Background: Intravesical immunotherapy with bacillus Calmette–Guerin (BCG) is the standard therapy for high-risk non-muscle invasive bladder cancer (NMIBC). The superiority of any BCG strain over another could not be demonstrated yet. Methods: Patients with NMIBCs underwent adjuvant induction ± maintenance schedule of intravesical immunotherapy with either BCG TICE or RIVM at two high-volume tertiary institutions. Only BCG-naïve patients and those treated with the same strain over the course of follow-up were included. One-to-one (1:1) propensity score matching (PSM) between the two cohorts was utilized to adjust for baseline demographic and tumor characteristics imbalances. Kaplan–Meier estimates and multivariable Cox regression models according to high-risk NMIBC prognostic factors were implemented to address survival differences between the strains. Sub-group analysis modeling of the influence of routine secondary resection (re-TUR) in the setting of the sole maintenance adjuvant schedule for the two strains was further performed. Results: 852 Ta-T1 NMIBCs (n = 719, 84.4% on TICE; n = 133, 15.6% on RIVM) with a median of 53 (24–77) months of follow-up were reviewed. After PSM, no differences at 5- years RFS, PFS, and CSS at both Kaplan–Meier and Cox regression analyses were detected for the whole cohort. In the sub-group setting of full adherence to European/American Urology Guidelines (EAU/NCCN), BCG TICE demonstrated longer 5-years RFS compared to RIVM (68% vs. 43%, p = 0.008; HR: 0.45 95% CI 0.25–0.81). Conclusion: When routinely performing re-TUR followed by a maintenance BCG schedule, TICE was superior to RIVM for RFS outcomes. However, no significant differences were detected for PFS and CSS, respectively.

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Purpose of review Radical cystectomy is the standard of care for patients with localized muscle-invasive bladder cancer (MIBC). In this context, bladder-sparing strategies (BSS) have been investigated as viable alternatives for patients who are unfit for radical cystectomy or aim to preserve their bladder without compromising oncological outcomes. This review aims to provide the most up-to-date evidence on BSSs as an alternative treatment for patients with MIBC. Recent findings Different studies have highlighted the long-term efficacy of trimodal therapy or chemoradiation protocols. However, due to the lack of randomized controlled trials, there is still a lack of high-level evidence on BSS efficacy as compared to radical cystectomy. Consequently, the adoption of these approaches is still limited. A possible turning point could be represented by the introduction of immunotherapy, as several studies are investigating the potential combination with chemoradiotherapy or radiotherapy alone. Patient selection, together with the implementation of new predictive biomarkers and imaging tools, may improve the efficacy of BSS in the near future. Summary Radical cystectomy with perioperative chemotherapy remains the gold standard treatment for MIBC patients. Nevertheless, BSS can be considered a viable option in selected patients who desire to preserve their bladder. Further evidence is needed to clearly state the role of BSS in MIBC.

To identify the characteristics of patients with sepsis or acute pyelonephritis (APN) combined with ureteral calculi and to analyze the risk factors in its causation. Methods: We included patients with sepsis or APN caused by ureteral calculi who received treatment in the United States from January 2003 to December 2017 using the Optum® deidentified Clinformatics® Datamart. Demographic factors and risk factors for the receipt of sepsis or APN were subsequently analyzed for statistical significance. Results: Of 467,502 urinary stone patients, age-matched multivariate analysis revealed that a history of urinary tract infection (OR 11.31, 95% CI 10.68–11.99, p < 0.0001) and female gender (OR 2.73, 95% CI 2.62–2.84, p < 0.0001) were significantly related to an increased risk of sepsis or APN. Conversely, a previous past medical history of urolithiasis (OR 0.91, 95% CI 0.87–0.95, p < 0.0001) and cancer (OR 0.91, 95% CI 0.87–0.95, p < 0.0001) were associated with a decreased risk of sepsis or APN. With regards to comorbidities, when more than one comorbidity was present, there was an additive effect with higher OR point estimates, rising to 11.31 (10.68–11.99) when three or more comorbidities present. History of urinary tract infection and female gender are risk factors for sepsis or APN in patients with ureteral calculi. Conclusions: This large national cohort reveals the characteristics of sepsis or APN combined with ureteral stone and provides an important baseline for the treatment of urolithiasis in the future.

