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Testicular teratomas are the major histologic type of testicular germ cell tumors and their incidence continues to grow. Moreover, teratomas can develop from undifferentiated cells in induced pluripotent stem (iPS) cell transplantation therapy, seriously hampering the progress of regenerative medicine. Germinal center-associated nuclear protein (GANP) is thought to be important to the biogenetic control of primordial germ cells and is among the genes susceptible to testicular germ cell tumors. Thus, we analyzed the expression of GANP in human testicular postpubertal-type teratomas and established a novel mouse model to reveal the association between GANP and teratomagenesis. We analyzed 31 cases of human testicular postpubertal-type teratomas and, in all cases, GANP was overexpressed. The aberrant expression was also detected in germ cell neoplasia in situ accompanied by the teratoma. GANP expression was particularly high in the epithelia of the epidermis, cutaneous appendages, and trachea-like ciliated epithelium. To further clarify the association between GANP and teratomagenesis, we established a novel teratomagenesis mouse model (CAG-ganp

Low-grade systemic inflammation and malnutrition are frequently observed in patients on dialysis and contribute to the development of endothelial dysfunction; however, the role of these conditions in erectile dysfunction (ED) severity remains to be elucidated.To investigate the relationships of low-grade systemic inflammation and nutritional status with ED severity in men on dialysis.The present study included 71 men on dialysis. The sexual health inventory for men (SHIM) was used to assess ED. Men were classified as the mild/moderate (SHIM score ≥ 8) and severe ED (SHIM score ≤ 7) groups. C-reactive protein/albumin ratio (CAR) and Geriatric Nutritional Risk Index (GNRI) were used to evaluate low-grade systemic inflammation and nutritional status, respectively. We performed multivariate analysis to assess the relationships of CAR and GNRI with severe ED.The median age of the included men was 64 years old. All men had any degree of ED with 65% having severe ED. In the univariate analyses, a significant association was observed between elevated CAR (≥0.09) and severe ED (odds ratio [OR]: 4.038, p = 0.025), whereas no significant association was observed between lower GNRI (lt;92) and severe ED (OR: 2.357, p = 0.109). In the multivariate analysis, an association between elevated CAR and severe ED was still significant (OR: 5.985, p = 0.010).Low-grade systemic inflammation was significantly associated with ED severity, whereas lower GNRI was not. These results may be helpful for further research to identify the optimal treatment for men suffering from severe ED.

Cell surface hyaluronidase transmembrane protein 2 (TMEM2), which also serves as a reportedly functions in malignancy of several solid tumors. However, TMEM2 involvement in bladder cancer (BCa) is unknown. Therefore, we investigate potential changes in expression of TMEM2 during BCa invasion and over the course of the epithelial mesenchymal transition (EMT). Immunohistochemical analysis of 127 clinical specimens revealed that TMEM2 expression changed with pathological stage (pT) and infiltration pattern (INF) and was highest in pTa-pT1 of INFa tumors and significantly lower at stages from pTa-pT1 to pT2 or 3 in INFb or INFc. E-cadherin expression was highest in INFa and lowest in INFc, a pattern comparable to TMEM2 expression. TMEM2 protein expression analysis of BCa cell lines showed that muscle-invasive T24 and YTS-1 cells with low TMEM2 expression exhibited EMT phenotypes in vitro, in contrast to high TMEM2-expressing non-muscle invasive RT4 cells. EMT-induced non-muscle invasive RT4 cells also showed significantly decreased plasma membrane expression of TMEM2. Our data suggested TMEM2 expression is higher in non-invasive cancers, whereas invasive cancer cells are less likely to express TMEM2 during muscle-invasion and "partial EMT".

Background Worldwide, prostate cancer (PC) is the second most diagnosed cancer and the fifth leading cause of cancer death in men. Hormonal therapies, commonly used for PC, are associated with a range of treatment-emergent adverse events (TEAEs). The population from Japan seems to be at higher risk of developing TEAEs of skin rash compared to the overall global population. This study was conducted to get a better insight into the incidence, management, and risk factors for skin rash during active treatment for advanced PC in Japan. Methods A retrospective cohort of PC patients was identified and subsequently categorized, into non-metastatic and metastatic castration-resistant prostate cancer patients (nmCRPC and mCRPC), and metastatic castration-naïve prostate cancer patients (mCNPC). The analysis was based on a dataset from the Medical Data Vision (MDV) database. Descriptive statistics were determined, and a multivariate Cox proportional hazards model was used to the associated risk factors for the onset of rash. Results Overall, 1,738 nmCRPC patients, 630 mCRPC patients, and 454 mCNPC patients were included in this analysis. The median age was 78 years old and similar across the three cohorts. The skin rash incidence was 19.97% for nmCRPC cohort, 28.89% for mCRPC cohort, and 28.85% for mCNPC cohort. The median duration of skin rash ranged from 29 to 42 days. Statistically significant risk factors for developing skin rash included a history of allergy or hypersensitivity (all cohorts), increased age (nmCRPC and mCRPC), a body mass index (BMI) of Conclusion This study provides a better understanding of the real-world incidence, onset, duration, management and risk factors of skin rash in patients on active PC treatment in Japan. It was observed that approximately 20–30% of PC patients experience skin rash. Development of skin rash was associated with previous allergy or hypersensitivity, BMI of

