A comparison of the efficacy of dutasteride on reducing lower urinary tract symptoms among patients with small versus large benign prostatic hyperplasia.

Background: Only a few reports have currently studied the efficacy of dutasteride in patients with small benign prostatic hyperplasia (BPH). We investigated the efficacy of dutasteride on reducing lower urinary tract symptoms among them. Materials and methods: A total of 81 patients with BPH who completed 52weeks of 0.5?mg dutasteride treatment were enrolled. Each patient filled out the International Prostatic Symptom Score (IPSS) and overactive bladder symptom score (OABSS) at baseline and at the 6- and 12-month follow-up visits. Total testosterone, prostate-specific antigen, adenoma/prostate volume (PV), uroflowmetry analysis, and postvoid residual volume were evaluated at baseline and at the 12-month follow-up visit. The enrolled patients were divided into 2 groups according to PV at baseline. The groups were as follows: Group A (PV ≥ 30 mL) and Group B (PV < 30 mL). Results: Groups A and B had mean PVs of 52.1 and 23.6 mL and mean IPSS scores of 16.7 and 14.4, respectively. Group A had significantly higher OABSS and prostate-specific antigen levels at baseline than Group B, while no significant differences in any other baseline characteristics was observed. After dutasteride treatment, adenoma volume and PV decreased significantly, while testosterone level showed a significant increase in both groups. Group A showed significant improvements in the total IPSS, voiding and storage subscore of the IPSS, OABSS, maximum flow rate, and postvoid residual volume. Group B, on the other hand, also showed significant improvements only in the total IPSS, voiding subscore of the IPSS, and maximum flow rate. Conclusions: The present study suggests a possible beneficial effect of dutasteride treatment on the reduction of lower urinary tract symptoms in patients with small and large BPH. However, the effectiveness of dutasteride was limited compared to patients with large BPH (PV ≥ 30 mL).

Dose modification in enzalutamide and abiraterone plus prednisolone for castration-resistant prostate cancer: A subanalysis from the ENABLE study for PCa.

BACKGROUND: A head-to-head comparison between enzalutamide (ENZ) and abiraterone plus prednisolone (ABI) revealed similar survival benefits for castration-resistant prostate cancer (CRPC) in the ENABLE study for PCa. Considering that a dose reduction of ENZ and ABI has demonstrated sufficient inhibitory ability of androgen receptor (AR) signaling, we analyzed the efficacy of modified doses of these agents in the ENABLE study for PCa. METHODS: This investigator-initiated, multicenter, randomized controlled trial that was conducted in Japan analyzed the prespecified survival endpoints, prostate-specific antigen (PSA) response rate ( ≥50% decline from baseline), and safety profile in patients treated with modified doses (ENZ ≤ 120 mg/day, ABI ≤ 750 mg/day) compared with those treated with a standard dose (ENZ 160 mg/day, ABI 1000 mg/day) as a starting dose. RESULTS: In total, 92 patients in each arm were treated and analyzed; 16 patients were treated with a modified dose in both the ENZ and ABI arms, respectively. Moreover, 32 patients treated with modified doses showed a significantly better time to PSA progression (TTPP) and overall survival (OS) compared with the 152 patients treated with a standard dose (HR 0.47, 95%CI 0.27-0.83, p = 0.0379, and HR 0.35, 95%CI 0.19-0.63, p = 0.0162). Despite a significantly longer TTPP in the modified ABI group than in the standard ABI group (HR 0.29, 95%CI 0.14-0.62, p = 0.0248), no significant difference was observed in the TTPP between the modified and standard ENZ groups (p = 0.5366). Furthermore, similar adverse event rates and grades were observed in each treatment dose group. CONCLUSIONS: The modified doses of ABI showed better TTPP than the standard dose of ABI and may be a potential treatment option for CRPC patients; however, its mechanism is still unclear, although its ability to suppress AR signaling is equivalent to that of a standard dose.

Therapeutic efficacy and safety of biweekly administration of enfortumab vedotin for urothelial carcinoma.

OBJECTIVES: Enfortumab vedotin (EV) is an established pharmacotherapy for metastatic urothelial carcinoma (mUC); however, its adverse events (AEs) cannot be overlooked. The study investigated the efficacy and safety of biweekly EV administration. METHODS: Patients with mUC who received EV at our institution were included in the study. Eligible patients were classified into two groups as follows: those who received EV on a standard schedule (standard group) and those who received EV on a biweekly schedule (biweekly group); the treatment outcomes and AEs between the two groups were compared. RESULTS: Nine and 19 patients were in the standard group and biweekly groups, respectively. The progression-free survival, overall survival, and overall response rate were not significantly different between the two groups. AEs following EV administration, such as decreased appetite (P < .01), pruritus (P < .01), rash maculopapular (P < .01), anemia (P = .04), and liver dysfunction (P = .04), were significantly more frequent in the standard group. Grade 3 or higher AEs, such as pruritus (P = .03) and rash maculopapular (P < .01), were significantly more frequent in the standard group. Furthermore, significantly more patients in the standard group had to be given a reduced dose due to adverse events (P = .02). CONCLUSIONS: Biweekly administration of EV may be safer without compromising therapeutic efficacy than the standard schedule.