Background: In an era of Bacillus of Calmette-Guérin (BCG) shortages, the comparative efficacy from different adjuvant intravesical BCG strains in non-muscle invasive bladder cancer (NMIBC) has not been clearly elucidated. We aim to compare, through a systematic review and meta-analysis, the cumulative BC recurrence rates and the best efficacy profile of worldwide available BCG strains over the last forty years. Methods: PubMed, Scopus, Web of Science, Embase, and Cochrane databases were searched from 1982 up to 2022. A meta-analysis of pooled BC recurrence rates was stratified for studies with ≤3-y vs. >3-y recurrence-free survival (RFS) endpoints and the strain of BCG. Sensitivity analysis, sub-group analysis, and meta-regression were implemented to investigate the contribution of moderators to heterogeneity. A random-effect network meta-analysis was performed to compare BCG strains on a multi-treatment level. Results: In total, n = 62 series with n = 15,412 patients in n = 100 study arms and n = 10 different BCG strains were reviewed. BCG Tokyo 172 exhibited the lowest pooled BC recurrence rate among studies with ≤3-y RFS (0.22 (95%CI 0.16–0.28). No clinically relevant difference was noted among strains at >3-y RFS outcomes. Sub-group and meta-regression analyses highlighted the influence of NMIBC risk-group classification and previous intravesical treated categories. Out of the n = 11 studies with n = 7 BCG strains included in the network, BCG RIVM, Tice, and Tokyo 172 presented with the best-predicted probability for efficacy, yet no single strain was significantly superior to another in preventing BC recurrence risk. Conclusion: We did not identify a BCG stain providing a clinically significant lower BC recurrence rate. While these findings might discourage investment in future head-to-head randomized comparison, we were, however, able to highlight some potential enhanced benefits from the genetically different BCG RIVM, Tice, and Tokyo 172. This evidence would support the use of such strains for future BCG trials in NMIBCs.

Purpose of reviewPenile cancer (PeCa) is an orphan disease due to its rare incidence in high-income countries. Traditional surgical options for clinical T1--2 disease, including partial and total penectomy, can dramatically affect patient's quality of life and mental health status. In selected patients, organ-sparing surgery (OSS) has the potential to remove the primary tumor with comparable oncologic outcomes while maintaining penile length, sexual and urinary function. In this review, we aim to discuss the indications, advantages, and outcomes of various OSSs currently available for men diagnosed with PeCa seeking an organ-preserving option. Recent findingsPatient survival largely depends on spotting and treating lymph node metastasis at an early stage. The required surgical and radiotherapy skill sets cannot be expected to be available in all centers. Consequently, patients should be referred to high-volume centers to receive the best available treatments for PeCa. SummaryOSS should be used for small and localized PeCa (T1-T2) as an alternative to partial penectomy to preserve patient's quality of life while maintaining sexual and urinary function and penile aesthetics. Overall, there are different techniques that can be used with different response and recurrence rates. In case of tumor recurrence, partial penectomy or radical penectomy is feasible, without impacting overall survival.

Background: Human Dachshund homologue 1 (DACH1) is involved in carcinogenesis with opposite roles reported in different tumor types. Four alternatively spliced transcripts encoding different DACH1 isoforms were described but their specific role in human cancers is still unknown. Prostate cancer (PCa) is a heterogeneous disease with a very wide variability, so there is yet a relevant need to find new diagnostic and therapeutic biomarkers to make a safe clinical evaluation. It is well known that the differential expression of protein isoforms can induce distinct transcriptional programs with opposing effects on tumor progression and therapy. Thus, in this study we aimed to correlate the functional role of DACH1 with its splicing variants expression in PCa.Methods: The expression and functional role of DACH1 splicing variants in PCa were investigated using tumor (PC3) and normal (RWPE-1) cell lines, patient biopsies and TCGA dataset. Flow-cytometry, western blots and RT-qPCR were used for in vitro molecular characterization; invasion, adhesion, clonogenic assays and cell cycle analysis for functional characterization. Immunohystochemistry and western blot were performed on human PCa biopsies.Results: RT-qPCR and Western Blot revealed that DACH1-positive PC3 cells predominantly expressed DACH1 variant 4 (DACH1-v4), whereas RWPE-1 cells mostly expressed DACH1 variant 3. Stable DACH1-v4 overexpression enhanced the transformed phenotype of PC3 cells by inducing proliferation, colony formation, invasion ability, epithelial to mesenchymal transition. Given its intrinsic radioresistance, PCa frequently recurs after radiotherapy. Of note, DACH1-v4-overexpressing PC3 cells displayed higher radioresistant behavior. Overexpression of DACH1-v4 also transformed RWPE-1 cells to oncogenic phenotype, suggesting a pro-oncogenic role for this specific isoform. PCa biopsies analysis showed DACH1 nuclear staining enhanced throughout the increase of the tumor grade. Remarkably, tumor glands were found to express a long DACH1 variant, while normal prostate tissue expressed the short DACH1 isoform, in line with data from TCGA-PRAD analysis and our data in RWPE-1 cells. Conclusions: Our findings highlight the oncogenic role of DACH1-v4 in PCa and suggest that the longer DACH1 variants could be associated to pro-tumor function, while the shortest DACH1 variant would perform tumor suppression. The expression of specific DACH1 isoforms could represent a novel diagnostic/prognostic marker in PCa.

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