Bladder cancer is a heterogeneous disease. Treatment decisions are mostly decided based on disease stage (non-muscle invasive or muscle invasive). Patients with muscle-invasive disease will be offered a radical treatment combined with systemic therapy, while in those with non-muscle-invasive disease, an attempt to resect the tumor endoscopically will usually be followed by different intravesical instillations. The goal of intravesical therapy is to decrease the recurrence and/or progression of the tumor. In the current landscape of bladder cancer treatment, BCG is given intravesically to induce an inflammatory response and recruit immune cells to attack the malignant cells and induce immune memory. While the response to BCG treatment has changed the course of bladder cancer management and spared many “bladders”, some patients may develop BCG-unresponsive disease, leaving radical surgery as the best choice of curative treatment. As a result, a lot of effort has been put into identifying novel therapies like systemic pembrolizumab and Nadofaragene-Firadenovac to continue sparing bladders if BCG is ineffective. Moreover, recent logistic issues with BCG production caused a worldwide BCG shortage, re-sparking interest in alternative BCG treatments including mitomycin C, sequential gemcitabine with docetaxel, and others. This review encompasses both the historic and current role of BCG in the treatment of non-muscle-invasive bladder cancer, revisiting BCG alternative therapies and reviewing the novel therapeutics that were approved for the BCG-unresponsive stage or are under active investigation.

Objective: To analyse surgical, functional, and mid‐term oncological outcomes of robot‐assisted nephroureterectomy (RANU) in a contemporary large multi‐institutional setting. Patients and Methods: Data were retrieved from the ROBotic surgery for Upper tract Urothelial cancer STtudy (ROBUUST) 2.0 database, an international, multicentre registry encompassing data of patients with upper urinary tract urothelial carcinoma undergoing curative surgery between 2015 and 2022. The analysis included all consecutive patients undergoing RANU except those with missing data in predictors. Detailed surgical, pathological, and postoperative functional data were recorded and analysed. Oncological time‐to‐event outcomes were: recurrence‐free survival (RFS), metastasis‐free survival (MFS), cancer‐specific survival (CSS), and overall survival (OS). Survival analysis was performed using the Kaplan–Meier method, with a 3‐year cut‐off. A multivariable Cox proportional hazard model was built to evaluate predictors of each oncological outcome. Results: A total of 1118 patients underwent RANU during the study period. The postoperative complications rate was 14.1%; the positive surgical margin rate was 4.7%. A postoperative median (interquartile range) estimated glomerular filtration rate decrease of −13.1 (−27.5 to 0) mL/min/1.73 m ² from baseline was observed. The 3‐year RFS was 59% and the 3‐year MFS was 76%, with a 3‐year OS and CSS of 76% and 88%, respectively. Significant predictors of worse oncological outcomes were bladder‐cuff excision, high‐grade tumour, pathological T stage ≥3, and nodal involvement. Conclusions: The present study contributes to the growing body of evidence supporting the increasing adoption of RANU. The procedure consistently offers low surgical morbidity and can provide favourable mid‐term oncological outcomes, mirroring those of open NU, even in non‐organ‐confined disease.

The extensive heterogeneity of prostate cancer (PCa) and multilayered complexity of progression to castration-resistant prostate cancer (CRPC) has contributed to the challenges of accurately monitoring advanced disease. Recent novel approaches have established more concrete profiling of the tumor microenvironment and potential for clinical progression beyond conventional tissue-pathology and imaging. Large-scale transcriptomic studies have identified gene signatures that predict biochemical recurrence, lymph-node invasion, metastases, and development of therapeutic resistance through critical determinants driving CRPC. This review encompasses understanding of the role of different molecular determinants of PCa progression to lethal disease including the phenotypic dynamic of cell plasticity EMT-MET interconversion, and signaling-pathways driving PCa cells to advance and metastasize. The value of liquid biopsies encompassing circulating tumor cells and extracellular vesicles to detect disease progression and emergence of therapeutic resistance in patients progressing to lethal disease is discussed. Relevant literature was added from PubMed portal. Despite progress in the tumor-targeted therapeutics and biomarker discovery, distant metastasis and therapeutic resistance remain the major cause of mortality in patients with advanced CRPC. No single signature can encompass the tremendous phenotypic and genomic heterogeneity of PCa, but rather multi-threaded omics-derived and phenotypic markers tailored and validated into a multimodal signature.