Evaluation of 68Ga-PSMA-11 PET/CT: a Phase 1 clinical study in Japanese patients with primary, recurrent, or suspected recurrent prostate cancer.

BACKGROUND: Prostate-specific membrane antigen (PSMA)-targeted radiopharmaceuticals allow whole-body imaging to detect prostate cancer (PC). Positron emission tomography imaging using gallium-68 (68Ga)-PSMA-11 has been shown to have a favorable safety and tolerability profile and high diagnostic performance. The study evaluates the safety and pharmacokinetics of 68Ga-PSMA-11 in Japanese patients with primary, recurrent, or suspected recurrent prostate cancer. METHODS: This single arm study enrolled Japanese patients with primary PC (n = 3), suspected recurrent PC following radical prostatectomy (n = 4), or suspected recurrent PC following radical radiotherapy (n = 3). All patients received a single intravenous dose of 68Ga-PSMA-11 2.0 MBq/kg (±10%) followed by PSMA PET imaging and safety and pharmacokinetic evaluations. Based on the blood concentrations of 68Ga-PSMA-11 and the radioactivity distribution rate in each organ/tissue, the absorbed doses in major organs/tissues and the whole-body effective dose were calculated by the Medical Internal Radiation Dose method. RESULTS: Ten patients were enrolled. Mean age was 73.3 ± 4.8 years, and median prostate-specific antigen was 8.250 ng/mL. Five patients (50%) experienced a total of 6 adverse events, and no grade ≥ 2 adverse events or serious adverse events were reported. No clinically significant changes in vital signs, haematology parameters, or blood chemistry or ECG abnormalities were observed. The estimated whole body effective dose of 68Ga-PSMA-11 (mean ± standard deviation) was 2.524 × 10-2 ± 2.546 × 10-3 mSv/MBq. Time to maximum concentration (1.16 × 10-4 ± 1.3 × 10-5% ID/mL) in whole blood was 2.15 ± 0.33 min. CONCLUSIONS: 68Ga-PSMA-11 has a favourable safety and tolerability profile in Japanese patients with primary, recurrent, or suspected recurrent prostate cancer, which is comparable to previous observations in other populations.

Comprehensive analysis of perioperative hypotension in photodynamic diagnosis-assisted transurethral resection of bladder tumor with 5-aminolevulinic acid.

OBJECTIVE: Intraoperative hypotension remains a serious adverse event of photodynamic diagnosis-assisted transurethral resection of bladder tumor with oral administration of 5-aminolevulinic acid. We conducted a re-analysis of perioperative hypotension in photodynamic diagnosis-assisted transurethral resection of the bladder tumor with oral 5-aminolevulinic acid to ascertain its safety. METHODS: A total of 407 cases who underwent transurethral resection of bladder tumors in our institution were reviewed (274 cases for the PDD group with photodynamic diagnosis and 133 for the white light (WL) group without). A classification of hypotension severity was devised to identify risk factors for clinically troublesome hypotension. The distribution of hypotension severity in each of the PDD and WL groups was compared. Additionally, the patient background and perioperative data by hypotension severity were compared only in the PDD group. RESULTS: More patients with moderate and severe hypotension were noted in the PDD group. The renal function was lower with increasing hypotension severity in the PDD group. More patients on general anesthesia were included in the mild and moderate hypotension group, whereas more patients on spinal anesthesia were included in the severe hypotension group. Furthermore, the frequency of side effects other than hypotension tended to increase with hypotension severity. CONCLUSIONS: Renal function impairment and the other adverse effects of 5-aminolevulinic acid may be risk factors for severe hypotension. Mild or moderate hypotension may be caused by general anesthesia and severe hypotension may be caused by spinal anesthesia. To elucidate specific risk factors, further case-control studies are warranted.

Salvage Androgen Deprivation Therapy as Potential Treatment for Recurrence after Robot-Assisted Radical Prostatectomy.

