Bladder cancer (BLCA) is a highly prevalent tumour and a health problem worldwide, especially among men. Recent work has highlighted the relevance of the tumour microenvironment (TME) in cancer biology with translational implications. Cancer-associated fibroblasts (CAFs) are a prominent, heterogeneous population of cells in the TME. CAFs have been associated with tumour development, progression, and poor prognosis in several neoplasms. However, their role in BLCA has not yet been exploited deeply. To review the role of CAFs in BLCA biology and provide an understanding of CAF origin, subtypes, markers, and phenotypic and functional characteristics to improve patient management. A PubMed search was performed to review manuscripts published using the terms "cancer associated fibroblast" and "bladder cancer" or "urothelial cancer". All abstracts were reviewed, and the full content of all relevant manuscripts was analysed. In addition, selected manuscripts on CAFs in other tumours were considered. CAFs have been studied less extensively in BLCA than in other tumours. Thanks to new techniques, such as single-cell RNA-seq and spatial transcriptomics, it is now possible to accurately map and molecularly define the phenotype of fibroblasts in normal bladder and BLCA. Bulk transcriptomic analyses have revealed the existence of subtypes among both non-muscle-invasive and muscle-invasive BLCA; these subtypes display distinct features regarding their CAF content. We provide a higher-resolution map of the phenotypic diversity of CAFs in these tumour subtypes. Preclinical studies and recent promising clinical trials leverage on this knowledge through the combined targeting of CAFs or their effectors and the immune microenvironment. Current knowledge of BLCA CAFs and the TME is being increasingly applied to improve BLCA therapy. There is a need to acquire a deeper understanding of CAF biology in BLCA. Tumour cells are surrounded by nontumoural cells that contribute to the determination of the behaviour of cancers. Among them are cancer-associated fibroblasts. The "neighbourhoods" established through these cellular interactions can now be studied with much greater resolution. Understanding these features of tumours will contribute to the designing of more effective therapies, especially in relationship to bladder cancer immunotherapy.

Background: Determining the infiltration of carcinomas is essential for the proper follow-up and treatment of cancer patients. However, it continues to be a diagnostic challenge for pathologists in multiple types of tumors. In previous studies (carried out in surgical specimens), the protein COL11A1 has been postulated as an infiltration marker mainly expressed in the extracellular matrix (ECM). We hypothesized that a differential expression of COL11A1 may exist in the peritumoral stroma of tumors that have acquired infiltrating properties and that it may be detected in the small biopsies usually available in normal clinical practice. Material and methods: In our study, we performed immunohistochemical staining in more than 350 invasive and noninvasive small samples obtained via core needle biopsy (CNB), colonoscopy, or transurethral resection of bladder tumor (TURBT) of breast, colorectal, bladder, and ovarian cancer. Results: Our results revealed that COL11A1 immunostaining had a sensitivity to classify the samples into infiltrative vs. noninfiltrative tumors of 94% (breast), 97% (colorectal), >90% (bladder), and 74% (ovarian); and a specificity of 97% (breast), 100% (colorectal), and >90% (bladder). In ovarian cancer, the negative predictive value (0.59) did not present improvement over the usual histopathological markers. In all samples tested, the cumulative sensitivity was 86% and the specificity 96% (p < 0.0001). Conclusions: COL11A1-positive immunostaining in small biopsies of breast, colon, bladder and ovarian cancer is an accurate predictive marker of tumor infiltration that can be easily implemented in daily clinical practice.

Background/Objectives: Determining homologous recombination repair (HRR) status in metastatic castration-resistant prostate cancer (mCRPC) is essential to ensure access to targeted therapies, particularly PARP inhibitors. Yet, variability in testing access and analysis performance exists. This study evaluated feasibility and outcomes of a centralized HRR testing strategy in Spain for prostate cancer patients. Methods: A total of 1412 formalin-fixed paraffin-embedded (FFPE) tumor samples from mCRPC patients from 89 Spanish institutions within a centralized multicenter molecular testing program were analyzed using a standardized 38-gene-based next-generation sequencing (NGS) assay in a central laboratory (HRR OncoKit, Health in Code, Valencia, Spain), which included five clinically relevant HRR genes: BRCA1, BRCA2, CHEK2, ATM, and CDK12. Results: HRR gene pathogenic or likely pathogenic alterations were identified in 18% (CI 95% = 16–20) of the patients, with BRCA2 being the most frequently altered gene (6%), followed by ATM (5%), CDK12 (4%), BRCA1 (2%), and CHEK2 (1%). Eleven percent had variants of uncertain significance. Only 13% of the samples were rejected due to poor DNA quality, low tumor content or sample age exceeding 5 years, and 2% of the samples analyzed failed since the minimum library technical quality score was not achieved. The average turnaround time for results was 18 ± 3 days. Conclusions: Centralized HRR testing in mCRPC patients in Spain was feasible, efficient and reliable, identifying pathogenic alterations in 18% of the cases, similarly to the prevalence described in the literature. This testing approach facilitates precision medicine by improving the detection of actionable HRR alterations.