Search

Unresectable, metastatic, advanced urothelial carcinoma (aUC) is an aggressive disease and is treated with platinum-containing first-line chemotherapy, followed by immune checkpoint inhibitors and antibody–drug conjugates. Response to first-line chemotherapy is a vital priority in sequential treatment strategies because a better response to first-line chemotherapy is associated with a better response to subsequent therapies. Gemcitabine plus carboplatin chemotherapy is conventionally recommended for cisplatin-ineligible patients. This multicenter, single-arm prospective trial will investigate whether dose-dense methotrexate, vinblastine, doxorubicin, and carboplatin (DD-MVACarbo) chemotherapy is superior to gemcitabine plus carboplatin chemotherapy in terms of efficacy in platinum-naïve, cisplatin-ineligible patients with aUC. After screening and registration, a total of 46 patients will be treated with this novel chemotherapy regimen. The primary endpoint is the objective response rate. The secondary endpoints include disease control rate, patient-reported outcomes, and adverse events. No evidence of this novel intervention is available as of July 2024. The results are expected to change the standard of care and improve the management of patients with aUC. [ABSTRACT FROM AUTHOR]

Key Clinical Message: In middle‐aged and older men, clinicians often suspect lumbar spine disease when gait is impaired with intermittent claudication, but spinal dural arteriovenous fistula (SDAVF) may be the etiology. An understanding of the key magnetic resonance imaging findings of SDAVF is necessary for early diagnosis, appropriate treatment, and minimization of complications. [ABSTRACT FROM AUTHOR]

In vertebrate embryos, the canonical Wnt ligand primes the formation of dorsal organizers that govern dorsal-ventral patterns by secreting BMP antagonists. In contrast, in Drosophila embryos, Toll-like receptor (Tlr)-mediated NFκB activation initiates dorsal-ventral patterning, wherein Wnt-mediated negative feedback regulation of Tlr/NFκB generates a BMP antagonist-secreting signalling centre to control the dorsal-ventral pattern. Although both Wnt and BMP antagonist are conserved among species, the involvement of Tlr/NFκB and feedback regulation in vertebrate organizer formation remains unclear. By imaging and genetic modification, we reveal that a negative feedback loop between canonical and non-canonical Wnts and Tlr4/NFκB determines the size of zebrafish organizer, and that Tlr/NFκB and Wnts switch initial cue and feedback mediator roles between Drosophila and zebrafish. Here, we show that canonical Wnt signalling stimulates the expression of the non-canonical Wnt5b ligand, activating the Tlr4 receptor to stimulate NFκB-mediated transcription of the Wnt antagonist frzb, restricting Wnt-dependent dorsal organizer formation. Dorsal organizer initiates the dorsal-ventral axis formation in vertebrates. Here, the authors demonstrate that Tlr4/NFκB-mediated negative feedback regulation of Wnt/β-catenin signaling determines the precise size of the zebrafish dorsal organizer. [ABSTRACT FROM AUTHOR]

Simple Summary: This was a phase III randomized controlled trial investigating the outcomes of low-dose interleukin-2 (IL-2) plus interferon alfa (IFNα) versus sunitinib as the first line and axitinib as the second line in patients with low- and intermediate-risk metastatic renal cell carcinoma (mRCC). There was a trend toward better total progression-free survival up to the end of the second line for IL-2 + IFNα but no significant advantage in terms of overall survival. The study was underpowered to draw any definitive conclusions. The results showed no clear advantage of IL-2 + IFNα over sunitinib in the first line; however, it may be an option in some relatively low-risk mRCC cases due to the difference in the adverse events profile. This trial was registered with the University Hospital Medical Information Network (UMIN), center identifier UMIN 000012522. Background: The sequence of first-line cytokine and second-line molecular targeted therapies may be suitable for some patients with metastatic renal cell carcinoma (mRCC) because of the expectation of complete remission and durable response achieved with cytokine therapy. Methods: This was a phase III randomized controlled trial investigating the outcomes of low-dose interleukin-2 (IL-2) plus interferon alfa (IFNα) versus sunitinib as the first line and axitinib as the second line in patients with low- and intermediate-risk mRCC. Results: Thirty-five patients were randomly assigned. The total progression-free survival (PFS) to the end of the second line was 29.0 months (95% CI, 11.7–46.3) in the IL-2 + IFNα group and 16.3 months (95% CI, 6.3–26.4) in the sunitinib group. The PFS hazard ratio for the IL-2 + IFNα group relative to the sunitinib group was 0.401 (95% CI, 0.121–1.328; p = 0.135). The hazard ratio for overall survival (OS) was 1.675 (95% CI, 0.418–6.705; p = 0.466), which was better in the sunitinib group than in the IL-2 + IFNα group but not statistically significant. The types of adverse events (AEs) differed significantly, although there was no significant difference in the incidence of AEs. Conclusions: There was a trend toward better total PFS for IL-2 + IFNα, but it was not significant. There was also no advantage of IL-2 + IFNα in terms of OS. The study was underpowered to draw any definitive conclusions. The results showed no clear advantage of IL-2 + IFNα over sunitinib in the first-line setting; however, it may be an option in some relatively low-risk mRCC cases due to the difference in the AE profile. This trial was registered with the University Hospital Medical Information Network (UMIN), center identifier UMIN 000012522. [ABSTRACT FROM AUTHOR]

Background: The phase 3 CLEAR study demonstrated statistically significantly improved efficacy with lenvatinib plus pembrolizumab versus sunitinib, including progression‐free survival and overall survival, in patients with previously untreated advanced renal cell carcinoma. This subset analysis investigated efficacy and safety in Japanese patients randomized to lenvatinib plus pembrolizumab or sunitinib in the CLEAR study. Methods: Progression‐free survival, overall survival, tumor response, and safety were assessed in Japanese patients with previously untreated advanced renal cell carcinoma randomized to receive lenvatinib plus pembrolizumab (n = 42) or sunitinib (n = 31). Efficacy outcomes were analyzed by independent imaging review per Response Evaluation Criteria in Solid Tumors, version 1.1. Results: Progression‐free survival was longer with lenvatinib plus pembrolizumab than with sunitinib (median, 22.1 vs. 10.9 months; hazard ratio, 0.39; 95% CI, 0.20–0.74). Median overall survival was not estimable in the lenvatinib plus pembrolizumab arm and 30.6 months in the sunitinib arm (HR, 1.20; 95% CI, 0.39–3.66). Overall survival adjusted for the imbalance of Memorial Sloan‐Kettering Cancer Center prognostic risk group favored lenvatinib plus pembrolizumab (hazard ratio, 0.67; 95% CI, 0.18–2.39). Objective response rate (69.0% vs. 45.2%; odds ratio, 2.71; 95% CI, 1.03–7.10) was higher and median duration of response (20.3 vs. 9.1 months) was longer with lenvatinib plus pembrolizumab versus sunitinib. Grade ≥ 3 treatment‐emergent adverse events occurred in 95.2% versus 87.1% of patients in the lenvatinib plus pembrolizumab versus sunitinib arms. Conclusions: These findings support lenvatinib plus pembrolizumab as a potential first‐line treatment for Japanese patients with advanced renal cell carcinoma. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to investigate the effect of available treatment modalities on primary treatment selection in patients with localized prostate cancer and that of introducing robotic surgery. Methods: We retrospectively studied 12 061 patients diagnosed with localized prostate cancer between 2004 and 2018 from 21 institutions. These institutions were divided into five groups according to the availability of surgery and radiotherapy. Differences in primary treatment selection between the institutions were investigated, and the predictive factors involved in the selection were explored. Results: Surgery, radiotherapy, androgen deprivation therapy, and active surveillance/watchful waiting were selected as primary treatment in 4115, 3621, 3188, and 821 patients, respectively, while the remaining 316 patients selected other modalities. The number of patients, particularly young patients, was much higher in institutions with both surgery and radiotherapy. With the introduction of robotic surgery, open radical prostatectomy has decreased, and robotic surgery made up approximately 70% of all prostatectomies. Institutions with both surgery and radiotherapy tended to treat patients with very low or low risk by surgery or radiotherapy, while institutions without surgery and radiotherapy tended to select active surveillance or watchful waiting. Multivariate analysis revealed that primary treatment selection for prostate cancer was affected not only by clinical factors, but also by the available modalities in each institution. Conclusions: Differences in available treatment modalities affect the selection of primary treatment for localized prostate cancer. Introduction of robotic surgery also has a strong influence on the number of patients in each institution. [ABSTRACT FROM AUTHOR]

