OBJECTIVES:The prostatic urethral lift (PUL) for benign prostatic hyperplasia (BPH) has been shown to deliver rapid, durable symptom relief with low morbidity. Most studies have been performed in Western populations. The objective was to understand how PUL performs in the real world in Japan among a broad patient population. METHODS:A post-market registry study of consecutive PUL subjects across 14 Japanese centers was conducted. International Prostate Symptom Score (IPSS), quality of life (QOL), maximum flow rate (Qmax) and sexual function were evaluated at baseline, 3- and 12- months post-procedure. Paired t-tests compared baseline and follow-up data. Subject demographics, adverse events, BPH medication use, catheterization, and surgical retreatment were reported. RESULTS:210 subjects were included. Baseline characteristics included age 74.3 ± 8.5 years, IPSS 18.0 ± 7.4, QOL 4.8 ± 1.3, Qmax 10.3 ± 5.5 mL/s and prostate volume 40.5 ± 16.1 cc. Paired analyses indicated IPSS improved 6.6 (36.9%), p < 0.0001; QOL improved 2.1 (43.3%), p < 0.0001 and Qmax improved 1.5 (14.7%) mL/s (p = 0.023) at 12 months. Sexual function measures were unchanged or significantly improved, although results should be interpreted with caution due to a high degree of missing data. BPH medication use decreased from 76.7% to 12.4%; One subject was surgically retreated by 12 months. Adverse events were typically mild-moderate and transient. CONCLUSIONS:This registry study from Japan indicates PUL is safe and effective; results corroborate those of previous studies. The data support the use of PUL in the broader BPH population in Japan. TRIAL REGISTRATION:Japan Registry of Clinical Trials (jRCT 2032220377).

With the increasing importance of nuclear medicine therapy in overall cancer care and the introduction of 177Lu-PSMA-617 to Japan being imminent, the Policy Recommendations for Promoting Nuclear Medicine Therapy in Japan from the Working Group for Promoting Nuclear Medicine Therapy of the Japan Society of Clinical Oncology (JSCO) aim to identify issues related to nuclear medicine therapy and propose measures to address them, in order to further advance nuclear medicine therapy in Japan. It is necessary to create an environment in which each medical institution can proactively introduce nuclear medicine therapy by taking measures that target discharge criteria, medical fees, and human resource development and link them organically. The Working Group believes that it is necessary to continue examining long-term issues taking into account the changes that have occurred since the introduction of 177Lu-PSMA-617, as well as trends in nuclear medicine therapy other than 177Lu-PSMA-617 that are expected to be introduced in the future. In addition, as the "Action Plans for Promoting the Production and Use of Medical Radioisotopes" have been formulated and the advancement of nuclear medicine therapy has become one of the nation's major policy priorities, JSCO will continue to actively work with relevant ministries and local governments to resolve the various issues of nuclear medicine therapy, including the smooth introduction of 177Lu-PSMA-617.

BACKGROUND:Triplet therapy with darolutamide and docetaxel has reshaped the treatment landscape of metastatic castration-sensitive prostate cancer (mCSPC). However, real-world evidence regarding its oncological outcomes and toxicity remains limited. METHODS:We retrospectively reviewed 112 consecutive patients with mCSPC who were treated with triplet therapy. A deep prostate-specific antigen (PSA) response was defined as a PSA level < 0.2 ng/ml or a ≥ 90% decline from baseline. Castration-resistant prostate cancer (CRPC)-free survival was used as the survival endpoint. Clinicopathological factors associated with CRPC-free survival were analysed using a Cox proportional hazards model. Treatment-related adverse events (AEs) were comprehensively documented by type and grade. RESULTS:During a median follow-up of 17.1 months, 15 patients developed CRPC and four died of prostate cancer; 1-year CRPC-free survival and overall survival rates were 89.8% (95% confidence interval, 83.9%-96.0%) and 98.8% (96.5%-100%), respectively. A deep PSA response was achieved in 73.2% of patients (PSA nadir <0.2 ng/ml) and in 96.4% (PSA ≥ 90% decline). In both the univariable and multivariable analyses, no baseline factor was significantly associated with CRPC-free survival. Grade ≥ 3 hematologic AEs occurred in 75.0% of patients. Among the 31 patients who discontinued docetaxel, 26 discontinued due to non-hematologic AEs. CONCLUSIONS:Triplet therapy demonstrated substantial clinical activity in real-world patients with mCSPC, with high rates of deep PSA response despite frequent AEs. These findings support the feasibility of triplet therapy in routine practice. Given the substantial toxicity burden, careful patient selection and proactive AE management remain important.

