Is trimodal therapy the current standard for muscle-invasive bladder cancer?

Objetivo: Esta revisión tiene como objetivo resumir la evidencia actual y las perspectivas futuras del tratamiento conservador de la vejiga para MIBC. Métodos: En octubre de 2023 se realizó una búsqueda bibliográfica no sistemática en Medline/Pubmed con las siguientes palabras clave «cáncer de vejiga», «preservación de la vejiga», «terapia trimodal», «quimiorradiación», «biomarcadores», «inmunoterapia», «quimioterapia neoadyuvante», «radioterapia». Resultados: Las guías urológicas recomiendan la cistectomía radical como tratamiento curativo estándar para el cáncer de vejiga urotelial con invasión muscular, reservando la radioterapia para pacientes no aptos o que quieran preservar su vejiga. Dada la morbimortalidad de la cistectomía y su impacto en la calidad de vida y la función de la vejiga, las terapias oncológicas modernas se orientan cada vez más hacia la preservación de órganos y la maximización de los resultados funcionales manteniendo al mismo tiempo la eficacia del tratamiento. La terapia trimodal que incorpora resección transuretral máxima seguida de radioterapia con quimioterapia radiosensibilizante concurrente es un régimen eficaz para preservar una vejiga funcional en pacientes bien seleccionados. A pesar de la ausencia de datos comparativos de ensayos aleatorios, los dos enfoques parecen proporcionar resultados oncológicos similares. Los estudios están evaluando ampliar los criterios de elegibilidad para la terapia trimodal y optimizar la administración de radioterapia e inmunoterapia para mejorar aún más los resultados, y validar biomarcadores para guiar la preservación de la vejiga. Conclusiones: La conservación de la vejiga con terapia trimodal produce resultados aceptables y, por lo tanto, puede considerarse una opción de tratamiento razonable en pacientes bien seleccionados.Objective:The aim of this review is to summarize the current evidence and future perspectives of bladder-sparing treatment for MIBC.Methods: A non-systematic literature search in Medline/Pubmed was performed in October 2023 with the following keywords ‘bladder cancer’, ‘bladder-sparing’, ‘trimodal therapy’, ‘chemoradiation’, ‘biomarkers’, ‘immunotherapy’, ‘neoadjuvant chemotherapy’, ‘radiotherapy’.Results: Urology guidelines recommend radical cystectomy as the standard curative treatment for muscle-invasive urothelial bladder cancer, reserving radiotherapy for patients who are unfit or who want to maintain their bladder. Given the morbidity and mortality of cystectomy and its impact on quality of life and bladder function, modern oncologic therapies are increasingly geared toward organ preservation and maximizing functional outcomes while maintaining treatment efficacy. Trimodal therapy, which incorporates maximal transurethral resection followed by radiotherapy with concurrent radiosensitizing chemotherapy, is an effective regimen for bladder function preservation in well-selected patients. Despite the absence of comparative data from randomized trials, the two approaches seem to provide comparable oncologic outcomes.Studies are evaluating the expansion of eligibility criteria for trimodal therapy, the optimization of radiotherapy and immunotherapy delivery to further improve outcomes, and the validation of biomarkers to guide bladder preservation. Conclusions: Trimodal therapy has shown acceptable outcomes for bladder preservation; therefore, it provides a valid treatment option in well-selected patients.Sin financiación1.1 JCR Q4 20220.308 SJR Q3 2022No data IDR 2022UE

Ramucirumab plus docetaxel versus placebo plus docetaxel in patients with locally advanced or metastatic urothelial carcinoma after platinum-based therapy (RANGE): overall survival and updated results of a randomised, double-blind, phase 3 trial

Background: Ramucirumab—an IgG1 vascular endothelial growth factor receptor 2 antagonist—plus docetaxel was previously reported to improve progression-free survival in platinum-refractory, advanced urothelial carcinoma. Here, we report the secondary endpoint of overall survival results for the RANGE trial. Methods: We did a randomised, double-blind, phase 3 trial in patients with advanced or metastatic urothelial carcinoma who progressed during or after platinum-based chemotherapy. Patients were enrolled from 124 investigative sites (hospitals, clinics, and academic centres) in 23 countries. Previous treatment with one immune checkpoint inhibitor was permitted. Patients were randomly assigned (1:1) using an interactive web response system to receive intravenous ramucirumab 10 mg/kg or placebo 10 mg/kg volume equivalent followed by intravenous docetaxel 75 mg/m2 (60 mg/m2 in Korea, Taiwan, and Japan) on day 1 of a 21-day cycle. Treatment continued until disease progression, unacceptable toxicity, or other discontinuation criteria were met. Randomisation was stratified by geographical region, Eastern Cooperative Oncology Group performance status at baseline, and visceral metastasis. Progression-free survival (the primary endpoint) and overall survival (a key secondary endpoint) were assessed in the intention-to-treat population. The study is registered with ClinicalTrials.gov, NCT02426125; patient enrolment is complete and the last patient on treatment is being followed up for safety issues. Findings: Between July 20, 2015, and April 4, 2017, 530 patients were randomly allocated to ramucirumab plus docetaxel (n=263) or placebo plus docetaxel (n=267) and comprised the intention-to-treat population. At database lock (March 21, 2018) for the final overall survival analysis, median follow-up was 7·4 months (IQR 3·5–13·9). In our sensitivity analysis of investigator-assessed progression-free survival at the overall survival database lock, median progression-free survival remained significantly improved with ramucirumab compared with placebo (4·1 months [95% CI 3·3–4·8] vs 2·8 months [2·6–2·9]; HR 0·696 [95% CI 0·573–0·845]; p=0·0002). Median overall survival was 9·4 months (95% CI 7·9–11·4) in the ramucirumab group versus 7·9 months (7·0–9·3) in the placebo group (stratified HR 0·887 [95% CI 0·724–1·086]; p=0·25). Grade 3 or worse treatment-related treatment-emergent adverse events in 5% or more of patients and with an incidence more than 2% higher with ramucirumab than with placebo were febrile neutropenia (24 [9%] of 258 patients in the ramucirumab group vs 16 [6%] of 265 patients in the placebo group) and neutropenia (17 [7%] of 258 vs six [2%] of 265). Serious adverse events were similar between groups (112 [43%] of 258 patients in the ramucirumab group vs 107 [40%] of 265 patients in the placebo group). Adverse events related to study treatment and leading to death occurred in eight (3%) patients in the ramucirumab group versus five (2%) patients in the placebo group. Interpretation: Additional follow-up supports that ramucirumab plus docetaxel significantly improves progression-free survival, without a significant improvement in overall survival, for patients with platinum-refractory advanced urothelial carcinoma. Clinically meaningful benefit might be restricted in an unselected population. Funding: Eli Lilly and Company