Impact of timing of urinary drainage on clinical outcomes in patients with obstructive pyelonephritis associated with upper urinary tract stones: a propensity score-matched analysis.

OBJECTIVE: We aimed to assess the impact of the timing of urinary drainage on clinical outcomes in patients with obstructive pyelonephritis (OPN) associated with upper urinary tract (UUT) stones. METHODS: We retrospectively evaluated the multicenter dataset of 240 patients with OPN associated with UUT stones who underwent urinary drainage. We divided the patients into two groups depending on the timing of urinary drainage; emergency drainage, defined as within 12 h from admission, and delayed drainage, defined as between 12 and 48 h from admission. The outcomes were the length of hospital stay, time to leukocyte normalization, and time to body temperature normalization. One-to-two propensity score matching (PSM) was applied to minimize the effect of confounders between the two groups. Subsequently, predictive patient factors for emergency drainage were analyzed using the logistic regression model. RESULTS: Only the time from admission to normal body temperature was significantly shorter in the emergency drainage group when compared with the delayed drainage group (median: 2 vs. 3 days; p = 0.02), while there was no difference in time from drainage to body temperature normalization between the two groups. On multivariable analysis, high pretreatment C-reactive protein (CRP) was associated with implementing emergency drainage within 12 h. CONCLUSIONS: The timing of urinary drainage was only associated with the duration of high fever, but it did not affect the postdrainage course. Emergency urinary drainage is more likely to be performed in severe patients, such as high pretreatment CRP.

Real-world evidence of triplet therapy efficacy in patients with metastatic castration-sensitive prostate cancer: a Japanese multicenter study.

BACKGROUND: Two randomized trials demonstrated that the survival benefits afforded by triplet therapy were greater than those of doublet therapy, thus changing the treatment paradigm for metastatic castration-sensitive prostate cancer (mCSPC). This is the first study to assess the real-world use, performance, and safety of triplet therapy in Japanese patients. METHODS: This retrospective multicenter study included 45 consecutive mCSPC patients who received triplet therapy composed of androgen deprivation therapy (ADT), docetaxel, and darolutamide between January 2023 and June 2024. Baseline patient characteristics and their clinical parameters during triplet therapy were collected. Adverse events (AEs) were graded using Common Terminology Criteria for Adverse Events version 5.0, and imaging responses were evaluated following the RECIST criteria. The prostate-specific antigen (PSA) nadir was defined as the lowest PSA value during follow-up, and the PSA decrease was the initial PSA value minus the PSA nadir. RESULTS: The median patient age was 70 years and the median follow-up duration was 10 months. High-volume disease was present in 82.2% of patients. Concurrent administration of docetaxel and darolutamide was scheduled for 22.2% of cases. The incidence of any AE was 86.7%, with 55.5% of patients experiencing grade 3-4 AEs. Neutropenia was common, but prophylactic granulocyte colony-stimulating factor (G-CSF) significantly reduced the incidence of neutropenia of grade 3 or higher. Febrile neutropenia occurred in four patients (8.9%); these patients had not received prophylactic G-CSF. A decline in PSA of 90% was observed in 95.6% of patients, and an imaging response was seen in 97.8%. CONCLUSIONS: Triplet therapy with ADT, darolutamide, and docetaxel was highly efficacious and tolerable in Japanese mCSPC patients, particularly those with high-volume disease. Prophylactic G-CSF prescription is crucial to manage neutropenia effectively. Further studies with longer follow-ups are needed to confirm these findings and explore the long-term outcomes.

Survival outcome of chemotherapy-naïve castration-resistant prostate cancer treated with new-generation androgen receptor axis-targeted agents in real-world analysis.