RATIONALE:Penile metastasis from renal cell carcinoma (RCC) is an extremely rare clinical entity, particularly in the era of immune-checkpoint inhibitor and tyrosine-kinase inhibitor combination therapy. The mechanisms, clinical presentation, and optimal management of such cases remain poorly understood. PATIENT CONCERNS:A 75-year-old man with metastatic RCC undergoing systemic therapy developed persistent, painful erections (malignant priapism), along with urinary retention, general malaise, and back pain, 2 years after initiating treatment. DIAGNOSIS:Magnetic resonance imaging of the penis revealed a hypointense lesion on T2-weighted imaging and restricted diffusion on diffusion-weighted imaging, suggestive of tumor infiltration into the corpus cavernosum. Blood gas analysis from corporal aspiration was consistent with nonischemic priapism. A diagnosis of penile metastasis from RCC was established. INTERVENTIONS:Embolization of the common penile artery was performed, followed by palliative radiotherapy (30 gray in 10 fractions). OUTCOMES:Despite these interventions, penile rigidity persisted, though partial symptomatic relief and pain reduction were achieved. Disease progression was noted, and the patient died approximately 3 months after the diagnosis of penile metastasis. LESSONS:This is the first reported case of penile metastasis from RCC during immune-checkpoint inhibitor-tyrosine-kinase inhibitor therapy, highlighting a rare but clinically important metastatic pattern potentially unmasked by prolonged survival. Retrograde dissemination via Batson venous plexus may underlie this presentation. Radiotherapy and embolization may offer partial symptomatic relief, but the prognosis remains poor. Accumulation of further cases is necessary to guide future management strategies.

OBJECTIVES:This study evaluated the cancer detection profile of magnetic resonance imaging/transrectal ultrasound fusion-guided biopsies (fusion biopsy) using the BiopSee® system in patients assessed with the Prostate Imaging Reporting and Data System (PI-RADS) version 2.1, focusing on clinically significant prostate cancer (csPCa) detection in regions of interest (ROI) and non-ROI areas. METHODS:We retrospectively analyzed 59 patients who underwent fusion biopsy between February and November 2024. Detection rates of csPCa (grade group ≥ 2) were compared between the ROI and non-ROI regions, and clinical and biopsy characteristics were compared between patients with and without csPCa. Univariate logistic regression analysis was performed to identify predictors of csPCa. RESULTS:The median patient age was 74 years, with a median prostate-specific antigen (PSA) level of 8.93 ng/mL. The csPCa detection rate was significantly higher in the ROI than in the non-ROI regions (61% vs. 44%, P = 0.012). Across the cohort, PI-RADS 4 and 5 lesions were more common than PI-RADS 3 lesions. A higher PI-RADS score (4 or 5) was identified as a significant predictor of csPCa detection (odds ratio 5.14, P = 0.034), whereas age, PSA, number of ROIs, and biopsy core numbers were not significant predictors. CONCLUSIONS:Fusion biopsy using the BiopSee® system achieved a high csPCa detection rate in targeted ROIs, especially for PI-RADS 4 and 5 lesions, while also highlighting the importance of combining systematic biopsy with targeted approaches because of the substantial proportion of csPCa detected in non-ROI regions.

Objective:To assess the impact of preoperative pelvic floor muscle thickness on the early recovery of urinary continence following robot-assisted radical prostatectomy (RARP). Patients and Methods:A retrospective study was conducted on 114 patients who underwent RARP at our institution between January 2019 and March 2021. Patients included were either confirmed to be pad-free or using only safety pads postoperatively or those with persistent incontinence, with a follow-up period of at least 6 months. Patient characteristics, perioperative outcomes, and pelvic floor muscle diameters were analysed. Preoperative magnetic resonance imaging or computed tomography was used to measure the diameters of the pelvic floor muscles, including the obturator internus and pubococcygeus muscles. Results:The median patient age was 68 years (interquartile ranges [IQR]: 64-72 years), with a median Prostate-Specific Antigen (PSA) of 7.8 ng/ml (IQR: 5.4-10.6 ng/ml). The median prostate volume was 26.6 ml (IQR: 23-35 ml) in the early recovery group and 29 ml (IQR: 19.5-40 ml) in the delayed recovery group. The median time to continence recovery was 5.0 months (95% confidence interval: 4.2-5.7 months), with an incontinence resolution rate of 85.1%. Significant associations were found between the thicknesses of the obturator internus (p = 0.025) and pubococcygeal muscles (p = 0.004) and early continence recovery. Nerve-sparing procedures were also associated with faster recovery (p = 0.016). Multivariate analysis identified the thickness of both muscles as independent predictors of early continence recovery. Conclusion:Preoperative evaluation of pelvic floor muscle thickness, particularly the obturator internus and pubococcygeal muscles, may help predict early postoperative urinary continence recovery in patients undergoing RARP. Preoperative pelvic floor muscle exercises to strengthen these muscles could improve the postoperative outcomes.

