Recent studies have identified a urinary microbiome, dispelling the myth of urine sterility. Intravesical bacillus Calmette–Guérin (BCG) therapy is the preferred treatment for intermediate to high-risk non-muscle-invasive bladder cancer (BCa), although resistance occurs in 30–50% of cases. Progression to muscle-invasive cancer necessitates radical cystectomy. Our research uses 16S rRNA gene sequencing to investigate how the urinary microbiome influences BCa and its response to BCG therapy. Urine samples were collected via urethral catheterization from patients with benign conditions and non-muscle-invasive BCa, all of whom underwent BCG therapy. We utilized 16S rRNA gene sequencing to analyze the bacterial profiles and metabolic pathways in these samples. These pathways were validated using a real metabolite dataset, and we developed predictive models for malignancy and BCG response. In this study, 87 patients participated, including 29 with benign diseases and 58 with BCa. We noted distinct bacterial compositions between benign and malignant samples, indicating the potential role of the toluene degradation pathway in mitigating BCa development. Responders to BCG had differing microbial compositions and higher quinolone synthesis than non-responders, with two Bifidobacterium species being prevalent among responders, associated with prolonged recurrence-free survival. Additionally, we developed highly accurate predictive models for malignancy and BCG response. Our study delved into the mechanisms behind malignancy and BCG responses by focusing on the urinary microbiome and metabolic pathways. We pinpointed specific beneficial microbes and developed clinical models to predict malignancy and BCG therapy outcomes. These models can track recurrence and facilitate early predictions of treatment responses.

To evaluate the utility of different risk assessments in non-muscle-invasive bladder cancer (NMIBC) patients, a total of 178 NMIBC patients from Chungbuk National University Hospital (CBNUH) were enrolled, and the predictive value of the molecular signature-based subtype predictor (MSP888) and risk calculators based on clinicopathological factors (EORTC, CUETO and 2021 EAU risk scores) was compared. Of the 178 patients, 49 were newly analyzed by the RNA-sequencing, and their MSP888 subtype was evaluated. The ability of the EORTC, MSP888 and two molecular subtyping systems of bladder cancer (Lund and UROMOL subtypes) to predict progression of 460 NMIBC patients from the UROMOL project was assessed. Cox regression analyses showed that the MSP888 was an independent predictor of NMIBC progression in the CBNUH cohort (p = 0.043). Particularly in patients without an intravesical BCG immunotherapy, MSP888 significantly linked with risk of disease recurrence and progression (both p < 0.05). However, the EORTC, CUETO and 2021 EAU risk scores showed disappointing results with respect to estimating the NMIBC prognosis. In the UROMOL cohort, the MSP888, Lund and UROMOL subtypes demonstrated a similar capacity to predict NMIBC progression (all p < 0.05). Conclusively, the MSP888 is favorable for stratifying patients to facilitate optimal treatment.

Microbes play different roles in metabolism, local or systemic inflammation, and immunity, and the human microbiome in tumor microenvironment (TME) is important for modulating the response to immunotherapy in cancer patients. Renal cell carcinoma (RCC) is an immunogenic tumor, and immunotherapy is the backbone of its treatment. Correlations between the microbiome and responsiveness to immune checkpoint inhibitors have been reported. This review summarizes the recent therapeutic strategies for RCC and the effects of TME on the systemic therapy of RCC. The current understanding and advances in microbiome research and the relationship between the microbiome and the response to immunotherapy for RCC are also discussed. Improving our understanding of the role of the microbiome in RCC treatment will facilitate the development of microbiome targeting therapies to modify the tumor microbiome and improve treatment outcomes.

Kang HW, et al. Investig Clin Urol. 2022 Mar;63(2):238-244. https://doi.org/10.4111/icu.20210493

Kim K, et al. Investig Clin Urol. 2024 Jan;65(1):94-103. https://doi.org/10.4111/icu.20230227

Prostate-specific antigen (PSA) is a marker of prostate cancer (PCa), although its efficacy as a diagnostic marker remains controversial. A high false-positive rate leads to repeat biopsy in approximately 70% of patients, which may not be necessary. Epigenetic biomarkers of field cancerization have been investigated widely as promising tools for the diagnosis of patients with suspected tumors. In the current study, we examined the diagnostic value of two microRNA (miRNA) candidates, hsv1-miR-H18 and hsv2-miR-H9, using formalin-fixed paraffin-embedded (FFPE) tissues from patients with PCa or benign prostate hyperplasia (BPH) (as controls) to determine the usefulness of these markers for detecting the presence of cancer. Expression of hsv1-miR-H18 and hsv2-miR-H9 in 201 FFPE tissues, including 52 primary tumors, 73 surrounding noncancerous tissues, and 90 BPH nontumor controls was examined by real-time PCR. Expression of hsv1-miR-H18 and hsv2-miR-H9 was significantly higher in primary tumors from PCa patients than in BPH controls (P < 0.0001). In patients within the PSA gray zone, the two viral miRNAs could distinguish PCa from controls with appropriate sensitivity and specificity. Expression of the two miRNAs did not differ between primary tumors and noncancerous surrounding tissues. The viral miRNAs hsv1-miR-H18 and hsv2-miR-H9 may be associated with field cancerization of PCa and could be promising supplemental biomarkers to the PSA assay to decrease the rate of unnecessary biopsy, particularly in patients within the PSA gray zone.