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Introduction The incidence of prostate cancer in Japan continues to increase, necessitating the continued development of effective therapies and strategies. Recent advances in treatments have improved the prognosis of metastatic disease and highlighted the importance of treating bone metastases to reduce the incidence of skeletal complications and improve patients’ quality of life. With the increasing number of treatment options that have become available, including bone-targeted therapy with the alpha emitter radium-223 dichloride (Ra-223), Japanese clinicians are faced with making difficult decisions on the choice of optimal treatment strategy. In such situations, guidance based on expert opinions can be beneficial. Methods A panel meeting of 27 Japanese experts in the management of prostate cancer was held to share opinions and to establish consensus recommendations on key clinical questions. Panelists were asked to vote on more than 40 questions pertinent to prostate cancer, and the answers helped guide a comprehensive discussion. Results The panel reached a consensus on key topics related to the optimal treatment strategy for Ra-223 therapy, namely, that patients with symptomatic, metastatic castration-resistant prostate cancer (CRPC) would benefit most from the use of this agent and that this treatment therapy should be provided before chemotherapy. Other topics that achieved consensus included: monitoring for osteoporosis and providing treatment if necessary during androgen deprivation therapy; performing magnetic resonance imaging in the presence of discrepancies in bone scintigram and computed tomography scans; monitoring alkaline phosphatase during CRPC treatment; using osteoclast-targeting in patients with CRPC with bone metastases; and using osteoclast-targeted agents combined with Ra-223. Conclusion These consensus recommendations and the updated information which became available subsequent to the panel meeting included here provide useful information for clinicians to aid in designing optimal treatment strategies for their patients. Funding Bayer Yakuhin Ltd. Electronic supplementary material The online version of this article (10.1007/s40487-018-0088-0) contains supplementary material, which is available to authorized users.

Background/Aim: Radium-223 therapy prolongs overall survival in castration-resistant prostate cancer (CRPC) patients with bone metastasis. Patients who are unable to complete six courses of radium-223 therapy reportedly have a poor prognosis. This study aimed to develop a risk score using the discontinuation factors of the above therapy modality. Patients and Methods: Seventy patients who received radium-223 therapy for metastatic CRPC at two Japanese Institutions were evaluated. Univariate and multivariate analyses were performed to identify the discontinuation factors and determine the risk scores. Results: The median survival time was 24.3 and 9.5 months in patients who did and did not complete the therapy, respectively. Multivariate analysis revealed haemoglobin and prostate-specific antigen as key factors. A risk score was developed using these factors, and patients were stratified into three groups. The discontinuation rate and survival after radium-223 therapy were significantly different. Conclusion: Our risk score may help evaluate the suitability of radium-223 in CRPC patients.

We performed test clamp procedure in robot-assisted partial nephrectomy (RAPN) to prevent massive bleeding during tumor resection and to omit dissection of non-feeding arteries around the tumor. We subsequently analyzed the safety and usefulness of the procedure. The Test clamp procedure was performed for 1 to 3 min during renal artery test ischemia prior to the actual ischemia and tumor resection. We confirmed the disappearance of blood flow around the renal tumor using color Doppler ultrasonography. If arterial blood flow around the tumor remained, we surveyed the site for other arteries that needed to be clamped and repeated the test clamp procedure until renal blood flow around the tumor disappeared. We retrospectively analyzed consecutive RAPN cases performed from July 2016 to March 2020 at our institutions and reviewed medical records. The clinical data of the RAPN cases were statistically analyzed. Sixty-four RAPN cases underwent the test clamp procedure, which was categorized as the TEST group. Test clamping was performed safely without any clamping-related complications in all cases. Eleven cases (17%) underwent partial ischemia, which was a significantly higher number than that in the control group. Massive bleeding during tumor resection was more frequent in the control group. Postoperative deterioration of estimated glomerular filtration rate did not differ significantly between both groups. Although further investigation was still necessary, our findings indicate that the test clamp procedure may be a safe and secure procedure to perform in RAPN for both patients and surgeons.

Background/aim Vintage hormone therapy for non-metastatic castration-resistant prostate cancer (nmCRPC) is not recommended under the current guidelines, but is widely practiced in Japan. This study assessed effectiveness of vintage hormone therapy as alternative androgen deprivation therapy (AADT) for treatment of nmCRPC. Patients and methods In this retrospective study we examined patients with nmCRPC that received vintage hormone therapy as AADT between 1999 and 2018. Results Of 53 patients with nmCRPC, 25 patients (47.2%) had stage 1 nodal disease (N1) at diagnosis of nmCRPC. Prostate specific antigen (PSA) reduction rate≥30% was observed in 32 patients (72.7%). The median PSA nadir was 0.7, and the duration of the response was 14.3 months. The median metastasis-free survival (MFS) for the entire patient population was 62.2 months, and the median overall survival (OS) was not reached. In the multivariate analysis, the duration of response in AADT>18 months was a predictor of prolonged OS. Conclusion There is a certain number of nmCRPC patients who respond well to vintage hormone therapy as AADT. Further studies are expected to differentiate such cases.