PURPOSE: The androgen receptor axis-targeted (ARAT) agents abiraterone and enzalutamide have been introduced against castration-resistant prostate cancer (CRPC). However, determining which of these agents should be used first is a clinical challenge. Therefore, in this study, we compared the efficacy of first-line abiraterone and enzalutamide treatments in chemotherapy-naïve patients with CRPC. METHODS: A total of 242 chemotherapy-naïve CRPC cases treated with first-line ARAT were analyzed. Outcome measures were PSA response, PSA progression-free survival (PSA-PFS), time to treatment failure (TTF), cancer specific survival (CSS), and overall survival (OS). RESULTS: Abiraterone (A) and enzalutamide (E) were administered to 61 and 181 patients, respectively. The median PSA response rate (- 65.4% [A] and - 78.8% [E], p = 0.0341), PSA decline ≥ 30% (55.7% [A] and 72.9% [E], p = 0.0183), PSA-PFS (median 4 months [A] and 8 months [E], p = 0.0126), TTF (median 6 months [A] and 14 months [E], p < 0.0001), CSS (median 45 months [A] and not reached [E], p < 0.0001), and OS (median 28 months [A] and 80 months [E], p < 0.001) were significantly better in the enzalutamide group. In the multivariate analyses for CSS and OS, ALP (p = 0.00376) and ARAT (p < 0.001) (CSS), evidence of metastasis (p = 0.0467), Hb (p = 0.00205), and ARAT (p = 0.00514) (OS) were significant factors, respectively. CONCLUSION: This study showed that PSA response, PSA-PFS, TTF, CSS, and OS were better with first-line enzalutamide administration. Direct inhibition of androgen receptor signaling by enzalutamide is associated with better clinical outcomes.

Docetaxel versus abiraterone for metastatic hormone-sensitive prostate cancer with focus on efficacy of sequential therapy.

PURPOSE: We aimed to assess the oncologic efficacy of combining docetaxel (DOC) versus abiraterone (ABI) with androgen deprivation therapy (ADT) in patients with high-risk metastatic hormone-sensitive prostate cancer (mHSPC), with a focus on the efficacy of sequential therapy, in a real-world clinical practice setting. METHODS: The records of 336 patients who harbored de novo high-risk mHSPC, based on the LATITUDE criteria, and had received ADT with either DOC (n = 109) or ABI (n = 227) were retrospectively analyzed. Overall survival (OS), cancer-specific survival (CSS), progression-free survival (PFS), including time to castration-resistant prostate cancer (CRPC), time to 2nd-line progression (PFS2), and 2nd- and 3rd-line PFS, were compared. We used one-to-two propensity score matching to minimize the confounders. The differential efficacy of 2nd-line therapy based on agents in each arm was evaluated using the unmatched cohort as an additional interest. RESULTS: After propensity score matching, 86 patients treated with DOC + ADT and 172 with ABI + ADT were available for analyses. The 3-year OS and CSS for DOC versus ABI were 76.2% versus 75.1% (p = 0.8) and 78.2% versus 78.6% (p = 1), respectively. There was no difference in the median PFS2 (49 vs. 43 months, p = 0.39), while the median time to CRPC in patients treated with ABI was significantly longer compared to those treated with DOC (42 vs. 22 months; p = 0.006). The median 2nd-line PFS (14 vs. 4 months, p < 0.001) and 3rd-line PFS (4 vs. 2 months, p = 0.012) were significantly better in the DOC group than in the ABI group. Among the unmatched cohort, after ABI for mHSPC, the median 2nd-line PFS did not differ between the patients treated with DOC and those treated with enzalutamide as 2nd-line therapy (both 3 months, p = 0.8). CONCLUSIONS: ADT with DOC or ABI has comparable oncologic outcomes in terms of OS, CSS, and PFS2 in patients with de novo high-risk mHSPC. Compared to DOC, ABI resulted in longer time to CRPC but worse 2nd and 3rd-line PFS. Further studies are needed to clarify the optimal sequence of therapy in the upfront intensive treatment era.

Comparison of efficacy and medical costs between upfront docetaxel and abiraterone treatments of metastatic hormone-sensitive prostate cancer patients in real-world practice: a multicenter retrospective study.

PURPOSE: We compared the real-world efficacy and medical costs for treatment with upfront docetaxel (DOC) and abiraterone acetate (ABI) up to progression-free survival 2 (PFS2) in patients with metastatic hormone-sensitive prostate cancer (mHSPC). METHODS: This multicenter retrospective study included 340 patients with mHSPC treated with either upfront DOC or upfront ABI between October 2015 and December 2021. We compared PFS2 and medical costs between the two treatment groups. PFS2 was defined as the time from first-line therapy to progression on second-line therapy. Medical costs were estimated using the National Health Insurance drug prices in 2022 in Japan. RESULTS: The upfront DOC and ABI groups included 107 and 233 patients, respectively. The incidence of metastatic castration-resistant PC progression was significantly higher in the upfront DOC group compared with the incidence in the upfront ABI group. However, no significant differences in PFS2 were observed between the two treatment groups. Monthly medical costs per patient were significantly higher in the upfront ABI group ($3453) compared with the costs in the upfront DOC group ($1239, P < 0.001). The cost differences were significantly influenced by differences in the length of androgen deprivation therapy monotherapy (DOC group, 13.4 months vs. ABI group, 0.0 months). CONCLUSIONS: We observed a significant cost benefit in the upfront DOC group in Japanese real-world practice, while the PFS2 rates were similar between the groups. Upfront DOC was a more cost-effective option for men with mHSPC who were eligible for toxic chemotherapy.

