2)

Cystoscopy

diagnostic performance based

on their sensitivity, specificity and diagnostic odds ratio, as well as positive and negative likelihood ratios.

AssureMDx (n=1)

·  Sensitivity: 0.973 (95% CI 0.907–0.993)

·  Specificity: 0.825 (95% CI 0.727–0.893)

·  DOR: 169.714 (37.164–775.022)

·  positive likelihood ratio: 5.560 (3.450–8.961)

·  negative likelihood ratio: 0.033 (0.008–0.129)

CxBladder (n=1)

·  Sensitivity: 0.818 (95% CI 0.709–0.893)

·  Specificity: 0.852 (95% CI 0.815–0.883)

·  DOR: 25.911 (13.112–51.205)

·  positive likelihood ratio: 5.529 (4.279–7.145)

·  negative likelihood ratio: 0.213 (0.128–0.357)

Bladder Tumour Antigen (n=4)

·  Sensitivity: 0.659 (95% CI 0.572–0.736)

·  Specificity: 0.7 (95% CI 0.636–0.756)

·  DOR: 4.494 (2.819–7.165)

·  positive likelihood ratio: 2.192 (1.731–2.777)

·  negative likelihood ratio: 0.488 (0.377–0.631)

Immunocyt (n=4)

·  Sensitivity: 0.844 (95% CI 0.805–0.876)

·  Specificity: 0.833 (95% CI 0.815– 0.850)

·  DOR: 26.923 (19.969–36.299)

·  positive likelihood ratio: 5.048 (4.509–5.653)

·  negative likelihood ratio: 0.188 (0.149–0.236)

NMP22 (n=8)

·  Sensitivity: 0.718 (95% CI 0.670–0.761)

·  Specificity: 0.577 (95% CI 0.542–0.611)

·  DOR: 3.465 (2.657–4.520)

·  positive likelihood ratio: 1.696 (1.530–1.880)

·  negative likelihood ratio: 0.489 (0.412–0.582)

Urovysion (n=2)

·  Sensitivity: 0.712 (95% CI 0.624–0.786)

·  Specificity: 0.818 (95% CI 0.790–0.844)

·  DOR: 11.135 (7.193–17.235)

·  positive likelihood ratio: 3.920 (3.254–4.723)

·  negative likelihood ratio: 0.352 (0.265–0.468)

no additional hand search, no complete search strategy reported, no information if efforts were made to minimise error in the data extraction, heterogenitiy and risk of bias of the included studies not addressed, no funnel plot

No information about conflict of interest and funding.

Dong, 2021

34585369

Systematic review with network meta-analysis

2-

n=58 studies

n=12038 participants

search date: September

30, 2020

·  BTA stat

·  BTA trak

·  fluorescence in situ hybridization

·  NMP-22

·  Hyaluronidase 1

·  ImmunoCyt

·  Survivin

·  urothelial carcinoma associated-1

cytology

To identify effective urine biomarkers for bladder cancer diagnosis.

Sensitivity

·  HYAL-1, UCA1, and survivin were the most sensitive group

·  urine cytology was the least sensitive group

Specificity

·  Urine cytology, FISH, and HYAL-1 were the highest

·  UCA1 was the lowest

Positive predictive value

·  Urine cytology, FISH, and HYAL-1 had the highest positive predictive value

·  BTA group had the lowest positive predictive value

Negative predictive indicators

·  HYAL-1, UCA1, and survivin had the highest negative predictive value

·  Urine cytology had the lowest negative predictive value

Accuracy indicators

·  HYAL-1, UCA1, and survivin had the highest accuracy

·  Urine cytology had the lowest accuracy

HYAL-1 and survivin were found to be the two most suitable urine biomarkers for bladder cancer diagnosis.

no complete search strategy reported, no information if efforts were made to minimise error in the study selection, no risk of bias assessment

The authors declare that they have no competing financial

interests.

No information about funding.

Dardeer, 2021

34465950

Systematic review with meta-analysis

2-

n=4 studies

n=771 participants (417 bladder cancer patients, 254 controls)

search date: up to March 2020

Apolipoprotein A1

·  Cystoscopy

·  cytology

diagnostic

accuracy

Pooled sensitivity

90.7% (95% CI, 87.5%–93.3%)

Pooled specificity

90% (95% CI, 86.1%–93%)

DOR

99.424 (95% CI, 29.6–333.96)

Positive likelihood ratio

9.478 (95% CI, 4.178–21.502)

Negative likelihood ratio

0.100 (95% CI, 0.073–0.138)

no additional hand search, no complete search strategy reported, no information if efforts were made to minimise error in the risk of bias assessment

serious heterogeneity (I²≥75%) in the specificity analysis

Conflicts of interest: There are no conflicts of interest.

Financial support and sponsorship: Nil.

