(A)voiding misdiagnosis: prediction of detrusor underactivity vs. bladder outlet obstruction using pre-urodynamic nomogram in male patients with LUTS.

PURPOSE: Our study aimed to develop a noninvasive model using a combination of the set of clinical data and uroflowmetry (UFL) to differentiate between detrusor underactivity (DU) and bladder outlet obstruction (BOO) in non-neurogenic male patients with lower urinary tract symptoms (LUTS). METHODS: Data from 229 men with LUTS, diagnosed with DU or BOO on a pressure-flow study (PFS), were retrospectively analyzed, including medical history, Core Lower Urinary Tract Symptoms score (CLSS) questionnaire, UFL and PFS. Uni- and multivariate logistic regression were utilized for the prediction analyses. RESULTS: Of the cohort, 128 (55.9%) patients were diagnosed with DU. A multivariate logistic regression analysis identified less prevalent nocturia (OR 0.27, p < 0.002), more prevalent intermittency (OR 2.33, p = 0.03), less prevalent weak stream (OR 0.14, p = 0.0004), lower straining points in CLSS (OR 0.67, p = 0.02), higher slow stream points in CLSS (OR 1.81, p = 0.002), higher incomplete emptying points in CLSS (OR 1.31, p < 0.02), lower PVR ratio (OR 0.20, p = 0.03), and present features of fluctuating (OR 2.00, p = 0.05), fluctuating-intermittent (OR 3.09, p < 0.006), and intermittent (OR 8.11, p = 0.076) UFL curve shapes as independent predictors of DU. The above prediction model demonstrated satisfactory accuracy (c-index of 0.783). CONCLUSION: Our 10-factor model provides a noninvasive approach to differentiate DU from BOO in male patients with non-neurogenic LUTS, offering a valuable alternative to invasive PFS.

Assessing the Predictive Accuracy of EORTC, CUETO and EAU Risk Stratification Models for High-Grade Recurrence and Progression after Bacillus Calmette-Guérin Therapy in Non-Muscle-Invasive Bladder Cancer.

The currently available EORTC, CUETO and EAU2021 risk stratifications were originally developed to predict recurrence and progression in non-muscle-invasive bladder cancer (NMIBC). However, they have not been validated to differentiate between high-grade (HG) and low-grade (LG) recurrence-free survival (RFS), which are distinct events with specific implications. We aimed to evaluate the accuracy of available risk models and identify additional risk factors for HG RFS and PFS among NMIBC patients treated with Bacillus Calmette-Guérin (BCG). We retrospectively included 171 patients who underwent transurethral resection of the bladder tumor (TURBT), of whom 73 patients (42.7%) experienced recurrence and 29 (17%) developed progression. Initially, there were 21 low-grade and 52 high-grade recurrences. EORTC2006, EORTC2016 and CUETO recurrence scoring systems lacked accuracy in the prediction of HG RFS (C-index 0.63/0.55/0.59, respectively). EAU2021 risk stratification, EORTC2006, EORTC2016, and CUETO progression scoring systems demonstrated low to moderate accuracy (C-index 0.59/0.68/0.65/0.65) in the prediction of PFS. In the multivariable analysis, T1HG at repeat TURBT (HR = 3.17 p < 0.01), tumor multiplicity (HR = 2.07 p < 0.05), previous history of HG NMIBC (HR = 2.37 p = 0.06) and EORTC2006 progression risk score (HR = 1.1 p < 0.01) were independent predictors for HG RFS. To conclude, available risk models lack accuracy in predicting HG RFS and PFS in -NMIBC patients treated with BCG.

Neutrophil-to-lymphocyte ratio predicts nodal involvement in unfavourable, clinically nonmetastatic prostate cancer patients and overall survival in pN1 patients.

The aim of our study was to determine the clinical utility of neutrophil-to-lymphocyte ratio (NLR) in predicting presence and prognosis of nodal involvement in patients treated with radical prostatectomy (RP) due to prostate cancer. This single-centre retrospective study included 205 patients treated with RP and lymphadenectomy between 2012 and 2018. Logistic regression and Kaplan-Meier analyses were performed to evaluate the prognostic value of preoperative NLR in terms of nodal spread and survival. Patients staged pN1 presented lower mean NLR (2.53 vs 3.86; p = 0.0025) compared to pN0 patients. On multivariable analysis of different haematological markers, only NLR exceeding the median (≥ 2.7) predicted pN1 (OR = 0.38; p = 0.0367) independently of biopsy grading and PSA. In internal validation (n = 31 pN1, n = 174 pN0) on the bootstrapped dataset using a spare cutoff of NLR ≥ 4.1 would allow sparing lymphadenectomy in 22.09% pN0 patients, missing 6.45% pN1 (NPV 92.66%; 95% CI 84.91-100%). Noticeably, in pN1 patients NLR ≥ 2.7 correlated with shorter overall survival (p = 0.0196), despite its association with reduced risk of pN1. High pre-prostatectomy NLR was negatively associated with pN1, yielding high NPV in internal validation. Simultaneously, high NLR in pN1 patients was associated with shorter survival.