Aim: Urolithiasis is a common disorder of the urinary tract. Medical expulsive therapy is recommended for calculi with diameters <10 mm. This study was conducted to determine the effect of choreito, an herbal medication with discharging effects, on the spontaneous passage of urinary calculi. Methods: This retrospective observational study included 109 adult patients with urinary calculi who were admitted to Hirao Hospital between April 2016 and March 2017. Choreito (7.5 g/day) was administered to 55 participants in the choreito group but not to the 54 participants of the control group. All patients were monitored until the calculi passed naturally. The period of spontaneous passage of the calculi was compared between the choreito and control groups, and the factors associated with this duration were identified using multivariate analysis. Results: Compared to the control group, the period of spontaneous passage of the proximal ureteric stones was significantly shorter in the choreito group (14 days vs 36 days, p = 0.0262). Calculus diameter (<3 mm) and choreito administration were identified as independent factors associated with a shorter period for spontaneous calculi passage. Conclusion: Oral administration of choreito may promote the spontaneous passage of proximal ureteric stones without the need for surgical intervention. [ABSTRACT FROM AUTHOR]

Background: The naturally occurring amino acid 5-aminolevulinic acid (5-ALA) is a precursor of protoporphyrin IX (PpIX) biosynthesised in the mitochondria. When accumulated PpIX is excited by light (wavelength of 625-635 nm), reactive oxygen species (ROS) are generated. Here, we investigated whether 5-ALA may increase the sensitisation of prostate cancer (PCA) cells to radiotherapy through the generation of ROS via its metabolite, PpIX.Methods: Effect of 5-ALA on PC-3 and DU-145 PCA cell lines treated with ionising radiation (IR) was examined in vitro and in vivo with assessment by clonogenic assay, mitochondrial function and ROS production under normoxia or hypoxia condition.Results: 5-ALA enhanced intra-mitochondrial ROS production immediately after exposure to IR and decreased mitochondrial membrane potential via increase of intra-cellular PpIX. IR with 5-ALA induced mitochondrial dysfunction and increased ATP production, switching energy metabolism to the quiescence. Under hypoxic condition, ROS burst and mitochondrial dysfunction were induced by IR with 5-ALA resulting reducing cancer stemness and radiation resistance.Conclusion: These results suggest that combined therapy with 5-ALA and radiation therapy is a novel strategy to improve the anti-cancer effects of radiation therapy for PCA. [ABSTRACT FROM AUTHOR]

Purpose: The level of 6-sulfatoxy-melatonin (SaMT), a metabolite of melatonin, in first-void morning urine reflects blood melatonin levels from the previous night. We investigated the association between urine SaMT and sleep quality deterioration in patients with non-muscle invasive bladder cancer (NMIBC) treated with intravesical Bacillus Calmette-Guerin induction therapy (iBCG).Methods: We enrolled 51 patients who received iBCG once weekly for 6 or 8 weeks. Patient-reported outcomes were assessed with questionnaires including the International Prostate Symptom Score (IPSS) and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (QLQC30). Questionnaires were completed before (baseline), during, at completion, and 1 and 3 months after iBCG. Melatonin and SaMT levels at baseline were measured in serum and first-void morning urine samples, respectively.Results: Based on changes in the QLQC30 insomnia subscale, 28 (55%) patients experienced sleep quality deterioration (deterioration group). Urine SaMT values in the deterioration group were lower than those in the non-deterioration group (P = 0.0015; 7.5 vs 15.4 ng/mg creatinine, respectively). Nocturia scores in the non-deterioration group decreased over time, while those of the deterioration group remained high after completion of iBCG. A binary logistic regression analysis revealed that low urine SaMT levels (≤ 9.6 ng/mg creatinine), high IPSS nocturia scores at baseline, and high IPSS storage subscores at baseline were associated with BCG-induced sleep quality deterioration.Conclusions: This study confirmed the association among urine SaMT levels, nocturia, and sleep disturbance in patients with NMIBC who receive iBCG. We should be aware of treatment-induced impairments to aid in appropriate decision-making. [ABSTRACT FROM AUTHOR]

Summary: This study evaluated erectile function and sexual quality of life (QoL), and predictive factors for erectile dysfunction (ED) and the deterioration of sexual QoL in 70 patients who underwent low‐dose‐rate brachytherapy (LDR‐BT) alone for prostate cancer without androgen deprivation therapy. Erectile function and sexual QoL were evaluated before and 1, 3, 6, 12, 24, 36, 48 and 60 months after LDR‐BT. Binary logistic regression analysis was used to determine whether age, prostate volume, hypertension, diabetes, Brinkman's index, testosterone, baseline Sexual Health Inventory for Men (SHIM) score and post‐implant dosimetry parameters could predict ED and deterioration of sexual QoL at 24 and 60 months after LDR‐BT. After 24 and 60 months, ED was noted in 39 of 70 patients and 42 of 64 patients respectively. Furthermore, sexual QoL worsened in 42 of 70 and 43 of 64 patients respectively. Baseline SHIM score was identified as a significant predictor of ED (24 months: odds ratio [OR]: 0.83, p = 0.02; 60 months: OR: 0.83, p = 0.03) and the deterioration of sexual QoL (24 months: OR: 0.84, p = 0.03). LDR‐BT for prostate cancer promoted decreased erectile function and sexual QoL, with high preimplant potency being a significant predictor of ED and the deterioration of sexual QoL. [ABSTRACT FROM AUTHOR]

