2012P - Role of first-line immunotherapy in urothelial cancer with bone metastases: A national cancer database analysis of 3971 patients

Background

Urothelial cancer (UC), especially with bone metastases, poses significant clinical challenges. Despite its occurrence in 25% to 47% of cases, with 5% to 15% experiencing exclusive bone metastasis, it remains underrecognized and challenging to treat. Despite the approval of multiple immune checkpoint inhibitors (ICIs), the survival benefit with ICIs in those with bone metastasis remains unclear. None of the randomized studies specifically investigated the outcomes and efficacy of bone metastases in subgroup analyses. We aim to assess the role and efficacy of ICIs in UC patients with bone metastases using the National Cancer Database (NCDB).

Methods

Using NCDB, we included de-novo metastatic UC cases (2017-2021). We subcategorized patients into bone-only metastases (BoM), bone (B) + brain metastases (mets), B + visceral mets (liver/lung), and B + lymph nodes. Demographics included primary site, first-line treatment (chemo/immunotherapy), age, race, gender, and survival status. OS was analyzed via Kaplan-Meier curves, Log-rank tests, and Cox proportional hazards model.

Results

3971 eligible UC cases were included. Primary sites were kidney/renal pelvis (82.4%), bladder (12.4%), and ureter (2.6%). BoM occurred in 27%, B + brain in 11%, B + visceral in 51%, and B+ lymph nodes in 11%. 48.1% received first-line chemo, 51.9% first-line ICIs. Most were aged 40-64 (40%), white (84.8%), and male (70%). Patients with B + brain mets had the worst outcomes (HR 1.58, p<0.001), followed by B + visceral mets (HR 1.48, p<0.001), and B + lymph node mets (HR 1.25, p=0.007) compared to BoM. In multivariate analysis, patients receiving first-line chemotherapy had worse outcomes than first-line immunotherapy (HR 1.24, p<0.001) in all cohorts. However, when specifically analyzing the treatment difference among BoM patients, no survival disparity was observed between chemo and ICIs (p=0.32).

Conclusions

Interestingly, our analysis revealed that upper tract UC displays a significantly heightened propensity for bone metastases compared to lower tract UC. Moreover, patients with de-novo metastatic UC with bone met who underwent first line chemo experienced poor outcomes relative to those treated with first-line ICIs.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.