BACKGROUND: The efficacy of intermittent androgen deprivation therapy (ADT) for biochemical recurrence (BCR) after robot-assisted radical prostatectomy (RARP) is unknown, and its usefulness in Japanese practice needs to be investigated. METHODS: We conducted a retrospective analysis of 85 patients who underwent RARP and were selected for intermittent ADT for postoperative recurrence at Kanazawa University Hospital between 2009 and 2019. Intermittent ADT was administered for 2 years. If prostate-specific antigen levels increased post-treatment, intermittent ADT was reinitiated. The median follow-up period was 47 months. RESULTS: The 73 patients had completed the initial course of ADT, and 12 were under initial ADT. The 5-year castration-resistant prostate-cancer-free survival rates, cancer-specific survival, and overall survival were 92.7%, 98.3%, and 94.7%, respectively. A subgroup analysis of 69 patients who completed intermittent ADT was conducted to evaluate the BCR rate following initial ADT. The 5-year BCR-free survival rate was 53.2%. Multivariate analysis identified testosterone ≤ 0.03 ng/mL during ADT as the sole predictor of BCR after ADT. CONCLUSIONS: Salvage intermittent ADT may be an effective treatment option for BCR after RARP. In addition, it would be useful to confirm strong testosterone suppression as a criterion for transition to intermittent therapy.

A seed link connector protruding into the bladder formed a bladder stone.

Introduction: Low-dose-rate brachytherapy is performed for localized prostate cancer. We report the first case of a bladder stone encompassing the seed migrated into the bladder in a patient treated with low-dose-rate brachytherapy. Case presentation: A man was diagnosed with prostate cancer and underwent low-dose-rate brachytherapy. After 2 months, dysuria occurred, and ultrasonography revealed a needle-shaped high-intensity protruding from the prostate into the bladder. Cystoscopy examination found a seed link connector. With the possibility of natural dissolution of the seed link, careful observation was chosen. However, 16 months later, hematuria occurred, and an X-ray revealed a bladder stone encompassing the seed. Compared with the X-ray right after seeding, the seed located near the right bladder neck had fallen. The seed was removed by transurethral bladder lithotripsy. Conclusion: Seeds should be carefully located within the prostate, otherwise a bladder stone may be formed encompassing the seed.

Does radical cystectomy have a better prognosis than bladder conservative treatment in the real world?

PURPOSE: To compare the prognosis and quality of life between radical cystectomy and bladder conservative treatment for muscle invasive bladder cancer in the real world. MATERIALS AND METHODS: Patients treated for muscle invasive bladder cancer without metastases were retrospectively evaluated for overall survival, progression-free survival, and rehospitalization. RESULTS: Of the 141 patients, 62 underwent bladder conservative treatment and 79 underwent radical cystectomy. Patients who underwent radical cystectomy had significantly better progression-free survival (HR: 1.83, 95% CI: 1.12-3.00; p < 0.01) and overall survival (HR: 1.82, 95% CI: 0.99-3.34; p = 0.03) than those who underwent conservative treatment. However, there was no significant difference in prognosis between patients who refused to undergo radical cystectomy and those who underwent. In addition, rehospitalization rates for complications and additional treatment were significantly higher in patients who received conservative treatment (69.3% vs. 34.2%; p < 0.01), and the length of hospital stay was also prolonged compared to patients who received radical cystectomy (26 vs. 9 days; p = 0.03). CONCLUSIONS: Overall, conservative treatment had a significantly poorer prognosis than radical cystectomy, but there was no significant difference in prognosis when comparing patients who refused radical cystectomy and received conservative treatment with those who received radical cystectomy. However, hospitalization rates and length of stay were significantly worse for patients who chose conservative treatment, which may lead to a decline in quality of life.

Enzalutamide versus Abiraterone Plus Prednisolone for Nonmetastatic Castration-Resistant Prostate Cancer: A Sub-Analysis from the ENABLE Study for PCa.

Enzalutamide (ENZ) and abiraterone plus prednisolone (ABI) can improve the survival of patients with castration-resistant prostate cancer (CRPC). However, the agent that is more effective against nonmetastatic CRPC remains unclear. To evaluate the agent that can be used as the first-line treatment for CRPC, an investigator-initiated, multicenter, randomized controlled trial (ENABLE Study for PCa) including both metastatic and nonmetastatic CRPC was conducted in Japan. The prostate-specific antigen (PSA) response rate, overall survival, some essential survival endpoints, and safety of patients with nonmetastatic CRPC were also analyzed. In this subanalysis, 15 and 26 patients in the ENZ and ABI arms, respectively, presented with nonmetastatic CRPC. There was no significant difference in terms of the PSA response rate between the ENZ and ABI arms (80% and 64%, respectively; p = 0.3048). The overall survival did not significantly differ between the two arms (HR: 0.68; 95% CI: 0.22-2.14, p = 0.5260). No significant differences were observed in terms of radiographic progression-free survival and cancer-specific survival between the ENZ and ABI arms (HR: 0.81; 95% CI: 0.35-1.84; p = 0.6056 and HR: 0.72; 95% CI: 0.19-2.73; p = 0.6443, respectively). Only four and six patients in the ENZ and ABI arms, respectively, had ≥grade 3 adverse events. ABI and ENZ had similar efficacy and safety profiles in patients with nonmetastatic CRPC.

