Abstract
Background
Sites of metastasis have prognostic significance in advanced urothelial carcinoma
(aUC), but more information is needed regarding outcomes based on metastatic sites
in patients treated with immune checkpoint inhibitors (ICI). We hypothesized that
presence of liver/bone metastases would be associated with worse outcomes with ICI.
Methods
We identified a retrospective cohort of patients with aUC across 26 institutions,
collecting demographics, clinicopathological, treatment, and outcomes information.
Outcomes were compared with logistic (observed response rate; ORR) and Cox (progression-free
survival; PFS, overall survival; OS) regression between patients with/without metastasis
beyond lymph nodes (LN) and those with/without bone/liver/lung metastasis. Analysis
was stratified by 1st or 2nd+ line.
Results
We identified 917 ICI-treated patients: in the 1st line, bone/liver metastases were
associated with shorter PFS (Hazard ratio; HR: 1.65 and 2.54), OS (HR: 1.60 and 2.35,
respectively) and lower ORR (OR: 0.48 and 0.31). In the 2nd+ line, bone/liver metastases were associated with shorter PFS (HR: 1.71 and 1.62),
OS (HR: 1.76 and 1.56) and, for bone-only metastases, lower ORR (OR: 0.29). In the
1st line, LN-confined metastasis was associated with longer PFS (HR: 0.53), OS (HR:0.49)
and higher ORR (OR: 2.97). In the 2nd+ line, LN-confined metastasis was associated with longer PFS (HR: 0.47), OS (HR: 0.54),
and higher ORR (OR: 2.79); all associations were significant.
Conclusion
Bone and/or liver metastases were associated with worse, while LN-confined metastases
were associated with better outcomes in patients with aUC receiving ICI. These findings
in a large population treated outside clinical trials corroborate data from trial
subset analyses.
Keywords
Abbreviations:
aUC (advanced urothelial carcinoma), ICI (immune checkpoint inhibitors), IRAEs (immune related adverse effects), LN (lymph node), MIBC (muscle-invasive bladder cancer), PDL1 (programmed death ligand 1), TME (tumor microenvironment)To read this article in full you will need to make a payment
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Article Info
Publication History
Published online: June 04, 2022
Accepted:
June 1,
2022
Received in revised form:
June 1,
2022
Received:
March 23,
2022
Identification
Copyright
© 2022 Elsevier Inc. All rights reserved.