Hentschel, 2021

32539176

Systematic review

2++

n=25 studies

patient with a risk of bladder cancer and bladder cancer patients

search date: October 2019

·  single mutation markers

·  marker panels

·  cystoscopy

·  histology

diagnostic accuracy of urinary mutation

analysis is separately assessed for primary bladder cancer diagnosis and for follow-up of bladder cancer patients

Diagnosis

Single-mutation markers

·  sensitivity: 1–85%

·  specificity: 84–100%

Marker panels

·  sensitivity: 50–94%

·  specificity: 43–97%

Follow-up

Single-mutation markers

·  sensitivity: 0–85%

·  specificity: 66–100%

Marker panels

·  sensitivity: 51–84%

·  specificity: 66–96%

no funnel plot

As studies were too heterogeneous, no quantitative analysis could be performed.

supported by the Weijerhorst Foundation

R.D.M. Steenbergen has a minority share in Self-screen BV, a

spin-off company of Amsterdam UMC, location VUmc. J.

Bosschieter, R.D.M. Steenbergen and J.A. Nieuwenhuijzen are inventors on patent(s) related to the work.

Sciarra, 2021

34084118

Systematic review

2-

n=35 studies

n=16691 patients at risk of bladder cancer

search period: 2000-2019

Mean age varied between 30.8-72.4 y

America, (n=8), Asia (n=10), Europe (n=15), Oceania (n=2)

·  Cytology

·  MCM5

·  Microsatellite

·  UroVysion

·  BTA stat

·  ImmunoCyt

·  NMP-22

·  cystoscopy

·  transurethral bladder biopsy or resection

critically analyze and compare results in the literature of promising molecular urinary tests for the initial

diagnosis of bladder cancer

Cytology (n=25 studies, 14375 patients)

·  Mean Sensitivity: 45.5±23.1 %

·  Mean Specificity: 89.7±13.2 %

·  Mean Negative Predictive Value: 82.6±16.1 %

·  Mean Positive Predictive Value: 64.9±28.5 %

MCM5 (n=3 studies, 2147 patients)

·  Mean Sensitivity: 72.8±12.7 %

·  Mean Specificity: 74.0±11.4 %

·  Mean Negative Predictive Value: 83.0±20.0 %

·  Mean Positive Predictive Value: 52.7±23.2 %

Microsatellite (n=3 studies, 592 patients)

·  Mean Sensitivity: 61.5±11.1 %

·  Mean Specificity: 90.1±2.6 %

·  Mean Negative Predictive Value:  86.9±22.2 %

·  Mean Positive Predictive Value: 53.7±43.9 %

UroVysion (n=12 studies, 5033 patients)

·  Mean Sensitivity: 64.3±19.0 %

·  Mean Specificity: 88.4±14.2 %

·  Mean Negative Predictive Value:  72.4±24.6 %

·  Mean Positive Predictive Value: 67.7±26.8 %

BTA stat (n=6 studies, 999 patients)

·  Mean Sensitivity: 70.2±5.8 %

·  Mean Specificity: 77.2±6.5 %

·  Mean Negative Predictive Value:  67.9±17.1 %

·  Mean Positive Predictive Value: 74.8±13.1 %

ImmunoCyt (n=7 studies, 4976 patients)

·  Mean Sensitivity: 76.4±8.9 %

·  Mean Specificity: 79.0±5.6 %

·  Mean Negative Predictive Value:  83.4±21.4 %

·  Mean Positive Predictive Value: 57.7±26.7 %

NMP-22 (n=19 studies, 8988 patients)

·  Mean Sensitivity: 60.1±21.0 %

·  Mean Specificity: 80.6±13.6 %

·  Mean Negative Predictive Value:  82.1±16.6 %

·  Mean Positive Predictive Value: 48.0±29.5 %

no complete search strategy reported, no information if efforts were made to minimise error in the risk of bias assessment, heterogenitiy and risk of bias of the included studies not addressed, no funnel plot

The authors declare that they have no financial conflict of interest with regard to the content of this report.

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

wrong search period in the abstract reported 

Referenz

Studientyp

Evidenz-graduierung

Teilnehmer

Intervention

Referenztest

Zielgrößen

Hauptergebnis

Methodische Bemerkung

Systematische Reviews*

Feng, 2022

35181798

Sytematic review and meta-analysis

2-

n=19 cohort studies (12 retrospective, 7 prospective)

n=2900 patients

Mean/Median age: 60.2-76 y

Search date: October 2021

VI-RADS based on mpMRI

·  TURBT (n=19 studies)

·  Radical cystectomy (n=13 studies)

·  Partial cystectomy (n=6 studies)

Diagnostic performence of VI-RADS

Pooled sensitivity

Score 3: 0.92 (95%CI 0.89–0.94)

Score 4: 0.78 (95%CI 0.72–0.83)

Pooled specificity

Score 3: 0.82 (95%CI 0.76–0.87)

Score 4: 0.96 (95%CI 0.93–0.97)

AUC

Score 3 and 4: 0.94 (95%CI 0.92–0.96)

Proportion of muscle invasive (n=9)

Sensitivity: 0.82 (0.76–0.88) p=0.11

specificity: 0.94 (0.90–0.97) p<0.01

no keywords or search strategy reported

serious heterogeneity (I²≥75%) in the analysis (except sensitivity analysis with score 3 I²=53.15%)

The authors declare that they have no conflict of

interest.

