Association of prior local therapy and outcomes with programmed-death
ligand-1 inhibitors in advanced urothelial cancer
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Abstract
Objectives To compare clinical outcomes with programmed-death ligand-1
immune checkpoint inhibitors (ICIs) in patients with advanced urothelial
carcinoma (aUC) who have vs have not undergone radical surgery (RS) or
radiation therapy (RT) prior to developing metastatic disease. Patients
and Methods We performed a retrospective cohort study collecting
clinicopathological, treatment and outcomes data for patients with aUC
receiving ICIs across 25 institutions. We compared outcomes (observed
response rate [ORR], progression-free survival [PFS], overall
survival [OS]) between patients with vs without prior RS, and by type
of prior locoregional treatment (RS vs RT vs no locoregional treatment).
Patients with de novo advanced disease were excluded. Analysis was
stratified by treatment line (first-line and second-line or greater
[second-plus line]). Logistic regression was used to compare ORR,
while Kaplan-Meier analysis and Cox regression were used for PFS and OS.
Multivariable models were adjusted for known prognostic factors. Results
We included 562 patients (first-line: 342 and second-plus line: 220).
There was no difference in outcomes based on prior locoregional
treatment among those treated with first-line ICIs. In the
second-plus-line setting, prior RS was associated with higher ORR
(adjusted odds ratio 2.61, 95% confidence interval [CI]1.19-5.74]),
longer OS (adjusted hazard ratio [aHR] 0.61, 95% CI 0.42-0.88) and
PFS (aHR 0.63, 95% CI 0.45-0.89) vs no prior RS. This association
remained significant when type of prior locoregional treatment (RS and
RT) was modelled separately. Conclusion Prior RS before developing
advanced disease was associated with better outcomes in patients with
aUC treated with ICIs in the second-plus-line but not in the first-line
setting. While further validation is needed, our findings could have
implications for prognostic estimates in clinical discussions and
benchmarking for clinical trials. Limitations include the study’s
retrospective nature, lack of randomization, and possible selection and
confounding biases