Bone Turnover Markers, n-Terminal Propeptide of Type I Procollagen and Tartrate-Resistant Acid Phosphatase Type 5b, for Predicting Castration Resistance in Prostate Cancer.

Bone is a common site of prostate cancer metastasis. Bone turnover markers n-terminal propeptide of type I procollagen (P1NP) and tartrate-resistant acid phosphatase type 5b (TRACP-5b) are highly sensitive to bone remodeling activity. However, their prognostic significance as markers of prostate cancer is unknown. This study retrospectively examined the usefulness of P1NP and TRACP-5b as prognostic biomarkers. Castration-resistant prostate cancer recurrence-free survival (CFS) was estimated using the Kaplan-Meier method. A predictive model for CFS was constructed using multivariate analysis. This study enrolled 255 patients diagnosed with prostate cancer at Kanazawa University Hospital. The median follow-up was 115.1 months. Patients with both high serum P1NP and TRACP-5b levels, defined as having a poor bone turnover category (BTC), had significantly shorter CFS. Multivariate analysis identified Gleason score, metastasis, and BTC poor as predictors for castration resistance in prostate cancer. Using these three factors, a prognostic model was established, categorizing patients into low-risk (no or one factor) and high-risk (two or three factors) groups. In the low-risk group, the median CFS was not reached, contrasting with 19.1 months in the high-risk group (hazard ratio, 32.23, p < 0.001). Combining P1NP and TRACP-5b may better predict castration resistance.

Does the quality of endoscopic equipment influence the recurrence rate after photodynamic diagnosis-assisted transurethral resection of bladder tumor?

BACKGROUND: Photodynamic diagnosis-assisted transurethral resection of bladder tumor (PDD-TURBT) for nonmuscle-invasive bladder cancer is superior to conventional white-light TURBT for cancer detection. However, when performing PDD-TURBT, cystoscopy findings vary depending on the quality of the endoscopic equipment. In this study, we compared the effects of different types of endoscopic equipment on postoperative outcomes. METHODS: Patients who underwent their first PDD-TURBT at our clinic were selected. Patients on whom PDD-TURBT was performed using endoscopic equipment A were sorted into Group A, and patients on whom PDD-TURBT was performed using equipment S were sorted into Group S. The characteristics, recurrence-free survival (RFS), and recurrence frequency of these patients were retrospectively investigated and compared. The prognostic factors for RFS were also analyzed. RESULTS: A total of 49 patients were included in Group A and 46 in Group S. In Group S, a higher detection rate (8.2% vs. 30.4 %, p < 0.01) of carcinoma in situ (CIS) was noted. RFS tended to be better in Group S (HR 0.63, p = 0.15). The frequency of recurrence also tended to be lower in Group S (4.92 vs. 3.66 per 10,000 person-days, p = 0.08). Furthermore, CIS (HR 0.30, p = 0.04) and Bacillus Calmette-Guerin therapy (HR: 0.26, p = 0.01) were significant favorable prognostic factors for RFS. CONCLUSION: The quality of the endoscopic equipment may influence postoperative recurrence after PDD-TURBT. Higher-quality endoscopic instruments have superior CIS detection capabilities, which can lead to improvements in postoperative outcomes with the appropriate selection of postoperative adjuvant therapy.

Procalcitonin in advanced urological cancer-bacterial versus non-bacterial infections: prospective cohort study.

OBJECTIVES: Patients with advanced cancer may develop bacterial infections (BI) as their general condition worsens, but general blood tests often find it difficult to distinguish them from non-bacterial infections (NBI). The present prospective study was undertaken to investigate the effectiveness of serum procalcitonin levels in distinguishing between BI and NBI in patients with advanced urological cancer. METHODS: This study prospectively evaluated patients diagnosed with locally advanced or metastatic or recurrent urological cancer in our department from September 2013 to December 2019. Body temperature was measured in the axilla and the measurement results were recorded. Febrile episodes of ≥38.0°C were analysed, and written patient consent was obtained at the onset of the fever. RESULTS: Of 75 patients enrolled in the present study, 90 febrile episodes were analysed. A total of 34 of 90 febrile episodes were regarded as BI, and the remaining 56 febrile episodes as NBI. The median procalcitonin value was significantly higher in the BI group (p=0.0015), while no significant difference was found between the two groups for white blood cell count and C reactive protein. Additionally, a white blood cell count of less than 1.0×10ˆ9/L resulted in BI in all cases. The procalcitonin receiver operating characteristic area under the curve was 0.710 (95% CI 0.586 to 0.83), excluding cases with white blood cell counts of <1.0 × 103/µL. CONCLUSIONS: Procalcitonin is a rapid and affordable marker for differentiation between BI and NBI in patients with advanced urological cancer.