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

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

To investigate whether a single intravesical instillation of chemotherapy is associated with improved oncological outcomes in patients with high-risk non-muscle-invasive bladder cancer who receive adjuvant induction bacillus Calmette-Guérin therapy.This multi-institutional retrospective study included 205 patients with high-risk non-muscle-invasive bladder cancer who received adjuvant induction bacillus Calmette-Guérin therapy. Patients were divided into two groups: those who received the combined therapy of a single instillation of chemotherapy plus subsequent adjuvant induction bacillus Calmette-Guérin therapy (combined therapy group), and those who received adjuvant induction bacillus Calmette-Guérin therapy alone (bacillus Calmette-Guérin monotherapy group). Multivariable analyses using the inverse probability of treatment weighting method and Fine-Gray competing risk regression models were performed to evaluate the impact of a single instillation of chemotherapy on intravesical recurrence-free survival and muscle-invasive bladder cancer-free survival.Among the 205 patients, 130 (63%) and 75 (37%) were classified as the combined therapy and bacillus Calmette-Guérin monotherapy groups, respectively. Multivariable analyses using the inverse probability of treatment weighting method showed that a single instillation of chemotherapy was significantly associated with longer intravesical recurrence-free survival (hazard ratio 0.279; P 0.001) and muscle-invasive bladder cancer-free survival (hazard ratio 0.078; P 0.001). Fine-Gray competing risk regression model revealed that a single instillation of chemotherapy was associated with a significantly lower probability of intravesical recurrence and muscle-invasive bladder cancer progression, with an adjusted subdistribution hazard ratio of 0.477 (P = 0.008) and 0.261 (P = 0.043), respectively.A single intravesical instillation of chemotherapy may be a potential treatment option in patients with high-risk non-muscle-invasive bladder cancer who receive adjuvant induction bacillus Calmette-Guérin therapy.

To evaluate the serologic response to the BNT162b2 messenger ribonucleic acid vaccine in patients with urothelial carcinoma and renal cell carcinoma.Between June 2021 and November 2021, we retrospectively evaluated blood samples from 60 healthy controls (control group), 57 patients with urothelial carcinoma, and 28 patients with renal cell carcinoma who had received two doses of the BNT162b2 vaccine at Hirosaki University Hospital. We determined the immunoglobulin G antibody titers against the severe acute respiratory syndrome coronavirus 2 spike receptor-binding domain. Seropositivity was defined as ≥15 U/mL. We investigate factors associated with antibody titers and seropositivity in the patients with urothelial carcinoma and renal cell carcinoma.Antibody titers in the control, urothelial carcinoma, and renal cell carcinoma groups were 813, 431, and 500 U/mL, respectively. Seropositivity was 100%, 90%, and 96% in the control, urothelial carcinoma, and renal cell carcinoma groups, respectively. Of the 85 patients, 37 of 57 (65%) and 21 of 28 (75%) were actively undergoing anticancer treatment for urothelial carcinoma and renal cell carcinoma, respectively. Anti-severe acute respiratory syndrome coronavirus 2 spike immunoglobulin G antibody titers and seropositivity was not significantly different between the patients with urothelial carcinoma and renal cell carcinoma. Anti-severe acute respiratory syndrome coronavirus 2 spike immunoglobulin G antibody titers were not significantly associated with active anticancer therapy or steroid treatment for immune-related adverse events. Univariable logistic regression analysis revealed that older age and metastatic disease were significantly and negatively associated with seropositivity.Patients with urothelial carcinoma or renal cell carcinoma exhibited an adequate antibody response to the BNT162b2 vaccine. Active anticancer therapy was not significantly associated with seropositivity following vaccination with severe acute respiratory syndrome coronavirus 2 BNT162b2 in patients with urothelial carcinoma and renal cell carcinoma.

