Purpose: Although mutations are associated with carcinogenesis, little is known about survival-specific genes in clear cell renal cell carcinoma (ccRCC). We developed a customized next-generation sequencing (NGS) gene panel with 156 genes. The purpose of this study was to investigate whether the survival-specific genes we found were present in Korean ccRCC patients, and their association with clinicopathological findings. Materials and Methods: DNA was extracted from the formalin-fixed, paraffin-embedded tissue of 22 ccRCC patients. NGS was performed using our survival-specific gene panel with an Illumina MiSeq. We analyzed NGS data and the correlations between mutations and clinicopathological findings and also compared them with data from the Cancer Genome Atlas-Kidney Renal Clear Cell Carcinoma (TCGA-KIRC) and Renal Cell Cancer-European Union (RECA-EU). Results: We found a total of 100 mutations in 37 of the 156 genes (23.7%) in 22 ccRCC patients. Of the 37 mutated genes, 11 were identified as clinicopathologically significant. Six were novel survival-specific genes (ADAMTS10, CARD6, NLRP2, OBSCN, SECISBP2L, and USP40), and five were top-ranked mutated genes (AKAP9, ARID1A, BAP1, KDM5C, and SETD2). Only CARD6 was validated as an overall survival-specific gene in this Korean study (p = 0.04, r = −0.441), TCGA-KIRC cohort (p = 0.0003), RECA-EU (p = 0.0005). The 10 remaining gene mutations were associated with clinicopathological findings; disease-free survival, mortality, nuclear grade, sarcomatoid component, N-stage, sex, and tumor size. Conclusions: We discovered 11 survival-specific genes in ccRCC using data from TCGA-KIRC, RECA-EU, and Korean patients. We are the first to find a correlation between CARD6 and overall survival in ccRCC. The 11 genes, including CARD6, NLRP2, OBSCN, and USP40, could be useful diagnostic, prognostic, and therapeutic markers in ccRCC. Full article

(1) Background: The adjustable transobturator male system (ATOMS) device serves to treat post-prostatectomy incontinence, as it enhances residual urinary sphincteric function by dorsal compression of the bulbar urethra. We investigated the clinical parameters affecting continence recovery using this device and developed a decision aid to predict success. (2) Methods: We reviewed consecutive men treated with first-time ATOMS for post-prostatectomy incontinence from 2014 to 2021 at our institution. Patient demographics, reported pads per day (PPD), 24-h pad-test and Standing Cough Test (SCT), results’ grades 1–4, according to Male Stress Incontinence Grading Scale (MSIGS), and the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) questionnaire were assessed. Treatment success was defined as no pads or a single PPD with ≤20-mL 24-h pad-test. Logistic regression was performed using a stepwise model (entry 0.15 and stay criterium 0.1) to evaluate independent variables’ determinant of dryness. Receiver-operating characteristic (ROC) curves for predictive variables were evaluated and their area under curve (AUC) was compared. A nomogram was generated and internally validated to predict probability of treatment success. (3) Results: Overall, 149 men (median age 70 years, IQR 7) were evaluated with a median follow-up of 45 months (IQR 26). Twelve patients (8%) had previous devices for incontinence, and 21 (14.1%) had pelvic radiation. Thirty-five men (23.5%) did not achieve continence after ATOMS adjustment (use of no or one security PPD with ≤20-mL 24-h pad-test). In univariate analysis, Charlson comorbidity index (p = 0.0412), previous urethroplasty (p = 0.0187), baseline PPD (p < 0.0001), 24-h pad-test (p < 0.0001), MSIGS (p < 0.0001), and ICIQ-SF questionnaire score (p < 0.0001) predicted ATOMS failure. In a multivariable model, 24-h pad-test (p = 0.0031), MSIGS (p = 0.0244), and radiotherapy (p = 0.0216) were independent variables, with AUC 0.8221. The association of MSIGS and 24-h pad-test was the superior combination (AUC 0.8236). A nomogram to predict the probability of ATOMS failure using the independent variables identified was proposed. (4) Conclusions: Several variables were identified as predictive of success for ATOMS using clinical history, physical examination (MSIGS), and factors that evaluate urine loss severity (PPD, 24-h pad-test, and ICIQ-SF questionnaire). MSIGS adds prognostic value to 24-h pad-test in assessing success of ATOMS device to treat post-prostatectomy incontinence. A nomogram was proposed to calculate the risk of ATOMS failure, which could be of interest to personalize the decision to use this device or not in the individual patient. Full article