Purpose: The treatment landscape for advanced, unresectable, or metastatic urothelial carcinoma (aUC) has shifted substantially since the advent of immune checkpoint inhibitors (ICIs). We investigated the extent to which pembrolizumab therapy is superior to conventional chemotherapy as a second-line treatment. Patients and Methods: A multicenter-derived database registered 454 patients diagnosed with aUC between 2008 and 2020. Of these, 94 patients (21%) who received second-line pembrolizumab and 75 (17%) who received second-line chemotherapy but never received third-line or later ICI therapy were included. We compared overall survival (OS) from the initial date of first-line chemotherapy between two groups by adjusting for prognostic factors through propensity score matching (PSM) and inverse probability of treatment weighting (IPTW). The IPTW-adjusted hazard ratio and 95% confidence interval were estimated using a multivariate Cox regression analysis. To identify patients who were more likely to benefit from second-line pembrolizumab than from chemotherapy, we performed a subgroup analysis for OS with an IPTW-adjusted model. Results: The PSM-adjusted comparison showed a significant improvement in the prognosis with second-line pembrolizumab use (P = 0.01). The OS benefit with the advent of pembrolizumab was 8 months (18 months vs 26 months). Multivariable analyses using IPTW adjustment demonstrated that lymph node metastasis (P = 0.001), lung metastasis (P = 0.013), and bone metastasis (P = 0.003) were poor independent prognostic factors, and pembrolizumab use (P = 0.021) was a favorable independent prognostic factor. Subgroup analyses revealed that pembrolizumab was associated with survival benefits over chemotherapy in all subgroups, including young patients (age < 70 years), those who received radical surgery, and those without visceral metastasis. Conclusion: We demonstrated a significant improvement in prognosis after the advent of pembrolizumab for patients with aUC. ICIs should not be restricted based on patient characteristics. [ABSTRACT FROM AUTHOR]

Objective: Higher quality of postimplant dosimetric evaluation is associated with higher biochemical recurrence‐free survival rates after low‐dose‐rate brachytherapy for localized prostate cancer. Postimplant prostate D90 is a key dosimetric parameter showing the quality of low‐dose‐rate brachytherapy. In this study, to improve the quality of low‐dose‐rate brachytherapy for localized prostate cancer, we investigated pre‐implant factors affecting the reduction of postimplant prostate D90. Methods: A total of 441 patients underwent low‐dose‐rate brachytherapy monotherapy and 474 patients underwent low‐dose‐rate brachytherapy with external beam radiation therapy. Logistic regression analysis was carried out to identify predictive factors for postimplant D90 decline. The cut‐off value of the D90 decline was set at 170 Gy and 130 Gy in the low‐dose‐rate brachytherapy monotherapy group and low‐dose‐rate brachytherapy with external beam radiation therapy group, respectively. Results: On multivariate analysis, neoadjuvant androgen deprivation therapy was identified as an independent predictive factor for the decline of postimplant D90 in both the low‐dose‐rate brachytherapy monotherapy group (P < 0.001) and low‐dose‐rate brachytherapy with external beam radiation therapy group (P = 0.003). Prostate volume changes and computed tomography/transrectal ultrasound prostate volume ratio were significantly and negatively correlated with the postimplant D90. The prostate volume changes and computed tomography/transrectal ultrasound prostate volume ratio were significantly higher in patients with neoadjuvant androgen deprivation therapy than those without neoadjuvant androgen deprivation therapy (P < 0.001). Conclusions: Neoadjuvant androgen deprivation therapy decreased postimplant D90 with substantial prostate gland swelling after low‐dose‐rate brachytherapy. When neoadjuvant androgen deprivation therapy is required to reduce prostate volume for patients with large prostate glands and offer adequate local control for patients with high‐risk prostate cancer before low‐dose‐rate brachytherapy, intraoperative D90 adjustment might be necessary. [ABSTRACT FROM AUTHOR]

Objectives: Lower urinary tract symptoms are transiently exacerbated by low‐dose‐rate brachytherapy (LDR‐BT) for prostate cancer and recover to pretreatment levels 1 year thereafter. Generally, these symptoms are influenced by temperature. We aimed to search for factors affecting the lower urinary tract symptoms after seed implant including seasons. Methods: We retrospectively enrolled 812 patients who underwent LDR‐BT at Nara Medical University Hospital from January 2010 to December 2018 and for whom the International Prostate Symptom Score, Overactive Bladder Symptom Score, and frequency volume charts were available. We investigated the relationships between lower urinary tract symptoms, 24‐hours urinary frequency, 24‐hours urinary volume before and after seed implant, radiation dose, and season of seed implant. Results: The mean age was 69.5 years. The mean prostate volume was 24.2 mL. The International Prostate Symptom Score, Overactive Bladder Symptom Score, and 24‐hours urinary frequency increased until 3 months and gradually decreased over 6 months after seed implant. Multiple linear regression analysis revealed that 24‐hours urinary frequency at 3 months after seed implant was significantly influenced by external beam radiotherapy, larger prostate volume before implant, higher 24‐hours urinary frequency at baseline, larger 24‐hours urinary volume at 3 months after implant, and performance of implant in summer. Conclusions: Lower urinary tract symptoms worsened 3 months after seed implant of LDR‐BT regardless of the season of implant. The urinary frequency 3 months after seed implant was slightly lower when seed implant was performed in the summer. [ABSTRACT FROM AUTHOR]

Background: In the phase III open-label KEYNOTE-426 (NCT02853331) study, first-line pembrolizumab and axitinib improved overall survival (OS) and progression-free survival (PFS) versus sunitinib for metastatic renal cell carcinoma (mRCC). KEYNOTE-426 evaluated patients enrolled from 25 sites in Japan. Methods: Patients enrolled in Japan were included in this post hoc subgroup analysis. Adults with clear cell mRCC were randomly assigned 1:1 to receive intravenous pembrolizumab 200 mg every 3 weeks plus oral axitinib 5 mg twice daily or oral sunitinib 50 mg once daily (4 weeks on/2 weeks off). Dual primary endpoints were OS and PFS as assessed by blinded independent central review. Objective response rate (ORR) and safety were secondary endpoints. Results: The Japanese subgroup comprised 94 patients (pembrolizumab–axitinib, n = 44; sunitinib, n = 50; 11% of the intent-to-treat population). Median time from randomization to data cutoff (January 6, 2020) was 29.5 months (range 24.6–37.3). Consistent with the intent-to-treat population, the OS, PFS, and ORR suggested improvement with pembrolizumab–axitinib versus sunitinib in the Japanese subgroup. Grade ≥ 3 treatment-related adverse events (TRAEs) occurred in 70% of patients receiving pembrolizumab–axitinib versus 78% receiving sunitinib; 11 (25%) patients receiving pembrolizumab–axitinib and 13 (27%) patients receiving sunitinib discontinued the study medication due to AEs. TRAEs led to the discontinuation of pembrolizumab, axitinib, pembrolizumab–axitinib, or sunitinib in 32%, 34%, 14%, and 20%, respectively. No deaths from TRAEs occurred. Conclusions: Efficacy outcomes for the Japanese subgroup were consistent with those of the global population. Safety in Japanese patients was consistent with the results from the global population. [ABSTRACT FROM AUTHOR]