Combination of docetaxel versus nonsteroidal antiandrogen with androgen deprivation therapy for high-volume metastatic hormone-sensitive prostate cancer: a propensity score-matched analysis.

PURPOSE: The aim of this study was to investigate the oncologic efficacy of combining docetaxel with androgen deprivation therapy (ADT) versus nonsteroidal antiandrogen (NSAA) with ADT in patients with high-volume metastatic hormone-sensitive prostate cancer (mHSPC) with focus on the effect of sequential therapy in a real-world clinical practice setting. METHODS: The records of 382 patients who harbored high-volume mHSPC, based on the CHAARTED criteria, and had received ADT with either docetaxel (n = 92) or NSAA (bicalutamide) (n = 290) were retrospectively analyzed. The cohorts were matched by one-to-one propensity scores based on patient demographics. Overall survival (OS), cancer-specific survival (CSS), progression-free survival (PFS), including time to castration-resistant prostate cancer (CRPC), and time to second-line progression (PFS2) were compared. 2nd-line PFS defined as the time from CRPC diagnosis to progression after second-line therapy was also compared. RESULTS: After matching, a total of 170 patients were retained: 85 patients treated with docetaxel + ADT and 85 patients treated with NSAA + ADT. The median OS and CSS for docetaxel + ADT versus NSAA + ADT were not reached (NR) vs. 49 months (p = 0.02) and NR vs. 55 months (p = 0.02), respectively. Median time to CRPC and PFS2 in patients treated with docetaxel + ADT was significantly longer compared to those treated with NSAA (22 vs. 12 months; p = 0.003 and, NR vs. 28 months; p < 0.001, respectively). There was no significant difference in 2nd-line PFS between the two groups. CONCLUSIONS: Our analysis suggested that ADT with docetaxel significantly prolonged OS and CSS owing to a better time to CRPC and PFS2 in comparison to NSAA + ADT in high-volume mHSPC.

Effect of upfront intensive therapy on oncological outcomes in older patients with high tumor burden metastatic castration-sensitive prostate cancer: A multicenter retrospective study.

BACKGROUND: The effect of upfront intensive therapy on the prognosis of older patients with metastatic castration-sensitive prostate cancer (mCSPC) remains unclear. Thus, we assessed the impact of older age (≥75 years) on oncological outcomes in mCSPC patients with a high tumor burden. METHODS: This multicenter retrospective study included 252 patients aged ≥75 years treated with either upfront or conventional therapy between 2014 and 2021. We compared castration-resistant prostate cancer (CRPC)-free survival (FS) and overall survival (OS) between patients with androgen deprivation therapy (ADT) plus upfront intensive therapy (docetaxel [DTX] or abiraterone acetate [ABI] plus prednisolone) and conventional therapy (ADT monotherapy or ADT combined with bicalutamide). We evaluated the effect of upfront intensive therapy on prognosis by multivariable Cox regression analysis. RESULTS: The 231 patients enrolled in our study were classified in the conventional group (n = 148) or the upfront group (n = 104; DTX = 27 and ABI = 77). The upfront group had significantly prolonged CRPC-FS and OS compared with the conventional group, and this was also the case in the background-adjusted multivariable Cox regression analysis. CONCLUSION: Patients aged ≥75 years who received upfront intensive therapy had significantly longer CRPC-FS and OS compared with similar age patients treated with conventional therapy in real-world practice. The oncological benefit may not diminish in this older population.

Does castration status affect docetaxel-related adverse events? :Identification of risk factors for docetaxel-related adverse events in metastatic prostate cancer.