In the over 80 years since androgens were found to play a pivotal role in prostate cancer (PCa) progression, androgen deprivation therapy (ADT) has been a cornerstone in treating advanced PCa. Castration-resistant PCa persists, however, with some of these tumors evolving to androgen receptor (AR)-independent forms like neuroendocrine PCa. The development of novel diagnostic and therapeutic approaches to PCa is therefore crucial. This review provides an overview of recent basic research in PCa, focusing on two main areas: PCa cells and their tumor microenvironments. The first section describes current knowledge on the intricate mechanisms of AR signaling pathways, emphasizing the roles of coactivators and chromatin state alterations in gene regulation. Genomic analyses have revealed recurrent mutations and copy number alterations critical for precision medicine. Liquid biopsy has become a promising tool for real-time tumor monitoring, identifying genetic alterations in circulating-tumor DNA or extracellular vesicles. The second section describes the tumor microenvironment of PCa, highlighting its immunosuppressive landscape and the potential of combining ADT with immunotherapy. Advanced techniques, including single-cell RNA sequencing and spatial transcriptomics offer insights into cellular heterogeneity and interactions within the tumor microenvironment, paving the way for novel therapeutic strategies. Integration of these diverse research areas will provide a comprehensive understanding of the current state and future directions of PCa research, underscoring the importance of personalized medicine and the dynamic nature of cancer treatment strategies.

We experienced four cases of high-risk metastatic castration-sensitive prostate cancer (mCSPC) in which first-line treatment with abiraterone showed a sustained long-term response of over 5 years. We conducted immunohistochemical staining of aldo-keto reductase family 1 member C3 (AKR1C3) expression, which associate with poor prognosis of metastatic castration-resistant prostate cancer (mCRPC), and all prostate cancer tissue from four cases showed negative. These results suggested that AKR1C3-negative high-risk mCSPC cases may respond well to first-line treatment with abiraterone. This is the first report describing association of high-risk mCSPC and negative AKR1C3.

BACKGROUND:Salvage robot-assisted radical prostatectomy (sRARP) after PSA failure in patients who underwent initial radiotherapy or focal therapy has rarely been reported in Japan. We aimed to report the oncologic and functional outcomes of the first 10 cases of sRARP. METHODS:Ten patients underwent sRARP after failing to respond to initial radiotherapy or focal therapy. Initial definitive treatment included volumetric modulated arc therapy, intensity-modulated radio therapy, stereotactic body radiotherapy, heavy-ion radiotherapy, low-dose-rate brachytherapy, and high-intensity focused ultrasound. We retrospectively investigated 10 cases on oncologic and functional outcomes of sRARP. RESULTS:The median PSA level at sRARP, amount of blood loss, and console time were 2.17 ng/mL, 100 mL, and 136 min, respectively. Positive surgical margins were found in half of the cases. Median follow-up was 1.1 years. There were no 30-day major complications. No patients had erections after sRARP. Urinary continence and biochemical recurrence (BCR) rate were 40% and 30% at 1 year after sRARP, respectively. CONCLUSIONS:Salvage RARP may be a feasible option after PSA failure in patients who underwent radiotherapy or focal therapy as initial treatment, showing acceptable BCR rate.

