A meta-analysis on the characteristics of placebo effects on urinary function in placebo-controlled clinical trials among Japanese patients.

OBJECTIVES: This study aimed to assess the effect sizes, changes over time, and ethnic differences in placebo effects on urinary function among Japanese patients participating in clinical trials. METHODS: A meta-analysis of 30 Japanese placebo-controlled clinical trials was conducted to determine the placebo effects on three functions: daily urinary frequency, nocturnal urinary frequency, and average urine volume per void. RESULTS: The I-square heterogeneity values for the basic values of the three functions ranged from 84.5% to 97.9%, with differences among trials. Longitudinal analysis (1 to 12 weeks) indicated an enhanced placebo effect for up to 8 weeks and no consistency among trials on nocturnal urinary frequency (p < 0.01), unlike those on daily urinary frequency and average urine volume per void (p = 1.0). Based on the random-effects model, the mean differences in urinary frequency at 4, 8, and 12 weeks were -0.70 (-0.80; -0.60), -1.06 (-1.16; -0.96), and -1.18 (-1.34; -1.01), respectively. Furthermore, the mean difference (95% confidence interval) in nocturnal urinary frequency and volume of urination per void at 12 weeks was -0.63 (-0.94; -0.31) and 9.67 (7.25; 12.1), respectively. CONCLUSIONS: My findings suggest an increase in the strength of placebo effects over time (up to 8 weeks). A comparison of my results to those published in previous global reports showed no meaningful differences in placebo effects among ethnic groups. The consistent placebo effect size on urinary function could be an external indicator in clinical trials.

Heterogeneity of placebo effects on urinary incontinence in overactive bladder syndrome: A meta-analysis of Japanese placebo-controlled clinical trials.

OBJECTIVES: The effect sizes, changes over time, and heterogeneity of placebo effects on frequency of urination for voiding disorders in Japanese clinical trials have been published. This study evaluated the characteristics of placebo effects on overall and urge incontinence in overactive bladder patients. METHODS: A meta-analysis of Japanese placebo-controlled clinical trials was conducted to determine placebo effects on the daily frequency of overall (n = 16) and urge (n = 11) incontinence and identify factors that should be considered in clinical trials. RESULTS: The between-study heterogeneity variance of placebo effects for overall and urge incontinence at 8 weeks was estimated as I2 = 70.3% and 64.2%, and the prediction interval for the ratio of means ranged from g = 0.31-0.91 and 0.32-0.81, respectively. Subgroup analysis using the random-effects model showed placebo effects in overall incontinence (p = 0.08) and urge incontinence (p < 0.0001). The ratio of means (95% confidence interval) of urge incontinence frequency from baseline to 4 (n = 10), 8 (n = 10), and 12 (n = 7) weeks were 0.65 (0.57, 0.74), 0.51 (0.42, 0.62), and 0.48 (0.36, 0.64), respectively, for the random-effects model. Regression analysis did not reveal any significant factors that influenced placebo effects. CONCLUSIONS: This meta-analysis confirmed the characterization of placebo effects on overall and urge incontinence, which demonstrates heterogeneity between trials. The impact of population, follow-up period, and endpoints on placebo effects should be considered when designing clinical trials for overactive bladder syndrome.

Oncological outcomes of a multicenter cohort treated with axitinib for metastatic renal cell carcinoma.

The present study aimed to evaluate the efficacy of the real-world use of axitinib and to develop a prognostic model for stratifying patients who could derive long-term benefit from axitinib. This was a retrospective, descriptive study evaluating the efficacy of axitinib in patients with metastatic renal cell carcinoma that had been treated with 1 or 2 systemic antiangiogenic therapy regimens at 1 of 36 hospitals belonging to the Japan Urologic Oncology Group between January 2012 and February 2019. The primary outcome was overall survival (OS). Using a split-sample method, candidate variables that exhibited significant relationships with OS were chosen to create a model. The new model was validated using the rest of the cohort. In total, 485 patients were enrolled. The median OS was 34 months in the entire study population, whereas it was not reached, 27 months, and 14 months in the favorable, intermediate, and poor risk groups, respectively, according to the new risk classification model. The following 4 variables were included in the final risk model: the disease stage at diagnosis, number of metastatic sites at the start of axitinib therapy, serum albumin level, and neutrophil : lymphocyte ratio. The adjusted area under the curve values of the new model at 12, 36, and 60 months were 0.77, 0.82, and 0.82, respectively. The efficacy of axitinib in routine practice is comparable or even superior to that reported previously. The patients in the new model's favorable risk group might derive a long-term survival benefit from axitinib treatment.