Purpose: We investigated sleep parameters and patient-reported outcomes before, during, and after induction Bacillus Calmette-Guerin therapy using questionnaires and actigraphy in patients with non-muscle invasive bladder cancer. Methods: We investigated 10 patients who received Bacillus Calmette-Guerin therapy once weekly for 8 weeks. The International Prostate Symptom Score, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30, Functional Assessment of Cancer Therapy-Bladder, and multi-item Short Form-8 tools were used to assess patient-reported outcomes. Participants completed all questionnaires before (baseline), at the 4th and 8th doses, and 1 month after the last Bacillus Calmette-Guerin dose. The MotionWatch8 was fastened to patients' waist throughout the study. Composite sleep quality was determined based on sleep duration, efficiency, and fragmentation. Results: We observed a transient increase in frequency/nocturia subscores and the insomnia subscore. The number of patients with poor sleep quality increased from 0 (0%) at baseline to 7 (70%) at the 4th dose and to 6 (60%) patients at the 8th dose. Among 10 patients, 6 (60%) were assigned to the sleep deterioration group and 4 (40%) to the non-deterioration group. Sleep quality was restored to baseline levels in 5 of 6 patients (83%) within 1 month after the last dose in the sleep deterioration group, and the nocturia subscore of the International Prostate Symptom Score was significantly increased only in this group (P=0.03). Conclusions: This is the first study that confirms intravesical Bacillus Calmette-Guerin-induced sleep quality deterioration based on a questionnaire survey and actigraphy. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the efficacy, safety and tolerability of vibegron for the treatment of antimuscarinic‐resistant neurogenic bladder dysfunction in patients with spina bifida. Methods: In this retrospective study, 15 patients with antimuscarinic‐resistant neurogenic bladder dysfunction due to spina bifida underwent a video‐urodynamic study before and during the administration of vibegron 50 mg once daily instead of antimuscarinic agents from February 2019 through April 2021. The video‐urodynamic study was carried out to evaluate bladder compliance, maximum cystometric bladder capacity, detrusor overactivity, detrusor leak point pressure and vesicoureteral reflux before and >3 months after the beginning of vibegron administration. Results: Treatment with vibegron significantly improved bladder compliance and maximum cystometric bladder capacity compared with antimuscarinic agents, respectively (7.4 ± 4.2 vs 30.4 ± 48.2 mL/cmH2O, P = 0.0001; 231.4 ± 81.2 vs 325.2 ± 106.5 mL, P = 0.0005). Detrusor overactivity did not change after the administration of vibegron. Bladder deformity, which was confirmed in 12 patients, improved in half of the patients after taking vibegron. Vesicoureteral reflux, which was confirmed in two patients, was extinguished after taking vibegron. Newly occurring adverse events were not observed, and all patients continued to take vibegron during the treatment period. Conclusions: Favorable efficacy of vibegron for antimuscarinic‐resistant neurogenic bladder dysfunction due to spina bifida was shown video‐urodynamically without apparent adverse events. Vibegron is a favorable option for the treatment of antimuscarinic‐resistant neurogenic bladder dysfunction in patients with spina bifida. [ABSTRACT FROM AUTHOR]

Objectives: To compare the effects of naftopidil and silodosin administration on the quality of life of patients with prostate cancer who underwent low‐dose‐rate brachytherapy. Methods: In total, 141 men diagnosed with localized prostate cancer who were treated with low‐dose‐rate brachytherapy were enrolled. Patients were randomized (1:1) to the naftopidil (75 mg/day, n = 63) or silodosin group (8 mg/day, n = 64). Naftopidil and silodosin were administered 1 day after low‐dose‐rate brachytherapy, and were continued for at least 3 months. Using the University of California at Los Angeles Prostate Cancer Index and Sexual Health Inventory for Men scores, the mean changes and rates of deterioration from baseline were compared. The deterioration rates in the quality of life of patients at 1 and 3 months after low‐dose‐rate brachytherapy were evaluated based on the minimal important difference. Results: The rates of deterioration from baseline to 1 and 3 months after low‐dose‐rate brachytherapy were not significantly different between the two groups in terms of urinary function, urinary bother, bowel bother, sexual function or Sexual Health Inventory for Men scores. In contrast, there were significant differences in bowel function (naftopidil 1 month, 52%; 3 months, 52%; silodosin 1 month, 28%; 3 months, 34%; 1 month, P < 0.01; 3 months, P = 0.048) and sexual bother (naftopidil 3 months, 11%; silodosin 3 months, 29%; P = 0.01). Conclusions: Naftopidil and silodosin provide different disease‐specific quality of life outcomes in patients undergoing, especially in terms of bowel function and sexual bother. These findings can help in the selection of α‐1 adrenoceptor antagonists after low‐dose‐rate brachytherapy. [ABSTRACT FROM AUTHOR]

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

Objectives: To investigate long‐term chronological changes in functional renal volume and renal function after nephron‐sparing surgery, and factors that contribute to the progression of postoperative chronic kidney disease. Methods: A total of 80 patients who underwent nephron‐sparing surgery were enrolled in this prospective observational study. The renal function deterioration group was defined as patients whose estimated glomerular filtration rate at 5 postoperative years decreased by ≥20% relative to that before surgery. Results: The predicted estimated glomerular filtration rate, calculated based on the functional renal volume at 5 postoperative years, was strongly correlated with the postoperative estimated glomerular filtration rate (Spearman's ρ = 0.89, P < 0.001). The rate of new‐onset stage IIIb chronic kidney disease was significantly higher in the renal function deterioration group than in the stable renal function group (P < 0.001). Multivariate analysis identified proteinuria (P = 0.017), small preoperative total functional renal volume (≤250 mL, P = 0.046) and large tumor volume (≥4.5 mL, P = 0.036) as independent factors associated with renal function deterioration. Conclusions: Our findings show that the functional renal volume is significantly associated with renal function, even in the long‐term postoperative period. Additionally, for patients with preoperative proteinuria, large tumor volume and small total preoperative functional renal volume, both oncological follow ups and medical interventions, including prevention of lifestyle‐related diseases, might prevent the progression of chronic kidney disease. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the diagnostic performance of fluorescent voided urine cytology (FVUC) using a novel automated detection technology to screen for primary bladder cancer and for surveillance of recurrent bladder tumour. Patients and Methods: We created a rapid, objective, automated, and high‐throughput detection device for hexylaminolevulinate‐mediated FVUC, named the cellular fluorescence analysis unit‐II (CFAU‐II). Two different cohorts were used in this study: (i) screening test for primary bladder cancer (165 patients with bladder cancer and 52 controls), and (ii) surveillance test for detecting intravesical recurrent tumour (192 patients with treated non‐muscle‐invasive bladder cancer and 15 with post‐nephroureterectomy upper urinary tract cancer). Voided urine samples were subjected to urine analysis, conventional VUC (cVUC), and FVUC. Diagnostic performance was compared between cVUC, FVUC, and a combination of the two. Results: A total of 614 urine samples were successfully collected, processed, and analysed. Comparative analysis of the screening test cohort demonstrated that the overall sensitivity of FVUC (63%, P < 0.001) and combination testing (72%, P < 0.001) was significantly higher than that of cVUC (29%). FVUC was found to be superior in most of the subgroups, especially in low‐grade, Ta, and small tumours. Analysis of the surveillance test cohort showed that combination testing achieved a sensitivity of 82% and a negative predictive value of 98%, whereas those of cVUC were 39% and 96%, respectively. According to the pathological finding of recurrent tumours presenting false‐negative result in the FVUC, the majority of the overlooked recurrent diseases were Ta low‐grade tumours. Logistic regression analysis suggested an association between the risk of false‐positive results and high density of urine white blood cells and alkaluria. Conclusion: The present findings clearly demonstrate that FVUC using the newly developed automation technology has superior sensitivity to cVUC for both screening for primary bladder cancer and recurrent tumour detection. It is essential to confirm the clinical usefulness of this method via further large‐scale studies, in addition to ensuring its affordability and availability. [ABSTRACT FROM AUTHOR]