Background:A new subtype of prostate cancer called treatment-related neuroendocrine prostate carcinoma (t-NEPC) was added to the revised World Health Organization classification of prostate cancer in 2022. t-NEPC cases are increasing, and there is no established standard treatment. Methods:A 49-year-old male patient was referred to our department for dysuria. A rectal examination and a prostate biopsy revealed stony hardness and prostate adenocarcinoma, respectively. Imaging studies confirmed the presence of multiple bone and lymph node metastases. The patient was started on upfront treatment with androgen deprivation therapy and an androgen receptor signaling inhibitor, which resulted in a significant (>90%) decrease in prostate-specific antigen (PSA) levels. The patient experienced postrenal failure 6 months later, attributable to local disease progression. Concurrently, there was an elevation in neuron-specific enolase (NSE) levels and an enlargement of pelvic lymph node metastases, without PSA progression. Results:Biopsy specimen for cancer genome profiling revealed deletion of BRCA 2 and PTEN, AR amplification, and the presence of the TMPRSS2-ERG fusion gene. Based on increased NSE and BRCA2 mutations, a diagnosis of t-NEPC with BRCA2 mutation was eventually made. The patient received docetaxel chemotherapy and pelvic radiotherapy. Subsequently, he was treated with olaparib. His NSE levels decreased, and he achieved a complete response (CR). However, 18 months following the olaparib administration, brain metastases appeared despite the absence of pelvic tumor relapse, and the patient's PSA levels remained low. Consequently, the patient underwent resection of the brain metastases using gamma knife and whole-brain radiotherapy but died approximately 3 months later. Conclusion subsections:Platinum-based chemotherapy is often administered for the treatment of t-NEPC, but there are few reports on the effectiveness of olaparib in patients with BRCA2 mutations. In a literature review, this case demonstrated the longest duration of effectiveness with olaparib alone without platinum-based chemotherapy. Additionally, the occurrence of relatively rare, fatal brain metastases in prostate cancer after a long period of CR suggests the necessity of regular brain imaging examinations.

Abstract Background Prostate cancer is dependent on androgen receptor (AR) signaling, and androgen deprivation therapy (ADT) has proven effective in targeting prostate cancer. However, castration-resistant prostate cancer (CRPC) eventually emerges. AR signaling inhibitors (ARSI) have been also used, but resistance to these agents develops due to genetic AR alterations and epigenetic dysregulation. Methods In this study, we investigated the role of OCT1, a member of the OCT family, in an AR-positive CRPC patient-derived xenograft established from a patient with resistance to ARSI and chemotherapy. We conducted a genome-wide analysis chromatin immunoprecipitation followed by sequencing and bioinformatic analyses using public database. Results Genome-wide analysis of OCT1 target genes in PDX 201.1 A revealed distinct OCT1 binding sites compared to treatment-naïve cells. Bioinformatic analyses revealed that OCT1-regulated genes were associated with cell migration and immune system regulation. In particular, C-terminal Binding Protein 2 (CTBP2), an OCT1/AR target gene, was correlated with poor prognosis and immunosuppressive effects in the tumor microenvironment. Metascape revealed that CTBP2 knockdown affects genes related to the immune response to bacteria. Furthermore, TISIDB analysis suggested the relationship between CTBP2 expression and immune cell infiltration in prostate cancer, suggesting that it may contribute to immune evasion in CRPC. Conclusions Our findings shed light on the genome-wide network of OCT1 and AR in AR-positive CRPC and highlight the potential role of CTBP2 in immune response and tumor progression. Targeting CTBP2 may represent a promising therapeutic approach for aggressive AR-positive CRPC. Further validation will be required to explore novel therapeutic strategies for CRPC management.

Androgen deprivation therapy has achieved significant success in treating prostate cancer through strategies centered on the androgen receptor. However, the emergence of castration-resistant prostate cancer highlights this therapy limitation, underscoring the need to elucidate the mechanisms of treatment resistance. This review aimed to focus on multifaceted resistance mechanisms, including androgen receptor overexpression, splice variants, missense mutations, the involvement of the glucocorticoid receptor, and alterations in coregulators and transcription factors, revealing their roles in castration-resistant prostate cancer progression. These mechanisms promote cell survival and proliferation, depending on the androgen receptor signaling pathway, leading to resistance to conventional therapies. Amplification and mutations in the androgen receptor gene facilitate selective adaptation in treatment-resistant cells, consequently diminishing therapeutic efficacy. Furthermore, the activation of glucocorticoid receptors and aberrant regulation of specific coregulators and transcription factors contribute to the activation of androgen receptor-independent signaling pathways, promoting cell survival and proliferation. These findings hold promise for identifying new targets for treating castration-resistant prostate cancer and developing personalized treatment strategies. The development of future therapies will hinge on precisely targeting the androgen receptor signaling pathway, necessitating a deeper understanding of the molecular targets unique to castration-resistant prostate cancer.