Nodule Size After Chemotherapy and Primary-Tumor Teratoma Components Predict Malignancy of Residual Pulmonary Nodules in Metastatic Nonseminomatous Germ Cell Tumor.

BACKGROUND: The treatment goal for visceral metastatic nonseminomatous germ cell tumor (NSGCT) is to remove any residual teratoma or viable NSGCT after chemotherapy. However, this provides no therapeutic benefit to patients whose metastases necrotize on their own. This study therefore analyzed NSGCTs with pulmonary metastases to determine preoperative factors that predict necrosis and could help identify patients who might be treated with monitoring rather than surgery. METHODS: The study retrospectively analyzed 41 patients (135 metastatic pulmonary nodules) treated from 1997 to 2016 for NSGCT who showed tumor marker normalization after chemotherapy. Relationships between clinicopathologic characteristics and necrosis in resected pulmonary specimens were analyzed. RESULTS: Receiver operating characteristic analysis of the pulmonary nodules showed 9 mm to be the optimal cutoff length for predicting necrosis. The logistic regression model showed that absence of teratoma components in the primary tumor and all pulmonary nodules shorter than 10 mm after chemotherapy both were independent predictors of pathologic necrosis in pulmonary specimens. No patients experienced late recurrence (i.e., > 2 years afterward). CONCLUSIONS: The presence of teratoma components in primary tumors and nodular size after chemotherapy predict the pathology of residual pulmonary nodules. Patients whose residual nodules all are shorter than 10 mm and who have no primary-tumor teratoma components might be candidates for careful monitoring before pulmonary resection.

Impact of lymph node dissection on clinical outcomes during nephroureterectomy in patients with clinically node-negative upper urinary tract urothelial cancer: subanalysis of a multi-institutional nationwide case series of the Japanese Urological Association.

OBJECTIVE: To evaluate the impact of lymph node dissection (LND) on the clinical outcomes during radical nephroureterectomy (RNU) in patients with clinically node-negative upper urinary tract urothelial cancer (UTUC). METHODS: Within the nationwide case series of the Japanese Urological Association, which comprises 1509 patients with UTUC diagnosed in 2005, we identified 823 patients with clinically node-negative UTUC who underwent RNU. The extent of limited LND was defined as the renal hilar region only for renal pelvic cancer and as either the pelvic region or para-aortic/paracaval region only for ureteral cancer, while the extent of wider LND was defined as at least one perilesional LND region in addition to limited LND. Multivariate analysis with a Cox regression hazard model was used to evaluate the survival benefit. RESULTS: Among the 823 patients, LND was performed in 197 (23.9%) patients, and 26 (13.2%) of them had pathologically node-positive disease. Of 197 patients who underwent LND, limited and wider LND was performed in 119 (60.4%) and 78 (39.6%) patients, respectively. Patients with node-positive disease showed significantly shorter overall survival than those with node-negative disease. No LND-associated survival improvement was observed in a direct comparison between patients with and without LND. In addition, limited or wider LND was not associated with overall survival or cancer-specific survival. CONCLUSIONS: The therapeutic benefit obtained by LND remains unclear regardless of the extent of LND, although LND has diagnostic value with respect to the prediction of a poor prognosis especially in patients with clinically muscle-invasive disease.

Active heavy cigarette smoking is associated with poor survival in Japanese patients with advanced renal cell carcinoma: sub-analysis of the multi-institutional national database of the Japanese Urological Association.

OBJECTIVE: The association between cigarette smoking and survival in patients with renal cell carcinoma is not well studied. We examined the impact of cigarette smoking on survival of patients with advanced renal cell carcinoma using the multi-institutional national database of the Japanese Urological Association. METHODS: From 340 Japanese institutions, 963 patients with renal cell carcinoma of clinical Stage 3 or higher were analyzed. Univariate analysis using the Kaplan-Meier method and multivariate Cox regression models with stepwise selection was used to evaluate overall and cause-specific survival. RESULTS: Median duration of follow-up was 842 days, and overall and cancer death occurred in 392 (40.7%) and 351 (36.4%) patients, respectively. In multivariate analysis, smoking 20 or more cigarettes daily at diagnosis was associated with poorer overall and cancer-specific survival, especially in Stage 3. According to a Cox proportional hazards model, heavy cigarette smoking at diagnosis and the variables of underweight, fever symptoms, serum lactic dehydrogenase value, serum C-reactive protein value, serum creatinine value, Eastern Cooperative Oncology Group performance status, nephrectomy and clinical stage were significant (P < 0.05) for overall and cancer-specific survival. CONCLUSIONS: We could compare the smoking status at diagnosis and the prognosis of renal cell carcinoma at national wide scale. Heavy active smoking was an independent prognostic factor for overall and cancer-specific survival in patients with advanced renal cell carcinoma, especially in Stage 3.

