Background and Objectives: Facing neoadjuvant chemotherapy followed by surgery, neoadjuvant immunotherapy is an innovative concept in localized muscle-invasive bladder cancer. Herein, we performed a review of the available and ongoing evidence supporting immune checkpoint inhibitor (ICI) administration in the early stages of bladder cancer treatment. Materials and Methods: A literature search was performed on Medline and clinical trials databases, using the terms: “bladder cancer” OR “urothelial carcinoma”, AND “neoadjuvant immunotherapy” OR “preoperative immunotherapy”. We restricted our investigations to prospective clinical trials evaluating anti-PD-(L)1 and anti-CTLA-4 monoclonal antibodies. Data on efficacy, toxicity and potential biomarkers of response were retrieved. Results: The search identified 6 ICIs that were tested in the neoadjuvant setting for localized bladder cancer—4 anti-PD-(L)1 inhibitors (Pembrolizumab, Atezolizumab, Nivolumab and Durvalumab) and 2 anti-CTLA-4 inhibitors (Ipilimumab and Tremelimumab). Most of the existing literature was based on single-arm phase 2 clinical trials that included from 23 to 143 patients. The pathological complete response rate (pCR) and pathological response rate (pRR) ranged from 31% to 46% and from 55.9% to 66%, respectively. Survival data were immature at this time. The safety profile was acceptable, with severe treatment-related adverse events ranging from 6% to 41%. Conclusions: The results of early phase trials are encouraging, and more investigations are needed to strengthen the rationale for immune checkpoint inhibitor administration in localized muscle-invasive bladder cancer.

Upper tract urothelial carcinoma (UTUC) is a rare and challenging-to-treat malignancy. In most patients it is a sporadic tumor entity, less commonly it falls on the spectrum of Lynch syndrome, an autosomal dominant familial tumor syndrome. Localized UTUC with high-risk features as well as the metastatic disease scenario might require systemic therapy. Platinum-based combination chemotherapy is currently the recommended management option. However, the introduction of immune checkpoint inhibitors into the therapeutic armamentarium has led to a paradigm shift in treatment standards. Immunotherapy has been shown to be safe and effective in treating at least metastatic UTUC, although UTUC-specific high-level evidence is still lacking. Recent technological advances and noteworthy research efforts have greatly improved the general understanding of the biological landscape of UTUC. According to the main findings, UTUC represent a particular subtype of urothelial carcinoma frequently associated with activated FGFR3 signaling, a luminal–papillary phenotype and a T-cell-depleted microenvironment. This improved knowledge promises precision oncology approaches that match treatment decision strategies and genomic profile to ultimately result in better clinical outcomes. The aim of this review was to summarize the main currently available evidence on immune checkpoint inhibition and clinical genomics in UTUC.

Background: An accurate estimation of the stone burden is the key factor for predicting retrograde intra-renal surgical outcomes. Volumetric calculations better stratify stone burden than linear measurements. We developed a free software to assess the stone volume and estimate the lithotrity duration according to 3D-segmented stone volumes, namely the Kidney Stone Calculator (KSC). The present study aimed to validate the KSC’s reproducibility in clinical cases evaluating its inter-observer and intra-observer correlations. Methods: Fifty patients that harbored renal stones were retrospectively selected from a prospective cohort. For each patient, three urologists with different experience levels in stone management made five measurements of the stone volume on non-contrast-enhanced computed tomography (NCCT) images using the KSC. Results: the overall inter-observer correlation (Kendall’s concordance coefficient) was 0.99 (p < 0.0001). All three paired analyses of the inter-observer reproducibility were superior to 0.8. The intra-observer variation coefficients varied from 4% to 6%, and Kendall’s intra-observer concordance coefficient was found to be superior to 0.98 (p < 0.0001) for each participant. Subgroup analyses showed that the segmentation of complex stones seems to be less reproductible. Conclusions: The Kidney Stone Calculator is a reliable tool for the stone burden estimation. Its extension for calculating the lithotrity duration is of major interest and could help the practitioner in surgical planning.