This study aimed to identify the predictive factors associated with oncological outcomes in metastatic hormone-sensitive prostate cancer-related genes. A nomogram for predicting prostate cancer-specific survival (CSS) was constructed based on biopsy samples from 103 patients with metastatic hormone-sensitive prostate cancer. We analyzed the association between clinical data and mRNA expression levels. The nomogram was externally validated in another cohort (n = 50) using a concordance index. Based on the cutoff value, determined by a receiver operating characteristic analysis, longer CSS was observed in the high osteoglycin and androgen receptor expression level groups (> 1.133 and > 0.00; median CSS, 85.3 vs. 52.7 months, p = 0.082, and 69.1 vs. 32.1 months, p = 0.034, respectively), compared with that of the low expression level groups. The nomogram predicting CSS included hemoglobin (≥ 13.7 g/dL or < 13.7 g/dL), serum albumin (≥ 3.1 g/dL or < 3.1 g/dL), serum lactate dehydrogenase (≥ 222 IU/L or < 222 IU/L), total Japan Cancer of the Prostate Risk Assessment score, androgen receptor expression level, and osteoglycin expression level. The concordance indices for internal and external validations were 0.664 and 0.798, respectively. A nomogram that integrates expression levels of androgen receptors and osteoglycin to predict CSS in metastatic hormone-sensitive prostate cancer was established.

BACKGROUND:While the occurrence of immune-related adverse events has been recognized as a prognostic marker in patients receiving immune checkpoint inhibitors, the prognostic significance of treatment-related adverse events (trAEs) in patients undergoing antibody-drug conjugates such as enfortumab vedotin (EV) is controversial. METHODS:We reviewed 106 patients with advanced urothelial carcinoma who were treated with EV therapy at 10 institutions between 2021 and 2023. Associations of clinical parameters with overall survival and progression-free survival were assessed using the Cox proportional hazards model. For the assessment of trAEs, landmark analysis was conducted to minimize immortal time bias. RESULTS:Of 106 patients, 55 (51.9%) experienced disease progression and 44 (41.5%) died during the follow-up period. Any grade and grade ≥3 trAEs occurred in 94 (88.7%) and 44 (41.5%) patients, respectively. Common trAEs included skin disorders (74.5%), gastrointestinal disorders (62.3%), fatigue (50.0%), peripheral neuropathy (36.8%), and hematological disorders (37.7%). One patient died of interstitial pneumonia (grade 5). According to landmark analysis using 88 patients who survived for 2 months or more, trAEs were significantly associated with longer survival. Furthermore, when trAEs were classified into "physical trAEs" such as skin disorders and "laboratory trAEs" such as hematological disorders, the former were associated with longer survival while the latter were associated with shorter survival. CONCLUSIONS:Physical, but not laboratory, trAEs are associated with favorable outcomes of EV therapy for advanced urothelial carcinoma. Both managing trAEs and utilizing them as prognostic markers are key points in the use of antibody-drug conjugates such as EV.

This study evaluated the association between pelvic organ prolapse (POP), frailty, and sarcopenia to explore how POP treatment can extend healthy life expectancy in elderly women. We conducted a retrospective study of prospectively collected data, comparing women with mild POP (stages 0–II) with those with advanced POP (stages III and IV). The inclusion criteria for this study were women who visited the clinic with at least one symptom of pelvic floor dysfunction and underwent imaging studies between April 2020 and November 2022. Initially, 119 patients met these inclusion criteria. Patients were excluded if they had a history of previous POP treatment, did not respond to the study survey, or were lost to follow-up. After applying these exclusion criteria, 82 patients were included in the final analysis, of whom 65 underwent surgery (laparoscopic sacrocolpopexy, colpocleisis, tension-free vaginal tape, and native tissue repair). Assessments included POP Quantification, Kihon Checklist, Pelvic Organ Prolapse Quality of Life (P-QOL) questionnaire, International Prostate Symptom Score (IPSS), Overactive Bladder Symptom Score (OABSS), and Incontinence Symptom Questionnaire (ICIQ-SF). Pelvic muscles were measured using MRI or CT. Immunohistochemical analysis of estrogen receptor alpha (ERα), estrogen receptor beta , and androgen receptor was performed on surgical specimens from 43 patients. The median age of participants was 75 years. Of the 82 patients, 48 (58.5

PDF file, 138K, The clinical and histopathological data of the patients in the studies.