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Immune checkpoint inhibitors (ICIs) are largely used in the treatment of patients with advanced non-small-cell lung cancer (NSCLC). Novel biomarkers that provide biological information that could be useful for clinical management are needed. In this respect, extracellular vesicles (EV)-associated microRNAs (miRNAs) that are the principal vehicle of intercellular communication may be important sources of biomarkers. We analyzed the levels of 799 EV-miRNAs in the pretreatment plasma of 88 advanced NSCLC patients who received anti-PD-1 therapy as single agent. After data normalization, we used a two-step approach to identify candidate biomarkers associated to both objective response (OR) by RECIST and longer overall survival (OS). Univariate and multivariate analyses including known clinicopathologic variables and new findings were performed. In our cohort, 24/88 (27.3%) patients showed OR by RECIST. Median OS in the whole cohort was 11.5 months. In total, 196 EV-miRNAs out 799 were selected as expressed above background. After multiplicity adjustment, abundance of EV-miR-625-5p was found to be correlated with PD-L1 expression and significantly associated to OR by RECIST (p = 0.0366) and OS (p = 0.0031). In multivariate analysis, PD-L1 staining and EV-miR-625-5p levels were constantly associated to OR and OS. Finally, we showed that EV-miR-625-5p levels could discriminate patients with longer survival, in particular in the class expressing PD-L1 ≥50%. EV-miRNAs represent a source of relevant biomarkers. EV-miR-625-5p is an independent biomarker of response and survival in ICI-treated NSCLC patients, in particular in patients with PD-L1 expression ≥50%.

Bone metastases are common in genitourinary cancers, but they are underreported and not well researched. Synchronous bone metastases occur in 1.39–5.5% of bladder cancer patients, while 30–40% of cases are metachronous. Bone morphogenetic proteins (BMPs) play a key role in regulating proliferation, migration and invasion of tumor cells in bone microenvironment of bone metastases from metastatic urothelial carcinoma (mUC). Bone metastases represent a poor prognostic factor due to high morbidity and mortality correlated to skeletal-related events (SREs). The incidence rate of SREs in bladder, renal pelvis, and ureteral cancer varies from 39 to 68%. Radiotherapy is the most frequent treatment for SREs. The early use of bone targeted therapies (BTT), zoledronic acid and denosumab, improves SREs incidence and morbidity and it seems to improve overall survival (OS). To date, several new agents (immunotherapy and targeted drugs) demonstrated efficacy in mUC. However, subgroup analysis for bone metastases is often not available, due to difficulties in analysing bone samples, non-RECIST lesions and delay in systemic treatment due to SREs that limit the enrolment of bone mUC patients in clinical trials. Larger solid tumor studies that included UC patients are the main source of data for the management of mUC patients with bone metastases. For these patients, multidisciplinary approach should be preferred, involving orthopaedics, radiotherapists and rehabilitation to improve outcome and quality of life. New prospective trials should characterize clinical and molecular features of patients with bone metastases and the impact of new drugs on this poor prognostic metastatic site.