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Early detection of primary bladder cancer (BCa) is vital, because stage and grade have been generally accepted not only as categorical but also as prognostic factors in patients with BCa. The widely accepted screening methods for BCa, cystoscopy and urine cytology, have unsatisfactory diagnostic accuracy, with high rates of false negatives, especially for flat-type BCa with cystoscopy and for low-risk disease with urine cytology. Currently, liquid biopsy has attracted much attention as being compensatory for that limited diagnostic power. In this review, we survey the literature on liquid biopsy for the detection of BCa, focusing on circulating tumor cells (CTCs), urinary cell-free DNA (ucfDNA), and urinary microRNA (umiRNA). In diagnostic terms, CTCs and umiRNA are determined by quantitative analysis, and ucfDNA relies on finding genetic and epigenetic changes. The ideal biomarkers should be highly sensitive in detecting BCa. Currently, CTCs produce an unfavorable result; however, umiRNA and ucfDNA, especially when analyzed using a panel of genes, produce promising results. However, given the small cohort size in most studies, no conclusions can yet be drawn about liquid biopsy’s immediate application to clinical practice. Further large studies to validate the diagnostic value of liquid biopsy for clinical use are mandatory.

Backgrounds: High-volume (HV) metastatic castration-sensitive prostate cancer (mCSPC) is an aggressive disease. Despite this, we aimed to assess the metastatic patterns associated with a favorable prognosis in HV disease with bone metastasis (BM), including BM’s coexistence with lung metastasis (LM). Methods: We retrospectively analyzed 379 patients with synchronous mCSPC. They were categorized using the CHAARTED criteria as low-volume (LV) or HV with BM, classified based on extent of the disease from 1 to 4 (HV-EOD1–4) with or without LM. Multivariate Cox models for overall survival and castration-resistance-free survival assessed the prognostic values of HV-EOD1–4 compared with LV disease and the presence of LM. Site-specific radiographic progression at the time of castration-resistant prostate diagnosis was assessed in patients with BM and LM. Results: Multivariate analyses for overall survival showed no prognostic value of HV-EOD1 (hazard ratio [HR] 0.90; 95% confidence interval [CI] 0.43–1.85; p = 0.77), HV-EOD2 (HR 1.17; 95% CI 0.69–1.99; p = 0.57), and LM (HR 1.29; 95% CI 0.80–2.07; p = 0.29). In the analyses, HV-EOD ≤ 2 and LM did not influence castration resistance-free survival. LM showed a significantly lower incidence of radiographic progression to castration-resistant prostate cancer than BM (6.0% vs. 29.9%, p < 0.001). Conclusions: This study indicates the prognostic heterogeneity of HV disease considering BM and LM. These findings may aid in determining the treatment intensity for mCSPC.

Robot-assisted radical prostatectomy (RARP) has emerged as the predominant surgical approach globally, and various techniques have been proposed to improve functional outcomes. Despite these advances, however, functional impairment associated with surgery remains a major concern that affects patients' quality of life. Retzius-sparing RARP (RS-RARP) has been proposed as a surgical technique to preserve the Retzius space, and increasing evidence has demonstrated its effectiveness. However, the effect of RS-RARP on other functions remains unknown. Although some reports show the positive effect of Retzius-sparing RARP (RS-RARP) on urinary incontinence, the effects on other functions remain unknown. The present study retrospectively analyzed 132 patients who underwent RARP at Kitasato University Hospital between January 2020 and July 2021 (49 and 83 patients in the RS-RARP and conventional RARP groups, respectively). We compared the functional outcomes of RS-RARP and conventional RARP (C-RARP) using the Expanded Prostate Cancer Index Composite (EPIC). In addition, sexual function was compared among patients who underwent nerve-sparing procedures. Our findings revealed that, even at 12 months postoperatively, RS-RARP demonstrated significant preservation of urinary continence ( < 0.01) and sexual function compared to C-RARP ( = 0.03). No significant differences were observed in the bowel or hormonal domains. Even in patients who underwent nerve-sparing surgery, the EPIC score 12 months postoperatively was significantly higher with RS-RARP than with C-RARP ( < 0.01). RS-RARP tended to result in positive surgical margins more often than C-RARP (RS-RARP: 44.9%, C-RARP: 28.9%, = 0.06), without affecting the rate of biochemical recurrence (RS-RARP: 14.2%, C-RARP: 15.7%, = 0.81). Our results suggest a potential advantage of RS-RARP in preserving both urinary and sexual function.