The Clinical Utility of Systemic Immune-Inflammation Index Supporting Charlson Comorbidity Index and CAPRA-S Score in Determining Survival after Radical Prostatectomy-A Single Centre Study.

The selection of candidates for the curative treatment of PCa requires a careful assessment of life expectancy. Recently, blood-count inflammatory markers have been introduced as prognosticators of oncological and non-oncological outcomes in different settings. This retrospective, monocentric study included 421 patients treated with radical prostatectomy (RP) for nonmetastatic PCa and aimed at determining the utility of a preoperative SII (neutrophil count × platelet count/lymphocyte count) in predicting survival after RP. Patients with high SIIs (≥900) presented significantly shorter survival (p = 0.02) and high SIIs constituted an independent predictor of overall survival [HR 2.54 (95%CI 1.24−5.21); p = 0.01] when adjusted for high (≥6) age-adjusted CCI (ACCI) [HR 2.75 (95%CI 1.27−5.95); p = 0.01] and high (≥6) CAPRA-S [HR 2.65 (95%CI 1.32−5.31); p = 0.006]. Patients with high scores (ACCI and/or CAPRA-S) and high SIIs were at the highest risk of death (p < 0.0001) with approximately a one-year survival loss during the first seven years after surgery. In subgroup of high CAPRA-S (≥6), patients with high ACCIs and high SIIs were at the highest risk of death (p <0.0001). Our study introduces the SII as a straightforward marker of mortality after RP that can be helpful in pre- and postoperative decision-making.

The Four-Feature Prognostic Models for Cancer-Specific and Overall Survival after Surgery for Localized Clear Cell Renal Cancer: Is There a Place for Inflammatory Markers?

We aimed at a determination of the relevance of comorbidities and selected inflammatory markers to the survival of patients with primary non-metastatic localized clear cell renal cancer (RCC). We retrospectively analyzed data from a single tertiary center on 294 patients who underwent a partial or radical nephrectomy in the years 2012-2018. The following parameters were incorporated in the risk score: tumor stage, grade, size, selected hematological markers (SIRI-systemic inflammatory response index; SII-systemic immune-inflammation index) and a comorbidities assessment tool (CCI-Charlson Comorbidity Index). For further analysis we compared our model with existing prognostic tools. In a multivariate analysis, tumor stage (p = 0.01), tumor grade (p = 0.03), tumor size (p = 0.006) and SII (p = 0.02) were significant predictors of CSS, while tumor grade (p = 0.02), CCI (p = 0.02), tumor size (p = 0.01) and SIRI (p = 0.03) were significant predictors of OS. We demonstrated that our model was characterized by higher accuracy in terms of OS prediction compared to the Leibovich and GRANT models and outperformed the GRANT model in terms of CSS prediction, while non-inferiority to the VENUSS model was revealed. Four different features were included in the predictive models for CSS (grade, size, stage and SII) and OS (grade, size, CCI and SIRI) and were characterized by adequate or even superior accuracy when compared with existing prognostic tools.

Complete blood count-derived inflammatory markers and survival in patients with localized renal cell cancer treated with partial or radical nephrectomy: a retrospective single-tertiary-center study.

We aimed to compare the predictive value of different inflammatory markers in renal cell carcinoma (RCC). Four hundred ninety-five patients treated with nephrectomy for primary localized or locally advanced RCC between 2010 and 2018 were included in the retrospective analysis. The median follow-up for the entire cohort was 48 months. Based on the preoperative laboratory measurements, patients with higher neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), systemic inflammatory response index (SIRI), systemic immune-inflammation index (SII), neutrophil/erythrocyte ratio (NER), derived neutrophil/lymphocyte ratio (dNLR), and lower lymphocyte/monocyte ratio (LMR) and hemoglobin/platelet ratio (HPR) had worse cancer-specific survival (CSS). In the multivariate analysis tumour stage, grade, age and high SIRI constituted independent factors predicting CSS. The model including SIRI values achieved C-index 0.903 (alternative multivariate models with SII and NLR 0.902 and 0.890, respectively). Age, tumour grade and high NER (or high SIRI/ SII in alternative models) were prognostic for overall survival. Markers of systemic inflammation might provide additional prognostic information (especially SIRI, SII, NLR and NER) and further increase the predictive accuracy of available models in localized and locally advanced renal cell carcinoma. For the first time, we show the prognostic value of neutrophil-to-erythrocyte ratio, which constitutes an independent risk factor of overall survival.

