EUROPEAN UROLOGY 82 (2022) 238–244

available at www.sciencedirect.com
journal homepage: www.europeanurology.com

Words of Wisdom

Re: One-year Results for the ROBUST III Randomized data on decision-making regarding the choice of treatment
Controlled Trial Evaluating the OptilumeÒ Drug-coated for the control subjects and more detailed stricture charac-
Balloon for Anterior Urethral Strictures teristics (eg, degree of obliteration, spongiofibrosis) could
Elliott SP, Coutinho K, Robertson KJ, et al.
have facilitated data interpretation. Furthermore, the over-
all credibility of the proposed effect modifications in sub-
group analyses is rather low when applying the
J Urol 2022;207:866–75 Instrument for Assessing the Credibility of Effect Modifica-
tion Analyses (ICEMAN) [4].
Experts’ summary:
Second, the European Association of Urology guidelines
ROBUST III was a phase 3, single-blind, randomized, con- on urethral strictures advise against repetitive DVIU/dila-
trolled trial in men with recurrent anterior urethral stric- tion (>2 procedures) when urethroplasty is an option [5].
tures with a median of three prior endoscopic Particularly regarding cost-effectiveness and long-term suc-
interventions [1]. The efficacy of dilation via a drug-coated cess, it would be interesting to evaluate the role of DCBs
balloon (DCB) with paclitaxel (n = 79) was tested against both at an earlier therapeutic stage as a DVIU adjunct in
control treatments (n = 48; balloon/sound dilation or the primary setting and randomized against urethroplasty
direct-vision internal urethrotomy [DVIU]). Randomization with narrow indications and less heterogeneity.
was stratified by pelvic radiotherapy and number of prior Nevertheless, DCBs represent a promising advance in
endoscopic procedures (<5 vs 5). The primary outcome endoscopic stricture treatment and we look forward to
was 6-mo efficacy (atraumatically passing a 16F cystoscope future studies taking the same line and substantiating the
or 14F catheter), which was superior in the treatment arm evidence from ROBUST III.
(75% vs 27%; p < 0.001).
Conflicts of interest: The authors have nothing to disclose.

Experts’ comments:
Given high recurrence rates after endoscopic treatment Acknowledgments: The other members of the Trauma and
for urethral strictures, several antifibrotic injectable Reconstructive Urology Working Party of the European Associa-
adjuncts have been proposed in the hope of mitigating scar tion of Urology Young Academic Urologists are as follows: Jan
formation [2]. The Optilume DCB is the first to release pacli- Adamowicz (Department of Regenerative Medicine, Collegium
taxel to the urethral lining [1] and has great potential for Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland);
filling a certain therapeutic gap for patients with recurrent Mikołaj Frankiewicz (Department of Urology, Medical University
strictures not undergoing urethroplasty because of (1) lim- of Gdańsk, Gdańsk, Poland); Felix Campos-Juanatey (Andrology
and Reconstructive Urology Unit, Marques de Valdecilla
ited access to care, (2) reluctance to undergo more invasive
University Hospital. IDIVAL, Santander, Spain); Fabio Castiglione
surgery, or (3) an unsuitable comorbidity profile. The 1-yr
(Department of Urology, University College London Hospital,
results from ROBUST III are promising hypothesis-generat-
London, UK; Division of Surgery and Interventional Science,
ing data and resulted in US Food and Drug Administration
University College London, London, UK; Division of Oncology/
approval in December 2021. Nonetheless, some important
Unit of Urology, Urological Research Institute, IRCCS Ospedale
clinical questions remain unanswered. San Raffaele, Milan, Italy); Andrea Cocci (Department of Urology
Optimal patient selection remains unaddressed, as we and Andrology, Careggi Hospital, University of Florence,
are not able to deduct which characteristics specifically Florence, Italy); Guglielmo Mantica (Department of Urology,
qualify for DCB treatment and which patients benefit the Policlinico San Martino Hospital, University of Genova, Genova,
most. While the treatment group was well defined and Italy); Clemens M. Rosenbaum (Department of Urology,
lumen goals were standardized (30F DCB), there is hetero- Asklepios Hospital Barmbek, Hamburg, Germany; Wesley Verla
geneity among the control subjects regarding the choice of (Department of Urology, Ghent University Hospital, Ghent,
procedure (DVIU 25%, balloon dilation 58%, and urethral Belgium); and Marjan Waterloos (Department of Urology, AZ
sound 17%; range 24–30F), for which the comparable effi- Maria Middelares, Ghent, Belgium; Department of Urology, Divi-
cacy is unclear [3]. However, stricture characteristics were sion of Reconstructive Urology, Ghent University Hospital,
similar between the groups and the DCB superiority was Ghent, Belgium).
consistent over all control group modalities. Still, granular
 EUROPEAN UROLOGY 82 (2022) 238–244 239