No funding received.

Ye, 2022

35362750

Systematic review with meta-analysis

2++

n=17 cohort studies (11 retrospective, 6 prospective)

n=2344 patients

Mean age: 57.2-74 y

search date: June 26, 2021

·  bpMRI (n=1041 patients)

·  conventional VI-RADS based on mpMRI (n=1303 ptients)

·  TURBT (n=17 studies)

·  re-TURBT (n=11 studies)

·  radical cystectomy (n=11 studies)

·  partial cystectomy (n=39 studies)

·  Diagnostic performance of the bpMRI and conventional VI-RADS

·  accuracy of conventional VI-RADS

bpMRI

Cutoff score 3 (n=6)

·  Sensitivities: 0.90 (95% CI 0.69–0.97)

·  specificities: 0.90 (95% CI 0.81–0.95)

·  accuracy: 0.88 (95% CI 0.81–0.93)

·  PPV: 0.78 (95% CI 0.65–0.87)

·  NPV: 0.95 (95% CI 0.86–0.99)

·  AUC: 0.95 (95% CI: 0.92–0.96)

Cutoff score 4 (n=6)

·  Sensitivities: 0.84 (95% CI 0.78–0.88)

·  specificities: 0.97 (95% CI 0.87–0.99)

·  accuracy: 0.92 (95% CI: 0.85–0.96)

·  PPV: 0.90 (95% CI: 0.65–0.98)

·  NPV: 0.95 (95% CI: 0.89–0.98)

·  AUC: 0.89 (95% CI: 0.86–0.91)

VI-RADS

Cutoff score 3 (n=16)

·  Sensitivities: 0.91 (95% CI 0.87–0.94)

·  specificities: 0.86 (95% CI 0.77–0.91)

·  accuracy: 0.87 (95% CI: 0.81–0.91)

·  PPV: 0.76 (95% CI: 0.66–0.84)

·  NPV: 0.95 (95% CI: 0.92–0.97)

·  AUC: 0.95 (95% CI: 0.92–0.96)

Cutoff score 4  (n=16)

·  Sensitivities: 0.85 (95% CI 0.77–0.90)

·  specificities: 0.93 (95% CI 0.89–0.96)

·  accuracy: 0.88 (95% CI 0.86–0.90)

·  PPV: 0.85 (0.76–0.91)

· NPV: 0.94 (0.89–0.96)

·  AUC: 0.95 (95% CI: 0.93–0.97)

bpMRI vs mpMRI

Cutoff score 3

·  sensitivities: p=0.15

·  specificity: bpMRI was significantly higher than VI-RADS (0.90 [95% CI 0.81–0.95] vs 0.86 [95% CI: 0.77–0.91], p = 0.02)

Cutoff score 4

·  sensitivities: p=0.19

·  specificity: bpMRI was significantly higher than VI-RADS (0.97 [95% CI 0.87–0.99] vs 0.93 [95% CI: 0.89–0.96], p = 0.02)

hsROC curves showed no difference between the 95% confidence regions with cutoff scores of 3 and 4.

T2 thickness (mm)

VI-RADS 3

≤ 4 (n=12)

·  Sensitivity: 0.89 (95% CI 0.85–0.94)

·  Specifity: 0.89 (95% CI 0.82–0.95)

p=0.35

VI-RADS 4

≤ 4 (n=11)

·  Sensitivity: 0.85 (95% CI 0.77–0.93)

·  Specifity: 0.93 (95% CI 0.88–0.98)

p=0.94

VI-RADS 3

> 4 (n=3)

·  Sensitivity: 0.92 (95% CI 0.87–0.97)

·  Specifity: 0.73 (95% CI 0.50–0.97)

p=0.35

VI-RADS 4

> 4 (n=3)

·  Sensitivity: 0.82 (95% CI 0.68–0.97)

·  Specifity: 0.94 (95% CI 0.87–1.00)

p=0.94

serious heterogeneity (I²≥75%) in the analysis (except sensitivity analysis with score 3 I²=73%)

The authors of this manuscript declare no relationships with any companies whose products or services may be related to the subject matter of the article.

National Science Foundation of China Youth Fund (No.