BackgroundLittle data on the preoperative prognostic factors in radical cystectomy (RC) patients have made it difficult to choose the appropriate type of urothelial diversion (UD). This study aimed to investigate the prognostic role of UD, with a subgroup analysis of that of preoperative renal function.MethodsFrom 1990 to 2015, 279 patients underwent RC for bladder cancer at six hospitals affiliated with Kitasato University in Japan. All patients were divided into three groups: cutaneous ureterostomy (CU; n = 54), ileal conduit (IC; n = 139), and orthotopic neobladder (NB; n = 86). Patients were also stratified into three groups based on preoperative estimated glomerular filtration rate (eGFR) (mL/min/1.73 m2): normal eGFR (> 60 mL/min/1.73 m2; n = 149), moderately reduced eGFR (45–60 mL/min/1.73 m2; n = 66), and severely reduced eGFR (< 45 mL/min/1.73 m2; n = 37). Statistical analyses were performed to investigate prognostic values of UD and preoperative eGFR.ResultsKaplan–Meier analyses showed that progression-free survival (PFS) and cancer-specific survival (CSS) did not differ between the three types of UD groups. With regard to renal function, the preoperative severely reduced group had significantly worse PFS and CSS than the other groups. The multivariate analysis showed that severely reduced preoperative eGFR was an independent risk factor of worse PFS and worse CSS.ConclusionThe present study demonstrated that preoperative severe renal function was shown as an independent risk factor of both PFS and CSS.

Background Wide-spectrum antibiotics have been favored to treat acute uncomplicated cystitis (AUC) for a long time, leading to the emergence of multi-drug resistant bacteria. We hypothesize that narrow-spectrum antibiotics might mitigate the issue and aim to investigate the clinical efficacy of cefaclor in patients with AUC. Methods We retrospectively reviewed the clinical data of female outpatients with AUC treated with cefaclor and evaluated the safety and clinical efficacy. Clinical cure was defined as the elimination of clinical symptom under 4 white blood cells (WBCs) per high power field on microscopy. Results Overall, 223 women with AUC were enrolled. Escherichia coli was the dominant pathogen ( n  = 160; 68.6%), followed by Klebsiella species and E. coli -extended spectrum β-lactamase (ESBL) ( n  = 19; 8.1% and n  = 18; 7.7%). Overall success rate was 94.0% ( n  = 219) and susceptibility rate of cefazolin was 84.1%, which was close to that of levofloxacin (82.9%). Ampicillin showed the lowest rate of 63.7% with a significantly greater resistance rate of 35.3% among all antibiotics ( P  < 0.001). In the subgroup analysis, the success rate in patients with resistance to levofloxacin or cefazolin was 100% ( n  = 24) or 93.3% ( n  = 14). The rate in patients with resistance to both antibiotics was 60.0% ( n  = 9), and the pathogens in the other 40.0% ( n  = 6) of patients with treatment failure were E. coli -ESBL. Conclusion Cefaclor showed excellent efficacy in AUC patients, even in those with in vitro resistance to cefazolin or levofloxacin. Cefaclor may be considered as a first-line option in patients with AUC and a second-line option for those with levofloxacin treatment failure.

Background/Objectives: While cytoskeleton-associated protein 4 (CKAP4) has been associated with prognosis in various malignancies, its prognostic value for bladder cancer (BCa) remains unclear. The aim of this study was to evaluate CKAP4 expression in tumor cells and cancer-associated fibroblasts (CAFs) following radical cystectomy (RC) in patients with BCa. Methods: In this study, CKAP4 in tumor cells was defined as CKAP4-1, while CKAP4 expressed in CAFs was defined as CKAP4-2. CKAP4-2 expression was evaluated to explore its potential association with tumor aggressiveness and patient outcomes. CKAP4 expression in 86 RC specimens was assessed using immunohistochemistry. CKAP4-1 positivity was considered when ≥5% cytoplasmic staining of cancer cells, with at least moderate staining intensity, was observed. CKAP4-2 positivity was evaluated using a point scale (0–3), with scores based on the number of CKAP4 positive CAFs in the tumor stroma. Scores of 2 (moderate number of CAFs) and 3 (significant number of CAFs) were considered to indicate positivity. Results: CKAP4-1 and CKAP4-2 were expressed in 53 (61.6%) and 34 (39.5%) patients, respectively. Kaplan–Meier analysis showed that patients with CKAP4-1 had significantly shorter cancer-specific survival and recurrence-free survival (RFS; p = 0.046 and p = 0.0173, respectively). Multivariate analysis showed that CKAP4-1 positivity was an independent predictor of RFS (p = 0.041, hazard ratio: 2.09, 95% confidence interval: 1.03–4.25). Conclusions: This study showed that CKAP4 expression in tumor cells may serve as a useful prognostic biomarker for patients with BCa who undergo RC.