Transurethral resection of bladder tumor with photodynamic diagnosis has been reported to result in lower residual tumor and intravesical recurrence rates in non-muscle invasive bladder cancer. We aimed to evaluate the usefulness of photodynamic diagnosis-transurethral resection of bladder tumor combined with oral 5-aminolevulinic acid hydrochloride for high-risk non-muscle invasive bladder cancer.High-risk non-muscle invasive bladder cancer patients with an initial photodynamic diagnosis-transurethral resection of bladder tumor (photodynamic diagnosis group) were prospectively registered between 2018 to 2020. High-risk non-muscle invasive bladder cancer cases with a history of initial white-light transurethral resection of bladder tumor (white-light group) were retrospectively registered. Propensity score-matching analysis was used to compare residual tumor rates, and factors that could predict residual tumors at the first transurethral resection of bladder tumor were evaluated.Analyses were conducted with 177 and 306 cases in the photodynamic diagnosis and white-light groups, respectively. The residual tumor rates in the photodynamic diagnosis and white-light groups were 25.7% and 47.3%, respectively. Factor analysis for predicting residual tumors in the photodynamic diagnosis group showed that the residual tumor rate was significantly higher in cases with a current/past smoking history, multiple tumors, and pT1/pTis. When each factor was set as a risk level of 1, cases with a total risk score ≤1 showed a significantly lower residual tumor rate than cases with a total risk score ≥2 (8.3% vs 33.3%, odds ratio 5.46 [1.81-22.28]).In high-risk non-muscle invasive bladder cancer cases, the odds of a residual tumor after initial photodynamic diagnosis-transurethral resection of bladder tumor were 0.39-fold that of the odds of those after initial white-light transurethral resection of bladder tumor. A risk stratification model could be used to omit the second transurethral resection of bladder tumor in 27% of the cases.

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

Background This retrospective multicenter study aimed to evaluate the survival benefit of upfront cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (RCC) patients stratified by International Metastatic RCC Database Consortium (IMDC) risk criteria. Methods We reviewed the medical records in the Michinoku Database between 2008 and 2019. Patients who received upfront CN, systemic therapy without CN (no CN) and CN after drug therapy (deferred CN) were analyzed. To exclude selection bias due to patient characteristics, baseline clinical data were adjusted by inverse probability of treatment weighting (IPTW). Overall survival (OS) was compared between upfront CN and non-upfront CN (no CN plus deferred CN). Associations between time-varying covariates including systemic therapies and OS stratified by IMDC risk criteria were analyzed by IPTW-adjusted Cox regression method. Results Of 259 patients who fulfilled the selection criteria, 107 were classified in upfront CN and 152 in non-upfront CN group. After IPTW-adjusted analysis, upfront CN showed survival benefit compared to non-upfront CN in patients with IMDC intermediate risk (median OS: 52.5 versus 31.3 months, p p p = 0.03) and in patients with IMDC poor risk (0.26, 0.11–0.59, p Conclusions Upfront CN may confer survival benefit in RCC patients with IMDC intermediate and poor risk.

Supplemental table 1. Peptide candidates for personalized peptide vaccination

Supplementary Data includes Supplementary Methods, Supplementary Results, Supplementary Table S1-S13, Supplementary Figure S1-S7, and Supplementary References.

Purpose: The prognosis of platinum-based chemotherapy–resistant metastatic urothelial cancer of the bladder remains poor. Personalized selection of the right peptides for each patient could be a novel approach for a cancer vaccine to boost anticancer immunity.Experimental Design: In this randomized, open-label, phase II study, patients ages ≥18 years with progressive bladder cancer after first-line platinum-based chemotherapy were randomly assigned (1:1) to receive personalized peptide vaccination (PPV) plus best supportive care (BSC) or BSC. PPV treatment used a maximum of four peptides chosen from 31 candidate peptides according to human leukocyte antigen types and peptide-reactive IgG titers, for 12 s.c. injections (8 injections, weekly; 4 injections, bi-weekly). The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), immune response, and toxicity.Results: Eighty patients were randomly assigned to receive either PPV plus BSC (n = 39) or BSC (n = 41). No significant improvement in PFS was noted [HR, 0.7; 95% confidence interval (CI), 0.4–1.2, P = 0.17]. For the secondary endpoints, PPV plus BSC significantly prolonged OS compared with BSC (HR, 0.58; 95% CI, 0.34–0.99, P = 0.049), with median OS of 7.9 months (95% CI, 3.5–12.0) in the PPV plus BSC and 4.1 months (95% CI, 2.8–6.9) in the BSC. PPV treatment was well tolerated, without serious adverse drug reactions.Conclusions: PPV could not prolong PFS, but OS appeared to be improved with low toxicity and immune responses. Further large-scale, randomized trials are needed to confirm these results. Clin Cancer Res; 22(1); 54–60. ©2015 AACR.