31801066)

Del Giudice, 2022

35294583

Systematic review with meta-analysis

2-

n=20 cohort studies (16 retrospective, 6 prospective)

n=2477 patients

Median age: 57-74 y

search date: May 26, 2021

VI-RADS based on mpMRI

·  TURBT (n=20 studies)

·  cystectomy (n=10 studies)

Diagnostic performence of VI-RADS

Pooled weighted sensitivity

cut-off ≥ 3: 0.87 (95% CI 0.82–0.91)

cut-off ≥ 4: 0.78 (95% CI 0.74–0.81)

Pooled weighted specificity

cut-off ≥ 3: 0.86 (95% CI 0.80–0.90)

cut-off ≥ 4: 0.94 (95% CI 0.91–0.96)

Area under the hsROC

cut-off ≥ 3: 0.93 (95% CI 0.90–0.95)

cut-off ≥ 4: 0.91 (95% CI 0.88–0.93)

no search strategy reported, unclear if efforts were made to minimise error in data collection by a second author

serious heterogeneity (I²≥75%) in the analysis (except sensitivity analysis with cut-off ≥ 4 I²=57%)

Regarding the content of this paper, the authors

declare that they have no conflict of interest to disclose.

Open access funding provided by Alma Mater Studiorum – Università di Bologna within the CRUI-CARE Agreement.

Jazayeri, 2022

34895996

Systematic review with meta-analysis

2++

n=22 cohort studies (14 retrospective, 8 prospective)

n=2576 participants

Mean age: 57.1-75.3 y

search date: 8 March 2021

VI-RADS based on mpMRI

·  TURBT (n=3 studies)

·  TURBT and re-TURBT/ cystectomy (n=18 studies)

·  Not reported (n=1 studies)

·  Diagnostic accuracy of VI-RADS

·  value for predicting MIBC

Sensitivity

Score 2: 82% to 100%

Score 3: 77% to 100%

Score 4: 36% to 100%

Score 5: 0% to 85%

Pooled sensitivity

VI-RADS ≥ 3: 89% (95%CI: 87%, 91%; I2 = 48.4%)

VI-RADS ≥ 4: 77% (95%CI: 73%, 82%; I2 = 67.7%)

Specificity

Score 2: 9% to 89%

Score 3: 44% to 97%

Score 4: 74% to 100%

Score 5: 5% to 100%

Pooled specificity

VI-RADS ≥ 3: 84% (95%CI: 80%, 87%; I2 = 90.9%)

VI-RADS ≥ 4: 77% (95%CI: 73%, 82%; I2 = 67.7%)

Accuracy

cutoff 3: 0.93 (95%CI: 0.91, 0.95)

cutoff 4: 0.93 (95%CI: 0.90, 0.95)

AUC

Score 3: 0.93 (95%CI: 0.91, 0.95)

Score 4: 0.93 (95%CI: 0.90, 0.95)

T2WI slice thickness (mm)

2&3 (n=4)

Sensitivity: 0.93 [0.89 – 0.97] p<0.01

Specifity: 0.82 [0.72 – 0.91] p<0.01

4&5 (n=9)

Sensitivity: 0.88 [0.85 – 0.90]

Specifity: 0.85 [0.80 – 0.90]

serious heterogeneity (I²≥75%) in the analysis for pooled sensitivity and specifity ≥ 3

publication bias was noted for VI-RADS ≥ 2 and ≥ 5 (P value = 0.002 with a slope coefficient

of -18.49 and P value < 0.001 with a slope coefficient of -25.41

The authors confirm that there is no conflict of interest to

declare.

No information about funding.

Seguier, 2021

34457041

Systematic review

2-

n=20 studies (3 meta-analysis, 12 retrospective studies, 5 prospective studies)

n=2144 patients in the cohort studies

search date: January 2018-December 2020

VI-RADS based on mpMRI

evaluate the performance of the VI-RADS score

·  Pooled sensitivity ranged from 74.1% to 97.3%

·  Pooled specificityranged from 77% to 100%

Retrospective studies

VI-RADS 2 (n=3)

·  sensitivity was 100%

·  specificity ranged from 21% to 81%

VI-RADS 3 (n=12)

·  sensitivity ranged from 78% to 100%

·  specificity ranged from 44% to 100%

VI-RADS 4 (n=7)

·  sensitivity ranged from 63 to 100%

·  specificity ranged from 76% to 96%

VI-RADS 5 (n=7)

·  sensitivity ranged from 68% to 86%

·  specificity ranged from 95% to 99%

Prospective studies

VI-RADS 3 (n=3)

·  sensitivity ranged from 78% to 92%

·  specificity ranged from 88% to 91%

VI-RADS 4 (n=1)

·  sensitivity: 85.7%

·  specificity: 86.9%

VI-RADS 5 (n=1)

·  sensitivity: 90.2%

·  specificity: 98.1%

Meta-analyses

Woo, 2020 (n=6)

Overall

·  sensitivity: 83%

·  specificity: 90%

Luo, 2020 (n=5)

Overall

·  sensitivity: 90%

·  specificity: 86%

VI-RADS 4

·  sensitivity: 77%

·  specificity: 97%

Del Guidice, 2020 (n=8)

·  able to confirm an excellent inter-reader agreement of the VI-RADS score to discriminate MIBCs from NMIBCs: mean kappa 0.83 (95% CI 0.78-0.88)

short search period, no search strategy reported, no information if efforts were made to minimise error in data collection and risk of bias assessment, no funnel plot, biases in primary studies were not  addressed in the synthesis

The authors declare that there is no conflict of interest.

