Page 2 - Canadian Urological Association/Genitourinary Medical Oncologists of Canada consensus statement: Management of unresectable locally advanced and metastatic urothelial carcinoma

CUAJ – Consensus Statement Warren et al
Unresectable locally advanced and metastatic urothelial carcinoma

advances in systemic therapy, especially due to the emergence of immunotherapy as a
therapeutic option, a consensus opinion has become necessary to guide the management of
unresectable locally advanced and metastatic urothelial carcinoma.

Methods
A literature review was undertaken evaluating studies of unresectable locally advanced and
metastatic urothelial carcinoma with a greater emphasis on prospective randomized studies. A
search of Medline, Embase and Pubmed in addition to other published guidelines was used to
identify relevant studies. A summary of the evidence was created with draft recommendations
pertaining to various aspects of the management of advanced urothelial carcinoma. This was
distributed to members of GUMOC for review and discussion through which a consensus
opinion was established.
The following statements focus predominantly on systemic management which falls in
the realm of the Medical Oncology specialty. Additionally, the management of advanced, un-
resectable urothelial cancer is multidisciplinary in nature as there are times when surgery and / or
radiotherapy have a role to play, particularly in patients with oligometastatic disease and those
with locally advanced disease. In this consensus statement, we define locally advanced disease as
cT4b and / or cN1-3. Statements pertaining to these aspects of management are intended to
provide guidance for treating clinicians as to when to consider referral for multidisciplinary
discussion. They are not intended to mandate a particular management plan that arises from such
a forum. All recommended systemic treatment regimens are outlined in Table 1.

Systemic therapy for unresectable locally advanced and metastatic urothelial carcinoma

Eligibility for cisplatin-based chemotherapy
– Routine eligibility for cisplatin chemotherapy includes all of: (1) creatinine
clearance > 60ml/min, (2) ECOG performance status of < 1, (3) absence of hearing
loss > Gr 2 (CTCAE), (4) absence of neuropathy > Gr 2 (CTCAE), and (5) absence
of NYHA grade III / IV heart failure.
– In select cases, eligibility criteria may be extended to patients with GFR of 45 -
60mls/min and / or ECOG 2 performance status. Administering split dose cisplatin
is an option for these patients.
A consensus definition of eligibility for cisplatin chemotherapy was developed by
members of a working party, who combined the results of a survey of 120 medical oncologists
involved in research of urothelial carcinoma with an evaluation of the available literature on this
topic. The purpose was to develop a consistent definition for clinical trial eligibility. The criteria
generated were good performance status (ECOG 0 -1); GFR > 60mls / min, and absence of
contra-indications to cisplatin such as grade > 2 neuropathy, grade > 2 hearing loss and NYHA
2
grade III/IV heart failure. Several studies have used split dose cisplatin to patients with a GFR