We compared the impact of treatment strategies on postoperative complications and prognosis between robot-assisted radical prostatectomy (RARP) plus extended pelvic lymph-node dissection (ePLND) and RARP plus neoadjuvant chemohormonal therapy (NCHT) without ePLND. We retrospectively evaluated 452 patients with high-risk prostate cancer (defined as any one of prostate-specific antigen ≥ 20 ng/mL, Gleason score 8–10, or cT2c–3) who were treated with RARP between January 2012 and February 2021. The patients were divided into two groups: RARP with ePLND (ePLND group) and NCHT plus RARP without ePLND (NCHT group). We compared the complication rate (Clavien–Dindo classification), biochemical recurrence-free survival, and castration-resistant prostate cancer (CRPC)-free survival between the groups. We performed multivariable Cox regression analysis using inverse probability weighting (IPTW) methods to assess the impact of the different treatments on prognosis. There were 150 and 302 patients in the ePLND and NCHT groups, respectively. The postoperative complication rate was significantly higher in the ePLND group than in the NCHT group (P P P = 0.010, respectively). NCHT plus RARP without ePLND may reduce the risk of postoperative complications compared with ePLND during RARP. The impact of treatment strategies on oncological outcomes needs further studies.

Noonan syndrome (NS) is a congenital genetic abnormality characterized by short stature, delayed onset of puberty, cardiac malformations, and characteristic external malformations. Congenital chromosomal or genetic abnormalities are sometimes associated with carcinomas. Furthermore, they are difficult to manage perioperatively because of multiple complications and mental retardation. The safety of kidney transplantation for patients with NS has not been established. We are reporting the case of a 31-year-old man with NS who received a kidney transplantation after a donor's brain death. He received kidney transplantation safely and was discharged without issues. Kidney transplantation for patients with congenital chromosomal or genetic abnormalities is feasible without serious complications, with a regular follow-up, and psychological support from patients and families.

PURPOSE To assess the influence of gut microbiome on overactive bladder (OAB) symptoms progression. METHODS This was a 3-year longitudinal study, Hirosaki in Japan. We assessed OAB symptoms and reviewed the medication records of each subject in 2016. We extracted 16S rRNA genes from fecal samples and analyzed gut microbiomes via next-generation sequencing. We evaluated the changes in urinary urgency (UU) and/or urgent urinary incontinence (UUI) from 2016 to 2019. We defined UU/UUI-progression as exacerbation of UU and/or UUI. We compared the clinical backgrounds and microbiota structure between UU/UUI-progression subjects and non-progression (controls). We assessed the impact of gut microbiome on the UU/UUI-progression via multivariate logistic regression analyses. RESULTS Of 669 subjects, 126 were UU/UUI-progression subjects. These subjects had a higher age and prevalence of proton pump inhibitor (PPI) use (14% vs. 5.4%, P = 0.003), irritable bowel syndrome, sleep disturbance, and metabolic syndrome than those without. We found the different microbiota structures between subjects with UU/UUI-progression and those without. A higher relative abundance of genus Streptococcus (harmful bacterial genus for human health) appeared in UU/UUI-progression subjects (3.8% vs. 2.3%, P

Objectives To investigate the eligibility for maintenance immunotherapy and its impact on the prognosis of advanced urothelial carcinoma treated with first‐line chemotherapy, as the selection biases of the eligible population in the JAVELIN Bladder 100 trial remain unclear. Methods We retrospectively evaluated 213 patients (median age, 71 years) with unresectable locally advanced or metastatic urothelial carcinoma treated with platinum‐based first‐line chemotherapy between May 2003 and April 2021. The patients were categorized into the following two groups: progressive disease (PD) within four cycles (trial ineligible group) and non‐PD within four cycles (trial eligible group). The primary outcomes were the estimated proportion of trial eligible patients for maintenance immunotherapy. The secondary outcomes were the comparison of the overall survival in the trial eligible and ineligible groups and the impact of radiologic response at the second cycle on the fourth cycle. Results Among the 213 patients, 81 (38%) were included in the trial eligible group. The trial eligible group had a significantly longer overall survival than the trial ineligible group (P