Atezolizumab plus chemotherapy versus placebo plus chemotherapy in untreated locally advanced or metastatic urothelial carcinoma (IMvigor130): final overall survival analysis results from a randomised, controlled, phase 3 study.

BACKGROUND: IMvigor130 demonstrated statistically significant investigator-assessed progression-free survival benefit with first-line atezolizumab plus platinum-based chemotherapy (group A) versus placebo plus platinum-based chemotherapy (group C) in patients with locally advanced or metastatic urothelial carcinoma. Overall survival was not improved in interim analyses. Here we report the final overall analysis for group A versus group C. METHODS: In this global, partially blinded, randomised, controlled, phase 3 study, patients (aged ≥18 years) with previously untreated locally advanced or metastatic urothelial cancer and who had an Eastern Cooperative Oncology Group performance status of 0-2 were enrolled at 221 hospitals and oncology centres in 35 countries. Patients were randomly assigned (1:1:1), with a permuted block method (block size of six) and an interactive voice and web response system, stratified by PD-L1 status, Bajorin risk factor score, and investigator's choice of platinum-based chemotherapy, to receive atezolizumab plus platinum-based chemotherapy (group A), atezolizumab monotherapy (group B), or placebo plus platinum-based chemotherapy (group C). Sponsors, investigators, and patients were masked to assignment to atezolizumab or placebo (ie, group A and group C) and atezolizumab monotherapy (group B) was open label. For groups A and C, all patients received gemcitabine (1000 mg/m2 intravenously; day 1 and day 8 of each 21-day cycle), plus investigator's choice of carboplatin (area under curve 4·5 mg/mL per min or 5 mg/mL per min; intravenously) or cisplatin (70 mg/m2 intravenously), plus either atezolizumab (1200 mg intravenously) or placebo on day 1 of each cycle. Co-primary endpoints of the study were investigator-assessed progression-free survival and overall survival for group A versus group C in the intention-to-treat (ITT) population (ie, all randomised patients), and overall survival for group B versus group C, tested hierarchically. Final overall survival and updated safety outcomes (safety population; all patients who received any amount of any study treatment component) for group A versus group C are reported here. The final prespecified boundary for significance of the overall survival analysis was one-sided p=0·021. The trial is registered with ClinicalTrials.gov, NCT02807636, and is active but no longer recruiting. FINDINGS: Between July 15, 2016, and July 20, 2018, 1213 patients were enrolled and randomly assigned to treatment, of whom 851 were assigned to group A (n=451) and group C (n=400). 338 (75%) patients in group A and 298 (75%) in group C were male, 113 (25%) in group A and 102 (25%) in group C were female, and 346 (77%) in group A and 304 (76%) in group C were White. At data cutoff (Aug 31, 2022), after a median follow up of 13·4 months (IQR 6·2-30·8), median overall survival was 16·1 months (95% CI 14·2-18·8; 336 deaths) in group A versus 13·4 months (12·0-15·3; 310 deaths) in group C (stratified hazard ratio 0·85 [95% CI 0·73-1·00]; one-sided p=0·023). The most common grade 3-4 treatment-related adverse events were anaemia (168 [37%] of 454 patients who received atezolizumab plus chemotherapy vs 133 [34%] of 389 who received placebo plus chemotherapy), neutropenia (167 [37%] vs 115 [30%]), decreased neutrophil count (98 [22%] vs 95 [24%]), thrombocytopenia (95 [21%] vs 70 [18%]), and decreased platelet count (92 [20%] vs 92 [24%]). Serious adverse events occurred in 243 (54%) patients who received atezolizumab plus chemotherapy and 196 (50%) patients who received placebo plus chemotherapy. Treatment-related deaths occurred in nine (2%; acute kidney injury, dyspnoea, hepatic failure, hepatitis, neutropenia, pneumonitis, respiratory failure, sepsis, and thrombocytopenia [n=1 each]) patients who received atezolizumab plus chemotherapy and four (1%; unexplained death, diarrhoea, febrile neutropenia, and toxic hepatitis [n=1 each]) who received placebo plus chemotherapy. INTERPRETATION: Progression-free survival benefit with first-line combination of atezolizumab plus platinum-based chemotherapy did not translate into a significant improvement in overall survival in the ITT population of IMvigor130. Further research is needed to understand which patients might benefit from first-line combination treatment. No new safety signals were observed. FUNDING: F Hoffmann-La Roche.