Emergence of malignant ureteral obstruction (MUO) has been reported as a sign of poor prognosis; however, the distribution of survival time in patients with MUO is considerably wide, and no risk classification score has been constructed. To evaluate whether a novel risk classification score for overall survival that we previously developed, is effective in a large cohort. Investigator-initiated, prospective, multicenter diagnostic/prognostic study was conducted. Patients with MUO were divided into three risk groups based on the score calculated using four prognostic factors (PLaCT: Primary site, Laterality, serum Creatinine level, and Treatment for primary site) at the first visit, and prospective follow-up was performed. Overall survival and ureteral stent failure-free survival of each risk group were compared. In total, 300 patients with 21 different primary sites were enrolled. The numbers of patients in good, intermediate, and poor risk groups were 105, 106, and 89, respectively. Median survival times of patients in good, intermediate, and poor risk groups were 406, 221, and 77 days, respectively (P P

Bone fracture due to osteoporosis is an important issue in decreasing the quality of life for elderly men in the current aging society. Thus, osteoporosis and bone fracture prevention is a clinical concern for many clinicians. Moreover, testosterone has an important role in maintaining bone mineral density (BMD) among men. Some testosterone molecular mechanisms on bone metabolism have been currently established by many experimental data. Concurrent with a decrease in testosterone with age, various clinical symptoms and signs associated with testosterone decline, including decreased BMD, are known to occur in elderly men. However, the relationship between testosterone levels and osteoporosis development has been conflicting in human epidemiological studies. Thus, testosterone replacement therapy (TRT) is a useful tool for managing clinical symptoms caused by hypogonadism. Many recent studies support the benefit of TRT on BMD, especially in hypogonadal men with osteopenia and osteoporosis, although a few studies failed to demonstrate its effects. However, no evidence supporting the hypothesis that TRT can prevent the incidence of bone fracture exists. Currently, TRT should be considered as one of the treatment options to improve hypogonadal symptoms and BMD simultaneously in symptomatic hypogonadal men with osteopenia.

Background The efficacy and safety of keishibukuryogan, a traditional Japanese medicine, were investigated for the treatment of hot flashes in prostate cancer (PC) patients receiving androgen deprivation therapy. Methods Thirty patients were enrolled and orally administered 2.5 g keishibukuryogan three times daily for 12 weeks. The frequency, strength, and duration of hot flashes were self-evaluated by the patients in a diary every 4 weeks. All patients also completed a questionnaire to determine their aging male symptoms (AMS) scale score and underwent blood biochemical testing. Results Twenty-five patients completed the 12-week treatment. Hot flash strength significantly improved 4, 8, and 12 weeks after treatment. Their frequency was significantly reduced at the 8-week visit, and duration was significantly shorter after the 8-week visit. In addition, the score of the AMS somatic subscale was improved at the 8- and 12-week visits. Among the somatic items, questions 3 (excessive sweating) and 5 (increased need for sleep) were significantly improved. Obesity, radiation, and a longer duration of PC were predictive factors for treatment response. Prostate specific antigen and total testosterone levels were unchanged, and no patients had severe adverse effects. Conclusions Keishibukuryogan was an effective and safe treatment for hot flashes in PC patients.

Despite improvements in systemic therapy options for renal cancer, it remains one of the most drug-resistant malignancies. Interestingly, reports have shown that kahweol and cafestol, natural diterpenes extracted from coffee beans, exhibit anti-cancer activity. However, the multiple potential pharmacological actions of both have yet to be fully understood. This study therefore investigated the effects of kahweol acetate and cafestol on human renal cancer ACHN and Caki-1 cells. Accordingly, the combination of kahweol acetate and cafestol administration synergistically inhibited cell proliferation and migration by inducing apoptosis and inhibiting epithelial–mesenchymal transition. Mechanistic dissection revealed that kahweol acetate and cafestol inhibited Akt and ERK phosphorylation. Moreover, kahweol acetate and cafestol downregulated the expression of not only C–C chemokine receptors 2, 5, and 6 but also programmed death-ligand 1, indicating their effects on the tumor microenvironment. Thus, kahweol acetate and cafestol may be novel therapeutic candidates for renal cancer considering that they exert multiple pharmacological effects.

The recommended treatment for high-risk localized or locally advanced prostate cancer is radical prostatectomy plus extended pelvic lymph node dissection or radiation therapy plus long-term androgen deprivation therapy. However, some patients are treated with androgen deprivation therapy alone for various reasons. In this review, we will discuss the position, indications, complications, and future prospects of androgen deprivation therapy for high-risk localized and locally advanced prostate cancer.

Background: Photodynamic diagnosis (PDD)-assisted transurethral resection of bladder tumor (TURBT) has different treatment outcomes across institutions, as seen in conventional TURBT. We retrospectively compared the difference in quality between the two types of endoscopic equipment used for PDD-assisted TURBT in our institution. Methods: This study enrolled 205 consecutive patients who underwent PDD-assisted TURBT. Patients were divided into two groups according to the endoscopic equipment used for PDD-assisted TURBT: Group A using the conventionally used endoscopic system and Aladuck LS-DLED and Group S using the Storz PDD system. Cystoscopy findings of white light (WL), fluorescence light (FL), and combination (positive if either WL or FL was positive) were recorded, and diagnostic quality of PDD was compared between both groups. Results: Group A had 105 cases and 336 specimens, while Group S had 100 cases and 361 specimens, with no significant differences between patient characteristics. The tumor sensitivities of WL, FL, and combination in Group A was 71.9%, 77.1%, 90.5%, respectively, while in Group S, these were 71.5%, 92.2%, 96.1%, respectively. Group S had significantly higher sensitivity of FL and combination than Group A, as well as higher detection of carcinoma in situ lesions. Conclusion: Both endoscopic systems had improved sensitivity with PDD-assistance versus WL only, with Group S having higher sensitivity. Differences in the quality of endoscopic equipment may influence the differences in treatment results with PDD-assisted TURBT across institutions.

C-C motif ligand 2 (CCL2) was originally reported as a chemical mediator attracting mononuclear cells to inflammatory tissue. Many studies have reported that CCL2 can directly activate cancer cells through a variety of mechanisms. CCL2 can also promote cancer progression indirectly through increasing the recruitment of tumor-associated macrophages into the tumor microenvironment. The role of CCL2 in cancer progression has gradually been understood, and various preclinical cancer models elucidate that CCL2 and its receptor C-C chemokine receptor 2 (CCR2) are attractive targets for intervention in cancer development. However, clinically available drugs that regulate the CCL2–CCR2 axis as anticancer agents are not available at this time. The complete elucidation of not only the oncological but also the physiological functions of the CCL2–CCR2 axis is required for achieving a satisfactory effect of the CCL2–CCR2 axis-targeted therapy.