Background The presence of glycosylated isoforms of prostate-specific antigen (PSA) in prostate cancer (PC) cells is a potential marker of their aggressiveness. We characterized the origin of α2,3-sialylated prostate-specific antigen (S23PSA) by tissue-based sialylation-related gene expression and studied the performance of S23PSA density (S23PSAD) alone and in combination with multiparametric magnetic resonance imaging (MRI) for the detection of clinically significant prostate cancer in men with elevated PSA. Methods Tissue-based quantification of S23PSA and sialyltransferase and sialidase gene expression was evaluated in 71 radical prostatectomy specimens. The diagnostic performance of S23PSAD was studied in 1099 men retrospectively enrolled in a multicenter systematic biopsy (SBx) cohort. We correlated the S23PSAD with Prostate Imaging Reporting and Data System (PI-RADS) scores in 98 men prospectively enrolled in a single-center MRI-targeted biopsy (MRI-TBx) cohort. The primary outcome was the PC-diagnostic performance of the S23PSAD, the secondary outcome was the avoidable biopsy rate of S23PSAD combined with DRE and total PSA (tPSA), and with or without PI-RADS. Results S23PSA was significantly higher in Gleason pattern 4 and 5 compared with benign prostate tissue. In the retrospective cohort, the performance of S23PSAD for detecting PC was superior to tPSA or PSA density (PSAD) (AUC: 0.7758 vs. 0.6360 and 0.7509, respectively). In the prospective cohort, S23PSAD was superior to tPSA, PSAD, and PI-RADS (AUC: 0.7725 vs. 0.5901, 0.7439 and 0.7305, respectively), and S23PSAD + PI-RADS + DRE + tPSA was superior to DRE + tPSA+PI-RADS with avoidance rate of MRI-TBx (13% vs. 1%) at 30% risk threshold. Conclusions The diagnostic performance of S23PSAD was superior to conventional strategies but comparable to mpMRI.

Purpose: Although cell-free DNA (cfDNA) testing is expected to drive cancer precision medicine, little is known about the significance of detecting low-frequency variants in circulating cell-free tumor DNA (ctDNA) in castration-resistant prostate cancer (CRPC). We aimed to identify genomic profile including low-frequency variants in ctDNA from patients with CRPC and investigate the clinical utility of detecting variants with variant allele frequency (VAF) below 1%. Experimental Design: This prospective, multicenter cohort study enrolled patients with CRPC eligible for treatment with abiraterone or enzalutamide. We performed targeted sequencing of pretreatment cfDNA and paired leukocyte DNA with molecular barcodes, and ctDNA variants with a VAF ≥0.1% were detected using an in-house pipeline. We investigated progression-free survival (PFS) and overall survival (OS) after different ctDNA fraction cutoffs were applied. Results: One hundred patients were analyzed (median follow-up 10.7 months). We detected deleterious ATM, BRCA2, and TP53 variants even in samples with ctDNA fraction below 2%. When the ctDNA fraction cutoff value of 0.4% was applied, significant differences in PFS and OS were found between patients with and without defects in ATM or BRCA2 [HR, 2.52; 95% confidence interval (CI), 1.24–5.11; P = 0.0091] and TP53 (HR, 3.74; 95% CI, 1.60–8.71; P = 0.0014). However, these differences were no longer observed when the ctDNA fraction cutoff value of 2% was applied, and approximately 50% of the samples were classified as ctDNA unquantifiable. Conclusions: Detecting low-frequency ctDNA variants with a VAF

We aimed to evaluate the effects of apalutamide dose reduction on skin-related adverse events (AEs) and castration-resistant prostate cancer (CRPC)-free survival in patients with advanced prostate cancer (PC).We retrospectively evaluated 35 patients with nonmetastatic CRPC and 72 patients with treatment-naïve metastatic castration-sensitive PC (mCSPC) who were treated with apalutamide. The primary outcome was the effect of apalutamide dose reduction on skin-related AEs. The secondary outcomes were the effect of apalutamide dose reduction on skin-related AEs in patients with small body size, postskin AE apalutamide discontinuation rate, and CRPC-free survival in patients with mCSPC treated with upfront apalutamide plus androgen deprivation therapy.Of the 107 patients, 65 (60.7%) and 42 (39.3%) were treated with full and reduced doses of apalutamide, respectively. The skin-related AE rate was not significantly different between the groups (55% vs. 43%, p = 0.761). In the group receiving reduced apalutamide dose, the incidence of skin-related AEs was significantly lower in patients with small body sizes (body weight67 kg and body mass index24 kg/mApalutamide dose reduction was not significantly associated with the incidence of skin-related AEs. However, dose reduction in patients with small body sizes may alleviate skin-related AEs without sacrificing oncological outcomes.