Atezolizumab monotherapy versus chemotherapy in untreated locally advanced or metastatic urothelial carcinoma (IMvigor130): final overall survival analysis from a randomised, controlled, phase 3 study.

BACKGROUND: The primary analysis of IMvigor130 showed a significant progression-free survival benefit with first-line atezolizumab plus platinum-based chemotherapy (group A) versus placebo plus platinum-based chemotherapy (group C) in patients with locally advanced or metastatic urothelial cancer. However, this finding did not translate into significant overall survival benefit for group A versus group C at the final analysis, precluding formal statistical testing of outcomes with atezolizumab monotherapy (group B) versus group C. Here we report the final overall survival results for group B versus group C; this report is descriptive and should be considered exploratory due to the study's statistical design. METHODS: In this global, partially blinded, randomised, controlled, phase 3 study, patients (aged ≥18 years) who had locally advanced or metastatic urothelial cancer previously untreated in the metastatic setting and Eastern Cooperative Oncology Group performance status of 0-2 were enrolled at 221 hospitals and oncology centres in 35 countries. Patients were randomly assigned (1:1:1), using a permuted block method (block size of six) and an interactive voice and web response system, stratified by PD-L1 status, Bajorin score, and investigator's choice of platinum-based chemotherapy, to receive either atezolizumab plus platinum-based chemotherapy (group A), atezolizumab alone (group B), or placebo plus platinum-based chemotherapy (group C). Sponsors, investigators, and patients were masked to assignment to atezolizumab or placebo in group A and group C; atezolizumab monotherapy in group B was open label. For groups B and C, atezolizumab (1200 mg) or placebo was administered intravenously every 3 weeks. Chemotherapy involved 21-day cycles of gemcitabine (1000 mg/m2 body surface area on day 1 and day 8 of each cycle) plus the investigator's choice of carboplatin (area under the curve 4·5 mg/mL per min or 5 mg/mL per min) or cisplatin (70 mg/m2 body surface area), administered intravenously. Co-primary endpoints were progression-free survival and overall survival in group A versus group C, and overall survival in group B versus group C, tested hierarchically, in the intention-to-treat (ITT) population, and then the populations with high PD-L1 tumour expression (immune cell [IC] expression score of IC2/3) if the results from group A versus group C were significant. Here, we report the co-primary endpoint of overall survival for group B versus group C in the ITT and IC2/3 populations. The ITT population for this analysis comprised concurrently enrolled patients in groups B and C who were randomly assigned to treatment. For the safety analysis, all patients enrolled in group B and group C who received any study treatment were included. The trial is registered with ClinicalTrials.gov, NCT02807636, and is active but no longer recruiting. FINDINGS: Between July 15, 2016, and July 20, 2018, 1213 patients were enrolled and randomly assigned to treatment, of whom 362 patients were assigned to group B and 400 to group C, of whom 360 and 359, respectively, were enrolled concurrently (ITT population). 543 (76%) of 719 patients were male, 176 (24%) were female, and 534 (74%) were White. As of data cutoff (Aug 31, 2022), after a median follow-up of 13·4 months (IQR 6·2-30·8), median overall survival was 15·2 months (95% CI 13·1-17·7; 271 deaths) in group B and 13·3 months (11·9-15·6; 275 deaths) in group C (stratified hazard ratio 0·98 [95% CI 0·82-1·16]). The most common grade 3-4 treatment-related adverse events were anaemia (two [1%] in patients who received atezolizumab monotherapy vs 133 [34%] in those who received placebo plus chemotherapy), neutropenia (one [<1%] vs 115 [30%]), decreased neutrophil count (0 vs 95 [24%]), and decreased platelet count (one [<1%] vs 92 [24%]). Serious adverse events occurred in 163 (46%) patients versus 196 (50%). Treatment-related deaths occurred in three (1%; n=1 each, pneumonia, interstitial lung disease, large intestinal obstruction) patients who received atezolizumab monotherapy and four (1%; n=1 each, diarrhoea, febrile neutropenia, unexplained death, toxic hepatitis) who received placebo plus chemotherapy. INTERPRETATION: The final analysis from IMvigor130 did not show a significant improvement in overall survival with first-line atezolizumab monotherapy compared with platinum-based chemotherapy in the intention-to-treat population. The safety profile of atezolizumab monotherapy remained acceptable after extended follow-up, with no new safety signals. FUNDING: F Hoffmann-La Roche.