Background/aim To investigate whether surgical margin (SM) status would affect the biochemical recurrence (BCR) after robot-associated RP (RARP). Patients and methods We evaluated BCR after RARP and the association between pre- and postoperative predictive factors and BCR. Results Positive SM (PSM) was observed in 97 out of 365 enrolled patients. On multivariate analysis, preoperative prostate specific antigen, biopsy Gleason score (GS), clinical stage, GS ≥7 at the PSM and pathological GS ≥7 were predictive factors for BCR. The 5-year BCR-free survival rate was 84.1% in the negative SM (NSM), 87.4% when GS=6 at the PSM, and 47.6% when GS ≥7 at the PSM. There was no statistically significant difference in BCR-free survival between the NSM group and GS=6 at the PSM group (p=0.966). Conclusion It would be desirable to evaluate GS at PSM when PSM is present in a specimen removed by RP.

Background: Pembrolizumab is currently considered the standard second-line treatment for advanced urothelial carcinoma (UC). This study aimed to investigate the efficacy and safety of pembrolizumab in patients with advanced UC in real-world data, which is not well-reported.Methods: The study included 98 patients with advanced UC who were treated with pembrolizumab after platinum-based chemotherapy at eight hospitals. The efficacy, safety, and risk factors for prognosis were evaluated. Results: The median age was 73 years. Nineteen patients (19%) with performance status (PS) 2-4 were included. The percentages of liver, lung, bone, and lymph node metastasis were 18%, 27%, 19%, and 76%, respectively. The best response was complete response in nine patients (9%) and partial response in 16 patients (17%). The median progression-free survival and overall survival were 3.7 months (95% confidence interval [CI]: 2.8–4.7) and 11.8 months (95% CI: 6.7–17.0), respectively. Poor PS, liver metastasis, and higher C-reactive protein were poor prognostic factors. Hyperprogression was observed in nine patients (9%), who were mostly of poor PS and had high-volume lesions. Severe adverse events (AEs) were observed in 18 patients (19%), and five patients died because of AEs (5%). Atypical AEs, such as pneumocystis pneumonia and acute myeloid leukemia, were observed in our cohort. Conclusion: The efficacy of pembrolizumab for advanced UC in our cohort was better than a previous phase III trial (KEYNOTE-045), possibly owing to lower cancer volume and fewer visceral metastases in our patients.

Purpose The purpose of this study is to investigate the incidence of rectal toxicity and to identify the associated dosimetric predictive parameters after I-125 seed low-dose-rate brachytherapy (LDR-BT) combined with volumetric modulated arc therapy (VMAT) and dose constraints. Methods and Materials In total, 110 patients with high-risk prostate cancer received 110 Gy LDR-BT, followed by 45 Gy VMAT. Rectal toxicity was recorded according to Common Terminology Criteria for Adverse Events v.4.03. The dosimetric factors associated with LDR-BT and VMAT were analyzed to determine their relationship with rectal toxicity. Receiver operating characteristic (ROC) curve analysis was performed for ≥ grade 2 (G2) rectal toxicity prediction. Results The follow-up duration was 10.1–115.2 months (median 60.5 months). Seven patients had G2 rectal hemorrhage, and none of the patients had grade 3 rectal hemorrhage. In the univariate analysis, the rectal volume receiving 100% of the prescribed dose (rV100) (p Conclusion Predictors of late ≥ G2 rectal hemorrhage are rV100, rD2cc, and combined rD2cc. The incidence of rectal toxicity is low and acceptable in this setting and is highly dependent on the rectal dose of LDR-BT. The use of higher-quality LDR-BT and VMAT dose constraints may further reduce the rate of rectal hemorrhage.

Five mg tadalafil was administered once-daily to 48 patients for 6 months. Their International Prostatic Symptoms Score (IPSS), Overactive Bladder Symptoms Score (OABSS), Sexual Health Inventory for Men (SHIM), post-voided residual (PVR) volume, free testosterone (FT) level, prostate-specific antigen level, and highly sensitive C-reactive protein (hsCRP) value obtained before and 6 months after the treatment were analyzed. The treatment significantly improved the IPSS, OABSS, SHIM score, and PVR volume (P0.05), and significantly increased the mean FT level from 6.68 to 7.10 pg/ml ; P0.05. We observed no significant changes in the hsCRP value and PSA level. However, elevated FT values were noted in 25 (52.1%) patients 6 months after the treatment (FT-increased group). Compared with the non-FT-increased group, the FT-increased group had markedly lower baseline FT value and higher prostatic volume. In both groups, IPSS and OABSS improved considerably. Moreover, the PVR volume, SHIM score, and hsCRP value markedly improved in the FT-increased group (P0.05). Thus, 5 mg tadalafil administered oncedaily improved IPSS, OABSS, and erectile function, and increased the FT value, in hypogonadal patients with lower urinary tract symptoms. Furthermore, the hsCRP value declined considerably in patients with posttreatment elevated FT level.