Purpose: Reports suggest that partial nephrectomy provides no significant benefit in terms of cancer-specific and overall survival (OS) compared to radical nephrectomy. Here, we focused on survival in terms of life expectancy and investigated the significance of partial nephrectomy for localized renal cell carcinoma (RCC) patients. Patients and Methods: Our retrospective study included 937 patients (median age 63 years) with localized RCC who underwent partial nephrectomy or radical nephrectomy. Various predictive factors were explored, and the association between actual OS and life expectancy was analyzed. Results: Performance status (PS) ≥ 1 and tumor size ≥ 40 mm were identified as independent poor prognostic factors for cancer-specific survival. Age ≥ 60, male sex, PS ≥ 1, C-reactive protein elevation, pT1b stage, and radical nephrectomy were identified as independent poor prognostic factors for OS. OS and life expectancy did not differ in the partial nephrectomy group (P=0.11). OS was significantly shorter than life expectancy in the radical nephrectomy group (P< 0.0001). In PS0 or pT1a patients, there was a significant difference between actual OS and life expectancy in the radical nephrectomy group (P< 0.0001), but not in the partial nephrectomy group (P=0.15). In patients with a life expectancy ≥ 10 years, PS0, and pTa, OS and life expectancy differed in the radical nephrectomy group, but not in the partial nephrectomy group. Conclusion: Partial nephrectomy can improve actual OS, and notably, PS and tumor size are crucial factors that determine the choice of surgical procedure. Further research is needed to establish appropriate treatment strategies and criteria for clinical practice. [ABSTRACT FROM AUTHOR]

Background: We describe the oncologic and functional outcomes and the surgical technique of the photodynamic diagnosis (PDD)-assisted en bloc transurethral resection of bladder tumor (EBTUR) using a rectangular cutting loop. Methods: We reviewed 40 patients with carcinoma in situ-free nonmuscle invasive bladder cancer undergoing PDD-TURBT. Of 40 patients, 12 underwent photodynamic diagnosis-assisted en bloc transurethral resection of bladder tumor (PDD-EBTUR) and 28 underwent PDD-assisted conventional TURBT (cTURBT). Two groups were matched in terms of clinicopathologic background and did not include patients treated with intravesical Bacillus Calmette–Guerin. The assessment of postoperative quality of life (QoL) was based on patient-reported outcome measure, including the International Prostate Symptom Score, Functional Assessment of Cancer Therapy-Bladder (FACT-BL), and 8-item Short Form (SF-8™) questionnaires before and 1 month after TUR. This study was approved by the Ethics committee and all participants provided informed consent. Results: PDD guidance provided substantial help for circumferent demarcation around the bladder tumor, which precedes tumor dissection. One female patient (12%) treated by PDD-EBTUR had grade II bladder perforation requiring prolonged catheterization. Pathologic assessment of horizontal and vertical margins in resected specimens by PDD-EBTUR revealed that all specimens had muscularis propria, and the rate of en bloc resection was 100%. No patient had intravesical recurrence in the PDD-EBTUR group (median follow-up, 11 months), while two patients in the PDD-cTURBT group had Ta low-grade recurrent tumors (8 months). Postoperatively, scores of daytime frequency and nocturia were increased in both groups. QoL assessment using the FACT-BL and SF-8 revealed that postoperative deterioration of bladder-specific subscale and emotional/mental scores was found in the EBTUR group but not in the cTURBT group. Conclusions: Based on the initial experience on 12 patients, we considered that PDD-EBTUR is an acceptable surgical method. Further experience and research are mandatory to determine whether this technique yields better outcomes and has true clinical advantage. [ABSTRACT FROM AUTHOR]

Background: Transurethral resection of bladder tumor (TURBT) is an essential procedure both for the treatment and staging of bladder cancer, particularly non-muscle invasive bladder cancer (NMIBC). The dissemination of cancer cells during resection and the consequent seeding into the bladder mucosa is the main cause of post-TURBT intravesical recurrence. Although the tumor dissemination is inevitable during conventional TURBT (cTURBT), this drawback can be overcome by tumor resection in one piece with intact surrounding normal tissues, referred to as en bloc resection. We previously described the photodynamic diagnosis (PDD)-assisted en bloc TURBT (EBTUR) technique and its favorable outcomes. Based on our preliminary studies, this randomized controlled trial was designed to evaluate the superiority of PDD-EBTUR to PDD-cTURBT.Methods: The FLEBER study is a single-center randomized controlled trial in NMIBC patients who require TURBT. The longest diameter of the tumor must be between 6 and 30 mm. A total of 160 eligible patients will be enrolled after screening and randomly allocated to the PDD-EBTUR (experimental) and PDD-cTURBT (control) groups in a 1:1 ratio (80 cases to 80 cases). All patients will be treated using a single, immediate postoperative intravesical chemotherapy with epirubicin. The primary endpoint of this trial is the 2-year recurrence-free survival after surgery in pathologically proven low- or intermediate-risk NMIBC. All patients will be monitored by cystoscopy and urine cytology every 3 months for 2 years. Patient data including adverse events and complications, and data from frequency volume charts, pain scales, and health-related QOL questionnaires will be collected before and after the TURBT at indicated visits.Discussion: The goal of this trial is to determine the potential benefits of PDD-cTURBT and PDD-EBTUR followed by a single immediate postoperative intravesical chemotherapy in patients with low- or intermediate-risk NMIBC who undergo TURBT. Ultimately, our findings will lead to the development of better interventions and potentially change the standard of care.Trial Registration: This clinical trial was prospectively registered with the UMIN Clinical Trials Registry on 1 August 2020. The reference number is UMIN000041273 , and the Ethics Committee of Nara Medical University Approval ID is 2702. [ABSTRACT FROM AUTHOR]