Overall Survival by Response to First-line Induction Treatment with Atezolizumab plus Platinum-based Chemotherapy or Placebo plus Platinum-based Chemotherapy for Metastatic Urothelial Carcinoma.

Standard-of-care first-line treatment for metastatic urothelial carcinoma (mUC) is platinum-based chemotherapy (CTx). Maintenance immunotherapy is a treatment option for patients without progressive disease (PD) after induction CTx. IMvigor130 was a randomised, phase 3 study evaluating atezolizumab plus platinum-based CTx (arm A), atezolizumab monotherapy (arm B), or placebo plus platinum-based CTx (arm C) as first-line treatment for mUC. The primary progression-free survival (PFS) analysis showed a statistically significant PFS benefit favouring arm A versus arm C, which did not translate into overall survival (OS) benefit at the final OS analysis. We report exploratory analyses based on response to combination induction treatment (arm A vs arm C) using final OS data. Post-induction OS was analysed for patients without PD during induction (4-6 CTx cycles) who received at least one dose of single-agent atezolizumab/placebo maintenance treatment. Post-progression OS was analysed for patients with PD during induction CTx. Addition of atezolizumab to CTx did not impact OS outcomes, regardless of response to induction CTx, with hazard ratios of 0.84 (95% confidence interval [CI] 0.63-1.10) for patients without PD and 0.75 (95% CI 0.54-1.05) for those with PD during induction CTx. Treatment effects appeared to be greatest for patients treated with cisplatin and for those with PD-L1-high tumours. Patient summary: The IMvigor130 trial showed that addition of atezolizumab to chemotherapy (CTx) did not improve survival over CTx alone in patients with bladder cancer. Overall, patients whose cancer did not progress during initial treatment tended to live longer than patients whose cancer did progress, but addition of atezolizumab to CTx did not help either group live longer in comparison to CTx alone. However, the results suggest that patients who received a certain CTx drug (cisplatin) or who had high levels of a marker called PD-L1 in their tumour may get the most improvement from addition of atezolizumab to CTx.The IMvigor130 trial is registered on ClinicalTrials.gov as NCT02807636.

Efficacy of keishibukuryogan for hot flashes in prostate cancer patients receiving androgen deprivation therapy: a sub-analysis focusing on hormonal and cytokine levels.

Background: The current study attempted to elucidate the mechanisms of keishibukuryogan (TJ-25) efficacy by focusing on hormonal and cytokine levels. This is a sub-analysis of serum hormonal and cytokine levels extracted from the single-arm prospective study. Methods: Twenty-five participants were administrated TJ-25 at a dose of 2.5 g three times daily for 12 weeks, and competed for a diary of their hot flashes conditions. Various hormonal and cytokine values, including interleukin (IL)-8 and tumor necrosis factor-α (TNF-α), were measured at the baseline and 12-week visits. The correlation of hot flashes with hormonal and cytokine levels at baseline was investigated. As part of the responder analyses, all participants were divided into two groups based on the median baseline values of all hormones and cytokines at baseline, and the change amounts in strength and frequency of hot flashes from baseline to 12-week visits in both groups were compared. Furthermore, a correlation in change amounts (Δ values) by TJ-25 administration between hot flashes and each parameter was also conducted. Results: Hot flashes intensity was inversely related to estradiol levels (r=-0.433, P=0.019), and frequency was inversely related to progesterone levels (r=-0.415, P=0.025). In the responder analyses, the effectiveness of TJ-25 for hot flash strength increased in the patients with higher levels of TNF-α at baseline (P=0.0372). TJ-25 was more efficient in frequency in the patients with higher levels of IL-8 (P=0.0312). TJ-25 efficacy, on the other hand, was not significantly associated with changes in any hormonal or cytokine levels between the baseline and 12-week visits. However, ΔIL-8 and ΔTNF-α were not significantly correlated with Δstrength and Δfrequency of hot flashes by TJ-25 administration. Conclusions: Hot flashes were inversely correlated with estradiol and progesterone levels. TJ-25 was more effective in patients with higher TNF-α and IL-8 levels, with no significant change in serum levels caused by the treatment. The suggestive mechanism for the effects of keishibukuryogan is that this drug doesn't suppress the production of IL-8 and TNF-α, but may inhibit some actions of these cytokines.

Role of Positive Biopsy Core Ratio in Prostate Cancer Patients.

