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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. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the prognostic role of C-reactive protein in patients with advanced renal cell carcinoma treated with sunitinib. Methods: A total of 41 consecutive patients with advanced clear-cell renal cell carcinoma treated with sunitinib between December 2008 and August 2011 were included in this study. Logistic regression analysis estimated the relative importance of non-tumor variables, including C-reactive protein, and selected adverse events as predictive factors for sunitinib responses. Results: Overall, 11 patients (26.8%) showed a partial response and 10 patients (24.4%) had stable disease. On univariate analysis, Memorial Sloan-Kettering Cancer Center non-poor risk, normal C-reactive protein, hand-foot skin reaction, altered taste, fatigue and leukopenia were significantly correlated with objective responses ( P = 0.020, 0.001, 0.006, 0.006, 0.023 and 0.037, respectively). On multivariate analysis, normal C-reactive protein was independently associated with objective response ( P = 0.016). Patients with a normal level of C-reactive protein (≤0.30 mg/dL) had a significantly higher partial response plus stable disease rate (84.6% vs 35.7%, P = 0.002) and significantly longer progression-free survival (median 19.0 vs 6.0 months, P = 0.036) than patients with an elevated level of C-reactive protein. Conclusions: C-reactive protein is an independent prognostic indicator for patients with advanced renal cell carcinoma treated with sunitinib. [ABSTRACT FROM AUTHOR]

Objectives: Although the tumor, node, metastasis (TNM) staging classification of renal cell carcinoma (RCC) was last modified in 2002, pT3 staging has continued to be debated. It has been suggested that direct adrenal gland involvement and pT3b with pT3a should be reclassified. This study accordingly explores reclassification of the current 2002 TNM staging in pT3 RCCs. Methods: A total of 111 patients with pT3 RCC who underwent radical nephrectomy at our institution between March 1972 and February 2006 were enrolled in this study. Histological samples were reviewed by a single pathologist. Disease-specific survival was compared according to reclassification as pT3a with perirenal fat involvement only (pT3a-fat), pT3a with adrenal gland involvement (pT3a-ad), pT3b without pT3a factors (pT3b-only), pT3b with pT3a factors (pT3b with pT3a), or pT3c. Results: Seven patients were identified as having pT3a-ad and 20 patients as having pT3b with pT3a. The mean disease-specific survival times in pT3a-fat and pT3b-only were significantly longer: 124.1 ± 13.2 (SE) months and 70.9 ± 9.1 (SE) months, respectively, compared with 24.7 ± 6.7 (SE) months in pT3a-ad ( P = 0.0004 and 0.0010, respectively), and 25.0 ± 4.4 (SE) months in pT3b with pT3a ( P = 0.0009 and 0.0032, respectively). On multivariate analysis, the presence of direct ipsilateral adrenal gland involvement was recognized as a predictor of poor prognosis ( P = 0.0331). Conclusions: Direct ipsilateral adrenal gland involvement for patients with pT3a, and perirenal fat or adrenal gland involvement for patients with pT3b should be reclassified nearly to pT4. [ABSTRACT FROM AUTHOR]

OBJECTIVES To evaluate maximum tumour length (MTL) in biopsy cores as a predictor of prostate-specific antigen (PSA)-failure, systemic failure, and death from prostate cancer after radical prostatectomy (RP). PATIENTS AND METHODS We assessed 209 men with clinically localized prostate cancer treated with RP; preoperative variables were correlated with unfavourable pathological characteristics in the RP specimens and with outcome after surgery, using univariate and multivariate analysis. RESULTS The median (range) MTL was 4 (0.2–19) mm and correlated with adverse pathological findings, including specimen Gleason score ( P = 0.003), pT3 ( P < 0.001), seminal vesicle invasion ( P < 0.001) and lymph node involvement ( P = 0.019) in multivariate analysis. Preoperative PSA ( P < 0.001), biopsy Gleason score ( P = 0.002), and MTL ( P = 0.045) were independent predictors of PSA failure, whereas only MTL remained a predictor of systemic-failure ( P < 0.001) and death from prostate cancer ( P = 0.004). The median (range) follow-up after surgery was 90 (17–152) months, during which 83 patients had PSA failure, 20 developed systemic failure and 15 died from prostate cancer. CONCLUSIONS The MTL correlates well with adverse pathological findings and appears to be an independent predictor of outcome after RP. Patients with a greater MTL might have cancer with an aggressive phenotype and therefore be candidates for more aggressive therapies. [ABSTRACT FROM AUTHOR]

Simple Summary: Unfavorable results following radical cystectomy for bladder cancer (BCa) highlights a critical need for a novel prognostic molecular biomarker with potential therapeutic benefits. In the present study, the expression levels of AHNAK2 in specimens obtained by radical cystectomy were classified as "low expression" or "high expression" by immunohistochemical staining. Then, we retrospectively evaluated associations between the two AHNAK2 expression patterns and the prognoses in terms of recurrence-free survival (RFS) and cancer-specific survival (CSS). Our multivariate analysis, adjusting for the effects of clinicopathological features, showed that the high expression level of AHNAK2 was an independent risk factor for RFS and CSS. The present study showed that AHNAK2 acts as a novel prognostic biomarker in patients with radical cystectomy for BCa. Data regarding expression levels of AHNAK2 in bladder cancer (BCa) have been very scarce. We retrospectively reviewed clinical data including clinicopathological features in 120 patients who underwent radical cystectomy (RC) for BCa. The expression levels of AHNAK2 in the specimens obtained by RC were classified as low expression (LE) or high expression (HE) by immunohistochemical staining. Statistical analyses were performed to compare associations between the two AHNAK2 expression patterns and the prognoses in terms of recurrence-free survival (RFS) and cancer-specific survival (CSS). A Kaplan–Meier analysis showed that patients with HE had a significantly worse RFS and CSS than those with LE (hazard ratio [HR]: 1.78, 95% confidence interval [CI]: 1.02–2.98, p = 0.027 and HR: 1.91, 95% CI: 1.08–3.38, p = 0.023, respectively). In a multivariate analysis, independent risk factors for worse RFS and CSS were shown as HE (HR: 1.96, 95% CI: 1.08–3.53, p = 0.026 and HR: 2.22, 95% CI: 1.14–4.31, p = 0.019, respectively) and lymph node metastasis (HR: 2.04, 95% CI: 1.09–3.84, p = 0.026 and HR: 1.19, 95% CI: 1.25–4.97, p = 0.009, respectively). The present study showed that AHNAK2 acts as a novel prognostic biomarker in patients with RC for BCa. [ABSTRACT FROM AUTHOR]