Background: The number of cycles of docetaxel required for castration-resistant prostate cancer (CRPC) is unclear. This study estimated peripheral neuropathy (PN) incidence and the optimal number of treatment cycles in patients receiving docetaxel for CRPC. Patients and Methods: The study retrospectively reviewed 82 patients receiving docetaxel for CRPC at an institution between January 2005 and January 2017. Docetaxel (70 or 75 mg/m2) was administered every 3 weeks, and prednisone 5 mg or dexamethasone 0.5 mg was administered twice a day. Results: PN (grade ≥2) was noted in 32 (39.0%) patients. The median cumulative dose of docetaxel associated with PN was 675 mg/m2. No factor significantly predicted the occurrence of PN. The prostate-specific antigen progression rate, prostate cancer-specific survival, and overall survival were significantly better with ≥8 cycles of docetaxel than with <8 cycles (p < 0.05). Conclusion: The incidence of PN is high, and 8 treatment cycles are optimal for patients receiving docetaxel for CRPC. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the use of cyclooxygenase‐2 inhibitors in patients receiving low‐dose‐rate brachytherapy for prostate cancer. Methods: A total of 310 patients with prostate cancer (cT1c‐3aN0M0) who received low‐dose‐rate brachytherapy between May 2010 and July 2013 were enrolled and allocated to one of the two treatment groups (tamsulosin alone 0.2 mg/day for 6 months vs tamsulosin 0.2 mg/day for 6 months plus celecoxib 200 mg/day for 3 months). The primary end‐point was the chronological change in international prostate symptom score, and the number of patients was assessed for the primary end‐point. Biochemical recurrence‐free, cancer‐specific survival and overall survival rates 5 years after the last patient received low‐dose‐rate brachytherapy were retrospectively examined. Results: The median follow‐up period after low‐dose‐rate brachytherapy was 72.0 months (range 3–99 months). A total of 12 (3.9%) patients experienced biochemical recurrence. The biochemical recurrence‐free rate in the celecoxib group (5‐year biochemical recurrence‐free rate 98.5%) was significantly better (log–rank test P = 0.023, 95% confidence interval 0.07–0.63, hazard ratio 0.20) than that in the tamsulosin group (5‐year biochemical recurrence‐free rate 93.4%). None of the patients died from prostate cancer. However, 14 (4.5%) patients died of other causes. No significant difference was observed in terms of overall survival between the celecoxib and tamsulosin groups. Conclusions: The combination of cyclooxygenase‐2 inhibitor and low‐dose‐rate brachytherapy can contribute to a better biochemical control of prostate cancer. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: A previous comparative study in Japan has demonstrated that the two consecutive UroVysion tests are useful tools to detect the presence of bladder cancer during follow-up after transurethral resection, but they also presented their high rates of false-positive results. Here, we aimed to evaluate the relationship between the UroVysion tests and subsequent intravesical recurrence. Methods: In the previous study, patients without bladder cancer during the first analysis showed the same examination set repeated 3 months later as the second analysis. In this follow-up study, 326 patients showed negative findings confirmed on cystoscopy during the second UroVysion test. Recurrence-free survival was assessed using a median follow-up of 27 months. Results: In the two consecutive UroVysion tests, 214 patients (65.6%) showed negative UroVysion results in both tests, whereas 91 presented a positive result on either tests and 21 patients presented positive results in both tests. During the follow-up, 40 patients (12.3%) had an intravesical recurrence with non-muscle-invasive bladder cancer. The recurrence rates in patients with negative results in both tests, those with one positive result in either tests, and those with positive results in both tests were 8.4%, 16.5%, and 33.3%, respectively. The multivariate analysis indicated that the history of bladder cancer and the consecutive UroVysion test pattern were independent risk factors for recurrence. Conclusions: Our data confirmed the effectiveness of two consecutive UroVysion tests in predicting intravesical recurrence after TURBT. Further prospective studies would help determine an appropriate interval for cystoscopy follow-up. [ABSTRACT FROM AUTHOR]

Background: Selecting the treatment procedure for cancer patients is a challenging task. We report our initial experience of complete laparoscopic radical nephroureterectomy (RNU) for patients with upper urinary tract urothelial cancer (UTUC). Methods: A total of four patients with UTUC underwent complete laparoscopic RNU combined with transvesical laparoscopic excision of the distal ureter using three 5-mm ports. Transvaginal specimen extraction was applied in female patients to reduce incisional pain and improve cosmesis. Peri-operative complications were evaluated using the Clavien-Dindo classification system. Postoperative pain was evaluated during hospitalization using a numeric pain rating scale (scales of 1 to 10). Patients who underwent retroperitoneal laparoscopic surgery combined with open excision of the distal ureter during the same period were included as a control group (conventional RNU, consisting of laparoscopic nephrectomy combined with open bladder cuff excision) for pain scale evaluation. Results: The novel surgery was successfully completed for all four patients (two males and two females). The mean pneumoperitoneum time for retroperitoneoscopic nephroureterectomy and specimen extraction was 174 min, while the mean pneumovesicum time for the ureteral orifice excision was 88 min. One male patient had bladder leakage at the suture site of the bladder wall, which lasted for 2 weeks. No patient experienced recurrent disease during the follow-up period (median, 10 months). Mild to moderate pain lasted for 5 or 6 days after RNU. A couple of days after surgery, the numeric pain rating scale of complete laparoscopic RNU and conventional RNU group reached its peak level at 3.0 ± 1.8 and 5.3 ± 2.8, respectively. There was no statistical difference in the degree of postoperative pain (P = 0.31). Conclusions: We described our initial experience and outcome of complete laparoscopic RNU for UTUC. Further experience and research are required to determine whether this advanced laparoscopic technique yields better outcomes and has true clinical value. [ABSTRACT FROM AUTHOR]

Background: It has been reported that 20% of lung cancer patients have renal impairment caused by chronic kidney disease (CKD). Since docetaxel is predominantly excreted by the hepatobiliary system, it is administered to non‐small cell lung cancer (NSCLC) patients with renal impairment. However, few clinical data are available on the toxicity and efficacy of docetaxel for patients with nondialysis renal impairment. Furthermore, some cases of tubular nephrotoxicity caused by docetaxel in NSCLC patients have been reported. Therefore, a retrospective cohort study was conducted to assess the influence of nondialysis CKD on the toxicity and efficacy of docetaxel in NSCLC patients. Methods: NSCLC patients who received docetaxel were assessed for renal function, occurrence of adverse events and treatment efficacy. Results: A total of 34 NSCLC patients who received docetaxel were studied. Eight (23.5%) patients had nondialysis CKD stage 3b or higher, with an estimated glomerular filtration rate (eGFR) <45 mL/min/1.73 m2. Although the differences were not statistically significant, the starting dose of docetaxel (mg/m2) was lower (60 mg/m2; 37.5% vs. 69.2%) in patients with an eGFR <45 than that in patients with an eGFR ≥45. No significant association was observed between pretreatment eGFR and hematological and nonhematological toxicities. No significant difference was observed in the disease control rate (62.5% vs. 65.4%, P = 1.000) or in the median overall survival (10.7 vs. 11.7, P = 0.735) between patients with an eGFR <45 and those with an eGFR ≥45. Conclusion: Docetaxel is a reasonable option for NSCLC patients with nondialysis CKD stage 3b or higher. Dose reduction of docetaxel is also a possibility for NSCLC patients with CKD stage 3b or higher. [ABSTRACT FROM AUTHOR]

Despite advances and refinements in surgery and perioperative chemotherapy, there are still unmet medical needs with respect to radical cystectomy for muscle‐invasive bladder cancer (MIBC). We investigated the potential benefit of supplementary granulocyte macrophage colony‐stimulating factor (GM‐CSF) to chemoimmunotherapy with programmed cell death protein‐1 (PD‐1)/programmed death‐ligand 1 (PD‐L1) axis blockade and standard neoadjuvant chemotherapy in bladder cancer. We inoculated 2 × 105MBT2 cells s.c. in C3H mice to create a syngeneic animal model of local recurrence (LR). When the tumor diameter reached 12 mm, the mice were allocated randomly as follows: (i) non‐treated control (vehicle only); (ii) anti‐mPD‐L1 monotherapy; (iii) mGM‐CSF monotherapy; (iv) anti‐mPD‐L1 plus mGM‐CSF; (v) gemcitabine and cisplatin (GC); (vi) GC plus anti‐mPD‐L1; (vii) GC plus mGM‐CSF; and (viii) GC plus anti‐mPD‐L1 plus mGM‐CSF. After completing 2‐week neoadjuvant therapy, tumors were resected for resection margin evaluation and immunohistochemical staining and blood was collected for flow cytometry and ELISA. Operative wounds were sutured, and the operative site was monitored to detect LR. Addition of anti‐mPD‐L1 and mGM‐CSF to neoadjuvant GC chemotherapy enhanced the antitumor effect and reduced positive resection margins (50% vs 12.5%). Combination of GC, anti‐mPD‐L1, and mGM‐CSF resulted in longer LR‐free survival and cancer‐specific survival compared to those in other groups. These effects involved an immunotherapy‐related decrease in oncological properties such as tumor invasion capacity and epithelial‐mesenchymal transition. mGM‐CSF significantly decreased the accumulation of myeloid‐derived suppressor cells in both the blood and tumor microenvironment and blood interleukin‐6 levels. Supplementary GM‐CSF to neoadjuvant GC plus PD‐L1 blockade could decrease LR after radical surgery by immune modulation in the blood and tumor microenvironment. [ABSTRACT FROM AUTHOR]