The authors received no financial support for the research, authorship, and/or publication of this article.

Carando, 2020

33029409

Systematic review

2-

n=6 cohort studies

n=1067 patients

search date: December, 2019

VI-RADS based on mpMRI

·  The effectiveness of mpMRI in differentiating NMIBC from MIBC

·  The effectiveness of mpMRI in avoiding second TURBT in high-risk NMIBC

·  Potential limitations of the VI-RADS score

cut-off VI-RADS score of >2

·  sensitivity: 78–91.9%

·  specificity: 85–91%

·  PPV: 69–78%

·  NPV: 88–97.1%

cut-off VI-RADS score of >3

·  sensitivity: 77–94.6%

·  specificity: 43.9-96.5%

·  PPV: 51.6-86%

·  NPV: 63.7–93%

Good interobserver agreement was demonstrated in the evaluated studies with a κ score of 0.73–0.89.

inclusion and exclusion criteria not clearly described, no search strategy reported, no efforts made to minimise error in study selection and data collection, no risk of bias assessment,

some study characteristics are missing (e. g. retrospective/ prospective, reference standard), heterogeneity not addressed

The authors declare that they have no conflicts of interest.

No information about funding.

Woo, 2020

32199915

Systematic review with meta-analysis

2++

n=6 studies (4 cohort studies, 2 prospective)

n=1170 patients

Mean age: 57.2-65.5 y

search date: November 10, 2019

VI-RADS based on mpMRI

·  TURBT (n=6 studies)

·  Partial cystectomy (n=2 studies)

·  Radical cystectomy (n=3 studies)

diagnostic performance of VI-RADS

Pooled sensitivity

0.83 (95% CI 0.70–0.90)

Pooled specificity

0.90 (95% CI 0.83–0.95)

Area under the HSROC curve

0.94 (95% CI 0.91–0.95)

T2WI slice thickness (mm)

3 (n=3)

Sensitivity: 0.90 (0.86–0.95)

Specifity: 0.85 (0.78–0.93)

p<0.01

4 (n=2)

Sensitivity: 0.84 (0.77–0.90)

Specifity: 0.96 (0.93–1.00)

p<0.01

serious heterogeneity (I²≥75%) for sensitvity and specificity

number of patients has been corrected: PMID: 34756363

Conflict of interest are reported in detail in the paper.

This research was funded in part through the NIH/NCI Cancer Center Support Grant P30 CA008748. However, all specific roles were performed only by authors, and NIH/NCI had no direct role or support in those roles.

Cornelissen, 2020

32721515

Systematic review with meta-analysis

2-

n=20 cohort studies (9 prospective, 8 retrospective, 3 unclear)

n=1724 patients

Mean age: 52-72 y

search date: October 2019

mpMRI

·  TURBT (n=1 studies)

·  cystectomy or TURBT (n=10 studies)

·  Cystectomy, cystoscopy+biopsy or TURBT (n=1 studies)

·  cystectomy (n=5 studies)

·  unclear (n=3 studies)

·  What is the overall accuracy of mpMRI in local tumorstaging?

·  Can mpMRI differentiate stage ≤T1 from ≥T2?

·  Can mpMRI differentiate stage ≤T2 from ≥T3?

·  What is the sensitivity and specificity of mpMRI per T-stage?

·  Can mpMRI differentiate stage T-any from pT0 after initial TURBT?

Accuracy

·  Overall (n=5): 56.0% (95% CI 49.6-62.3)

·  T2W (n=1): 85.0% (95% CI 62.1-96.8)

·  DCE (n=1): 64.4% (95% CI 48.8-78.1)

· Overstaging was reported more often than understaging: 28.1% (95% CI 22.3-34.4) vs 18.4% (95% CI 13.6-24.1)

Stage ≤T1 vs stage ≥T2 (n=19)

Sensitivity: 0.92 (95% CI 0.88-0.95)

Specifity: 0.88 (95% CI 0.78-0.94)

Stage ≤T2 vs stage ≥T3 (n=3)

Sensitivity: 0.71 (95% CI 0.59-0.82)

Specifity: 0.77 (95% CI 0.68-0.84)

Stage T0 (n=1)

Sensitivity: 0.14 (95% CI 0.02-0.43)

Specifity: 0.95 (95% CI 0.90-0.98)

Stage T1 (n=7)

