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Radical cystectomy (RC) is considered the standard treatment for muscle invasive bladder cancer (MIBC). However, RC is often burdened by significant impact on quality of life (QoL); Continence preserving methods (e.g., continent cutaneous urinary diversion and orthotopic neobladder-ONB), have been proposed as alternatives to improve postoperative QoL. Trimodal therapy (TMT) emerged as alternative to surgery. To assess the impact of these treatments from the patients' perspective, we undertook a systematic review and meta-analysis of literature, focusing on studies reporting QoL data about each of the abovementioned approaches. A systematic review was carried out including all prospective and retrospective studies enrolling patientstreated with radical intent for non-metastatic MIBC from 1999 to 2021 (either RC or TMT). All studies included specifically reported QoL for one of the main treatment approaches explored (RC followed by ileal conduit urinary diversion-ICUD, ONB or TMT). Pooled analysis for EORTC QLQ-C30 and BLM-30 questionnaires showed that ONB yielded a significant advantage only for Physical Functioning (pooled mean standardized difference -0.73 SD, p-value 0.019, I 2 = 93 %) and for Emotional Functioning (pooled mean standardized difference -0.16 SD, p-value 0.029, I 2 = 0 %). A trend in favour of higher mean reported values after TMT for Global Health Score, Physical Functioning and Role Functioning was found, if compared to both RC approaches. Significant benefit for ONB if compared to ICUD was detected only for specific subdomains of QoL questionnaires. No direct comparison with TMT is available, but data suggest advantage of this approach when compared to both reconstructive scenarios., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Conflict of Interest IM received a small fee for occasional attendance at the advisory board supported by Lilly, Novartis, Pfizer, Seagen, Accuray which is not related to the contents of this manuscript., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Purpose: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) currently represent the standard of care for the initial treatment of patients with metastatic hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer. The aim of our study is to evaluate the safety of the use of concomitant radiation therapy (RT) in a consecutive series of HR+/HER2- patients treated in two academic institutions with CDK4/6i in the metastatic setting., Methods and Materials: From September 2017 to February 2020, we retrospectively collected and analysed data on a sequential series of patients treated with CDK4/6i, receiving RT or not, at two European institutions. Primary outcome of the study was the association between RT and any adverse events (AEs) ≥ G3. Secondary outcomes were the association between RT and any AEs (any grade), CDK4/6i dose reduction rate, and CDK4/6i treatment discontinuation rate., Results: We analysed a total of 132 consecutive women; RT was prescribed in 57 (43.2%) patients (70 irradiated lesions). The median age of the series was 52.1 years (range 32.3-78.2). Concomitant RT administration was not significantly related to higher AEs ≥ G3 (p = 0.19) and any grade AEs (p = 1.0); there was no association with RT and CDK4/6i dose reduction (p = 0.49) and discontinuation rates (p = 0.14). At a median follow-up of 18.8 months, the progression-free survival (PFS) rate was 35% and the overall survival (OS) rate was 38.7% in the whole group. The use of concomitant RT did not affect both PFS (p = 0.71) and OS rates (p = 0.55)., Conclusions: Our data are encouraging regarding the safety of this combination, showing that concurrent RT did not increase severe toxicity and did not have an impact on systemic treatment conduction., (Copyright © 2022 Elsevier B.V. All rights reserved.)