To assess the clinical impact of implementing a molecular urine test in the diagnostic workup of patients presenting with microscopic hematuria.
ID
Source
Brief title
Condition
- Renal and urinary tract neoplasms malignant and unspecified
- Bladder and bladder neck disorders (excl calculi)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is the net benefit of the *urine-first* strategy versus
the *care-as-usual*, which is a cystoscopy in all patients presenting with
microscopic hematuria. The net benefit is a decision analytic measure to
evaluate the clinical implementation of an intervention commonly used in
health.(17) In clinical decision models, the net benefit calculation determines
whether implementing an intervention would do more good or harm (a positive
value indicates a positive effect). This is achieved by putting the benefits
(detection of a bladder tumor) and harms (performing diagnostic evaluation
without any abnormal finding) on the same scale and multiplying the harms with
a decision threshold. The decision threshold represents the estimated harms of
the diagnostic intervention, such as the risk for a urinary tract infection,
patients* burden, and use of available resources, against the harms of an
outcome event, i.e. missing a bladder tumor. As previously reported, the
decision threshold for evaluation of microscopic hematuria patients is
determined at 3% (1 divided by 30). Meaning that a urologist is willing to
conduct 30 cystoscopies to detect 1 bladder tumor.
Secondary outcome
The secondary outcomes are I) the number of cystoscopies and upper tract
imaging modalities (CT or ultrasound) II) cost-effectiveness and III) patient
burden. These outcomes will be directly compared between the *care-as-usual*
arm, a cystoscopy and upper tract imaging for all patients presenting with
microscopic hematuria versus the *urine-first* strategy, in which only patients
with an abnormal test result undergo diagnostic evaluation.
Background summary
Visual inspection of the bladder (cystoscopy) is commonly performed to rule out
the presence of bladder cancer (BC) in patients presenting with microscopic
hematuria.(2) However, only 2-3% of patients presenting with microscopic
hematuria are diagnosed with bladder cancer, meaning that the majority of
cystoscopies are redundant.(1, 5) The estimated direct medical costs of a
cystoscopy is estimated to be $161-$222, which poses high burden on urological
healthcare costs in addition to patient burden/discomfort.(4, 15) Moreover, the
sensitivity of cystoscopy for the detection of bladder tumors is not 100%.(16)
We propose to tackle these problems by performing a molecular urine test to
triage microscopic hematuria patients for cystoscopy, a *urine-first* strategy.
Due to the low incidence of bladder cancer in the microscopic hematuria
population, three conditions have to be met for a urine test in this setting:
i) the test must have a high negative predictive value (NPV) in order to
prevent unnecessary invasive cystoscopies (urine test negative, absence of
bladder tumor) ii) the test must have a high sensitivity for the detection of
bladder cancer to minimize the number of false negative outcomes: i.e. urine
test negative, presence of bladder tumor, and iii) the test must have a high
specificity as this indicates the proportion of patients who unnecessarily
undergo cystoscopy because of false-positive results.(19, 20) Given the robust
test performance of the diagnostic urine assay in previous studies, the test
seems to be an accurate diagnostic tool for the detection of bladder cancer in
patients presenting with microscopic hematuria.(8) To justify clinical
implementation of the novel urine test in daily practice, we argue that a
direct comparison between the novel diagnostic strategy and care-as-usual is
required.(14) Therefore, we propose to conduct a randomized controlled trial
(RCT) to compare the clinical outcomes by implementing a *urine-first*
strategy, in which only patients with an abnormal test result undergo a
cystoscopic evaluation versus care-as-usual, which is a cystoscopy in all
patients presenting with microscopic hematuria.
Study objective
To assess the clinical impact of implementing a molecular urine test in the
diagnostic workup of patients presenting with microscopic hematuria.
Study design
A multicenter, prospective randomized controlled clinical trial in seven
hospitals: Amphia ziekenhuis, Elisabeth-TweeSteden Hospital, Erasmus MC,
Franciscus Gasthuis & Vlietland, Haga hospital, IJsselland hospital, Isala
hospital, Rijnstate hospital, Treant zorggroep, and Onze Lieve Vrouwe Gasthuis.
Study burden and risks
The potential risk for patients in this study is a false negative exit test,
i.e. two consecutive negative test results. In the three previous studies, the
urine test had a robust performance for the detection of bladder cancer in
microscopic hematuria with a consistent sensitivity >90% corresponding with
negative predictive value (NPV) of >=99%. In a prior prospective study we
conducted (N=838 patients), in which only a single urine assay was performed,
the test result of the assay was false negative in only one out of 14 patients
with microscopic hematuria. The tumor missed was a low risk bladder cancer
(stage Ta Grade 1) with a very low risk for progression of disease.(8, 18) In
the proposed study, the patient is asked to send in a second urine test which
lower the possibility of a false negative test result. Although the chance of
having a bladder tumor is extremely low (0.13%) after two consecutive negative
urine tests, patients still have the possibility to undergo a diagnostic
cystoscopy afterwards, if requested.
Implementation of a urine test as a triage tool for patients with microscopic
hematuria has several beneficial effects;
I) The patient does not need to undergo a cystoscopy, which is an invasive
procedure causing discomfort to the patient.(4, 9)
II) the assay might pick up upper urinary tract tumors, as the previous
prospective study showed that the urine test detected all six upper urinary
tract tumors.(8)
III) Only patients who are at high risk to have upper urinary tract cancer,
i.e. positive test result but no abnormalities at cystoscopy are triaged to
undergo imaging with CT, reducing the exposure to radiation in low risk
patients.(11)
IV) Awareness of a positive urine test result significantly improves the
bladder cancer detection rate at cystoscopy, i.e. diagnostic review bias.(12)
V) A *urine-first* strategy might be a more cost-effective approach.(13)
Dr. Molewaterplein 40
Rotterdam 3015 GD
NL
Dr. Molewaterplein 40
Rotterdam 3015 GD
NL
Listed location countries
Age
Inclusion criteria
In order to be eligible to participate in this study a written informed consent
is required. Thereby, a subject must meet the following criteria based on the
most recent American Urological Association guideline on microscopic hematuria
2020.
- Microscopically confirmed microscopic hematuria of voided urine defined as >=3
erythrocytes per high power field
- Male patients >=40 years
- Female patients >=50 years
Exclusion criteria
- History of urothelial bladder- or urinary tract cancer
- Presence of macroscopic (visible) hematuria
- Woman who is or may be pregnant
Design
Recruitment
Medical products/devices used
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In other registers
| Register | ID |
|---|---|
| CCMO | NL77949.078.22 |