Sensitivity: 0.75 (95% CI 0.47-0.91)

Specifity: 0.95 (95% CI 0.91-0.97)

Stage T2 (n=3)

Sensitivity: 0.62 (95% CI 0.49-0.74)

Specifity: 0.66 (95% CI 0.57-0.75)

Stage T3 (n=3)

Sensitivity: 0.59 (95% CI 0.43-0.74)

Specifity: 0.80 (95% CI 0.72-0.86)

Stage T4 (n=3)

Sensitivity: 0.77 (95% CI 0.55-0.92)

Specifity: 0.97 (95% CI 0.92-0.99)

title screening were performed by 1 author, no information if efforts were made in the data collection, no funnel plot

serious heterogeneity (I²≥75%)

The authors declare that they have no relevant financial interests.

No information about funding.

Woo, 2017

28987698

Systematic review with meta-analysis

2-

n=24 cohort studies (13 rerospective, 11 prospective)

n=1774 patients

Mean age: 52.1-72.1 y

search date: February 21, 2017

VI-RADS based on mpMRI

·  TURBT (n=3 studies)

·  either cystectomy or TURBR (n=16 studies)

·  cystectomy (n=4 studies)

·  not reported (n=1 studies)

·  Diagnostic performance of ≥1.5-T MRI

Conventional + ≥2 functional (n=5)

Sensitivity: 0.94 [0.89 – 1.00]

Specifity: 0.95 [0.89 – 0.98] p<0.01

Using multiparametric 3-T MRI seemed to improve both sensitivity and specificity.

no information to heterogenity in the subgroups, publication bias is present (Fig. 5)

There are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome.

Primärstudien

Aslan, 2022

34919161

Diagnostic study

2+

n=114 patients

2019-2021

·  T2-WI

·  DWI

·  DCE

·  bpMRI

·  mpMRI

TUR-B and/or radical cystectomy

·  accuracy and validity of the bpMRI

·  diagnostic performance and agreement of readers with different experiences

Range: results of both readers

T2-WI

·  Sensitivity: 88.3-37.1%

·  Specificity: 84.8-90.7%

·  PPV: 60-71.7%

·  NPV: 96.1-97.3%

·  Accuracy: 85.3-90.6%

·  AUC: 0.86-0.91

DWI

·  Sensitivity: 90.3%

·  Specificity: 95.8-99.1%

·  PPV: 84.3-96.5%

·  NPV: 96.6-97.5%

·  Accuracy: 94-97.3%

·  AUC: 0.91-0.95

DCE

·  Sensitivity: 87.1-89.7%

·  Specificity: 90.7-97.4%

·  PPV: 71.7-90.3%

·  NPV: 97.3-97.4%

·  Accuracy: 90.6-96%

·  AUC: 0.91-0.94

bpMRI

·  Sensitivity: 87.1-90.3%

·  Specificity: 91.6-96.6%

·  PPV: 87.1-96.5%

·  NPV: 97.5-96.6%

·  Accuracy: 91.3-96%

·  AUC: 0.92-0.95

mpMRI

·  Sensitivity: 90.3-93.5%

·  Specificity: 99.1-96.6%

·  PPV: 73.6-87.8%

·  NPV: 97.3-98.2%

·  Accuracy: 94.6-97.3%

·  AUC: 0.92-0.95

No significant differences were shown in diagnostic performance for either reader between both the protocols (p = 0.238 and 0.318).

consecutive recruitment unclear, unclear if TURBT/cystectomy results were interpreted without knowledge of the results of magnet resonance images

No funding was received for this study.

The authors declare that they have no conflict of

interest.

Bricio, 2022

35505425

Diagnostic study

2+

n=44 patients

Male: 19/44 (43.2%)

Mean age: 68.7 y (35-91 y)

2018-2020

Brazil

·  biparametric VI-RADS

·  multiparametric VI-RADS

·  TURBT

·  Radical cystectomy

accuracy and reproducibility of the VI-RADS score

Diagnostic accuracy

Small lesions (n=25)

Biparametric Vi-RADS

·  Reader 1: 0.747 +/− 0.12 (0.50–0.99)

·  Reader 2: 0.800 +/− 0.11 (0.57–1.0)

p=0.04

Multiparametric VI-RADS

·  Reader 1: 0.795 +/− 0.11 (0.57–1.0)

·  Reader 2: 0.800 +/− 0.11 (0.57–1.0)

p=0.56

All cases (n=50)

Biparametric Vi-RADS

·  Reader 1: 0.879+/−0.05 (0.78–0.95)

·  Reader 2: 0.885 +/− 0.04 (0.79–0.98)

p=0.07

Multiparametric VI-RADS

·  Reader 1: 0.916 +/− 0.04 (0.85–0.99)

·  Reader 2: 0.924 +/− 0.04 (0.84–0.99)

p=0.24

unclear if TURBT/cystectomy results were interpreted without knowledge of the results of bpMRI and mpMRI

The authors declare that they have no competing interests.

