A total of 30 patients with LA-MIBC were included in the study, among whom 50% had T3 disease, 40% had T4 disease, and 27% had node-positive disease. All patients were not suitable candidates for RC and underwent radiotherapy (RT). Most patients (87 %) were treated with one of the following concurrent systemic therapies: pembrolizumab (37%), gemcitabine (17%), cisplatin (10%), 5-FU (10%), carboplatin (7%), and paclitaxel (7%). The remaining 13% of patients received RT only. Neoadjuvant therapy (NAC) was delivered to 63% of patients, with 40% receiving multiple lines of systemic therapy prior to RT. The most common neoadjuvant systemic therapy was dose-dense MVAC (methotrexate, vinblastine, doxorubicin, and cisplatin; 17%), followed by gemcitabine plus cisplatin (13%), GTA (gemcitabine, paclitaxel, and doxorubicin; 13%), pembrolizumab (10%), avelumab (5%), durvalumab plus tremelimumab (5%), and GCI (cisplatin, gemcitabine, ifosfamide; 5%). Maintenance therapy was delivered in 37% of patients, with the most common being pembrolizumab (23%), avelumab (7%), ipilimumab/nivolumab (3%), and enfortumab vedotin (3%).
The median follow-up time from completion of RT was 20 months. Median overall survival (OS) was 25.1 months (95% CI, 13.8 – 74.6). The 1- and 2-year OS rates were 73% and 61%, respectively. The 1-year progression-free survival (PFS) rate was 50%. Patients who received concurrent chemotherapy and RT (50%) had a 2-year OS of 73% and a 1-year PFS of 54%. Patients receiving immunotherapy and RT (37%) had a 2-year OS of 47% and a 1-year PFS of 55%. Most patients who experienced recurrence had distant recurrence (83%). Among patients receiving nodal RT (57%), there were no recurrences in regional lymph nodes. At the last follow-up, 33% of patients were alive without evidence of disease, and 7% were alive with stable disease. A multivariate analysis revealed that variant histology (p = 0.007) and hydronephrosis (p = 0.02) were significant predictors of worse OS. The frequency of toxicities was relatively low, with 10% of patients exhibiting acute grade 3 genitourinary toxicity, 7% of patients experiencing a late grade 3+ genitourinary toxicity, and 5% of patients experiencing a late grade 3+ gastrointestinal toxicity.
Overall, patients with LA-MIBC showed a promising response to RT and had a low incidence of local recurrence. However, additional systemic therapy options need to be investigated to address common distant metastasis to increase survival. Several ongoing bladder preservation studies with chemo-radiotherapy with and without immunotherapy are ongoing. Newer combination regimens of antibody-conjugates, immunotherapy, and radiation in the treatment of LA-MIBC will be investigated to identify the optimal methods for bladder preservation.
Written by: Bishoy M. Faltas, MD, Director of Bladder Cancer Research, Englander Institute for Precision Medicine, Weill Cornell Medicine
References:
- Carriere P, Alhalabi O, Gao J, et al. Bladder-preserving radiation therapy for patients with locally advanced and node-positive bladder cancer. Clin Transl Radiat Oncol. 2024;49:100866. Published 2024 Sep 28. doi:10.1016/j.ctro.2024.100866
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