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

It remains unknown whether the early response to vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR-TKI) management in malignancies links to long-term survival. The objective of this study was to investigate the survival rates and predictive factors of early response in patients with metastatic renal cell carcinoma (mRCC) managed by VEGFR-TKIs. From Jan. 2008 to Oct. 2018, 496 patients were treated with VEGFR-TKIs as first-line treatment at the eight Japanese hospitals (Michinoku RCC). Early cessation was defined as VEGFR-TKIs being given up within 3 months after their initiation. The number of patients in early cessation VEGFR-TKIs (Cohort I) was 173 (34.9%), and in long-term use (Cohort II) was 323 (65.1%). The cancer-specific survival (CSS) and overall survival (OS) were better in Cohort II. IMDC Poor-risk was at risk of early cessation of a first-line VEGFR-TKI. Axitinib was the most preferred drug for long-term treatment. On closer examination, both Cohort I and II were divided into two groups, the patients ceased VEGFR-TKI due to adverse events (Group A [67 from Cohort I] and Group C [51 from Cohort II]) and disease progression (Group B [106 from Cohort I] and Group D [272 from Cohort II]). Despite that the cessation was adverse events, CSS and OS in Group A were worse than both Group C and D. Axitinib was administered with the safer profile. IMDC Poor risk was the risk factor for the early disease progression. Managing early adverse events may contribute to a better prognosis in mRCC patients treated VEGFR-TKIs.

To investigate the association between oxidative stress and erectile dysfunction (ED) in community-dwelling men and men on dialysis.This cross-sectional study included 398 community-dwelling men and 42 men on dialysis. Oxidative stress was assessed using 8-hydroxy-2'-deoxyguanosine (8-OHdG). Univariable and multivariable logistic regression analyses were performed to evaluate the association between oxidative stress and ED.Spearman's rank correlation test showed no significant correlation between urine 8-OHdG levels and the 5-Item International Index of Erectile Function scores in community-dwelling men (ρ = -0.005,Oxidative stress was not significantly associated with ED prevalence and severity in community-dwelling men and men on dialysis.

The aims of this study were to investigate prognosis and validate prognostic models [Memorial Sloan-Kettering Cancer Center (MSKCC), International Metastatic Renal Cell Carcinoma Data Consortium (IMDC), and Japanese metastatic renal cancer (JMRC) models] in the targeted therapy era in Japanese patients with metastatic renal cell carcinoma. We retrospectively analyzed 692 patients who were diagnosed with mRCC from January 2008 to August 2018 in the Michinoku Japan Urological Cancer Study Group database. Nivolumab as sequential therapy was widely used. Other immune checkpoint inhibitors were excluded from this study. The median overall survival (95% confident interval) in all, MSKCC favorable, intermediate, and poor risk patients was 41.0 months (33.9–46.8), not reached (63.5 to not estimable), 46.8 months (37.1–52.9), and 10.4 months (8.9–14.4), respectively. The median overall survival (95% confident interval) in IMDC favorable, intermediate, and poor risk patients was not reached (61.6 to not estimable), 47.4 months (41.4–56.5), and 11.5 (9.9–16.3), respectively. The c-index of the MSKCC, IMDC, and JMRC models calculated at mRCC diagnosis was 0.680, 0.689, and 0.700, respectively. No statistical differences were found in the c-index among the models. While the real-world overall survival in Japanese patients with mRCC in the targeted therapy era improved compared to that previously reported in the cytokine era, there was no clear difference in the survival of poor risk patients between these eras. There were no differences in the superiority among the models.

Aims To investigate the relationship between urinary urgency (UU) and aponeurotic ptosis (AP) in a health promotion project. Methods This cross-sectional study analyzed 658 women in Aomori, Japan. The presence of UU was evaluated using the Overactive Bladder Symptom Score. The distance from the light reflex on the cornea to the upper eyelid (margin reflex distance-1 [MRD-1]) was measured. AP was defined as MRD-1 of less than 2.0 mm. The daily salt intake amount was estimated using the dietary questionnaire. Daily salt intake was defined as excessive if it was 10 g/day or higher. Independent factors of UU and AP were analyzed via multivariable logistic regression model. Results The number of women with UU and AP was 193 and 65, respectively. Similar background differences were observed in age, cardiovascular disease history, renal function, hypertension, diabetes mellitus, dyslipidemia, and daily salt intake between participants with UU and those with AP. Participants with UU had a higher prevalence of AP (19% vs. 6.2%) than those without. Moreover, more than 50% of the women with AP experienced UU. Multivariable logistic analysis on UU showed that age (≥65 years), diabetes mellitus, daily salt intake (≥10 g/day), and AP (odds ratio, 2.07, p = .014) were independent factors. Multivariable analysis on AP revealed that age (≥65 years), hypertension, daily salt intake (≥10 g/day), and UU were independent factors. Conclusions AP was an independent indicator of UU, in addition to excessive daily salt intake. Women with AP may tend to intake excessive salt and experience UU.