Histiocytic sarcoma is considered an extremely rare condition. We herein report on a case of histiocytic sarcoma following combination chemotherapy for a primary mediastinal germ cell tumor in a 26-year-old Asian man who visited the General Medicine Department of a hospital with complaints of cough and high fever. Chest computed tomography (CT) imaging revealed a tumor (diameter 10.5 cm) in the anterior mediastinum, with no signs of metastasis, and CT-guided biopsy of the mediastinal tumor revealed the presence of some necrotic cartilages. The patient’s serum α-fetoprotein (AFP) level was determined to be high at 160.4 ng/mL and a primary mediastinal non-seminomatous germ cell tumor was suspected, so the patient was referred to the Department of Urology. Despite the presence of severe thrombocytopenia, the patient was treated using a combination of chemotherapy and intermittent transfusion, which was able to normalize his serum AFP level. However, resection of the mediastinal tumor was unsuccessful due to persistent thrombocytopenia and the patient was subsequently transferred to our hospital for further examination and treatment. Despite management by hematologists, the condition of the patient did not improve; although his AFP level remained normal, the tumor increased in size and then metastasized to the liver and spleen. The general condition of the patient deteriorated and he died 9 months after his first visit. The patient was diagnosed with histiocytic sarcoma following a pathological autopsy. Due to the extremely rare incidence of histiocytic sarcoma, this condition should be a differential diagnosis and the appropriate tests must be conducted to give an exact treatment.

The hamster is useful for the study of male reproductive biology. However, unlike in the mouse and rat, the gross structure of seminiferous tubules in the hamster is largely unknown. The aim of the present study was to clarify the precise 3-dimensional (3D) structure of seminiferous tubules in hamsters. We reconstructed all seminiferous tubules in 3 and 1 testes from 0-day (P0) and 10-week (adult) Syrian hamsters, respectively, using serial paraffin sections and high-performance 3D reconstruction software. In P0 hamsters, the average numbers of seminiferous tubules, terminating points, branching points, and blind ends per testis were 9.0, 89.7, 93.0, and 0.7, respectively. There were two types of tubules: shorter and dominant ones. The dominant tubules, 2-4 in number per testis and accounting for 86% of the total tubule length, had many terminating and branching points and appeared to be derived from the anastomosis of many shorter tubules. In an adult hamster, there were 11 seminiferous tubules with a total length of 22 m, 98 terminating points, 88 branching points, and 2 blind ends per testis. Three of the 11 tubules were dominant ones, accounting for 83% of the total length, and occupied the testis from the surface over the circumference to the center, while the others were short and occupied only one side of the testis. The amplitude and direction of the curves of tubules were random, and there were no funnel-shaped networks of tubules present, in contrast to the mouse testis. The present study revealed the 3D structure of seminiferous tubules in developing and adult Syrian hamsters, which is different from that in mice and rats.

Background: Survival outcomes are poor for patients with metastatic urothelial carcinoma who receive standard, first-line, platinum-based chemotherapy. We assessed the overall survival of patients who received durvalumab (a PD-L1 inhibitor), with or without tremelimumab (a CTLA-4 inhibitor), as a first-line treatment for metastatic urothelial carcinoma.Methods: DANUBE is an open-label, randomised, controlled, phase 3 trial in patients with untreated, unresectable, locally advanced or metastatic urothelial carcinoma, conducted at 224 academic research centres, hospitals, and oncology clinics in 23 countries. Eligible patients were aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0 or 1. We randomly assigned patients (1:1:1) to receive durvalumab monotherapy (1500 mg) administered intravenously every 4 weeks; durvalumab (1500 mg) plus tremelimumab (75 mg) administered intravenously every 4 weeks for up to four doses, followed by durvalumab maintenance (1500 mg) every 4 weeks; or standard-of-care chemotherapy (gemcitabine plus cisplatin or gemcitabine plus carboplatin, depending on cisplatin eligibility) administered intravenously for up to six cycles. Randomisation was done through an interactive voice–web response system, with stratification by cisplatin eligibility, PD-L1 status, and presence or absence of liver metastases, lung metastases, or both. The coprimary endpoints were overall survival compared between the durvalumab monotherapy versus chemotherapy groups in the population of patients with high PD-L1 expression (the high PD-L1 population) and between the durvalumab plus tremelimumab versus chemotherapy groups in the intention-to-treat population (all randomly assigned patients). The study has completed enrolment and the final analysis of overall survival is reported. The trial is registered with ClinicalTrials.gov, NCT02516241, and the EU Clinical Trials Register, EudraCT number 2015-001633-24.Findings: Between Nov 24, 2015, and March 21, 2017, we randomly assigned 1032 patients to receive durvalumab (n=346), durvalumab plus tremelimumab (n=342), or chemotherapy (n=344). At data cutoff (Jan 27, 2020), median follow-up for survival was 41·2 months (IQR 37·9–43·2) for all patients. In the high PD-L1 population, median overall survival was 14·4 months (95% CI 10·4–17·3) in the durvalumab monotherapy group (n=209) versus 12·1 months (10·4–15·0) in the chemotherapy group (n=207; hazard ratio 0·89, 95% CI 0·71–1·11; p=0·30). In the intention-to-treat population, median overall survival was 15·1 months (13·1–18·0) in the durvalumab plus tremelimumab group versus 12·1 months (10·9–14·0) in the chemotherapy group (0·85, 95% CI 0·72–1·02; p=0·075). In the safety population, grade 3 or 4 treatment-related adverse events occurred in 47 (14%) of 345 patients in the durvalumab group, 93 (27%) of 340 patients in the durvalumab plus tremelimumab group, and in 188 (60%) of 313 patients in the chemotherapy group. The most common grade 3 or 4 treatment-related adverse event was increased lipase in the durvalumab group (seven [2%] of 345 patients) and in the durvalumab plus tremelimumab group (16 [5%] of 340 patients), and neutropenia in the chemotherapy group (66 [21%] of 313 patients). Serious treatment-related adverse events occurred in 30 (9%) of 345 patients in the durvalumab group, 78 (23%) of 340 patients in the durvalumab plus tremelimumab group, and 50 (16%) of 313 patients in the chemotherapy group. Deaths due to study drug toxicity were reported in two (1%) patients in the durvalumab group (acute hepatic failure and hepatitis), two (1%) patients in the durvalumab plus tremelimumab group (septic shock and pneumonitis), and one (Interpretation: This study did not meet either of its coprimary endpoints. Further research to identify the patients with previously untreated metastatic urothelial carcinoma who benefit from treatment with immune checkpoint inhibitors, either alone or in combination regimens, is warranted.Funding: AstraZeneca.