BACKGROUND: Docetaxel-related adverse events (AEs) such as neutropenia and febrile neutropenia (FN) can be life-threatening. A previous in vivo study raised the hypothesis that the castration status affects the rate of hematologic AEs. We aimed to investigate the impact of castration status on the incidence of docetaxel-related AE in metastatic prostate cancer (mPCa) patients. METHODS: We retrospectively analyzed the records of 265 mPCa patients treated with docetaxel, comprising 92 patients with metastatic hormone-sensitive prostate cancer (mHSPC) and 173 patients with metastatic castration-resistant prostate cancer (mCRPC) between January 2015 and December 2021. Common terminology Criteria for Adverse Events (CTCAE) was applied to evaluate AEs. We analyzed the differential incidences between mHSPC and mCRPC, and risk factors of hematologic and nonhematologic AEs using a logistic regression model. RESULTS: The rate of patients who received primary prophylaxis against neutropenia was higher in those with the mHSPC compared with those with the mCRPC (7.5% vs. 33%, p < 0.001). Among the patients without primary prophylaxis, incidence rates of severe neutropenia (CTCAE ≥ Grade3) and FN were 89% and 16% in patients with mCRPC compared to 81% and 18% in those with mHSPC. Logistic regression analysis revealed that age ≥ 75 years and failure to provide primary prophylaxis were independent risk factors of severe neutropenia (odds ratio [OR]: 2.39, 95% confidential interval [CI]: 1.10-5.18 and OR: 15.8, 95% CI: 7.23-34.6, respectively). Eastern Cooperative Oncology Group Performance Status (ECOG-PS) ≧ 1 was an independent risk factor of FN (OR: 2.26, 95% CI: 1.13-4.54). Castration status (mHSPC vs. mCRPC) was not associated with the risks of severe neutropenia and FN. CONCLUSIONS: Castration status did not affect the risk of severe neutropenia or FN in mPCa patients treated with docetaxel regardless of the disease state. Failure to provide primary prophylaxis and advanced patient age are independent risk factors of severe neutropenia; while patients with poor PS are more likely to develop FN. These findings may help guide the clinical decision-making for proper candidate selection of docetaxel treatment.

Abiraterone acetate versus nonsteroidal antiandrogen with androgen deprivation therapy for high-risk metastatic hormone-sensitive prostate cancer.

BACKGROUND: Although prostate cancer is a very common form of malignancy in men, the clinical significance of androgen deprivation therapy (ADT) with abiraterone acetate versus the nonsteroidal antiandrogen bicalutamide has not yet been verified in patients with high-risk metastatic hormone-sensitive prostate cancer (mHSPC). The present study was designed to initiate this verification in real-world Japanese clinical practice. METHODS: We retrospectively analyzed the records of 312 patients with high-risk mHSPC based on LATITUDE criteria and had received ADT with bicalutamide (n = 212) or abiraterone acetate (n = 100) between September 2015 and December 2020. Bicalutamide was given at 80 mg daily and abiraterone was given at 1000 mg daily as four 250-mg tablets plus prednisolone (5-10 mg daily). Overall survival (OS), cancer-specific survival (CSS), and time to castration-resistant prostate cancer (CRPC) were compared. The prognostic factor for time to CRPC was analyzed by Cox proportional hazard model. RESULTS: Patients in the bicalutamide group were older, and more of them had poor performance status (≧2), than in the abiraterone group. Impaired liver function was noted in 2% of the bicalutamide group and 16% of the abiraterone group (p < 0.001). Median follow-up was 22.5 months for bicalutamide and 17 months for abiraterone (p < 0.001). Two-year OS and CSS for bicalutamide versus abiraterone was 77.8% versus 79.5% (p = 0.793) and 81.1% versus 82.5% (p = 0.698), respectively. Median time to CRPC was significantly longer in the abiraterone group than in the bicalutamide group (NA vs. 13 months, p < 0.001). In multivariate analysis, Gleason score ≧9, high alkaline phosphatase, high lactate dehydrogenase, liver metastasis, and bicalutamide were independent prognostic risk factors for time to CRPC. Abiraterone prolonged the time to CRPC in patients with each of these prognostic factors. CONCLUSIONS: Despite limitations regarding the time-dependent bias, ADT with abiraterone acetate significantly prolonged the time to CRPC compared to bicalutamide in patients with high-risk mHSPC. However, further study with longer follow-up is needed.

