The prognostic impact of bone metastasis in patients with metastatic urothelial carcinoma treated with first-line platinum-based chemotherapy

Abstract

Background: In metastatic urothelial cancer (mUC), bone metastasis (BM) are associated with significant morbidity and mortality, yet their role as an independent prognostic variable remains unclear. We aimed to determine the impact of BM on overall survival (OS) in patients with mUC treated with first-line platinum-based chemotherapy (PBC). Methods: mUC patients receiving PBC at the Princess Margaret Cancer Center, Tom Baker Cancer Center, or Cross Cancer Institute from January 2005 to January 2018 were identified retrospectively using central pharmacy database records. Patient disease, treatment, and response characteristics were collected. Progression-free survival (PFS) and OS were estimated using the Kaplan–Meier method. Variables reaching significance ( p < 0.05) in univariable analysis (UVA) of survival (OS) were included in multivariable analysis (MVA) (Cox). Results: Overall, 376 patients with a median follow-up of 16.8 (range: 2.2–218.3) months were included. Median age was 67 (range: 28–91) years, 76% were male, 63% had an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0–1, and 41% had BM. All patients received first-line PBC. Patients with BM had inferior median PFS (4.9 months (95% CI 3.6–6.2) versus 6.5 months (95% CI 5.4–7.6), p = 0.03) and median OS (8.8 months (95% CI 7.8–9.7) versus 10.8 months (95% CI 9.1–12.5), p = 0.002). In UVA, ECOG PS 2–3 ( p < 0.001), presence of BM ( p = 0.002), and WBC count ⩾ 11,000 cells/mm3 ( p = 0.001) were associated with inferior survival. Prior cystectomy ( p < 0.001) and lack of progression (stable disease, partial or complete response) on treatment was associated with improved OS ( p < 0.001). These variables maintained significance in MVA. Conclusion: In this retrospective study, mUC patients with BM had worse OS suggesting that BM may be an independent negative prognostic factor and including BM as a stratification factor in future mUC clinical trial designs may be warranted. A greater focus must be placed on novel therapeutic strategies to better manage BM to reduce both morbidity and mortality.

Establishment and validation of a nomogram for predicting overall survival of upper-tract urothelial carcinoma with bone metastasis: a population-based study

“…Platinum-based chemotherapy (PBC) remains a crucial component of first-line treatment for metastatic urothelial carcinoma, extending median OS by three months [ 17 ]. Consistent with our findings, Alqaisi et al reported improved OS in patients with BM after chemotherapy [ 18 ]. Additionally, chemotherapy facilitates the downstaging of UTUC, enabling surgical interventions [ 2 , 19 ].…”

Clinical variables associated with immune checkpoint inhibitor outcomes in patients with metastatic urothelial carcinoma

“…Bone metastasis are a validated negative prognostic factor in mUC treated with platinum based chemotherapy [55, 56]. In our study, poor response and survival outcome of bone and liver metastasis was significant, while lymph nodes metastasis correlated with higher ORR.…”

“…Prognostic models for mUC patients treated with ICI identified liver or visceral metastases as poor prognostic factors [62, 63]. However, most prospective trials of ICI in mUC do not use presence/absence of bone metastases as a stratification factor, despite the fact that bone metastases are associated with poor response to chemotherapy, and impact quality of life [55, 56, 64]. Owari et al validated a specific prognostic scoring system, B-FOM, to predict survival for patients with bone metastasis from different genito-urinary cancers, based on 5 prognostic factors: primary tumor (prostate, renal or urothelial cancers), poor performance status, visceral metastasis, high Glasgow-prognostic score and elevated neutrophil-to-lymphocyte ratio [65].…”

Clinical variables associated with immune checkpoint inhibitor outcomes in patients with metastatic urothelial carcinoma: a multicentre retrospective cohort study

“…Bone metastases are a validated negative prognostic factor in mUC treated with platinum-based chemotherapy 55 56. In our study, poor response and survival outcome of bone and liver metastases was significant, while lymph nodes metastases correlated with higher ORR.…”

“…Therefore, we could not compare the prognostic utility of this tool in our cohort of patients. Most prospective trials of ICI in mUC do not use presence/absence of bone metastases as a stratification factor, despite the fact that bone metastases are associated with poor response to chemotherapy and impact quality of life 55 56 65. Owari et al validated a specific prognostic scoring system, B-FOM, to predict survival for patients with bone metastasis from different genitourinary cancers based on five prognostic factors: primary tumour (prostate, renal or urothelial cancers), poor performance status, visceral metastases, high Glasgow-prognostic score and elevated NLR 66.…”