EURURO Vol. 73 No. 1

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1. Introduction
The previous European Association of Urology (EAU)
guidelines on upper urinary tract carcinoma (UTUC) were
published in 2015 . The EAU Guidelines Panel has
prepared updated guidelines to provide evidence-based
information on the management to guide and facilitate
clinical decision-making.
2. Evidence acquisition
2.1. Methodology
2.1.1. Data identification
A Medline search was performed using combinations of the
following terms: urinary tract cancer; urothelial carcinomas
(UCs); upper urinary tract, carcinoma; renal pelvis; ureter;
bladder cancer (BCa); chemotherapy; ureteroscopy; neph-
roureterectomy; adjuvant treatment; instillation; recur-
rence; risk factors; and survival. The publications identified
weremainly retrospective including some large multicentre
studies. Owing to the scarcity of randomised data, articles
were selected based on the following criteria: evolution of
concepts, intermediate- and long-term clinical outcomes,
study quality, and relevance. Older studies were only
included if they were historically relevant. To facilitate
evaluation of the quality of information provided, levels of
evidence (LEs) and grades of recommendation were
included according to the general principles of evidence-
based medicine
3. Evidence synthesis
3.1. Epidemiology, aetiology, and pathology
3.1.1. Epidemiology
Urothelial carcinomas are the fourth most common
tumours They can be located in the lower (bladder
and urethra) or the upper (pyelocaliceal cavities and ureter)
urinary tract. Bladder tumours account for 90– 95% of UCs
and are the most common urinary tract malignancy .
UTUCs are uncommon and account for only 5–10% of UCs
with an estimated annual incidence in Western
countries of almost two cases per 100 000 inhabitants.
Pyelocaliceal tumours are approximately twice as common
as ureteral tumours. In 17% of cases, concurrent BCa is
present . Recurrence in the bladder occurs in 22–47% of
UTUC patients compared with 2–6% in the contralat-
eral upper tract .
Overall, 60% of UTUCs are invasive at diagnosis compared
with 15–25% of bladder tumours . UTUCs have a peak
incidence in individuals aged 70–90 yr and are three times
more common in men .
Familial/hereditary UTUCs are linked to hereditary
nonpolyposis colorectal carcinoma , and these patients
can be screened during a short interview )
. Patients identified at high risk for HNPCC syndrome
should undergo DNA sequencing for patient and family
councelling .
3.1.2. Risk factors
Many environmental factors contribute to the development
of UTUC . Tobacco exposure increases the relative risk
from 2.5 to 7 .
Historically, UTUC “amino tumours” were related to
occupational exposure to carcinogenic aromatic amines
including benzidine and b-naphthalene, both of which have
been banned since the 1960s inmost industrialised countries.
The average duration of exposure needed to develop
UTUC is̴7 yr, with a latency of up to 20 yr following
termination of exposure.
Several studies have demonstrated the carcinogenic
potential of aristolochic acid contained in Aristolochia
fangchi and clematis plants. The aristolochic acid–derivative
d-aristolactam is associated with a specific mutation in the
p53 gene at codon 139 that occurs mainly in patients with
nephropathy due to Chinese herbs or Balkan endemic
nephropathy who present with UTUC . Although
the incidence of Balkan endemic nephropathy is also
declining, aristolochic acid plays a key role in the
pathophysiology of this nephropathy.
There is a high incidence of UTUC in Taiwan, especially on
the southwest coast, which represents 20–25% of UCs in the
region . There is a possible association between UTUC,
blackfoot disease, and arsenic exposure in drinking water in
this population as well as aristolochic acid in Chinese
herbs .
Differences in the ability to counteract carcinogens may
contribute to host susceptibility to UTUC. Some genetic
polymorphisms are associated with an increased risk of
cancer or faster disease progression that introduces
variability in the interindividual susceptibility to the risk
factors previously mentioned. UTUC may share some
risk factors and molecular pathways with bladder UC. So
far, two UTUC-specific polymorphisms have been reported
3.1.3. Histology and classification
3.1.3.1. Histological types. UTUC with pure nonurothelial his-
tology is rare , but variants are present in approximately
25% of cases . These variants correspond to high-
grade tumours with worse prognosis compared with pure
UC. Squamous cell carcinoma of the upper urinary tract
represents <10% of pyelocaliceal tumours and is even rarer
within the ureter. Squamous cell carcinoma of the urinary
tract is assumed to be associated with chronic inflammatory
diseases and infections arising from urolithiasis . Other
variants include: micropapillary and sarcomatoid carcino-
mas, and lymphoepithelioma. Collecting duct carcinoma
can have similar characteristics to UTUC due to its common
embryological origin . They are, however, considered as
kidney cancers and not UTUC.
3.2. Staging and classification systems
3.2.1. Classification
The classification and morphology of UTUC and bladder
carcinoma are similar . It is possible to distinguish
between noninvasive papillary tumours (papillary urothelial
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