Diversity in treatment modalities of Stage II/III urothelial cancer in Japan: sub-analysis of the multi-institutional national database of the Japanese Urological Association.

OBJECTIVE: We aimed to survey treatment modalities for the patients with Stage II/III urothelial cancer in Japan. METHODS: We used the multi-institutional national database of the Japanese Urological Association from 348 Japanese institutions, in which a total of 3707 patients with muscle-invasive bladder cancer and 1538 with upper urinary tract urothelial carcinoma were registered in 2008 and 2011, respectively. Primary treatment was classified as surgery alone, surgery with chemotherapy, surgery with radiation, radiation alone, chemotherapy alone, combination of radiation and chemotherapy and observation. Overall and cancer-specific survivals were examined using the Kaplan-Meier method, and survival in the subgroups was analyzed using the log-rank test. RESULTS: In Stage II/III bladder cancer patients, 49.7% of those were treated with radical operation and 22.3% received observation only. A total 97.2% of Stage II/III upper urinary tract urothelial carcinoma patients treated with radical surgery. A total 30.4% of Stage II/III bladder cancer patients received chemotherapy. Majority of the patients received cisplatin-based regimen, however, regimens of chemotherapy was rich in variety up to 13 regimens. Chemotherapy regimens for the patients with upper urinary tract urothelial carcinoma were also various up to eight regimens. Overall and cancer-specific survivals were statistically significantly stratified according to the clinical stage. The upper urinary tract urothelial carcinoma patients diagnosed with clinical stage T3 had significantly poor prognosis compared with those diagnosed with clinical stage T2. CONCLUSIONS: This study demonstrated the variety of treatments used for Japanese patients with Stage II/III urothelial cancer. Treatment standardization for these entities may be necessary.

Impact of multimodal treatment on prognosis for patients with metastatic upper urinary tract urothelial cancer: Subanalysis of the multi-institutional nationwide case series study of the Japanese Urological Association.

OBJECTIVES: To describe the nature of metastatic upper urinary tract urothelial cancer and determine the prognostic predictors or treatment modality associated with all-cause mortality. METHODS: Within the nationwide case series study of the Japanese Urological Association, consisting of 1509 patients with urinary tract urothelial cancer diagnosed in 2005, we identified 102 patients with metastatic urinary tract urothelial cancer. Univariate and multivariate survival analyses identified prognostic outcome variables. RESULTS: Predominant sites of distant metastasis at diagnosis were the lungs (54.9%), distant lymph nodes (37.3%), bone (32.4%) and liver (19.6%). Of 102 patients, 70 patients (68.6%) died during the median follow-up period of 6 months, and the 2-year overall survival rate was estimated at 22%. The median survival time to all-cause mortality was 8.5 months (95% confidence interval 6.4-10.7 months). On multivariate analysis, independent predictive factors for all-cause mortality were age (hazard ratio 2.36, P = 0.015) and liver metastasis (hazard ratio 2.35, P = 0.037). Patients who received multimodal treatment including chemotherapy and surgery showed significantly better prognosis (median survival time 25.8 months) compared with patients treated with chemotherapy alone (median survival time 7.3 months) or best supportive care (median survival time 4.3 months). CONCLUSIONS: Age at diagnosis and the presence of liver metastasis seem to have an impact on survival of metastatic urinary tract urothelial cancer patients. Multimodal treatment including systemic chemotherapy and surgery might result in better prognosis in some of these patients.

Tumour multifocality and grade predict intravesical recurrence after nephroureterectomy in patients with upper urinary tract urothelial carcinoma without a history of bladder cancer.

