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costs and the reprocessing and sterilization costs. The benefits
were estimated using Medicare reimbursements.
The average number of cases before the scope was
damaged was 12.5 cases (range 3–24) and the mean
operative time was 69.4 36.1 min. The authors performed a
CBA and calculated the BCR to compare the cost effectiveness
of disposable and reusable ureteroscopes. The break-even
point was achieved at the 99th case and the CBA favored the
use of a reusable ureteroscope after that point.
The authors concluded that in centers with a high case
volume, reusable ureteroscopes seem to be cost-effective.
Disposable ureteroscopes may be most beneficial in centers
with lower case numbers.
Experts’ comments:
Despite great improvements in flexible ureteroscope technol-
ogy, there are twomajor limitations: first, scope durability; and
second, more importantly, the risk of infection with reusable
scopes during their routine use. The limited durability of
scopes, which is more commonly a problem in departments
providing residency and fellowship training programs, togeth-
er with high reprocessing and sterilization costs, resulted in the
development of disposable flexible ureteroscopes. The perfor-
mance of these devices has been confirmed in previous studies
. However, comparative studies evaluating cost effective-
ness are lacking. The main problem with cost-effectiveness
studies is that both the costs and benefits vary among different
institutions and among the countries, so careful and cautious
interpretation is required. The 99 cases/yr cutoff in the current
study emphasizes the importance of the institutional case load
when planning routine use of this device. Several other factors,
including the targeted location within the kidney and the
experience of the surgeon or resident, should also be consid-
ered when making a decision on permanent use of these
disposable devices.
Conflicts of interest: The authors have nothing to disclose.
References
[1]
.
[2]
Kemal Saricaa, Emrah Yuruk b,*
aDepartment of Urology, University of Health Sciences,[3_TD$DIFF]
Kartal Dr[1_TD$DIFF] Lutfi Kirdar [4_TD$DIFF]Training and [5_TD$DIFF]Research Hospital, Istanbul, Turkey
bDepartment of Urology[2_TD$DIFF], University of Health Sciences,
Bagcilar Training and Research Hospital, Istanbul, Turkey
*Corresponding author. Department of Urology, Bagcilar Training and
Research Hospital, Istanbul 34200, Turkey.
E-mail address: (E. Yuruk).
# 2017 European Association of Urology.
Published by Elsevier B.V. All rights reserved.
Re: Clonal Evolution of Chemotherapy-resistant
Urothelial Carcinoma
Faltas BM, Prandi D, Tagawa ST, et al
Nat Genet 2016;48:1490–9
Expert’s summary:
Faltas et al [1] performed whole exome sequencing on
72 urothelial carcinoma samples from 32 patients, including
16 matched samples before and after chemotherapy. The
results showed a high rate of intratumoral heterogeneity in
urothelial carcinoma treated with chemotherapy. This het-
erogeneity was both spatial (ie, found in different tumor
sites in the same patient) and temporal (ie, found at differ-
ent time points in the course of the disease). Only 28% of
mutations were shared between prechemotherapy and
postchemotherapy tumors in the same patient. Even altera-
tions in known driver genes such as p53 varied between
tumor sites. This suggests that different clones branch off
early in urothelial carcinoma, that metastasis also occurs
early, and that chemotherapy induces significant molecular
changes.
Expert’s comments:
Intratumoral heterogeneity is a key limitation of molecularly-
guided precision oncology. The high degree of heterogeneity
reported for urothelial carcinoma in this manuscript [1] sug-
gests that a biopsy from one area of a urothelial tumor will not
necessarily represent a complete molecular profile of that
tumor. It also suggests that treatment targeted to a specific
molecular change is likely to fail due to the high probability
that variant clones lacking that specific change will persist.
For example, alterations in ATM, RB1 , and FANCC were
found frequently (73%) in prechemotherapy samples, but
less frequently in postchemotherapy samples (38%), sug-
gesting that these alterations predispose to chemosensi-
tivity, as previously reported [2]. Importantly, however, this
shift in mutation frequency demonstrates that chemother-
apy-resistant clones lacking the targeted alterations repop-
ulate the tumor and lead to disease progression. The
molecular landscape of the tumor evolves under the
selective pressure of chemotherapy.
It must be recognized, however, that the small cohort of
patients studied here was enriched for high-risk features.
Prior reports indicate that patients with a mutation in ERCC2 ,
ATM, RB1, or FANCC have a high rate of complete pathologic
response to neoadjuvant cisplatin-based chemotherapy
[3,4], suggesting that tumor heterogeneity will not thwart
all efforts towards precision oncology.
The observations of Faltas et al [1] do, however, suggest
that rebiopsy of recurrent tumor after chemotherapy will be
necessary as molecularly-targeted therapies become avail-
able for urothelial carcinoma. Serial molecular characteri-
zation will be required at the time of progression on any
specific therapy to aid in the determination of optimal
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