Objective: The present study evaluated the clinical relevance of an integrative preoperative assessment of inflammation-, nutrition-, and muscle-based markers for patients with upper urinary tract urothelial carcinoma (UTUC) undergoing curative nephroureterectomy (NUx). Methods: The study enrolled 125 patients and the preoperative variables assessed included age, body mass index, neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), serum fibrinogen level (Fib), C-reactive protein (CRP), modified Glasgow prognostic score, serum albumin level (Alb), prognostic nutritional index (PNI), skeletal muscle index (SMI), psoas muscle index (PMI), and peak expiratory flow (PEF). The correlations among the variables and their prognostic values after NUx were evaluated. Results: Five inflammation markers (NLR, MLR, PLR, Fib and CRP) were positively correlated. Fib was positively correlated with NLR, PLR and CRP, but inversely correlated with SMI. PNI was inversely correlated with age and the four inflammation markers (p < 0.001). Age was not significantly correlated with the inflammation markers, but older age was associated with lower Alb, PNI, SMI, PMI, and PEF. Disease-specific survival was independently predicted by preoperative ipsilateral hydronephrosis and low PNI. Overall survival was independently associated with high Fib and low PNI. Conclusion: The preoperative inflammation-, nutrition-, and muscle-based markers would be useful risk assessment tools for UTUC. [ABSTRACT FROM AUTHOR]

Renal cell carcinoma (RCC) is an immunogenic tumor and pathological specimen generally contain large quantities of tumor-infiltrating lymphocytes (TILs). Numerous cell types and cytokines could affect the immune escape mechanism of tumor cells. The aim of the present study was to investigate the prognostic impact of TILs and the associated circulating cytokines on localized clear cell RCC following radical nephrectomy. A total of 87 patients who had undergone radical nephrectomy and were pathologically diagnosed with localized clear cell RCC were included. The present study evaluated the profile of TILs with immunohistochemical analysis of tumor specimens using a panel of antibodies [cluster of differentiation (CD)-4, CD8, CD80, CD86, CD276, and Forkhead box p3 (Foxp3)]. Counts of each TIL were compared with clinicopathological variables. Based on the results of immunohistochemical analyses, putative cytokines, including interleukin (IL)-6, IL-10, IL-17, interferon-γ, tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-β, were selected, and their levels in preoperative serum were measured by ELISA. The levels were compared with TIL counts in tumor specimens. High counts of the CD276+ and Foxp3+ TILs were identified as independent factors for poor prognosis for metastasis and local recurrence following radical nephrectomy (P=0.033 and 0.006, respectively). A high CD276+ TIL count was associated with preoperative serum levels of TNF-α and IFN-γ (P=0.027 and P=0.035, respectively), whereas a high count of Foxp3+ TILs was associated with preoperative serum levels of TGF-β (P=0.021). High levels of TNF-α and TGF-β were associated with recurrence-free survival (P=0.035 and P=0.031, respectively). Topical intra-tumoral immunoreaction and systemic immune status may be associated with patients with localized RCC. The topical induction of the CD276+ and Foxp3+ TILs was suggested to be associated with high levels of serum TNF-α and IFN-γ. Preoperative serum levels of TNF-α and TGF-β could be simple and non-invasive biomarkers for risk stratification before radical surgery. [ABSTRACT FROM AUTHOR]

Background: The aim of this study is to evaluate the efficacy of two different Nara Urological Research and Treatment Group (NURTG) nomograms allocating 6–12 biopsy cores based on age and prostate volume. Materials and methods: From April 2006 to July 2014, a total of 1,605 patients who underwent initial prostate biopsy were enrolled. Based on a nomogram taking the patient's age and prostate volume into consideration, 6–12 biopsy cores were allocated. Two types of nomogram were used, for the former group (before March 2009) and latter group (March 2009 onward). Cancer detection rates in all patients and those with prostate-specific antigen values in the gray zone (4.0–10 ng/mL) were compared. Predictive parameters for detection of prostate cancer in gray-zone patients were also investigated. Results: The cancer detection rates in all patients and those in the gray zone were 48% and 38% in the former group and 54% and 41% in the latter group, respectively. The cancer detection rate in all patients was significantly higher in the latter group compared with the former group, but detection in gray-zone patients did not show a significant difference between the two groups (P=0.011 and P=0.37, respectively). Multivariate analysis indicated that age, digital rectal examination, prostate volume, transrectal ultrasonography findings, and volume/biopsy ratio were significant predictive parameters in gray-zone patients. The clinically insignificant cancer detection rate was significantly lower in the latter group compared with the former group (P=0.0008). Conclusion: The latter nomogram provided more acceptable detection rates of clinically significant and insignificant cancer than the former one, and we consider that an initial maximum 12-core transrectal ultrasound-guided needle biopsy may be sufficient for prostate cancer diagnosis. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate quality of life (QOL) in prostate cancer patients treated with 125I brachytherapy (BT), 125I brachytherapy combined with 3D conformal radiation therapy (BT+3D-CRT), or intensity-modulated radiation therapy (IMRT). We evaluated disease-related QOL in patients who underwent BT, BT+3D-CRT, or IMRT, using the Expanded Prostate Cancer Index Composite questionnaire before treatment and at 3 and 24 months post-treatment. Multivariate analyses were conducted to determine factors associated with a minimum important difference (MID) in urinary, bowel, sexual, and hormone domain scores at 3 and 24 months post-treatment. Of 558 enrolled patients (IMRT, 123; BT, 230; and BT+3D-CRT, 205), urinary domain scores showed a MID after BT, BT+3D-CRT and IMRT at 3 months in 69%, 84% and 25% of patients, respectively, and at 24 months in 43%, 54% and 28% of patients, respectively. On multivariate analysis, BT+3D-CRT [3 months: odds ratio (OR) = 12.7; P < 0.001; 24 months: OR = 3.29; P = 0.001] and BT (3 months: OR = 6.28; P < 0.001 and 24 months: OR = 2.22; P = 0.027) were associated with more severely worsened urinary QOL than IMRT. Bowel domain scores showed a MID at 3 months after BT, BT+3D-CRT, and IMRT in 37%, 68% and 41% of patients, respectively, and at 24 months in 29%, 46% and 43% of patients, respectively. On multivariate analysis, BT+3D-CRT (3 months: OR = 4.20; P < 0.001 and 24 months: OR = 2.63; P < 0.001) and IMRT (24 months: OR = 1.98; P = 0.029) were associated with more severely worsened bowel QOL than was BT. Information about the changes in QOL outcomes associated with radiotherapy modalities could guide treatment decisions. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to evaluate the chronological changes in lower urinary tract symptoms (LUTSs), disease-related quality of life (QOL), and health-related QOL (HR-QOL) of patients who received intensity-modulated radiotherapy (IMRT).Patients and methods: In 121 patients who had received IMRT and were followed up for >2 years, the International Prostate Symptom Score (IPSS), Overactive Bladder Symptom Score (OABSS), Expanded Prostate Cancer Index Composite (EPIC), and 8-Item Short-Form Health Survey (SF-8) were used before IMRT, at the halfway point in IMRT, immediately after IMRT, and 1–24 months after the completion of IMRT.Results: The IPSS and OABSS and the urinary and bowel domains of the EPIC indicated that QOL worsened at the halfway point in IMRT, further worsened more severely immediately after IMRT, and then improved. The sexual domain of the EPIC significantly decreased at the halfway point in IMRT, which significantly lowered until 24 months. The scores of physical functioning, role physical, bodily pain, vitality, social functioning, and role emotional domains in the SF-8 significantly decreased and reached their lowest points immediately after IMRT.Conclusion: QOL worsened the most severely in patients immediately after IMRT for prostate cancer. This knowledge can influence treatment recommendations and enable patients to make better informed decisions. [ABSTRACT FROM AUTHOR]