The study was carried out using the authors’ department resources only.

Elshetry, 2022

35381566

Diagnostic study

2+

n=54 patients

Mean age: 60.1 y (45-76 y)

Male: 47/54 (87%)

2019-2021

Egypt

·  bpMRI

·  mpMRI

TURBT

diagnostic accuracy and discriminative power of bpMRI and mpMRI

Reader 1

bpMRI (VI-RADS cut-off values ≥3)

Sensitivity: 100% (92-100)

Specificity: 85.7% (57-98%)

PPV: 95.7% (86-98%)

NPV: 100%

Accuracy: 96.5% (88-99%)

mpMRI (VI-RADS cut-off values ≥3)

Sensitivity: 100% (92-100)

Specificity: 64.3% (35-87%)

PPV: 89.8% (81-95%)

NPV: 100%

Accuracy: 91.3% (81-97%)

Reader 2

bpMRI (VI-RADS cut-off values ≥3)

Sensitivity: 100% (92-100)

Specificity: 71.4% (42-92%)

PPV: 91.7% (83-96%)

NPV: 100%

Accuracy: 93.1% (83-98%)

mpMRI (VI-RADS cut-off values ≥3)

Sensitivity: 100% (92-100)

Specificity: 64.3% (35-87%)

PPV: 89.8% (81-95%)

NPV: 100%

Accuracy: 91.3% (81-97%)

Reader 3

bpMRI (VI-RADS cut-off values ≥3)

Sensitivity: 100% (92-100)

Specificity: 93.6% (84-97%)

PPV: 93.6% (84-97%)

NPV: 100%

Accuracy: 94.8% (87-99%)

mpMRI (VI-RADS cut-off values ≥3)

Sensitivity: 100% (92-100)

Specificity: 71.4% (42-92%)

PPV: 91.7% (83-96%)

NPV: 100%

Accuracy: 93.1% (83-98%)

Comparable diagnostic accuracy with insignificant differences for the three readers (P = 0.364,0.718,0.702).

consecutive recruitment unclear, unclear if TURBT results were interpreted without knowledge of the results of bpMRI and mpMRI

The authors declare no conflict of interests.

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Hagen, 2022

34839167

Diagnostic study

2-

n=33 patient

Median age: 70 y (59-81 y)

Male: 29/33 (88%)

2019-2020

Germany

·  VI-RADS based on mpMRI (n=33)

·  CECT (n=33)

·  Radical cystectomy (n=16)

·  TURBT (n=17)

 clinical applicability of local tumor staging with VI-RADS compared to CECT

Radiologist 1

mpMRI (VI-RADS cut-off values ≥3)

Sensitivity: 80%

Specificity: 73.9%

Accuracy: 75.6%

CECT

Sensitivity: 80%

Specificity: 60.9%

Accuracy: 66.7%

p=0.839

Radiologist 2

mpMRI (VI-RADS cut-off values ≥3)

Sensitivity: 70%

Specificity: 82.6%

Accuracy: 78.9%

CECT

Sensitivity: 90%

Specificity: 69.5%

Accuracy: 75.6%

p=0.307

unclear if TURBT/cystectomy results were interpreted without knowledge of the results of VI-RADS and CECT results, no time interval between VI-RADS and CECT and TURBT/radical cystectomy reported

No information about conflict of interest and funding.

Kufukihara, 2022

34332846

Diagnostic study

2-

n=61 patients

Age: 71.2 (49-88) y

Male: 55/61 (90.2%)

2010-2018

Japan

·  VI-RADS based on mpMRI

·  Diagnostic cystoscopy

TURBT

Comparison oft he diagnostic performance

VI-RADS (cut-off values ≥3)

Radiologist 1

Sensitivity: 93.8%

Specificity: 88.9%

Radiologist 2

Sensitivity: 87.5%

Specificity: 86.7%

Cystoscopy

Urologist 1

Sensitivity: 56.3%

Specificity: 68.9%

Urologist 2

Sensitivity: 68.8%

Specificity: 84.4%

·  sensitivity of cystoscopy was significantly lower than that of VI-RADS scores (p=0.006)

·  specificity of cystoscopy was slightly lower than that of VI-RADS scores (P = 0.089)

consecutive recruitment unclear, unclear if TURBT results were interpreted without knowledge of the results of VI-RADS and cystoscopy results, no time interval between bpMRI and mpMRI and TURBT reported

No information about conflict of interest.