Germ cell tumors with somatic-type malignancy (GCTSTM) are rare, and patients with GCTSTM have extremely poor prognoses with a median survival of nine months. Somatic-type malignancy, which are mainly sarcomas, usually exhibit chemoresistance. The recommended therapy for GCTSTM is radical resection; however, Pazopanib, which is a multityrosine kinase inhibitor, has indicated therapeutic effects for some soft tissue sarcoma components. The current study reports the case of a 21-year-old Asian man who presented with GCTSTM after combined chemotherapy for a primary mediastinal germ cell tumor with multiple lung metastases. Despite the metastases, his disease was stable after continuous administration of Pazopanib for two years and then stopping the medication for four years. To the best of our knowledge, the current report is the first report of a durable response by Pazopanib for GCTSTM, which is a rare outcome.

Background/aim Hypertension is a risk factor for occurrence of renal cell carcinoma; however, it remains unclear whether hypertension affects development and prognosis of renal cell carcinoma. This study evaluated the impact of hypertension on the progression of renal cell carcinoma. Patients and methods Renal cell carcinoma patients who were treated from October 2007 to December 2018 at our Institution were retrospectively analyzed. Results Of 462 patients, the number of patients with and without hypertension was 234 (including 227 treated with anti-hypertensive agents) and 228, respectively. The tumor size was significantly smaller in the hypertension group than in the non-hypertension group (median 32 and 45 mm, respectively, p=0.010). The 5-year cancer-specific and metastasis-free survival in the hypertension group were significantly better than those in the non-hypertension group (93.6% and 80.4%, and 84.6% and 73.0%, respectively, p=0.021 and p=0.017). Propensity score matching revealed significantly better metastatic-free survival in the hypertension group than the non-hypertension group (p=0.022). Conclusion Renal cell carcinoma patients with hypertension show better prognosis with low metastasis possibility.

INTRODUCTION AND OBJECTIVE:The patients in some instances experienced hypotension after the oral administration of 5-aminolevulinic acid. In this study, we analyzed the pre- and intraoperative bloo...

The present study investigated the efficacy of 6 months of testosterone replacement therapy (TRT) on chronic pain syndrome in late-onset hypogonadal (LOH) men. Sixty hypogonadal patients with chronic pain syndrome (31 patients in TRT group and 29 controls) were extracted from a previous randomised controlled study in Japan. Chronic pain was evaluated based on bodily pain (BP) subscale of Short-form (36) Health Survey (SF-36), and patients with a score of 50.0 or less were defined as suffering from chronic pain. SF-36 scores, Aging Male Symptoms (AMS) scale, international prostatic symptoms score (IPSS) and prostate-specific antigen (PSA) levels at baseline and a 6-month visit for the two groups were collected and compared. There were no statistically significant differences in baseline backgrounds between the two groups. Six-month TRT could contribute to significant improvements in BP, mental health of SF-36 and sleep disturbance (AMS question 4). Though the PSA level in the TRT group also significantly elevated at 6 months, the increase was not clinically significant. No significant improvements were evident in any characteristics in the controls. In conclusion, 6-month TRT can improve pain and some aspects of quality of life in LOH men with chronic pain.

To investigate the time course of total testosterone (TT) recovery after cessation of androgen deprivation therapy (ADT) in Japanese patients treated with brachytherapy.In total, 125 patients with prostate cancer received 6 months of neoadjuvant ADT (nADT) followed by low-dose rate (LDR) brachytherapy. TT was measured every 3 months after cessation of nADT, and some predictive factors affecting TT recovery were analyzed.The cumulative incidence rates of TT recovery to normal levels (TT ≥ 3.0 ng/mL) after 12 and 24 months cessation were 49.6% and 81.6%, respectively. The median interval to recover to normal TT was 15 months. In multivariate analysis, the use of a gonadotropin-releasing hormone (GnRH) antagonist as nADT significantly earlier improved to recovery to normal TT level (Approximately one-fifth of patients still had low TT levels 2 years after the cessation of 6 months nADT before LDR brachytherapy. Use of a GnRH agonist, higher BMI, and hypertension were the predictive factors for slower TT recovery to normal TT levels after the cessation of nADT.

Background/aim The best sequential treatment for castration-resistant prostate cancer (CRPC) remains unclear. This study evaluated the therapeutic effects of ethinylestradiol (EE) on CRPC. Patients and methods A total of 80 patients with CRPC, treated with 0.5-1.5 mg/day of EE, were retrospectively assessed. Results The median duration from the initial treatment to the beginning of EE was 48.3 months. A decline in the prostate-specific antigen (PSA) from the baseline was noted in 60 patients (75%) and a >50% PSA decline in 27 patients (34%). The median time of PSA progression, overall survival, and cancer-specific survival after EE were 5.60 months, 24.00 months, and 27.93 months, respectively. Conclusion EE administration for CRPC showed a relatively high PSA response regardless of timing of sequential treatment. The frequency of cardiovascular adverse events was not significantly high. EE administration is a potential treatment option for CRPC.

