Despite advancements in molecular classification, tumor stage and grade still remain the most relevant prognosticators used by clinicians to decide on patient management. Here, we leverage publicly available data to characterize bladder cancer (BLCA)’s stage biology based on increased sample sizes, identify potential therapeutic targets, and extract putative biomarkers. A total of 1135 primary BLCA transcriptomes from 12 microarray studies were compiled in a meta-cohort and analyzed for monotonal alterations in pathway activities, gene expression, and co-expression patterns with increasing stage (Ta–T1–T2–T3–T4), starting from the non-malignant tumor-adjacent urothelium. The TCGA-2017 and IMvigor-210 RNA-Seq data were used to validate our findings. Wnt, MTORC1 signaling, and MYC activity were monotonically increased with increasing stage, while an opposite trend was detected for the catabolism of fatty acids, circadian clock genes, and the metabolism of heme. Co-expression network analysis highlighted stage- and cell-type-specific genes of potentially synergistic therapeutic value. An eight-gene signature, consisting of the genes AKAP7, ANLN, CBX7, CDC14B, ENO1, GTPBP4, MED19, and ZFP2, had independent prognostic value in both the discovery and validation sets. This novel eight-gene signature may increase the granularity of current risk-to-progression estimators.

Background: The Paris System for Reporting Urinary Cytology (TPS) is considered the gold standard when it comes to diagnostic classifications of urine specimens. Its second edition brought some important changes, including the abolition of the diagnostic category of “low-grade urothelial neoplasm (LGUN)”, acknowledging the inability of cytology to reliably discern low-grade urothelial lesions. Methods: In this retrospective study, we assessed the validity of this change, studying the cytological diagnoses of histologically diagnosed low-grade urothelial carcinomas during a three-year period. Moreover, we correlated the sum of the urinary cytology diagnoses of this period with the histological diagnoses, whenever available. Results: Although all the cytological diagnoses of LGUN were concordant with the histological diagnoses, most low-grade urothelial carcinomas were misdiagnosed cytologically. Subsequently, the positive predictive value (PPV) of urinary cytology for the diagnosis of LGUN was 100%, while the sensitivity was only 21.7%. Following the cyto-histopathological correlation of the sum of the urinary cytology cases, the sensitivity of urinary cytology for the diagnosis of high-grade urothelial carcinoma (HGUC) was demonstrated to be 90.1%, the specificity 70.8%, the positive predictive value (PPV) 60.3%, the negative predictive value (NPV) 93.6% and the overall accuracy 77.2%, while for LGUN, the values were 21.7%, 97.2%, 87.5%, 58.6% and 61.9%, respectively. Risk of high-grade malignancy was 0% for the non-diagnostic (ND), 4.8% for the non-high-grade urothelial carcinoma (NHGUC), 33.3% for the atypical urothelial cells (AUCs), 65% for the suspicious for high-grade urothelial carcinoma (SHGUC), 100% for the HGUC and 12.5% for the LGUN diagnostic categories. Conclusions: This study validates the incorporation of the LGUN in the NHGUC diagnostic category in the second edition of TPS. Moreover, it proves the ability of urinary cytology to safely diagnose HGUC and stresses the pivotal role of its diagnosis.

Background/Objectives: Multiparametric-Magnetic Resonance Imaging(mp-MRI) presents the ability to detect clinically significant cancer, aiming to avoid biopsy if the results are negative or target an abnormal lesion if a suspected lesion of the prostate is found. Recent guidelines recommend the performance of 12 standard biopsies along with 3 to 5 targeted biopsies in suspected prostate lesions, depending on the size of the prostate lesion. In addition, prostate biopsy can be performed by either the transperineal or the transrectal approach. The aim of this comprehensive review is to highlight the role of both standard and targeted MRI/Ultrasound (US) fusion transperineal biopsy (TPB) in the diagnostic approach of prostate cancer cases, to report its diagnostic efficacy and complication rates and to suggest the promising usage of MRI/US fusion TPB in the future. Methods: A comprehensive review of the existing literature, including systematic reviews, meta-analyses, and clinical guidelines, was conducted to compare the efficacy and safety of transperineal and transrectal approaches in prostate cancer detection. Special emphasis was placed on mp-MRI-guided targeted biopsy and its combination with systematic sampling. Results: Prostate biopsy via the transperineal approach is related to increased detection rates, especially for anterior lesions, and decreased infection risk compared to the transrectal approach, while complication rates (hematuria, hemospermia, etc.) remain similar. Due to lower infection rates via the transperineal route, the performance of prostate biopsy using the transperineal approach is strongly recommended. Finally, transperineal fusion MRI/US biopsy can be valuable for repeat biopsies in patients who had an initial negative biopsy or for the follow-up of patients that undergo active surveillance. Conclusions: MRI/US fusion-guided TPB represents a significant advancement in prostate cancer diagnostics, combining improved precision with reduced infection risks. Although TPB presents higher detection rates for anterior prostatic lesions and lower post-biopsy infection rates, there is no significant difference in cancer detection rates compared to TRB. Targeted training and investment may reduce long-term expenses of TPB by lowering hospitalizations, antibiotic usage, and related costs. Future research should further refine this approach and explore its integration with emerging technologies like artificial intelligence for enhanced lesion targeting and diagnostic accuracy.

Background: While the clinical application of SII-ONCO-Bacillus Calmette–Guerin (BCG) for non-muscle-invasive bladder cancer (NMIBC) is well established in Greece, there is a lack of real-world data on its effectiveness and safety. This retrospective, observational, multicenter, chart-review study aims to provide real-life data on the effectiveness and safety of SII-ONCO-BCG in patients with intermediate- and high-risk NMIBC. Methods: From January 2016 to December 2023, medical records from six hospital centers were reviewed for adult patients with histologically confirmed stage Ta or T1 NMIBC (with or without carcinoma in situ [CIS]) who received at least one maintenance course of SII-ONCO-BCG after induction. Tumor recurrence and progression were monitored at scheduled time intervals. Primary outcomes included recurrence-free survival (RFS) and progression-free survival (PFS), while adverse events (AEs) constituted secondary outcomes. Results: A total of 162 patients receiving SII-ONCO-BCG were enrolled. Among all patients, 145 (89.5%) patients were men, 88 (54.3%) aged 70 years or older, 103 (63.6%) had T1, 43 (26.5%) Ta, and 21 (12.9%) concurrent CIS. The median follow-up duration was 28.9 months (range, 5–36) and the mean BCG intravesical instillation courses were 13.7 (range, 9–27). After 3-, 2-, and 1-year follow-up, RFS rates of 85.2% (95% CI, 79.7–90.7%), 85.8% (80.4–91.2%), and 87.0% (81.8–92.3%) were observed, respectively. The corresponding 3-, 2-, and 1-year PFS rates were 96.9% (94.2–99.6%), 96.9% (94.2–99.6%), and 97.5% (95.1–99.9%), respectively. During the whole follow-up period, 24 (14.8%) patients experienced at least one AE. Conclusions: This real-world study demonstrates that SII-ONCO-BCG is an effective and safe treatment for patients with intermediate- and high-risk NMIBC.