To evaluate the feasibility of photodynamic diagnosis using 5-aminolevulinic acid (PDD-ALA) for detection of prostate cancer (PCa) cells in urine samples after prostate massage in patients who were suspected to have PCa. One hundred and eighty-nine patients with abnormal digital rectal examination and/or an elevated prostate-specific antigen (PSA) level who underwent initial prostate biopsy were recruited. After prostate massage, the first 60 mL of voided urine was collected. For PDD-ALA, 50 mL was used. The rest of collected urine was used for polymerase chain reaction (PCR) of PSA and glyceraldehyde 3-phosphate dehydrogenase (GAPDH). After incubation for 2 h, the intensity was measured at 635 nm under a 405-nm wavelength excitation. The results of PDD-ALA were compared with those of an initial transrectal ultrasound (TRUS)-guided prostate biopsy. Overall, 126/189 (67%) samples that showed bands of both PSA and GAPDH on PCR in urine samples were analyzed. The area under the curve, sensitivity, and specificity of PDD-ALA were 0.74, 77, and 67%, respectively. The value of PDD-ALA was significantly higher in patients with Gleason scores of 6 (p = 0.03), 7 (p = 0.005), and 8-10 (p = 0.0002) than in those with negative biopsy results. In the multivariate analysis, high PSA density, abnormal findings on TRUS, and a high value of PDD-ALA were significant markers for prediction of positive biopsy results. PDD-ALA was useful to predict positive biopsy results in patients who underwent initial prostate biopsy with suspected PCa. This PCa-detection method has potential for clinical use. [ABSTRACT FROM AUTHOR]

Objective: The objective of the present study was to report the incidence of skeletal-related events (SREs) and identify risk factors for SREs in patients with genitourinary cancer with newly diagnosed bone metastasis. Methods: This retrospective study included 180 patients with bone metastasis from prostate cancer (PCa; n = 111), renal cell carcinoma (RCC; n = 43), and urothelial carcinoma (UC; n = 26). Clinical factors at the time of diagnosis of bone metastasis were evaluated with Cox proportional hazards regression analysis to identify independent risk factors for SREs. Results: During follow-up, 29 (26%) patients with PCa, 30 (70%) with RCC, and 15 (58%) with UC developed SREs. Treatment with bone-modifying agents (BMAs) before the development of SREs and within 6 months from the diagnosis of bone metastasis significantly delayed the time to first SRE as compared to nonuse of BMAs. Multivariate analysis identified type of primary cancer (PCa vs. RCC, PCa vs. UC), performance status, and bone pain as significant independent predictive risk factors for SREs. Conclusions: Treatment with BMAs significantly delayed the development of first SREs. The identified predictors of SREs might be useful to select patients who would benefit most from early treatment with BMAs. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to determine the clinical utility of bioelectrical impedance analysis (BIA) in a cohort of patients with advanced urothelial carcinoma (UC).Methods: We prospectively evaluated body composition in 35 patients with locoregional muscle invasive (≥ T2 and N0-2M0) or metastatic UC. Body composition was evaluated using multifrequency BIA at baseline (n = 35) and during chemotherapy in patients receiving neoadjuvant chemotherapy (n = 14). The BIA-predicted body composition index was compared with the computed tomography-measured muscle index and the prognostic nutrition index. Changes in body composition during neoadjuvant chemotherapy were recorded and compared with the incidence of hematological adverse events.Results: There was a significant correlation between the BIA-predicted skeletal muscle index and the computed tomography-measured skeletal muscle index (P = 0.004), while there was no significant correlation between the prognostic nutrition index and the BIA-predicted nutrition index. After the completion of 3 cycles of neoadjuvant chemotherapy, the skeletal muscle index showed a significant decrease (P = 0.016), while the total body fat mass (P = 0.025), body fat percentage (P = 0.013), and body mass index (P = 0.004) showed a significant increase (a tendency toward "sarcopenic obesity"). Patients who experienced grade 2-3 anemia during neoadjuvant chemotherapy showed a significantly lower increase in body mass index compared with patients who did not experience high-grade toxicities (P = 0.032).Conclusions: BIA could contribute to other methods of nutrition and muscle assessment for pretreatment risk stratification in patients with UC. Further study of a larger cohort is required to elucidate the clinical impact of changes in body composition during chemotherapy. [ABSTRACT FROM AUTHOR]

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

Background: To assess the trends in risk classification and primary therapy of Japanese prostate cancer patients who were diagnosed between 2004 and 2012.Methods: A total of 7768 patients who were newly diagnosed with prostate cancer at Nara Medical University and its 23 affiliated hospitals between 2004 and 2012 were enrolled. The trends in risk classification and primary therapy in 2004-2006 (prior period), 2007-2009 (middle period), and 2010-2012 (latter period) were compared.Results: The proportion of high-risk and worse patients significantly decreased in the latter period compared to the prior period (p < 0.001), while that of intermediate-risk patients significantly increased over the years (p < 0.001). The proportion of primary androgen deprivation therapy (PADT) was 50% in the prior period, 40% in the middle period, and 30% in the latter period, respectively. The proportions of radiation therapy and active surveillance significantly increased. The proportion of radical prostatectomy remained similar over these periods (30%). The primary therapy was significantly different between the three periods (p < 0.001).Conclusions: High-risk patients significantly decreased in the latter period. The use of PADT also significantly decreased, while radiation therapy and active surveillance significantly increased over these periods. [ABSTRACT FROM AUTHOR]

Objective: The present study evaluated the clinical relevance of an integrative preoperative assessment of inflammation-, nutrition-, and muscle-based markers for patients with muscle-invasive bladder cancer (MIBC) undergoing curative radical cystectomy (RC). Methods: The analysis enrolled 117 patients and the variables included age, body mass index (BMI), neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, platelet-to-lymphocyte ratio, modified Glasgow Prognostic Score (mGPS), prognostic nutritional index (PNI), Controlling Nutritional Status score, psoas muscle index (PMI), and peak expiratory flow (PEF). The correlations among the variables were evaluated and their prognostic values after RC were tested. Results: Three inflammation markers (ratios of blood cell counts) were positively correlated (p < 0.0001). The PNI and the BMI were positively correlated (p = 0.04), although they were inversely correlated with the three inflammation markers (p < 0.0001). Age was not significantly correlated with the inflammation markers and PMI, although older age was associated with lower PNI and lower PEF. The disease-specific survival was independently predicted by T4 tumor, positive N status, and decreased PNI. Overall survival was independently predicted by T4 tumor, mGPS, and pretreatment sarcopenia status. Conclusions: The inflammation-, nutrition-, and muscle-based markers would be useful risk assessment tools for MIBC. [ABSTRACT FROM AUTHOR]