We appreciate Zins and Abraham [1] commenting on our paper studying the role of the CCL20-CCR6 axis on renal cell carcinoma (RCC) cells [2]. As they pointed out, our study has certain limitations. Although M1- and M2-types cannot be separated clearly and a consecutive change of character might exist between them, it has been reported that plural specific markers express on M1- and M2-types. Unfortunately, a definite difference between M1 and M2 macrophages was not confirmed in our study. For more differentiation, multiple stimulations, such as suggested in the comments of Zins and Abraham, might be needed. Hence, we needed to expediently use “M1-like” and “M2-like” to mention specific status of these macrophage-like cells. Meanwhile, CCL20 expression levels of M2-like-THP-1 cells co-cultured with RCC cells were dramatically increased compared with parental THP-1 cells, indicating that certain stimulations within the tumor microenvironment rather than theoretical stimulations make macrophages differentiated; however, further studies are needed to clarify this mechanism using a more appropriate co-culture system mimicking the tumor microenvironment. Immunohistochemistry of CCL20 and M2 markers will help to better understand the role of tissue infiltrating macrophages, even tissue CD68 staining intensity itself was reported to correlate with prognosis of RCC patients [3]. [...]

122 Background: Enzalutamide and abiraterone plus prednisolone demonstrated improvement of survival for castration-resistant prostate cancer (CRPC). However, it remains quite unclear which agent is better in terms of efficacy and safety for Asian patients. Methods: An investigator-initiated, multicenter, randomized controlled trial was conducted in Japan. CRPC patients before chemotherapy were randomly assigned to the enzalutamide or the abiraterone plus prednisolone arm (1:1). The primary endpoint is time to prostate-specific antigen (PSA) progression and secondary endpoints include PSA response rate (≥50% decline from baseline), overall survival, radiographic progression-free survival, and safety assessment. Results: Between February 20, 2015 and July 30, 2019, 203 patients were enrolled. After randomization, 92 in the enzalutamide and 92 in the abiraterone plus prednisolone arm were treated and analyzed. Time to PSA progression was not significantly different between arms (median 21.2 and 11.9 months in the enzalutamide and the abiraterone plus prednisolone arm, respectively; hazard ration 0.81, 95% CI 0.51-1.27, p = 0.1732). There was a significant difference in PSA response rate between arms (72% and 57% in the enzalutamide and the abiraterone plus prednisolone arm, respectively, p = 0.0425). There were no significant differences in overall and radiographic progression-free survival between arms (median 32.9 and 35.5months in the enzalutamide and the abiraterone plus prednisolone arm, respectively; hazard ration 1.17, 95% CI 0.72-1.88, p = 0.5290 and median 17.6 and 14.0 months in the enzalutamide and the abiraterone plus prednisolone arm, respectively; hazard ration 0.92, 95% CI 0.63-1.34, p = 0.6532). Grade ≥3 of adverse events were observed in 11% and 21% in the enzalutamide and the abiraterone plus prednisolone arm, respectively ( p = 0.1044). Conclusions: Enzalutamide did not show any survival benefits compared with abiraterone plus prednisolone but showed better PSA response rate with no significant differences of severe adverse event rate for Japanese CRPC patients. Our data suggest that antecedent use of enzalutamide to abiraterone plus prednisolone have potentially clinical benefits in Asian CRPC populations. Clinical trial information: UMIN000015529.

489 Background: High-risk non-muscle invasive bladder cancer (NMIBC) has high tumor residual rate of 40–60% after TURBT, and second TUR is strongly recommended. Photodynamic diagnosis-assisted TURBT (PDD-TURBT) using 5-aminolevulinic acid (5-ALA) has been reported to reduce residual tumors and intravesical recurrence. The purpose of this study is to investigate the residual tumor-reducing effect of PDD-TURBT for high-risk NMIBC and to explore the possibility that second TUR could be omitted by PDD-TURBT. Methods: We conducted an investigator-initiated multicenter prospective observational study (BRIGHT study; UMIN000035712) involving patients who underwent PDD-TURBT using 5-ALA and second TUR for high-risk NMIBC (high-grade UC or pT1 or concurrent CIS). The primary endpoint was tumor residual rate and the secondary endpoint was recurrence-free survival, which were compared with historical data (conventional TURBT) using propensity score-matching (PSM; caliper: 0.2). Assuming that the difference between the two groups was 20%, the planned number of cases was statistically set to 200 PDD-TURBT cases and 300 historical data cases, and the registration period was 2 years from January 2019 to December 2020, and the follow-up period was 2 years after second TUR. Results: In this study, 188 patients in the PDD-TURBT group and 313 patients in the historical group were enrolled, and 177 patients and 306 patients were included in the final analysis, respectively. After PSM adjustment, 167 patients in both groups were compared, and no significant differences were observed in age, gender, history of bladder cancer, tumor diameter, number of tumors, history of upper tract urothelial cancer, and period from initial TURBT to second TUR. The tumor residual rate was 25.8% in the PDD-TURBT group compared with 47.3% in the historical group, showing a significant decrease (odds ratio 0.39 [95% CI: 0.24–0.63]; p = 0.000064). Logistic regression analysis revealed that significant factors predicting residual tumors in PDD-TURBT were current or past smoking history, multiple tumors, and non-pTa (pT1 or pTis) tumors. Focusing on these three factors, patients with 0–1 of these three factors have a significant less tumor residual rate compared with patients with 2–3 factors (8.33% vs. 33.3%; odds ratio 5.46 [95% CI: 1.81–22.3]; p = 0.00052). Conclusions: PDD-TURBT for high-risk NMIBC significantly reduced the tumor residual rate at the second TUR compared to the conventional TURBT. PDD-TURBT using 5-ALA may enable to omit second TUR in some high-risk NMIBC cases. Clinical trial information: UMIN000035712.