OBJECTIVE: Patients with upper urinary tract urothelial carcinoma (UUT-UC) without a history of bladder cancer have a different natural history of intravesical recurrence after nephroureterectomy compared with those with a history of bladder cancer. The aim of this study was to identify predictive factors for post-operative intravesical recurrence in patients with non-metastatic upper urinary tract-localized urothelial carcinoma without a history of bladder cancer and who were not taking medication during the perioperative period. METHODS: This retrospective study included 133 patients who were treated between 1995 and 2012. Univariate and multivariate analyses were used to evaluate the clinical and pathological factors associated with the cumulative incidence of bladder cancer. RESULTS: Of the 133 patients, 51 (38.3%) developed intravesical recurrence during a median follow-up of 71 months (range, 0.8-210.8). In the multivariate analysis, multifocality (P = 0.03) and high tumour grade (P = 0.007) were significantly associated with the cumulative incidence of bladder cancer. We constructed a prediction classification model on the basis of the total number of risk factors. The 2-year cumulative incidence rates were 5.6, 34.8 and 50.0% in individuals with no, one and two risk factors, respectively. There was a significant difference between patients with no risk factors and those with two risk factors (P = 0.01). CONCLUSIONS: Although this retrospective study had several limitations, tumour multifocality and tumour grade were found to be potential risk factors for intravesical recurrence in our cases.

Prognostic factors of recurrent disease in upper urinary tract urothelial cancer after radical nephroureterectomy: Subanalysis of the multi-institutional national database of the Japanese Urological Association.

OBJECTIVES: To explore predictive factors of disease recurrence after radical nephroureterectomy in patients with upper urinary tract urothelial cancer. METHODS: A multi-institutional national database promoted by the Japanese Urological Association including 293 institutions and 1172 patients was used for the present study. Patient with non-metastatic upper urinary tract urothelial cancer who underwent primary radical nephroureterectomy with curative intent were analyzed. Univariate analysis using the Kaplan-Meier method and multivariate Cox regression models with stepwise selection was used to evaluate time to recurrence after surgery. RESULTS: The median duration of follow up was 55.8 months, and disease recurred in 325 (27.7%) patients at a median of 11.4 months after radical nephroureterectomy. According to a Cox proportional hazards model, the Union International Contre le Cancer 2002 pathological stage of the primary tumor, lymph node status, presence of lymphatic and/or vascular invasion, infiltrative growth pattern, and age were independent predictors (P < 0.05) of recurrence-free survival. CONCLUSIONS: Despite several limitations, our analysis suggests that pathological tumor stage, lymph node status, lymphovascular invasion, infiltrative growth pattern and age represent important prognostic variables after radical nephroureterectomy in Japanese patients with upper urinary tract urothelial cancer. This information could be potentially used to select patients for adjuvant systemic therapy.

Impact of smoking on the age at diagnosis of upper tract urothelial carcinoma: Subanalysis of the Japanese Urological Association multi-institutional national database.

OBJECTIVES: To examine the influence of smoking history on the diagnosis and other tumor characteristics of upper tract urothelial carcinoma in Japan. METHODS: A total of 1509 patients with upper tract urothelial carcinoma who were diagnosed in 2005 from 348 Japanese institutions were registered using the multi-institutional national database of the Japanese Urological Association and included in this analysis. Clinical data of the patients were collected in 2011. The associations between the patients' self-reported smoking history and their age at the diagnosis of upper tract urothelial carcinoma, sex, pathological T stage and tumor grade were analyzed. RESULTS: The mean age at the diagnosis of upper tract urothelial carcinoma was approximately 5 years earlier for the 238 current smokers than for the 618 current non-smokers (P < 0.0001). Similar associations between smoking and the early diagnosis of upper tract urothelial carcinoma were shown in the sex subgroups and in subgroups stratified by pathological T stages. Among the current smokers, the age at diagnosis for the smoking ≥ 20 cigarettes per day group was 6.5 years lower than that of the < 20 cigarettes per day group, which was significantly different (P < 0.0001). CONCLUSION: Current smoking is a significant risk factor for the earlier diagnosis of upper tract urothelial carcinoma. The finding is important from the perspective of both healthcare and medical economies.

Metastatic Sites in Rare Genitourinary Malignancies and Primary Cancer Sites in Genitourinary Organ Metastases: A Secondary Analysis Using the Japanese Pathological Autopsy Registry Database.