Background Data are scarce regarding intravesical maintenance therapy (MT) with the low-dose bacillus Calmette–Guérin (BCG) Tokyo strain. We investigated the efficacy and safety of MT with a half dose of the Tokyo strain for patients following transurethral resection of nonmuscle invasive bladder cancer (NMIBC). Methods This study retrospectively reviewed clinical data on 78 patients diagnosed with intermediate or high-risk NMIBC followed by either MT (n = 38) or IT alone (n = 40) between January 2012 and March 2018. Statistical analysis was performed to compare recurrence-free survival (RFS) and adverse effects between the two groups. BCG was instilled once weekly for 6 weeks as IT, then once weekly in 2-week for a total of 20 instillations over 3 years. Results Kaplan–Meier analyses showed that patients undergoing MT had significantly better RFS than did those undergoing IT alone (hazard ratio (HR):0.32, 95% confidence interval (CI):0.12–0.89, P  = 0.02). The 3-year RFS was 65.0% in the IT group and 89.5% in the MT group. Multivariate analysis showed that MT was associated with a reduced risk of recurrence (HR: 0.32, 95% CI:0.11–0.93, P  = 0.03). One MT patient (2.6%) exhibited progression. Conclusions The BCG Tokyo strain showed acceptable efficacy and safety in patients undergoing MT; thus, it is a potential treatment for preventing bladder cancer recurrence.

Objective: To investigate the correlation between total protein expression of heart development protein with EGF-like domain 1 (HEG1) and clinicopathological characteristics in patients with bladder cancer (BC) after radical cystectomy (RC). Patients and Methods: We retrospectively analyzed data from 110 patients who underwent RC at Kitasato University Hospital. And we prepared an anti-HEG1 monoclonal antibody W10B9, which can detect total HEG1 protein. HEG1 protein expression in tumor cells was evaluated separately for membrane and cytoplasmic staining using immunohistochemistry. Results: Membranous HEG1 expression was associated with absent lymphovascular invasion (p < 0.01) and low pT stage (p < 0.01). Kaplan–Meier analysis revealed that the membranous HEG1-positive group had significantly long recurrence-free survival (RFS) (p < 0.01) and cancer-specific survival (p = 0.01). Expression of membranous HEG1 was identified as an independent prognostic factor for RFS (p = 0.04). There were no significant differences between cytoplasmic HEG1 expression and clinicopathologic factors including prognosis. Conclusion: The expression of membranous HEG1 could serve as a favorable prognostic indicator in patients with BC treated with RC.

Background In patients experiencing disease recurrence after radical cystectomy (RC) for bladder cancer, data about the impact of clinicopathologic factors, including salvage treatment using cytotoxic chemotherapy, on the survival are scarce. We investigated the prognostic value of clinicopathologic factors and the treatment effect of salvage cytotoxic chemotherapy (SC) in such patients. Methods In this retrospective study, we evaluated the clinical data for 86 patients who experienced recurrence after RC. Administration of SC or of best supportive care (BSC) was determined in consultation with the urologist in charge and in accordance with each patient’s performance status, wishes for treatment, and renal function. Statistical analyses explored for prognostic factors and evaluated the treatment effect of SC compared with BSC in terms of cancer-specific survival (CSS). Results Multivariate analyses showed that liver metastasis after RC (hazard ratio [HR] 2.13; 95% confidence interval [CI] 1.17 to 3.85; P  = 0.01) and locally advanced disease at RC (HR 1.92; 95% CI 1.06 to 3.46; P  = 0.03) are independent risk factors for worse CSS in patients experiencing recurrence after RC. In a risk stratification model, patients were assigned to one of two groups based on liver metastasis and locally advanced stage. In the high-risk group, which included 68 patients with 1–2 risk factors, CSS was significantly better for patients receiving SC than for those receiving BSC (median survival duration: 9.4 months vs. 2.4 months, P  = 0.005). The therapeutic effect of SC was not related to a history of adjuvant chemotherapy. Conclusions The present study indicated the potential value of 1st-line SC in patients experiencing recurrence after RC even with advanced features, such as liver metastasis after RC and locally advanced disease at RC.

BackgroundNo definitive evidence exists regarding the clinical significance of histologic variants (HV) in upper urinary tract cancer. We investigated the impact of HV on prognosis in patients with upper urinary tract cancer following radical surgery.Patients and methodsWe retrospectively analyzed 451 patients with upper urinary tract cancer who underwent radical nephroureterectomy at six affiliated hospitals from 1990 to 2015. Patients with distant metastatic disease prior to surgery and those who received neoadjuvant chemotherapy were excluded, leaving 441 eligible patients. Patients were classified into two groups: pure urothelial carcinoma (UC) and HV. The clinicopathological variables of each group were examined using Kaplan–Meier plots and proportional Cox hazard ratios (HR) to compare the oncological outcomes between the two groups.ResultsHV included 37 patients (8%). Compared with the pure UC patients, HV patients had significantly worse recurrence-free survival (RFS) and cancer-specific survival (CSS; RFS p = 0.0002, CSS p = 0.0001). Multivariate analysis for RFS revealed HV were independent predictors (HR 1.92; p = 0.026), but the association did not remain significant for CSS. There was no significant difference in CSS between the adjuvant chemotherapy (AC) group and the non-AC group for all HV patients, except in patients with ≥ pT3 tumor or positive lymph node status where the AC group had significantly favorable CSS.ConclusionsHV in upper urinary tract cancer are independent predictors for RFS, but not for CSS. AC improved CSS for HV patients with ≥ pT3 tumor or positive lymph node status.