Objective The present study aimed to investigate human papillomavirus (HPV) prevalence and identify risk factors for HPV detection in urine samples among heterosexual men attending urological clinics. Materials and Methods Spot urine samples including initial stream were collected from 845 participants, and the cell pellets were preserved into liquid-based cytological solution. After DNA extraction from each sample, HPV-DNA amplification and genotyping were performed using Luminex multiplex polymerase chain reaction. Participants completed a questionnaire on their age, education, smoking status, sexuality, age of sexual debut, marital status, and present history of sexually transmitted infections. Results Data from 803 patients were included in the analysis. Overall HPV and high-risk (HR) HPV prevalence in urine samples were 6.2% and 3.1%, respectively. HPV and HR-HPV prevalences were the highest in men with urethritis, and were significantly higher than those without urethritis. HPV detection was the most common in men aged 40–49 years, although significant detection differences were not age-related. Urethritis was an independent risk factor for HPV detection from urine samples, with an odds ratio (OR) of 4.548 (95%CI; 1.802–11.476) (p = 0.001). On the other hand, a sub-analysis excluding men with urethritis demonstrated that prostate cancer was a significant risk factor for HPV detection, with OR of 2.844 (95%CI; 1.046–7.732) (p = 0.0410), whereas was not a significant risk for HR-HPV detection in urine samples. Conclusion Prostate cancer may represent a risk factor for HPV detection in the urine of men without urethritis. Registration of clinical trials The authors did not register to Clinical Trial because this is observational and cross-sectional study.

This study investigated tumor-associated macrophages activity in the microenvironment of renal cell carcinoma. Via a co-culture with macrophage-like cells differentiated from human monocyte cell line THP-1 and U937 cells, the migration ability of ACHN and Caki-1 cells, which are human renal cell carcinoma cell line cells, was significantly increased, as was the epithelial&ndash, mesenchymal transition change. A chemokine array identified the CCL20-CCR6 axis as a concentration-dependent signal in ACHN and Caki-1 cell migration. Akt in the ACHN and Caki-1 cells was activated by macrophage-like cells, and the CCL20 neutralizing antibody suppressed migration ability, epithelial&ndash, mesenchymal transition, and Akt phosphorylation in the ACHN and Caki-1 cells. Akt inhibitor AZD5363 also decreased the epithelial&ndash, mesenchymal transition change and migration ability in the ACHN and Caki-1 cells. In 42 renal cell carcinoma tissues, patients with CCR6 and macrophage infiltration indicated poor prognoses. In the tumor microenvironment of renal cell carcinoma, cancer cells are activated by CCL20 secreted by tumor-associated macrophages through Akt activation, followed by epithelial&ndash, mesenchymal transition and an acquired migration ability. Thus, inhibition of the CCL20-CCR6 axis may be a potential therapeutic strategy for renal cell carcinoma.

We investigated the effect of testosterone replacement therapy (TRT) on glycemic control and sexual function among hypogonadal men with type 2 diabetes mellitus (T2DM). From the EARTH study, 86 patients (47 in the TRT and 39 in the non-TRT groups) with a diagnosis of T2DM were extracted. We collected data on waist circumference, body mass index, body fat volume, free testosterone, hemoglobin (Hb), fasting blood sugar, and hemoglobin A1c (HbA1c) at baseline and after 12 months. Aging Male Symptoms (AMS) score and International Prostate Symptom Score were obtained. Sexual function was assessed by questions 15 (sexual ability), 16 (morning erections), and 17 (sexual desire) of AMS subscores. The TRT group received intramuscular testosterone enanthate (250 mg) injections every 4 weeks for 12 months. Body fat percentage, Hb, and HbA1c were significantly improved in the TRT group. In addition, sexual ability and frequency, and sexual desire showed a significant improvement in the TRT group after 1 year TRT. On the other hand, any parameters including glycemic control and sexual functions were not significantly improved in non-TRT groups. One-year TRT can improve sexual function and glycemic control among hypogonadal men with T2DM.

Although reports have shown evidence for penile length (PL) shortening after radical prostatectomy (RP), the association between neoadjuvant androgen deprivation therapy (NADT) and PL after RP has yet to be determined. This study evaluates chronological changes in PL after NADT and RP. Stretched PLs (SPLs) of 143 patients, 41 of whom had undergone NADT, were measured before, 10 days after, and 1, 3, 6, 9, 12, 18, and 24 months after RP. Chronological erectile function and testosterone levels were then evaluated. SPL was shortest 10 days after RP in both the NADT (-) and NADT (+) groups and gradually recovered in length thereafter. SPL in the NADT (-) group was significantly longer than that in the NADT (+) group before RP. However, no significant differences in SPLs were found between both groups 6 months after RP. Although all subjects in the NADT (+) group had testosterone levels of

Neuroendocrine-differentiated prostate cancer (NEPC) is a rare pathophysiology. We herein report a patient diagnosed with conventional prostate adenocarcinoma before hormone therapy, which was later diagnosed as NEPC. The nadir of prostate-specific antigen (PSA) was achieved once. However, adenocarcinoma changed to NEPC in recurrence, and the serum progastrin-releasing peptide (Pro-GRP) and neuron-specific enolase (NSE) values increased. A prostate needle biopsy revealed neuroendocrine differentiation. The chemotherapy regimen was changed, and somatostatin receptor scintigraphy (SRS) helped to determine the distribution and features of lesions as well as the effects of therapy. When prostate cancer worsens despite conventional therapy, NEPC should be considered.