Background: The epidemiology of metastases from rare genitourinary cancer and metastases to genitourinary organs from other primary neoplasms remains poorly understood. Objective: To investigate the epidemiology of rare genitourinary metastases from rare genitourinary organ-type cancer and to genitourinary organs using data from a large national autopsy registry in Japan. Design setting and participants: A secondary analysis of the data reported in the Annual of the Pathological Autopsy Cases in Japan and the Japanese Mortality Database from 1993 to 2020 was performed. Outcome measurements and statistical analysis: Via a retrospective epidemiologic analysis, we evaluated the frequency (probability of occurrence [number per person]) and proportion (percentage) of metastases from upper urinary tract, adrenal, testicular, urethral, and penile cancers. Moreover, the sites of primary tumors metastasizing to genitourinary organs were examined. Results and limitations: In Japan, the mortality rate of upper urinary tract cancer is increasing rapidly. In the integrated database with 365 099 autopsies and 835 959 metastatic organs, the major metastatic sites (range of frequency ratios) of rare genitourinary organ-type cancers were the lungs (0.38-0.47), liver (0.21-0.56), bone (0.16-0.33), adrenal gland (0.10-0.20), peritoneum (0.0-0.16), and kidneys (0.07-0.22). The major primary sites (range of proportions) of genitourinary organ metastases were the respiratory tract (5.6-34.0%), stomach (4.7-27.0%), hematologic site (0.9-24.9%), lymphoid (2.4-22.2%), bladder (0.8-20.0%), prostate (0.7-14.1%), rectal (2.0-11.7%), and pancreas (2.6-11.0%). The cancers with a high likelihood of genitourinary metastasis were respiratory and stomach cancers. However, the study lacked individual-level information, and there might be a concomitant selection bias in this autopsy study. Conclusions: This large-scale autopsy database analysis identified the epidemiology of metastasis from rare genitourinary organ-type cancer and the origins of metastasis to genitourinary organs. Patient summary: This study provides valuable metastatic epidemiologic data and clinical information that are fundamental to the mechanisms of genitourinary metastasis.

Prognostic risk stratification of patients with urothelial carcinoma of the bladder with recurrence after radical cystectomy.

PURPOSE: We identify clinicopathological variables predicting overall survival in patients with recurrent bladder urothelial carcinoma after radical cystectomy. MATERIALS AND METHODS: We retrospectively collected data on 114 patients treated with radical cystectomy for bladder urothelial carcinoma who subsequently had remote metastasis and/or local recurrence. The Kaplan-Meier method with the log rank test and multivariate Cox regression models were used to address overall survival after recurrence. RESULTS: During followup 99 of the 114 patients died. Median survival in the 114 patients was 11.2 months. One and 3-year overall survival rates were 48.0% and 12.1%, respectively. On multivariate analysis independent predictors of poorer overall survival included less than 1 year to recurrence, symptoms at recurrence, 2 or more metastatic organs at recurrence, high serum C-reactive protein, high lactate dehydrogenase, no post-recurrence platinum based chemotherapy and no metastasectomy. Based on the 4 variables (time to recurrence, symptoms, number of metastatic organs and C-reactive protein), we constructed a risk model predicting post-recurrence overall survival that classified patients into 3 groups with significantly different overall survival (p <0.0001). CONCLUSIONS: Our data confirm that recurrent urothelial carcinoma after radical cystectomy is a highly aggressive, lethal disease. Seven clinicopathological factors were identified that predicted post-recurrence overall survival. Our risk model based on the 4 variables could be useful to provide relevant prognostic information to patients and physicians, and better stratify patients in clinical trials.

Ability of preoperative 3.0-Tesla magnetic resonance imaging to predict the absence of side-specific extracapsular extension of prostate cancer.