Prostate cancer is a heterogeneous disease that remains dormant for long periods or acts aggressively with poor clinical outcomes. Identifying aggressive prostate tumor behavior using current glandular-focused histopathological criteria is challenging. Recent evidence has implicated the stroma in modulating prostate tumor behavior and in predicting post-surgical outcomes. However, the emergence of stromal signatures has been limited, due in part to the lack of adoption of imaging modalities for stromal-specific profiling. Herein, label-free multiphoton microscopy (MPM), with its ability to image tissue with stromal-specific contrast, is used to identify prostate stromal features associated with aggressive tumor behavior and clinical outcome. MPM was performed on unstained prostatectomy specimens from 59 patients and on biopsy specimens from 17 patients with known post-surgery recurrence status. MPM-identified collagen content, organization, and morphological tumor signatures were extracted for each patient and screened for association with recurrent disease. Compared to tumors from patients whose disease did not recur, tumors from patients with recurrent disease exhibited higher MPM-identified collagen amount and collagen fiber intensity signal and width. Our study shows an association between MPM-identified stromal collagen features of prostate tumors and post-surgical disease recurrence, suggesting their potential for prostate cancer risk assessment. Full article

Liquid biopsy is an accessible, non-invasive diagnostic tool for advanced prostate cancer (PC) patients, potentially representing a real-time monitoring test for tumor evolution and response to treatment through the analysis of circulating tumor cells (CTCs) and exosomes. We performed a systematic literature review (PRISMA guidelines) to describe the current knowledge about PD-L1 expression in liquid biopsies of PC patients: 101/159 (64%) cases revealed a variable number of PD-L1+ CTCs. Outcome correlations should be investigated in larger series. Nuclear PD-L1 expression by CTCs was occasionally associated with worse prognosis. Treatment (abiraterone, enzalutamide, radiotherapy, checkpoint-inhibitors) influenced PD-L1+ CTC levels. Discordance in PD-L1 status was detected between primary vs. metastatic PC tissue biopsies and CTCs vs. corresponding tumor tissues. PD-L1 is also released by PC cells through soluble exosomes, which could inhibit the T cell function, causing immune evasion. PD-L1+ PC-CTC monitoring and genomic profiling may better characterize the ongoing aggressive PC forms compared to PD-L1 evaluation on primary tumor biopsies/prostatectomy specimens (sometimes sampled a long time before recurrence/progression). Myeloid-derived suppressor cells and dendritic cells (DCs), which may have immune-suppressive effects in tumor microenvironment, have been found in PC patients circulation, sometimes expressing PD-L1. Occasionally, their levels correlated to clinical outcome. Enzalutamide-progressing castration-resistant PC patients revealed increased PD-1+ T cells and circulating PD-L1/2+ DCs. Full article

The treatment for nonmetastatic castration-resistant prostate cancer (nmCRPC) is a highly unmet medical need. The classic treatment approach for these patients—androgen deprivation therapy (ADT) alone—until metastatic progression is now considered suboptimal. Several randomized phase III clinical trials have demonstrated significant clinical benefits—including significantly better overall survival (OS)—for treatments that combine ADT with apalutamide, enzalutamide, and darolutamide. As a result, these approaches are now included in treatment guidelines and are considered a standard of care. In the present article, we discuss the changing landscape of the management of patients with nmCRPC. Full article