Real-world survival outcomes of adding docetaxel or abiraterone in patients with high-volume metastatic castration-sensitive prostate cancer: historically controlled, propensity score matched comparison with androgen deprivation therapy.

PURPOSE: This study investigated the impact of treatment intensification with upfront docetaxel (DOC) or abiraterone (ABI) plus prednisolone on survival outcomes in patients with metastatic castration-sensitive prostate cancer (mCSPC) by comparing it with androgen deprivation therapy (ADT) monotherapy or combined androgen blockade (CAB) using propensity score matching (PSM). METHODS: Outcomes from 278 CHAARTED high-volume patients receiving upfront DOC (92 patients) or upfront ABI (186 patients) were compared to those from 354 patients receiving ADT or CAB. PSM was conducted to assess castration-resistant prostate cancer-free survival (CRPCFS) and overall survival (OS). RESULTS: After PSM, patient distributions between the three groups were well balanced. After 1:1 PSM, patients receiving upfront ABI had significantly better CRPCFS than those receiving ADT/CAB or upfront DOC [hazard ratio (HR) 0.39; 95% CI 0.27-0.56 vs. HR 0.50; 95% CI 0.30-0.82, respectively]. No significant difference in CRPCFS was observed between the upfront DOC and ADT/CAB groups (HR 0.75; 95% CI 0.50-1.12). Patients receiving upfront DOC and upfront ABI had significantly better OS than those receiving ADT/CAB (HR 0.54; 95% CI 0.0.30-0.98 vs. HR 0.49; 95% CI 0.29-0.84, respectively). However, no significant difference in OS was observed between upfront ABI and upfront DOC (hazard ratio 0.84; 95% CI 0.34-2.06). CONCLUSION: The comparison of real-world retrospective cohorts showed that treatment intensification with upfront DOC or upfront ABI promoted better OS compared to ADT alone or CAB in patients with high-volume mCSPC after PSM. However, no difference in OS was observed between upfront DOC and upfront ABI.

Effects of External Radiation Exposure on Perinatal Outcomes in Pregnant Women After the Fukushima Daiichi Nuclear Power Plant Accident: the Fukushima Health Management Survey.

BACKGROUND: This study aimed to investigate the effects of maternal exposure to external radiation on perinatal outcomes among women who experienced the Fukushima Daiichi Nuclear Disaster (FDND) using the Fukushima Health Management Survey (FHMS). METHODS: Data from the Pregnancy and Birth Survey and Basic Survey in the FHMS were combined to analyze external maternal radiation exposure following the FDND, and the relationship between radiation dose and perinatal outcomes was analyzed using binomial logistic regression analysis. Missing dose data were supplemented using multiple imputation. RESULTS: A total of 6,875 individuals responded to the survey. Congenital anomalies occurred in 2.9% of patients, low birth weight (LBW) in 7.6%, small for gestation age (SGA; <10th percentile) in 8.9%, and preterm birth in 4.1%. The median maternal external radiation dose was 0.5 mSv (maximum, 5.2 mSv). Doses were classified as follows: <1 mSv (reference), 1 to <2 mSv, and ≥2 mSv. For congenital anomalies, the crude odds ratio for 1 to <2 mSv was 0.81 (95% confidence interval [CI], 0.56-1.17) (no participants with congenital anomaly were exposed to ≥2 mSv). At 1 to <2 mSv and ≥2 mSv, the respective adjusted odds ratios were 0.91 (95% CI, 0.71-1.18) and 1.21 (95% CI, 0.53-2.79) for LBW, 1.14 (95% CI, 0.92-1.42) and 0.84 (95% CI, 0.30-2.37) for SGA, and 0.91 (95% CI, 0.65-1.29) and 1.05 (95% CI, 0.22-4.87) for preterm birth. CONCLUSION: External radiation dose due to the FDND was not associated with congenital anomalies, LBW, SGA, or preterm birth.

The Effects of the Great East Japan Earthquake on Perinatal Outcomes: Results of the Pregnancy and Birth Survey in the Fukushima Health Management Survey.