Objectives To assess the clinical benefit of pembrolizumab as second-line therapy for advanced urothelial carcinoma. Methods We retrospectively compared the effects of pembrolizumab with those of conventional chemotherapy on the prognosis of patients with advanced urothelial carcinoma at six hospitals between January 2004 and August 2020. We compared the oncological outcomes between the patients treated with pembrolizumab and those treated with conventional chemotherapy using Kaplan-Meier curve analysis and multivariate Cox regression analysis with the inverse probability of treatment weighting method. Results The numbers of patients in the pembrolizumab and chemotherapy groups were 121 and 67, respectively. Patients in the pembrolizumab group were significantly older (median 72 vs 66 years, P = 0.001), and had poor Eastern Cooperative Oncology Group performance status (median 1 vs 0, P = 0.001). The unadjusted Kaplan-Meier curve analysis showed no significant differences in the median overall survival from the first-line chemotherapy (24.7 months vs 16.3 months, P = 0.159). Inverse probability of treatment weighting-adjusted multivariate Cox proportional hazards analyses showed a significant difference between the pembrolizumab and chemotherapy groups in overall survival (P = 0.003, hazard ratio 0.63). Conclusions Despite the non-negligible age difference between the trial and our clinical practice, our study supports the benefit of second-line pembrolizumab over chemotherapy in real-world practice.

To examine the oncological and urinary functional outcomes of reproductive organ-sparing radical cystectomy (ROS-RC) and U-shaped ileal neobladder construction in females compared with male patients.We retrospectively examined 357 patients (281 male and 76 female) with muscle-invasive bladder cancer who were treated with RC plus U-shaped ileal neobladder construction between May 1996 and July 2021. All female patients were treated with ROS-RC. We compared disease-free survival (DFS), cancer-specific survival (CSS), overall survival (OS), and urinary functional outcomes between male and female patients. We evaluated the effect of gender on DFS, CSS, and OS. Furthermore, urinary functional outcomes were evaluated in 140 males and 48 females using a pressure-flow study at 3, 6, 9, and 12 months postoperatively.Female patients were considerably older than male patients at the time of radical cystectomy. No significant difference was noted in the tumor stage preoperatively. The multivariable Cox regression analysis with an inverse probability treatment weighted model revealed that the female gender was not significantly related to DFS, CSS, and OS. Moreover, urinary functions at 12 months were not markedly different between males and females, except for the capacity of the neobladder, detrusor pressure, and maximum urethral closure pressure.This study demonstrates that female patients with ROS-RC and U-shaped ileal neobladder construction did not significantly correlate with worse oncological outcomes. The combination of ROS-RC and U-shaped ileal neobladder construction might attain adequate urinary function without sacrificing oncologic outcomes.

To investigate the prognostic significance of total cell-free DNA (cfDNA) level and androgen receptor amplification (AR-amp) in patients with castration-resistant prostate cancer (CRPC). We retrospectively compared the total cfDNA level and AR-amp in 42 individuals without prostate cancer, 57 patients with localized prostate cancer without androgen-deprivation therapy (ADT), 97 patients with castration-sensitive prostate cancer (CSPC) with ADT, and 97 patients with CRPC. The association of these cfDNA biomarkers on disease status and overall survival was evaluated using Kaplan–Meier analysis and multivariable Cox regression analysis. Finally, a simple risk model was developed including total cfDNA and AR-amp to predict poor prognosis. The median total cfDNA level and AR-amp in patients with CRPC was 387 pg/μL and 1.07 copies, respectively. The total cfDNA levels and AR-amp were significantly higher in the patients with CRPC than in individuals without prostate cancer, patients with localized prostate cancer without ADT, and patients with CSPC with ADT. Total cfDNA-high (> 600 pg/μL) and AR-amp-high (> 1.26 copies) were significantly associated with poor overall survival. Multivariable Cox regression analysis showed cfDNA-high and AR-amp-high were significantly associated with poor overall survival in patients with CRPC. We developed a risk model using cfDNA-high (score 1) and AR-amp-high (score 1). The risk score 1–2 was significantly associated with worse overall survival than score 0. Total cfDNA level and AR-amp are potential biomarkers for poor prognosis in patients with CRPC.

