Melissa Bersanelli1, Sebastiano Buti2, Patrizia Giannatempo3, Daniele Raggi3, Andrea Necchi3, Alessandro Leonetti4, Giuseppe Luigi Banna5, Fausto Petrelli6. 1. Medicine and Surgery Department, University of Parma, Parma, Italy; Medical Oncology Unit, University Hospital of Parma, Parma, Italy. Electronic address: bersamel@libero.it. 2. Medical Oncology Unit, University Hospital of Parma, Parma, Italy. 3. Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. 4. Medicine and Surgery Department, University of Parma, Parma, Italy; Medical Oncology Unit, University Hospital of Parma, Parma, Italy. 5. Portsmouth Hospitals NHS Trust, Portsmouth, UK. 6. Medical Oncology Unit, ASST Bergamo Ovest, Treviglio, BG, Italy.
Abstract
BACKGROUND: Advanced upper tract urothelial carcinoma (UTUC) has different molecular and genetic features from the commonest carcinoma of the bladder, suggesting a possible different sensitivity to immune-checkpoint inhibitors (ICI). METHODS: A systematic review and meta-analysis of all relevant clinical studies including advanced UTUC patients treated with ICI was conducted according to PRISMA guidelines. RESULTS: Six prospective trials for a total 2537 patients, including 396 (15.6 %) with advanced UTUC, were eligible for the analysis. In UTUC patients, the pooled ORR was 21.2 % (95 % CI, 12.5 %-33.7 %); the risk of death was reduced by 24 % over the standard platinum-based chemotherapy, but this was not statistically significant (hazard ratio = 0.76; 95 % confidence interval, 0.41-1.40; p = 0.37, χ2 = 3.28, p = 0.07; I2 = 70 %). CONCLUSIONS: The current evidence does not support a statistically significant effect from ICI over the standard treatment for advanced UTUC patients. Properly performed pre-planned subgroup analyses from randomized clinical trials are eagerly awaited.
BACKGROUND: Advanced upper tract urothelial carcinoma (UTUC) has different molecular and genetic features from the commonest carcinoma of the bladder, suggesting a possible different sensitivity to immune-checkpoint inhibitors (ICI). METHODS: A systematic review and meta-analysis of all relevant clinical studies including advanced UTUC patients treated with ICI was conducted according to PRISMA guidelines. RESULTS: Six prospective trials for a total 2537 patients, including 396 (15.6 %) with advanced UTUC, were eligible for the analysis. In UTUC patients, the pooled ORR was 21.2 % (95 % CI, 12.5 %-33.7 %); the risk of death was reduced by 24 % over the standard platinum-based chemotherapy, but this was not statistically significant (hazard ratio = 0.76; 95 % confidence interval, 0.41-1.40; p = 0.37, χ2 = 3.28, p = 0.07; I2 = 70 %). CONCLUSIONS: The current evidence does not support a statistically significant effect from ICI over the standard treatment for advanced UTUC patients. Properly performed pre-planned subgroup analyses from randomized clinical trials are eagerly awaited.