There are limited studies on the long-term effects of natural/environmental disasters, especially nuclear disasters, on obstetric outcomes. This study aimed to review the results of perinatal outcomes immediately after the Great East Japan Earthquake (GEJE) and the Fukushima Daiichi Nuclear Power Plant accident, as well as their long-term trends over 8 years, in the Fukushima Health Management Survey. The annual population-based Pregnancy and Birth Survey is conducted as part of the Fukushima Health Management Survey. The Fukushima Prefecture government launched it to assess the health conditions of pregnant women and their neonates after the GEJE. The self-reported questionnaire was sent to 115,976 pregnant women by mail from January 2012, with 58,344 women responding to the questionnaire (50.3% response rate). Pregnancy complications, such as gestational hypertension, respiratory diseases, and mental disorders, increased in some women who were pregnant at the time of the earthquake and immediately after the earthquake. However, the direct effects on newborns, such as preterm birth, low birth weight, and congenital anomalies, were not immediately clear after the earthquake. Although there were significant differences in the occurrence of preterm birth and low birth weight among the districts, there was no change in the occurrences of preterm birth, low birth weight, or anomalies in newborns in Fukushima Prefecture from the fiscal year 2011 to the fiscal year 2018. Therefore, the long-term effects of the post-disaster radiation accident on perinatal outcomes are considered to be very small.

Real-world outcomes and risk stratification in patients with metastatic castration-sensitive prostate cancer treated with upfront abiraterone acetate and docetaxel.

PURPOSE: We assessed clinical outcomes in patients with metastatic castration-sensitive prostate cancer (mCSPC) treated with two upfront therapies. METHODS: The medical records of 301 patients with mCSPC treated with androgen deprivation therapy plus upfront abiraterone acetate (ABI) or docetaxel (DOC) between 2014 and 2021 were retrospectively reviewed. Propensity score matching (PSM) was performed to compare survival outcomes. Subgroup analyses of risk factors for second progression were conducted. RESULTS: A total of 95 patients received upfront DOC, whereas 206 received upfront ABI. After PSM, the ABI group had a significantly better castration-resistant prostate cancer (CRPC)-free survival than the DOC group [hazard ratio (HR), 0.53; 95% confidence interval (CI), 0.34-0.82]. Second progression-free survival (PFS2) tended to be longer in the ABI group than in the DOC group, but the difference was not statistically significant (HR, 0.64; 95% CI, 0.33-1.22). No significant difference in overall survival (OS) was found between the two groups (HR, 0.92; 95% CI, 0.42-2.03). In the subgroup analysis, upfront ABI had significantly favorable PFS2 in patients aged ≥ 75 years compared with upfront DOC (p = 0.038). Four risk factors for second progression (primary Gleason 5, liver metastasis, high serum alkaline phosphatase level, and high serum lactate dehydrogenase level) successfully stratified patients into three risk groups. CONCLUSIONS: Upfront ABI provided better CRPC-free survival than upfront DOC; however, no significant differences in PFS2 or OS were observed between the two groups. Personalized management based on prognostic risk factors may benefit patients with mCSPC treated with upfront intensified therapies.

Modified Glasgow prognostic score is a pre-surgical prognostic marker of disease mortality in upper urinary tract urothelial carcinoma.

BACKGROUND: To investigate the prognostic value of pre-surgical modified Glasgow prognostic score in upper urinary tract urothelial carcinoma patients treated with radical nephroureterectomy. METHODS: We retrospectively reviewed the clinical records of 273 urinary tract urothelial carcinoma patients treated with radical nephroureterectomy. The modified Glasgow prognostic score was evaluated based on pre-surgical serum C-reactive protein and albumin. Association of modified Glasgow prognostic score with recurrence-free survival, cancer-specific survival and overall survival rates was estimated using Kaplan-Meier method and log-rank test was used to compare survival outcome. Cox regression analyses were performed for the assessment of the modified Glasgow prognostic score with recurrence-free survival, cancer-specific survival and overall survival. RESULTS: Of total 273 patients, the modified Glasgow prognostic score 0, 1 and 2 were assigned in 216 (79%), 45 (17%) and 12 (4%), respectively. The recurrence-free survival, cancer-specific survival and overall survival of urinary tract urothelial carcinoma patients with modified Glasgow prognostic score 2 were significantly worse than those with modified Glasgow prognostic score 0. On univariate analysis, modified Glasgow prognostic score 2 was associated with worse recurrence-free survival, cancer-specific survival and overall survival (all P value <0.01). On multivariate analyses, modified Glasgow prognostic score 2 was independently associated with worse cancer-specific survival and overall survival (hazard ratio: 4.73, 95% confidence interval: 1.31-17.2 and hazard ratio: 3.66, 95% confidence interval: 1.08-12.4, respectively). In the subgroup analyses of advanced urinary tract urothelial carcinoma patients, modified Glasgow prognostic score 2 was independently associated with worse recurrence-free survival (hazard ratio 4.31, 95% confidence interval: 1.69-11.1). CONCLUSIONS: Pre-surgical modified Glasgow prognostic score independently predicts cancer-specific survival and overall survival of urinary tract urothelial carcinoma patients. Assessment of pre-surgical modified Glasgow prognostic score status could help identifying the worse survivor of urinary tract urothelial carcinoma patients.