Objective To evaluate temporal trends in neoadjuvant chemotherapy (NAC) utilisation and outcomes in patients with locally advanced upper tract urothelial carcinoma (UTUC). Patients and methods We included 289 patients from seven hospitals who underwent radical nephroureterectomy (RNU) for locally advanced UTUC (≥cT3 or cN+) between 2000 and 2020. These patients received RNU alone or two to four courses of NAC with either a cisplatin- or carboplatin-based regimen. We evaluated the temporal changes in NAC use and compared the visceral recurrence-free, cancer-specific, and overall survival rates. The effect of NAC on oncological outcomes was examined using multivariate Cox regression analysis with inverse probability of treatment weighting (IPTW) models. Results Of 289 patients, 144 underwent NAC followed by RNU (NAC group) and 145 underwent RNU alone (Control [Ctrl] group). NAC use increased significantly from 19% (2006-2010), 58% (2011-2015), to 79% (2016-2020). Pathological downstaging was significantly higher in the NAC group than in the Ctrl group. The IPTW-adjusted multivariable analyses showed that NAC significantly improved the oncological outcomes in the NAC group compared with the Ctrl group. Moreover, carboplatin-based NAC significantly improved the oncological outcomes in the NAC group compared with the Ctrl group among patients with chronic kidney disease Stage ≥3. There were no significant differences in oncological outcomes between the cisplatin- and carboplatin-based regimens. Conclusions The use of NAC for high-risk UTUC increased significantly after 2010. Platinum-based short-term NAC followed by immediate RNU may not impede and potentially improves oncological outcomes.

Discriminating between urothelial carcinoma (UC), including bladder cancer (BCa) and upper urinary tract UC (UTUC), is often challenging. Thus, the current study evaluated the diagnostic performance of N‐glycosylation signatures of immunoglobulins (Igs) for detecting UC, including BCa and UTUC. N‐glycosylation signatures of Igs from serum samples of the training cohort, including 104 BCa, 68 UTUC, 10 urinary tract infection, and 5 cystitis cases, as well as 62 healthy volunteers, were measured retrospectively using automated capillary‐electrophoresis‐based N‐glycomics. UTUC or BCa scores were then established through discriminant analysis using N‐glycan signatures of Igs. Diagnostic performance was evaluated using the area under receiver operating characteristics curve (AUC) and decision curve analyses (DCA). Our result showed that BCa and UTUC scores for discriminating BCa (AUC: 0.977) and UTUC (AUC: 0.867), respectively, provided significantly better clinical performance compared to urine cytology, gross hematuria, or clinical T1 cases. DCA revealed that adding BCa and UTUC scores to gross hematuria status was the best combination for detecting UC and avoiding the need for more intervention without overlooking UC (risk threshold: 13%–93%). The UC nomogram based on the combination of gross hematuria, UTUC score, and BCa score could detect UC with an AUC of 0.891, indicating significantly better performance compared to gross hematuria status in the validation cohort (251 patients). The limitations of this study include its small sample size and retrospective nature. The UC nomogram based on gross hematuria and N‐glycosylation signatures of Igs can be a promising approach for the diagnosis of UC., We evaluated the diagnostic performance of Bladder cancer (BCa) and upper urinary tract urothelial carcinoma (UTUC) discrimination scores that we developed based on N‐glycosylation signatures of immunoglobulins. The BCa score and UTUC score provided significantly better clinical performance than urine cytology negative or gross hematuria negative or clinical T1 cases.

Background The clinical benefit of the combined androgen blockade (CAB) therapy over luteinizing hormone-releasing hormone analog (LH-RHa) monotherapy for hormone naive metastatic prostate cancer (mHNPC) is unclear. Therefore, we retrospectively compare the effectiveness of CAB with the LH-RHa monotherapy on the prognosis of Japanese patients with mHNPC. Methods We retrospectively evaluated the prognosis of 517 patients diagnosed with mHNPC between August 2001 and May 2017. The patients' data were obtained from the Michinoku Urological Cancer Research Group database and Hirosaki University-related hospitals. Patients were divided into the CAB and LH-RHa monotherapy groups based on primary androgen deprivation therapy (ADT). Overall survival (OS), cancer-specific survival (CSS), and castrate-resistant prostate cancer-free survival (CRPC-FS) were compared between the two groups using the Kaplan-Meier curve analysis. Inverse probability of treatment weighting (IPTW)-adjusted Cox hazard proportional analyses was performed to investigate the effect of primary ADT on oncological outcomes. Results The median age was 73 years old. The numbers of patients in the CAB and LH-RHa monotherapy groups were 447 and 70, respectively. The Kaplan-Meier curve analysis showed no significant differences in either 5-year OS (56.7% vs. 52.5%, P=0.277), CSS (61.1% vs. 56.4%, P=0.400), and CRPC-FS (33.1% vs. 31.1%, P=0.529) between the groups. IPTW-adjusted multivariate Cox hazard proportional analyses showed no significant differences in OS, CSS, and CRPC-FS between the two groups. Conclusions No significant differences in oncological outcomes were observed between the CAB and LH-RHa monotherapy groups in patients with mHNPC.