References Malte W. Vetterlein a,*

Phillip Marks a
[1] Elliott SP, Coutinho K, Robertson KJ, et al. One-year results for the Margit Fisch a
ROBUST III randomized controlled trial evaluating the OptilumeÒ Luis A. Kluth b,
drug-coated balloon for anterior urethral strictures. J Urol
on behalf of the Trauma and Reconstructive Urology Working Party of the
2022;207:866–75. https://doi.org/10.1097/ju.0000000000002346.
European Association of Urology Young Academic Urologists
[2] Pang KH, Chapple CR, Chatters R, et al. A systematic review and
meta-analysis of adjuncts to minimally invasive treatment of a
Department of Urology, University Medical Center Hamburg-Eppendorf,
urethral stricture in men. Eur Urol 2021;80:467–79.
[3] Wong SSW, Aboumarzouk OM, Narahari R, O’Riordan A, Pickard R. Hamburg, Germany
b
Simple urethral dilatation, endoscopic urethrotomy, and Department of Urology, University Hospital Frankfurt, Goethe University
urethroplasty for urethral stricture disease in adult men. Cochrane Frankfurt, Frankfurt am Main, Germany
Database Syst Rev 2012;2012:CD006934.
[4] Kilpeläinen TP, Tikkinen KAO, Guyatt GH, Vernooij RWM. Evidence- * Corresponding author. Department of Urology, University Medical
based urology: subgroup analysis in randomized controlled trials. Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.
Eur Urol Focus 2021;7:1237–9. E-mail addresses: malte.vetterlein@gmail.com, m.vetterlein@uke.de
[5] Lumen N, Campos-Juanatey F, Greenwell T, et al. European (M.W. Vetterlein)
Association of Urology guidelines on urethral stricture disease
(part 1): management of male urethral stricture disease. Eur Urol
0302-2838/Ó 2022 European Association of Urology. Published by
2021;80:190–200.
Elsevier B.V. All rights reserved.
https://doi.org/10.1016/j.eururo.2022.04.011

Re: Multiparametric Ultrasound Versus Multiparametric tate cancer. Moreover, mpUS has additional diagnostic value
MRI To Diagnose Prostate Cancer (CADMUS): A as it detected MRI-invisible significant disease in 7% of the
Prospective, Multicentre, Paired-cohort, Confirmatory patients. By contrast, mpUS missed mpMRI-visible lesions
Study in 20% of the patients. In addition, the mpUS-based diagnos-
Grey ADR, Scott R, Shah B, et al. tic pathway would increase prostate biopsy referrals by 11%.
The patients who benefit from mpUS should be informed of
the higher risk of undergoing an invasive procedure.
Lancet Oncol 2022;23:428–38 A few recent publications have reported on alternative
imaging approaches for the current diagnostic pathway for
Experts’ summary: prostate cancer. These include studies on mpUS, biparamet-
The CADMUS trial included 370 patients from seven dif- ric MRI and micro-ultrasound.
ferent hospitals in the UK. Patients with clinical or biologi- The PROSTAGRAM trial explored the concept of short
cal suspicion of prostate cancer underwent multiparametric biparametric MRI and diagnostic ultrasound as popula-
magnetic resonance imaging (mpMRI) and multiparametric tion-based screening tests [3]. The MRI findings were
ultrasound (mpUS). The subjects were blinded to the test associated with detection of twice as many clinically sig-
results and underwent a targeted prostate biopsy only if nificant cancers in comparison to prostate-specific anti-
one of the imaging modalities was positive. The threshold gen (PSA) testing alone. However, ultrasonography
for defining significant disease was set at Gleason score detected fewer clinically significant cancers than PSA
4 + 3 and/or a maximum cancer core length of 6 mm. testing.
In total, 257 patients underwent a prostate biopsy, with In a prospective study by Klotz et al. [4], 1040 patients
mpMRI and mpUS being positive in 78% and 89%, respec- with prior mpMRI underwent micro-ultrasound biopsy.
tively. Positive test concordance was observed in 73.2% of According to their findings, micro-ultrasound had compara-
the cases. Overall, clinically significant disease was detected ble or higher sensitivity for detection of clinically significant
in 83 patients (32%), with mpMRI slightly outperforming prostate cancer with similar specificity.
mpUS, resulting in a difference of 4.3%. The diagnostic yield While the CADMUS results are promising, mpMRI
was highest when targeting was performed using a combi- remains the gold standard. The use of alternative diagnos-
nation of the two imaging modalities. tic imaging should remain limited to centres with very
limited mpMRI availability or as an addition to mpMRI.
In the near future, randomised controlled trials such as
Experts’ comments: OPTIMUM [5] might lead to validation of alternative
Prostate mpMRI is the current gold standard before pros- imaging modalities.
tate biopsy. However, the availability and cost of the mpMRI
vary greatly worldwide [1]. Moreover, mpMRI quality dif-
fers considerably between institutions, as well as interpre- Conflicts of interest: The authors have nothing to disclose.
tation between readers [2]. There is a clear need for
imaging techniques with greater utility that could be an
References
alternative to mpMRI.
Grey et al conclude that mpUS could be used as the first- [1] Grey ADR, Scott R, Shah B, et al. Multiparametric ultrasound versus
line imaging modality for patients with a suspicion of pros- multiparametric MRI to diagnose prostate cancer (CADMUS): a