Prognostic model with alkaline phosphatase, lactate dehydrogenase and presence of Gleason pattern 5 for worse overall survival in low-risk metastatic hormone-sensitive prostate cancer.

BACKGROUND: Randomized trials showed the survival benefits of the combined use of androgen receptor axis-targeted agents with androgen deprivation therapy in metastatic hormone-sensitive prostate cancer (mHSPC), regardless of the risk. However, treating patients with low-risk mHSPC with such intensive treatment is still debatable. METHODS: This retrospective study included 155 low-risk patients among 467 mHSPC patients treated in our affiliated institutions. The association between predictive factors and treatment outcomes was estimated using the Kaplan-Meier method and log-rank test. Predictive factors for castration resistant prostate cancer (CRPC)-free survival were investigated using Cox regression analyses. RESULTS: During the median follow-up of 39 months, 38.7% of patients developed CRPC and 14.2% died. In the multivariate analyses, a presence of Gleason pattern 5 (hazard ratio [HR] 2.04), high alkaline phosphatase (HR 1.007) and high lactate dehydrogenase (HR 1.009) were significant predictive factors for shorter CRPC-free survival. Finally, 155 patients were stratified into favorable- and unfavorable-risk groups based on the numbers of the predictive factors. The overall survival (OS) in the unfavorable-risk group (total scores: 2-3) was significantly worse than that of the favorable-risk group (total score: 0-1) (P = 0.02). This prognostic model was assessed with 50 low-risk mHSPC patients from the external validation dataset and found both the time to CRPC, and the OS in the unfavorable-risk group was significantly worse than that of the favorable-risk group (P < 0.01). CONCLUSIONS: The combination of Gleason pattern 5, high alkaline phosphatase and lactate dehydrogenase can predict those with worse OS in low-risk mHSPC patients.

Safety of fondaparinux for prevention of postoperative venous thromboembolism in urological malignancy: A prospective randomized clinical trial.

OBJECTIVES: To prospectively evaluate the safety of postoperative fondaparinux in comparison with low molecular weight heparin in patients undergoing uro-oncological surgery. METHODS: The present study was a prospective, single-blind, non-inferiority randomized trial. A total of 359 patients undergoing surgery for urological malignancy were enrolled from January 2011 to December 2012. A total of 298 of these patients (fondaparinux group, 152; low molecular weight heparin group, 146) were evaluable for the intention-to-treat-analysis. Patients were randomly assigned to low-dose unfractionated heparin, 5000 units twice daily until postoperative day 1 plus either fondaparinux 2.5 mg once daily or low molecular weight heparin 2000 units twice daily until postoperative day 5. The primary end-point was postoperative bleeding as by independent review, and the study was powered to show the non-inferiority of fondaparinux versus low molecular weight heparin. The other adverse events were evaluated. D-dimer and soluble fibrin monomer complex levels were measured perioperatively. RESULTS: Bleeding occurred in 21 patients (12 in the fondaparinux group and 9 in low molecular weight heparin group, respectively). No significant differences were detected in the incidence of postoperative bleeding and the other adverse events between the two groups. The D-dimer was elevated on postoperative day 1 in one patient (16.6 µg/mL). In another patient, the soluble fibrin monomer complex was elevated (109 µg/mL). CONCLUSIONS: Fondaparinux is non-inferior to low molecular weight heparin with respect to risk of bleeding. The favorable safety profile of fondparinux supports its prophylactic use as an alternative to low molecular weight heparin after surgery for urological malignancy.