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Nikulainen, 2021

34448679

Diagnostic study

2+

n=45 patients

Mean age: 67.5 y (34-86 y)

Male: 39/45 (87%)

2014-2017

Finland

mpMRI

·  T-category

·  VI-Rads

TURBT

·  performance of mpMRI using a subjective magnetic resonance imaging

·  performance of VI-RADS

Reader 1

T-category

Sensitivity: 100%

Specificity: 51% (95% CI 0.37–0.66)

AUC: 0.76 (95% CI 0.59–0.85)

PPV: 17% (95% CI 0.13–0.22)

NPV: 100%

VI-Rads

Sensitivity: 75% (95% CI 0.75–1.00)

Specificity: 51% (95% CI 0.37–0.66)

AUC: 0.63 (95% CI 0.51–0.86)

PPV: 14% (95% CI 0.05–0.21)

NPV: 96% (95% CI 0.87–1.00)

Reader 2

T-category

Sensitivity: 75% (95% CI 0.75–1.00)

Specificity: 37% (95% CI 0.22–0.51)

AUC: 0.56 (95% CI 0.52–0.88)

PPV: 10% (95% CI 0.04–0.15)

NPV: 94% (95% CI 0.82–1.00)

VI-Rads

Sensitivity: 75% (95% CI 0.75–1.00)

Specificity: 39% (95% CI 0.24–0.54)

AUC: 0.57 (95% CI 0.47–0.80)

PPV: 11% (95% CI 0.04–0.17)

NPV: 94% (95% CI 0.83–1.00)

no statistically significant difference between the reporting systems

consecutive recruitment unclear

Peter J. Boström, is an associate editor of Scandinavian Journal of Urology.

The article was partly funded by grants from the Finnish Urology Association and the Turku University Hospital Research Foundation.

Gmeiner, 2021

34252867

Diagnostic study

2+

n=59 patients

Mean age: 68.2 y (SD ±13.6 y)

Male: 48/59 (81.4%)

2012-2014

Austria

·  VI-RADS based on mpMRI

·  TURBT

·  cystectomy

Diagnostic performance of overall VI-RADS

Range: results of both readers

Cut-off value > 2

T2W

Sensitivity: 76.9%

Specificity: 92.3-96.2%

DWI

Sensitivity: 65.4-69.2%

Specificity: 88.5-96.2%

DCE

Sensitivity: 72%

Specificity: 96.15-96.2%

Cut-off value > 3

T2W

Sensitivity: 92.9-100%

Specificity: 97.6%

DWI

Sensitivity: 78.6-92.9%

Specificity: 95-95.1%

DCE

Sensitivity: 92.9-100%

Specificity: 92.5-95%

Muscle invasivnesss

T2W

AUC: 0.976-0.985

DWI

AUC: 0.952-0.985

DCE

AUC: 0.974-0979

Tumor grade

T2W

AUC: 0.911-0.913

DWI

AUC: 0.868-0.872

DCE

AUC: 0.898-0.902

Upon multivariate logistic regression, only the T2w VI-RADS score contributed independently to the diagnosis of high grade and muscle invasive bladder cancer (P = 0.001 (Reader 1) and P = 0.0022 (Reader 2) for high grade cancer; P = 0.0007 (Reader 1) and P = 0.0019 (Reader 2) for muscle invasiveness).

consecutive recruitment unclear, unclear if TURBT/ cystectomy results were interpreted without knowledge of the results of VI-RADS results

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

No information about funding.

Wang, 2015

25615755

Diagnostic study

2+

n=39 patients

(6 excluded)

Mean age: 60.8 ± SD 11.2 y

Male: 28/33 (85%)

2011-2013

·  T2-Weighted Plus DCE-MRI

·  T2-Weighted Plus DWI

·  T2-Weighted Plus DWI Plus DCE-MRI

·  radical cystectomy (n=11)

·  partial cystectomy (n=2)

·  TURBT (n=26)

determine an optimal mpMRI protocol for characterizing tumors of low versus high grade and differentiating tumors as T1 versus T2 for preoperative staging of bladder urothelial carcinoma

Reader 1

T2-Weighted Plus DCE-MRI

AUC: 0.731 (0.587–0.874)

T2-Weighted Plus DWI

AUC: 0.980 (0.948–1.000)

T2-Weighted Plus DWI Plus DCE-MRI

AUC: 0.988 (0.966–1.000)

p < 0.05

Reader 2

T2-Weighted Plus DCE-MRI

AUC: 0.717 (0.571–0.843)

T2-Weighted Plus DWI

AUC: 0.983 (0.954–1.000)

T2-Weighted Plus DWI Plus DCE-MRI

AUC: 0.991 (0.974–1.000)

p < 0.05

·  The combination of T2-weighted imaging, DWI, and DCE-MRI is most accurate for preoperative staging of organ-confined urothelial bladder cancer.

·  With a cutoff apparent diffusion coefficient value of 0.899 × 10−3 mm2/s, the sensitivity and specificity for differentiating high- and low-grade bladder urothelial carcinoma were 100% and 95%.

unclear if surgery results were interpreted without knowledge of the results of mpMRI results

No information about conflict of interest or funding.