OBJECTIVE: Recent studies have shown an improvement in prostate cancer diagnosis with the use of 3.0-Tesla magnetic resonance imaging. We retrospectively assessed the ability of this imaging technique to predict side-specific extracapsular extension of prostate cancer. METHODS: From October 2007 to August 2011, prostatectomy was carried out in 396 patients after preoperative 3.0-Tesla magnetic resonance imaging. Among these, 132 (primary sample) and 134 patients (validation sample) underwent 12-core prostate biopsy at the National Cancer Center Hospital of Tokyo, Japan, and at other institutions, respectively. In the primary dataset, univariate and multivariate analyses were carried out to predict side-specific extracapsular extension using variables determined preoperatively, including 3.0-Tesla magnetic resonance imaging findings (T2-weighted and diffusion-weighted imaging). A prediction model was then constructed and applied to the validation study sample. RESULTS: Multivariate analysis identified four significant independent predictors (P < 0.05), including a biopsy Gleason score of ≥8, positive 3.0-Tesla diffusion-weighted magnetic resonance imaging findings, ≥2 positive biopsy cores on each side and a maximum percentage of positive cores ≥31% on each side. The negative predictive value was 93.9% in the combination model with these four predictors, meanwhile the positive predictive value was 33.8%. Good reproducibility of these four significant predictors and the combination model was observed in the validation study sample. CONCLUSIONS: The side-specific extracapsular extension prediction by the biopsy Gleason score and factors associated with tumor location, including a positive 3.0-Tesla diffusion-weighted magnetic resonance imaging finding, have a high negative predictive value, but a low positive predictive value.

The CST complex facilitates cell survival under oxidative genotoxic stress.

Genomic DNA is constantly exposed to a variety of genotoxic stresses, and it is crucial for organisms to be equipped with mechanisms for repairing the damaged genome. Previously, it was demonstrated that the mammalian CST (CTC1-STN1-TEN1) complex, which was originally identified as a single-stranded DNA-binding trimeric protein complex essential for telomere maintenance, is required for survival in response to hydroxyurea (HU), which induces DNA replication fork stalling. It is still unclear, however, how the CST complex is involved in the repair of diverse types of DNA damage induced by oxidizing agents such as H2O2. STN1 knockdown (KD) sensitized HeLa cells to high doses of H2O2. While H2O2 induced DNA strand breaks throughout the cell cycle, STN1 KD cells were as resistant as control cells to H2O2 treatment when challenged in the G1 phase of the cell cycle, but they were sensitive when exposed to H2O2 in S/G2/M phase. STN1 KD cells showed a failure of DNA synthesis and RAD51 foci formation upon H2O2 treatment. Chemical inhibition of RAD51 in shSTN1 cells did not exacerbate the sensitivity to H2O2, implying that the CST complex and RAD51 act in the same pathway. Collectively, our results suggest that the CST complex is required for maintaining genomic stability in response to oxidative DNA damage, possibly through RAD51-dependent DNA repair/protection mechanisms.

Efficacy and safety of axitinib for metastatic renal cell carcinoma: Real-world data on patients with renal impairment.

OBJECTIVES: Limited information is currently available on the efficacy and safety of axitinib for metastatic renal cell carcinoma (mRCC) patients with renal impairment. Therefore, the present study investigated the efficacy and toxicity of axitinib in patients with chronic kidney disease. METHODS: Post-hoc analyses were performed on a Japanese multicenter cohort study of 477 mRCC patients who received axitinib followed by 1 or 2 regimens of systemic antiangiogenic therapy between January 2012 and December 2016. Differences in clinical characteristics and the efficacy and safety of axitinib were assessed based on pretreatment renal function. RESULTS: Patients were categorized into the following 5 renal function groups according to baseline renal function: estimated glomerular filtration rate (eGFR) ≥60 ml/min (n = 133), 45 ml/min ≤eGFR <60 ml/min (n = 153), 30 ml/min ≤eGFR< 45 ml/min (n = 130), eGFR <30 ml/min (n = 45), and dialysis (n = 16). Median progression-free survival (PFS) (95% confidence interval [CI]) in the 5 groups was 11 (8-16), 14 (11-19), 14 (10-19), 12 (8-24), and 6 (3-NR) months, respectively (p = 0.781). After adjustments for treatment-related confounders, the renal function group was not a significant prognostic factor for PFS. Objective response rates in the 5 groups were 22%, 23%, 23%, 18%, 20%, and 38%, respectively (p = 0.468). Regarding adverse events of all grades, hypertension (p = 0.0006) and renal and urinary disorders (p < 0.0001) were more frequently observed in the eGFR <30 ml/min group than in the other groups. CONCLUSIONS: Since renal function at the initiation of treatment with axitinib does not adversely affect the efficacy of VEGF-TKI therapy, clinicians do not need to avoid its administration to mRCC patients with impaired renal function in consideration of the risk of progression to end-stage renal disease.

Ki67 and BUBR1 may discriminate clinically insignificant prostate cancer in the PSA range <4 ng/ml.

