Collagen type 4 alpha 1 (COL4A1) and collagen type 13 alpha 1 (COL13A1) produced by urothelial cancer cells support the vital oncogenic property of tumor invasion. We investigated the diagnostic and prognostic capability of COL4A1 and COL13A1 in voided urine and compared the observed values with those of fragments of cytokeratin‐19 (CYFRA21‐1), nuclear matrix protein 22 (NMP‐22), and voided urine cytology in bladder cancer (BCa). We collected voided urine samples from 154 patients newly diagnosed with BCa, before surgery and from 61 control subjects. Protein levels of COL4A1, COL13A1, CYFRA21‐1, and NMP‐22 in urine supernatants were measured using enzyme‐linked immunosorbent assays. Diagnostic performance and optimal cut‐off values were determined by receiver operating characteristic analysis. Urine levels of COL4A1, COL13A1, the combined values of COL4A1 and COL13A1 (COL4A1 + COL13A1), and CYFRA21‐1 were significantly elevated in urine from patients with BCa compared to the controls. Among these biomarkers, the optimal cut‐off value of COL4A1 + COL13A1 at 1.33 ng/mL resulted in 57.4%, 83.7%, 56.1%, 80.7%, and 91.7% sensitivity for low‐grade tumors, high‐grade tumors, Ta, T1, and muscle invasive disease, respectively. We evaluated the prognostic value of preoperative urine levels in 130 non‐muscle invasive BCa samples after the initial transurethral surgery. A high urinary COL4A1 + COL13A1 was found to be an independent risk factor for intravesical recurrence. Although these data need to be externally validated, urinary COL4A1 and COL13A1 could be a potential diagnostic and prognostic biomarker for BCa. This easy‐to‐use urinary signature identifies a subgroup of patients with a high probability of recurrence and progression in non‐muscle invasive and muscle invasive BCa.

HighlightsPatients who received BT experienced acute urinary morbidity 3 months after BT of the prostate.Acute urinary symptoms gradually improved with time and returned to BL at 36 months.Storage symptoms take longer to return to BL compared with voiding symptoms.

Alpha-Klotho (KLα) and beta-Klotho (KLβ) have recently been reported to correlate with cancer prognosis in some malignancies and we previously reported the association between KLα, KLβ, and urothelial carcinoma of the bladder (UCB), indicating that KLβ acts as a tumor promoter. However, the association between gamma-Klotho (KLγ) and cancer prognosis remains unclear. In the present study, we evaluated the association between KLγ and UCB. To evaluate the effect of KLγ on human bladder cancer cell lines in vitro assays were performed. Exogenous KLγ increased the ability of human bladder cancer cells to proliferate, migrate, invade, form colonies, and provide anchorage-independent growth potential. In in vivo assays, eighteen mice bearing xenografts inoculated using UM-UC-3, were randomly divided into three groups and treated with a small interfering RNA (siRNA) by intratumoral administration once a week for four weeks. Knockdown of KLγ with siRNA led to a dramatic change in tumor growth and suggested that KLγ had effects on tumor growth, including promotion of cell proliferation, inhibition of apoptosis, and enhancement of the epithelial-mesenchymal transition. To confirm the study, human tissue samples were used and patients were divided into two groups according to KLγ expression level. High expression of KLγ was significantly associated with higher stage and grade cancer and the presence of lymphovascular invasion compared to patients with lower expression of KLγ. Our results suggest that KLγ plays an important role in tumor invasion and progression and these results may lead to the development of new therapies and diagnostic methods for UCB.

To evaluate trends in risk classification at diagnosis and choice of primary therapy in patients diagnosed with prostate cancer. Methods: This retrospective study included 10 839 patients who were newly diagnosed with prostate cancer between 2004 and 2015 at 23 Japanese institutions. Risk classification and primary therapies between 2004 and 2015 were evaluated. The trends in risk classification and primary therapy were evaluated using chi-squared tests for trend during four periods (2004-2006; 2007-2009; 2010-2012; and 2013-2015). Binary logistic analysis was used to evaluate the extent to which factors such as age, risk classification, and institution influenced primary therapy choice in the 2013-2015 cohort.Results: The number of patients with very-low or low-risk classification (P < 0.001) and metastasis (P = 0.04) decreased and the number with intermediate-risk classification (P < 0.001) increased during the four periods. A tendency to choose radical prostatectomy as primary therapy for prostate cancer was not observed during the four periods (P = 0.90). The number of patients who chose radiation therapy (P < 0.001) and active surveillance/watchful waiting (P < 0.001) as primary therapies increased during the four periods and the number of patients who chose androgen deprivation therapy (P < 0.001) decreased. Age, institution, and risk classification significantly influenced primary therapy choice. Conclusions: We have shown the trends in risk classification of prostate cancer and primary therapy choices between 2004 and 2015 in Japan. Age, institution, and risk classification significantly influenced the decision on primary therapy for prostate cancer.

We aimed to determine the oncological outcomes of patients with clinical T1 renal cell carcinoma (RCC) upstaged to pathological T3a and to identify the preoperative predictive factors for upstaging. We retrospectively reviewed 272 patients with clinical T1 RCC who underwent surgical treatment. Thirty-three patients (12%) were upstaged to pathological T3a. These patients had a significantly larger tumor size on computed tomography (p < 0.0001), a higher aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio (p = 0.037), and an elevated c-reactive protein (CRP) level (p = 0.014) preoperatively compared with those with pathological T1 RCC. On multivariate analysis, tumor diameter was the only significant preoperative predictive factor for upstaging [hazard ratio (HR), 3.61; 95% confidence interval (CI), 1.32–9.84; p = 0.01]. The AST/ALT ratio tended to be a preoperative predictive factor for upstaging, although it was not significant (HR, 2.14; 95% CI, 0.97–4.73; p = 0.06). Pathological T3a upstaging occurred in 25% of those with a tumor diameter ≥30 mm and a preoperative AST/ALT ratio ≥1.1. There was a significant correlation between pathological T3a upstaging and the number of preoperative risk factors (p = 0.0002). The preoperative tumor diameter and serum AST/ALT ratio can be predictive factors for pathological T3a upstaging in patients with clinical T1 RCC.