Non-muscle-invasive bladder cancer (NMIBC) accounts for approximately 70% of newly diagnosed bladder cancer cases but exhibits significant clinical heterogeneity in treatment response and progression risk. While intravesical bacillus Calmette–GuérinCa (BCG) therapy remains the gold standard for high-risk disease, approximately 30–50% of patients experience BCG failure, creating a critical decision point between additional bladder-sparing therapy (BST) and early radical cystectomy (RC). Recent clinical data from the CISTO study suggest that, in appropriately selected patients, RC may be associated with higher 12-month recurrence-free survival while maintaining comparable cancer-specific survival and physical functioning. In this narrative review, we synthesize contemporary evidence on NMIBC genomic and transcriptomic subtypes, immune contexture, and clinicopathologic features associated with BCG response and progression risk, with emphasis on clinically oriented classification systems such as BCG Response Subtypes (BRS1–3) and UROMOL21. We highlight how tumor-intrinsic biology (e.g., EMT-associated programs), immune phenotypes (inflamed vs. immune-cold microenvironments), and genomic alterations may help refine risk stratification beyond traditional clinicopathologic models. To facilitate clinical integration, we propose a conceptual decisional framework that combines molecular subtype assignment, immune profiling, key pathologic risk factors, and patient considerations to generate probabilistic risk tiers that support selection among early RC, BST, and clinical trial strategies. Standardized multicenter cohorts and prospective evaluation are needed to validate integrated models and define their clinical utility for the precision timing of cystectomy in BCG-unresponsive NMIBC.
Trimodality therapy (TMT)—maximal transurethral resection of bladder tumor (TURBT) followed by concurrent chemoradiotherapy—can offer oncologic outcomes comparable to radical cystectomy (RC) in carefully selected muscle-invasive bladder cancer (MIBC) patients while preserving the bladder and, possibly, the quality of life. Systematic reviews and long-term series support durable bladder-intact survival in responders, yet there is still a significant percentage of patients who exhibit incomplete response or invasive intravesical recurrence requiring salvage RC. This review covers computational genomics, transcriptomics, immune contexture, radiogenomics, and digital pathology approaches for predicting response in order to avoid preventable TMT failures. We discuss clinically relevant endpoints (complete response, invasive recurrence, bladder-intact survival, and salvage RC), patient selection (carcinoma in situ, hydronephrosis, debulking feasibility, and histology), and DNA damage response (DDR) biology—highlighting ERCC2 and related pathways as determinants of chemo-radiation sensitivity. We then review reproducible transcriptomic subtype classifiers and immune deconvolution methods, emphasizing translational constraints and reporting standards. Finally, we propose an integrated hypothetical modeling framework (calibration, external validation, and decision-curve thresholds) to guide recommendations for upfront RC versus bladder preservation with intensified surveillance and timely salvage RC.
Background and clinical significance:Pasteurella spp. are Gram-negative coccobacilli, aerobic facultatively anaerobic, belonging to the Pasteurellaceae family. In humans, they are known to cause zoonotic diseases, which usually develop after dog or cat bites, licks or scratches. Case presentation: We present the case of a 61-year-old patient, with cardiovascular comorbidities, who presented to the Orthopedics Department, 38 days after knee replacement surgery, with recurrence of pain on walking, an antalgic gait with auxiliary support, and local signs of inflammation at the level of the left knee joint. The patient admitted to owning a dog who accidentally licked the post-surgical wound. The symptoms were suggestive of a post-surgical wound infection with extension to the periprosthetic area. A purulent discharge was collected from the wound during surgical debridement and sent to the microbiological laboratory for diagnosis, where Pasteurella canis was identified using MALDI-TOF MS. Antibiotic susceptibility testing (AST) was performed according to the EUCAST guidelines and empiric antibiotic treatment was started with Cefuroxime. During his future admissions to the Orthopedics and Infectious Diseases departments, two more samples were collected, in which Pasteurella canis was isolated, along with Klebsiella oxytoca (second sample), and Klebsiella oxytoca and Pseudomonas aeruginosa (third sample). Patient evolution was favorable due to the debridement of the wound and combined antibiotic treatment, with Ceftazidime and Gentamicin. Conclusions: Infections with Pasteurella canis are rare but slowly increasing due to more and more humans owning pets. The present case underlines the importance of interdisciplinary collaborations when rare pathogens are identified.