E-Cadherin, Integrin Alpha2 (Cd49b), and Transferrin Receptor-1 (Tfr1) Are Promising Immunohistochemical Markers of Selected Adverse Pathological Features in Patients Treated with Radical Prostatectomy.

In patients treated for prostate cancer (PCa) with radical prostatectomy (RP), determining the risk of extraprostatic extension (EPE) and nodal involvement (NI) remains crucial for planning nerve-sparing and extended lymphadenectomy. The study aimed to determine proteins that could serve as immunohistochemical markers of locally advanced PCa. To select candidate proteins associated with adverse pathologic features (APF) reverse-phase protein array data of 498 patients was retrieved from The Cancer Genome Atlas. The analysis yielded 6 proteins which were then validated as predictors of APF utilizing immunohistochemistry in a randomly selected retrospective cohort of 53 patients. For univariate and multivariate analysis, logistic regression was used. Positive expression of TfR1 (OR 13.74; p = 0.015), reduced expression of CD49b (OR 10.15; p = 0.013), and PSA (OR 1.29; p = 0.013) constituted independent predictors of EPE, whereas reduced expression of e-cadherin (OR 10.22; p = 0.005), reduced expression of CD49b (OR 24.44; p = 0.017), and PSA (OR 1.18; p = 0.002) were independently associated with NI. Both models achieved high discrimination (AUROC 0.879 and 0.888, respectively). Immunohistochemistry constitutes a straightforward tool that might be easily utilized before RP. Expression of TfR1 and CD49b is associated with EPE, whereas expression of e-cadherin and CD49b is associated with NI. Since following immunohistochemical markers predicts respective APFs independently from PSA, in the future they might supplement existing preoperative nomograms or be implemented in novel tools.

The Role of Microbial Factors in Prostate Cancer Development-An Up-to-Date Review.

Up-to-date studies emphasize the role of human urinary and intestinal microbiome in maintaining urogenital health. Both microbial flora and sexually transmitted pathogens may affect metabolic or immune mechanisms and consequently promote or inhibit prostate carcinogenesis. Hereby, we review the most current evidence regarding the microbial factors and their link to prostate cancer. We conducted a literature search up to December 2020. The microbial impact on prostate cancer initiation and progression is complex. The proposed mechanisms of action include induction of chronic inflammatory microenvironment (Propionibacterium spp., sexually-transmitted pathogens) and direct dysregulation of cell cycle (Helicobacter pylori, Kaposi's sarcoma-associated herpesvirus- KSHV, human papilloma virus 18- HPV18). Suppression of immune cell expression and downregulating immune-associated genes are also observed (Gardnerella vaginalis). Additionally, the impact of the gut microbiome proved relevant in promoting tumorigenesis (Bacteroides massiliensis). Nevertheless, certain microbes appear to possess anti-tumor properties (Listeria monocytogenes, Pseudomonas spp.), such as triggering a robust immune response and apoptotic cancer cell death. The role of microbial factors in prostate cancer development is an emerging field that merits further studies. In the future, translating microbial research into clinical action may prove helpful in predicting diagnosis and potential outcomes of the disease.

Oncological outcomes of high-grade T1 non-muscle-invasive bladder cancer treatment in octogenarians.

PURPOSE: To evaluate the outcomes of high-grade T1 non-muscle-invasive bladder cancer treatment (NMIBC) in elderly patients over 80 years of age. METHODS: This is a retrospective single tertiary-centre study. Medical records of patients with T1 high-grade NMIBC treated with transurethral resection of the bladder tumour (TURBT) were reviewed. Among 269 patients with high-grade T1 NMIBC, 74 individuals were over 80 years of age at the time of surgery. Finally, 67 patients met the inclusion criteria. RESULTS: Only 47.8% of patients (N = 32) received at least five of the six instillations of the BCG immunotherapy induction course. Oncological outcomes were compared between patients who received at least the induction course of BCG and non-BCG-treated patients matched to each other based on age and Charlson comorbidity index. Thirty case-control pairs were included in the final analysis. Rates of disease recurrence (80% vs. 53%) and cancer-specific mortality (40% vs. 10%) were significantly higher in the group of patients who did not receive BCG. BCG therapy, Charlson comorbidity index, haemoglobin concentration and the number of tumours > 3 in TURBT constituted independent prognostic factors for cancer-specific survival (CSS). CONCLUSION: BCG should be strongly recommended to patients with T1HG NMIBC despite advanced age and comorbidities. Already BCG induction improves CSS and reduces the recurrence rate in octogenarians with T1HG bladder cancer.