BACKGROUND/AIM: The percentage of positive cores (PPC) is increasingly recognized as a prognostic factor in prostate cancer. However, the usefulness of PPC for patients undergoing androgen deprivation therapy (ADT) and high-risk group has not been adequately studied. PATIENTS AND METHODS: A retrospective analysis was conducted of 255 patients who underwent prostate biopsy (all-case group). We examined the efficacy of PPC as a prognostic biomarker. RESULTS: Eighty-nine patients were treated with ADT alone (ADT group), and 107 patients were classified as high-risk (high-risk group). The median duration of follow-up was 112.4 months, 85.3 months, and 110.0 months for the all-case, ADT, and high-risk groups, respectively. Patients with PPC >60% had significantly shorter prostate cancer-specific survival (CSS) and castration-resistant prostate cancer-free survival (CFS) in the all-case and ADT groups. In the high-risk group, patients with PPC >60% had shorter CFS but no difference in CSS. Multivariate analysis showed that significant independent predictors of prostate CSS were the presence of metastasis at diagnosis and PPC >60% in the all-case and ADT groups. CONCLUSION: PPC may be a prognostic factor in ADT treated and high-risk prostate patients.

Relation between athletic club affiliation from school age and future serum free testosterone levels in Japan: A cross-sectional study.

Background and Aims: Testosterone deficiency is often related to geriatric syndrome including erectile dysfunction, osteo-porosis, depression, cognitive impairment, cardiovascular diseases and frailty. Despite the existence of many studies on short-term exercise and serum testosterone levels, few research have focused on exercise habits from young age and testosterone values in middle-aged male. In this study, we investigated whether belonging to an athletic club from school age could predict serum-free testosterone (FT) levels. Methods: The subjects were 1609 middle-aged male outpatients aged 40 years or older (median: 61 years, interquartile range: 54-69) who visited our hospital. Participants had their FT values measured in the morning hours during the period from December 2007 to June 2009. A questionnaire survey on exercise habits was conducted at the same time as the measurements. The exercise habit questionnaire was created based on whether the patients belonged to an athletic club in (a) elementary school, (b) junior high school, (c) high school, (d) college, (e) adult life, and (f) at the time of the test. Results: There was only one positive response to the questionnaire among 456 patients (28% of total), followed by zero for 358 patients (22% of total). The number of patients with low-testosterone levels (FT < 8.5 pg/mL) according to the Japanese diagnostic criteria for late-onset of hypogonadism was 839 (52.1%). In multivariate analysis, it was shown that with low-testosterone levels (FT < 8.5 pg/mL), age (odds ratio [OR]: 1.065, 95% confidence interval [CI]: 1.052-1.079; p < 0.001), hypertension (OR: 3.489, 95% CI: 2.728-4.462; p < 0.001), type-2 diabetes (OR: 3.035, 95% CI: 2.296-4.01; p < 0.001), and dyslipidemia (OR: 2.039, 95% CI: 1.558-2.668; p < 0.001) were risk factors, and more than two positive responses to the questionnaire (OR: 0.886, 95% CI: 0.802-0.980; p = 0.018) were also a significant independent factor. Conclusion: A sports club membership during school years may affect future testosterone levels.

Combination of Sarcopenia and Hypoalbuminemia Is a Poor Prognostic Factor in Surgically Treated Nonmetastatic Renal Cell Carcinoma.

PURPOSE: The purpose of this study is to observe how preoperative sarcopenia and hypoalbuminemia affect the oncological outcome of nonmetastatic renal cell carcinoma (RCC) after partial or radical nephrectomy. METHODS: This study retrospectively analyzes 288 Japanese patients with nonmetastatic RCC who underwent radical treatment at Kanazawa University Hospital between October 2007 and December 2018. Relationships between sarcopenia as indicated by the psoas muscle mass index and hypoalbuminemia (albumin ≤ 3.5 g/dL) with overall survival (OS) and metastasis-free survival (MFS) were determined. RESULTS: The study found that 110 (38.2%) of the 288 patients were sarcopenic and 29 (10.1%) had hypoalbuminemia. The combination of sarcopenia and hypoalbuminemia was associated with a shorter OS and MFS (p for trend = 0.0007 and <0.0001, respectively), according to Kaplan-Meier curves. The concurrent presence of sarcopenia and hypoalbuminemia were found to be significant and independent predictors of poor MFS (hazard ratio (HR), 2.96; 95% confidence interval (95% CI), 1.05-8.39; p = 0.041) and poor OS (HR, 6.87; 95% CI, 1.75-26.94; p = 0.006), respectively. CONCLUSIONS: In Japanese patients with surgically treated nonmetastatic RCC, combined preoperative sarcopenia and hypoalbuminemia was a significant predictor of poor survival.