Page 8 - 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

(Food and Drug Administration) and the EMA (European Medicines Agency) for cisplatin-
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ineligible patients, 50,52 and are endorsed by NCCN in this population. Recently the indication
has been narrowed to those patients whose tumours are PD-L1 positive, or who are not eligible
for any platinum chemotherapy regardless of PD-L1 expression. An application for first line
pembrolizumab along similar lines to FDA and EMA approvals has been made to the Pan-
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Canadian Oncology Drug Review (pCODR).
In the second line setting, pembrolizumab, atezolizumab, durvalumab and avelumab have
been approved by Health Canada for use in patients progressing during or following platinum-
based chemotherapy or those who relapse within 12 months of receiving neoadjuvant or adjuvant
50
platinum based chemotherapy for earlier stage disease. An expert review committee on behalf
of pCODR recommended approval of pembrolizumab in this setting conditional upon ‘cost
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effectiveness being improved to an acceptable level’. All five PD-1 / PD-L1 inhibitors
discussed have FDA approval in this setting and pembrolizumab, atezolizumab and nivolumab
have EMA approval. 50,52
There was robust debate about the level of evidence required to recommend these agents
particularly in first line setting for patients not suitable for platinum based chemotherapy.
Nonetheless, the majority of GUMOC members preferred to maintain the standard of endorsing
new treatments on the basis of both statistically significant and clinically meaningful benefit
demonstrated in randomized phase III trials. Currently this level of evidence has not been
achieved for pembrolizumab or atezolizumab in the first line setting. By the same standard,
pembrolizumab is the only checkpoint inhibitor to have demonstrated this level of evidence in
the second line setting. GUMOC recognize that the current consensus statements may need
updating depending on the results of several ongoing phase III trials of checkpoint inhibitors
(table 5).

Management of cT4b and / or cN1-3 urothelial carcinoma of the bladder:
– Patients with clinically staged T4b or N1-3 urothelial carcinoma of the bladder
should be discussed in a multidisciplinary forum including an experienced Urologist
/ Uro-Oncologist and Radiation Oncologist.
– Patients with cT4b and / or cN1-3 urothelial carcinoma of the bladder can be cured
using multi-modality treatment.
– In suitable patients, the preferred approach is to commence systemic chemotherapy
with 4 – 6 cycles of platinum based chemotherapy as per ‘first line systemic
therapy’.
– Depending on response to initial chemotherapy, consolidation with either RC +
pelvic lymph node dissection (PLND) or radical radiotherapy (+/- concurrent
chemotherapy) can be administered.