OUTCOMES AFTER SURGICAL TREATMENT OF UPPER TRACT UROTHELIAL CARCINOMA.

(Objectives) We retrospectively investigated the prognostic factors and the role of adjuvant chemotherapy against upper tract urothelial carcinoma (UTUC) after surgery. (Materials and methods) 343 patients of UTUC who underwent radical nephroureterectomy at Jikei University Hospital and affiliated institutions between January 2004 and February 2012 were retrospectively analyzed. A chi-squared test was used for categorical variables. Survival probabilities after surgery were estimated using the Kaplan-Meier method. Multivariate Cox regression models addressed overall survival and cancer-specific survival after surgery. (Results) The 5-year overall and cancer-specific survival rates were 64.6% and 74.6%, respectively. On multivariate analysis, higher age, male, higher pT-stage and lymphovascular invasion (LVI) were associated with worse overall survival and higher pT-stage and LVI were associated with worse cancer-specific survival. 44 patients (G3 and ≥pT3) who received cisplatin-based adjuvant chemotherapy had improved overall survival (P=0.044). (Conclusions) Higher pT-stage, LVI were important prognostic variables associated with oncologic outcomes. Cisplatin-based adjuvant chemotherapy offered a significant benefit to overall survival in high risk UTUC (G3 and ≥pT3), but more investigations are needed to confirm its utility.

[Treatment of osteoporosis in hypogonadal men].

About 3million men have been reported to have osteoporosis in Japan. One of known causes of osteoporosis in men is late-onset-hypogonadism. Androgen replacement therapy has been reporte to be effective in seveal literatures, however, patitiets should be excluded if prostate cancer is suspected. Addition of bisphosphpnate and active vitain D derivatives are recommended.

High pressure balloon dilation for vesicourethral anastomotic strictures after radical prostatectomy.

BACKGROUND: Vesicourethral anastomotic stricture (VAS) is a rare but serious complication following radical prostatectomy (RP), and various types of managements for VAS have been proposed. We investigated the efficacy of transurethral balloon dilation in the management of VAS after RP. METHODS: A total of 128 consecutive patients underwent open RP at our hospital between 2008 and 2013; of these, 10 patients (7.8%) developed VAS. Transurethral balloon dilation was performed in all 10 patients, using a high pressure balloon catheter under fluoroscopic and endoscopic guidance. Follow-up endoscopy was performed, and patients in whom the stricture had recurred underwent repeat dilation. We retrospectively evaluated the management of VAS and short-term efficacy of high pressure balloon dilation. RESULTS: The mean time from RP to diagnosis of VAS was 9 months (2-40 months); eight patients (80%) were diagnosed within 6 months of RP. Balloon dilation of VAS was technically successful in all patients, and no perioperative complications were recorded. The median follow-up after balloon dilation was 24 months (7-67 months). There was no recurrence of VAS in eight patients (80%) after the first balloon dilation, and all patients were controlled within the twice. CONCLUSION: High pressure balloon dilation is a highly effective and minimally invasive procedure for treating VAS.

[RISK FACTORS FOR INTRAVESICAL RECURRENCE AFTER SURGICAL MANAGEMENT OF UROTHERIAL CARCINOMA OF THE UPPER URINARY TRACT].

OBJECTIVES: To identify risk factors for developing recurrent bladder cancer in patients who underwent surgical resection for urothelial carcinoma of the upper urinary tract. METHODS: We retrospectively analyzed 322 patients who underwent surgical resection for urothelial carcinoma of the upper urinary tract at the Jikei University Hospital and our affiliated hospitals between January 2005 and July 2011. Univariate and multivariate analyses by using the Cox proportional hazards model were performed to determine the risk factors for intravesical recurrence after nephroureterectomy in these 322 patients. RESULTS: Of the 322 patients, 111 patients (34.5%) developed recurrent bladder cancer after a median interval of 8.0 months. On multivariate analysis, the presence of a superficial tumor and the presence of a ureteral tumor were independent predictors for intravesical recurrence. CONCLUSION: The risk factors for developing recurrent bladder cancer were the presence of a superficial tumor and the presence of a ureteral tumor. Further investigation is required to evaluate the efficacy of perioperative intravesical therapy for the prevention of intravesical recurrence.