OBJECTIVE: We aimed to evaluate the Epstein criteria and the eligibility criteria for active surveillance in the Prostate Cancer Research International study by using immunohistochemical staining. METHODS: We reviewed the clinicopathological data of 119 patients who underwent prostate biopsy, with prostate-specific antigen levels being ≤4 ng/ml. The data of patients with detected prostate cancer were compared with those of patients with clinically significant prostate cancer. To discriminate insignificant prostate cancer, immunohistochemical staining for Ki67, p53, bcl-2, BUBR1, PTEN and E-cadherin was performed. RESULTS: Ki67, BUBR1 and E-cadherin staining showed significant correlation with the Gleason score. Ki67 and BUBR1 staining showed significant correlations with the Epstein criteria, and Ki67, BUBR1 and E-cadherin staining correlated with the Gleason score and Prostate Cancer Research International criteria. The sensitivity and specificity of Ki67 or BUBR1 staining in discriminating the prostate cancer cases classified as clinically insignificant according to the Epstein criteria were 62.5 and 84.2%, or 57.1 and 100%, respectively. The sensitivity and specificity of Ki67, BUBR1 or E-cadherin staining in discriminating prostate cancer cases classified as clinically insignificant according to the Prostate Cancer Research International criteria were 75 and 87.5%, 66.7 and 100% or 50 and 100%, respectively. The predictive accuracy of Ki67 and BUBR1 staining was equivalently high in relation to both sets of criteria (77.6 and 83.3%, respectively). CONCLUSIONS: These data could provide pathological evidence to support the suitability of the Epstein and Prostate Cancer Research International criteria. Ki67 and BUBR1 may be potential markers in selecting candidates for active surveillance.

Treatment results of radiotherapy to both the prostate and metastatic sites in patients with bone metastatic prostate cancer.

Although systemic therapy is the standard treatment for metastatic prostate cancer, a randomized controlled trial showed radiotherapy to the prostate improved overall survival of metastatic prostate cancer patients with the low metastatic burden. Additionally, a randomized phase II trial showed that metastasis-directed therapy for oligo-recurrent prostate cancer improved androgen-deprivation therapy (ADT)-free survival. Therefore, administering radiotherapy to both prostate and metastatic regions might result in better outcomes. Thus, we report the treatment results of radiotherapy to both prostate and metastatic regions. Our institutional database was searched for patients who received radiotherapy to the prostate and metastatic regions. We summarized patient characteristics and treatment efficacy and performed statistical analysis to find possible prognostic factors. A total of 35 patients were included in this study. The median age was 66 years, and the median initial prostate-specific antigen (PSA) level was 32 ng/ml. The Gleason score was 7 in 10 patients, 8 in 13 patients, and 9 in 12 patients. The median radiotherapy dose was 72 Gy to the prostate and 50 Gy to the metastatic bone region. The 8-year overall survival, cause-specific survival, progression-free survival, and freedom from biochemical failure rate were 81, 85, 53, and 57%. Among the 35 patients, 12 were disease-free even after ADT was discontinued. In selected patients with metastatic prostate cancer, ADT and radiotherapy to the prostate and metastatic sites were effective. Patients with good response to ADT may benefit from radiotherapy to both prostate and metastatic regions.

Preoperative erythrocyte sedimentation rate is an independent prognostic factor in Japanese patients with localized clear cell renal cell carcinoma.

INTRODUCTION: Few studies have examined the prognostic significance of common laboratory variables in Japanese patients with localized clear cell renal cell carcinoma (CCRCC). We evaluate the prognostic significance of preoperative laboratory variables in Japanese patients with localized CCRCC. PATIENTS AND METHODS: The study included 110 Japanese patients who were pathologically confirmed as nonmetastatic CCRCC (pT1-3 N0M0) after radical nephrectomy at our institution. We assessed the clinical (including laboratory measurements) and pathological findings, with the survival rates after surgery. RESULTS: Tumor stage and erythrocyte sedimentation rate (ESR) were identified as significant independent prognostic factors of progression-free survival in multivariate analysis. As for the prognostic factors for disease-specific survival, tumor stage and ESR had prognostic significance both in univariate and multivariate analyses. When the analysis was limited to pT1, multivariate analysis showed that only ESR was an independent prognostic factor for disease-specific survival. CONCLUSIONS: Preoperative ESR is an independent prognostic factor in Japanese patients with localized CCRCC, especially in patients with pT1.