Purpose: To report results from our phase I dose-escalation study of stereotactic body radiotherapy (SBRT) using 4 fractions for patients with localized prostate cancer.Materials& Methods: Fraction sizes of 8 Gy, 8.5 Gy, and 9 Gy were defined as levels 1, 2, and 3. The prescribed dose was delivered to at least 95% of the planning target volume. Image-guided, intensity-modulated radiotherapy was delivered to all patients. Dose-limiting toxicity (DLT) was defined as acute toxicity of Grade 3 or higher. The maximum tolerated dose (MTD) was defined as the level at which ≥30% of patients showed DLT. The recommended dose (RD) was defined to be one dose level below the MTD. If no patients at level 3 showed DLT, level 3 was defined as the recommended dose (RD).Results: Nine patients were enrolled in each level. All patients were low or intermediate risk. Median durations of follow-up for patients at levels 1-3 were 48.9 months, 42.6 months, and 18.4 months, respectively. Protocol treatment was completed for all patients. No patient showed DLT at each dose level. Level 3 was therefore designated as the RD for the phase II study. Although most toxicities were Grade 1, genitourinary toxicity was common compared to gastrointestinal toxicity. Three-year biochemical control rate was 90.3%.Conclusion: The dose level of 36 Gy in 4 fractions with a 2-day break was tolerable and highly encouraging for SBRT of localized prostate cancer. The phase II trial to confirm the efficacy and toxicity of this treatment is now on going.Trial Registration: UMIN, UMIN000010236 . Registered 13 March 2013. [ABSTRACT FROM AUTHOR]

Objective: We sought to identify heterogeneous nuclear ribonucleoprotein A3 (HNRNPA3) expression in bladder cancer and its relationship to clinicopathological findings and prognosis.Methods: Immunohistochemical staining for HNRNPA3 was performed on 122 archived radical cystectomy specimens, with immunoreactivity being stratified on a 0 to 3 scale. The percentage of HNRNPA3 expressing tumor cells was calculated and multiplied by the staining score over an average of 5 areas to obtain a semiquantitative H-score (maximum value: 300). HNRNPA3 expression was categorized as high (≥80) or low (<80).Results: The patients' median age was 70 years, and the median follow-up period was 39.4 months. High HNRNPA3 expression was significantly associated with lymph node metastasis (P= 0.014) and S100A8, S100A9 and uroplakin III expression (P= 0.028, 0.002, and 0.047, respectively). Log-rank tests indicated that high HNRNPA3 expression was significantly associated with disease progression and cancer-specific death (P= 0.013 and 0.006, respectively). In the Cox proportional hazards regression analysis, only lymph node metastasis was associated with disease progression and cancer-specific survival.Conclusion: HNRNPA3 may be a new biomarker to predict biologically aggressive cancers and determine the appropriate treatment modality in patients after radical cystectomy. [ABSTRACT FROM AUTHOR]

Objectives: Checkpoint inhibitors have led to a paradigm shift in urothelial carcinoma (UC) treatment. However, the relationship between PD-L1 expression status and oncological outcomes in UC patients remains uncertain. Here, we investigated the prognostic value of PD-L1 expression status in patients with UC of the bladder (UCB) who underwent radical cystectomy (RC).Materials and Methods: We retrospectively analyzed pathological specimens from 97 UCB patients treated with RC from 1990 to 2015 at Kitasato University Hospital. Immunohistochemical staining using SP263 was performed to evaluate PD-L1 expression in tumor cells (TCs) and tumor-infiltrating lymphocytes (TILs). Kaplan-Meier plots and proportional Cox hazard ratios were examined to assess the relationship between PD-L1 expression and clinicopathological parameters and survival outcomes.Results: Of the 97 specimens, 19.5% contained PD-L1-positive TCs, and 35.0% contained PD-L1-positive TILs. Regarding clinicopathological factors, PD-L1-positive TCs and TILs were significantly associated with high-grade tumors (TCs, P = 0.01; TILs, P = 0.003). Kaplan-Meier analyses showed that PD-L1-positive TCs were not correlated with survival rates. However, PD-L1-positive TILs were significantly associated with better recurrence-free survival (RFS; P = 0.03) and better cancer-specific survival (CSS; P = 0.02). Univariate analysis, but not multivariate analysis, CSS indicated that PD-L1-positive TILs were significant predictors of patient prognoses. Multivariate analysis showed that PD-L1-positive TILs independently predicted CSS in patients without lymph node metastasis (pN0).Conclusion: Positive PD-L1 expression is associated with high-grade tumors. PD-L1-positive TILs are independent predictors of favorable survival outcomes in surgically resected UCB patients at stage pN0. [ABSTRACT FROM AUTHOR]