Objective: To present the study design and rationale of Prostatic Cancer Registry of Standard Hormonal and Chemotherapy Using Bone Scan Index, a prospective study aiming to determine the role of the bone scan index, the amount of bone metastasis, in the treatment and prognosis of prostate cancer patients. Methods: A total of 237 patients were recruited at 30 hospitals in Japan. All had prostate cancer with bone metastasis and were scheduled to undergo either hormonal therapy (group H) or chemotherapy (group C). Bone scans were carried out with (99m)Tc-methylenediphosphonate. Follow-up studies are planned to continue for 3 years, and changes in biochemical and tumor markers in response to hormonal therapy and chemotherapy will be recorded in addition to skeletal-related events, recurrence, disease progression and death. Results: The basic characteristics of the patients (n = 200) at the time of registration during December 2016 were as follows: mean age 71 ± 8 years; median bone scan index calculated on-site 1.9% (range 0.02–13.3%); median number of hot spots 18 (range 1–128); median prostate-specific antigen 155 ng/mL (range 0.04–22 412 ng/mL); and the most frequent Gleason score 9 (47%). The prostate-specific antigen value was higher in group H than group C (288 vs 33 ng/mL, P < 0.0001), whereas bone scan indexes were comparable (1.7 vs 2.3%, not significant) between the two groups. Liver metastasis was more frequent in group C than group H (6.1% vs 0.8%, P = 0.035). Conclusions: The baseline characteristics of the Prostatic Cancer Registry of Standard Hormonal and Chemotherapy Using Bone Scan Index database have been established. This collaborative study can now proceed with clarifying the role of the bone scan index for patient management including treatment strategies and prognosis.

Once castration-resistant prostate cancer (CRPC) become resistant for cabazitaxel treatment, the patients are obliged to best supportive care. Therefore, the elucidation of the mechanism of the cabazitaxel-resistance and the conquest are important themes to improve the prognosis of the patients. Then we tried to establish cabazitaxel-resistant CRPC cell lines and characterized them. We established two cabazitaxel-resistant cell lines, PC-3-TxR/CxR and DU145-TxR/CxR from PC-3-TxR and DU145-TxR cell lines previously we established. PC-3-TxR/CxR and DU145-TxR/CxR cells became resistant for cabazitaxel by 11.8-fold and 4.4-fold, respectively. The TxR/CxR cells showed cabazitaxel-resistant using SCID mice in vivo. Although expression of multi-drug resistance gene 1 (MDR1) was up-regulated in DU145-TxR compared with DU145 cells, it was not up-regulated in DU145-TxR/CxR cells any more. In contrast, expression of MDR1 gene was up-regulated in PC-3-TxR compared with PC-3 cells and it was further up-regulated in PC-3-TxR/CxR compared with PC-3-TxR cells. Comparison of cDNA microarray between PC-3-TxR and PC-3-TxR/CxR cells or between DU145-TxR and DU145-TxR/CxR cells revealed that many genes were up-regulated or down-regulated. Finally, knockdown of MDR1 recovered the sensitivity to cabazitaxel not only in PC-3-TxR/CxR cells but also DU145-TxR/CxR cells. Together, regulation of MDR1 gene is important for conquest of the cabazitaxel-resistance.

Background: This prospective observational study elucidated the usefulness of hormonal therapy for localized prostate cancer. Background factors and the health-related quality of life in patients who initially underwent radical prostatectomy (RP) or primary androgen deprivation therapy (PADT) for localized prostate cancer are summarized. Materials and methods: Patients aged 67–76 years with clinical stage T1c or T2 localized prostate cancer treated with PADT or RP, a prostate-specific antigen concentration of

Chemokines and their receptors have key roles in cancer progression. The present study investigated chemokine activity in the prostate cancer bone metastasis microenvironment. Growth and migration of human prostate cancer cells were assayed in cocultures with bone stromal cells. The migration of LNCaP cells significantly increased when co-cultured with bone stromal cells isolated from prostate cancer bone metastases. Cytokine array analysis of conditioned medium from bone stromal cell cultures identified CCL5 as a concentration-dependent promoter of LNCaP cell migration. The migration of LNCaP cells was suppressed when C-C motif ligand 5 (CCL5) neutralizing antibody was added to cocultures with bone stromal cells. Knockdown of androgen receptor with small interfering RNA increased the migration of LNCaP cells compared with control cells, and CCL5 did not promote the migration of androgen receptor knockdown LNCaP. Elevated CCL5 secretion in bone stromal cells from metastatic lesions induced prostate cancer cell migration by a mechanism consistent with CCL5 activity upstream of androgen receptor signaling.

Metastasis causes high mortality in various malignancies, including prostate cancer (PCa). Accumulating data has suggested that cancer cells spread from the primary tumor to distant sites at early stage, which is characterized by disseminated tumor cells (DTCs). However, lack of direct evidence of partial localized PCa cells occurring epithelial-to-mesenchymal transition (EMT) and disseminating to distant sites (e.g bone marrow). In this study, we used luciferase labeled PCa cells to establish an EMT mouse model and to detect whether DTCs spread into the bone marrow. We observed tumor cells existing in mouse bone marrow when tumor grew subcutaneously at palpable stage. Studies also showed that ex vivo tumor cells exhibited increased proliferative, migratory, invasive and angiogenesis abilities. When compared ex vivo tumor cells with parental cells, hallmarks of EMT including E-cadherin, Vimentin, Snail, and ZO-1 were altered significantly. Specifically, the ex vivo tumor cells showed more mesenchymal properties. Angiogenesis markers, including VEGFR2, VEGFR3, MCP-3, I-TAC, I309, uPAR and GROα, were also increased in the ex vivo tumor cells. Intriguingly, MCP-1 expression was dramatically increased in those cells. Mechanistic analyses indicated that AP1 mediates PCa EMT and the appearance of DTCs via the Akt/mTOR pathway. This study may provide potential therapeutic targets and diagnostic biomarkers of PCa progression and metastasis.

The non-POU domain-containing octamer binding protein p54nrb/NONO is a multifunctional nuclear protein involved in RNA splicing, processing, and transcriptional regulation of nuclear hormone receptors. Through chromosome copy number analysis via whole-exome sequencing, we revealed amplification of the chromosome Xq11.22-q21.33 locus containing the androgen receptor (AR) and NONO genes in androgen-independent, castration-resistant prostate cancer (CRPC)-like LNCaP-SF cells. Moreover, NONO was frequently amplified and overexpressed in patients with CRPC. RNA sequencing data revealed that a truncated ephrin type-A receptor 6 (EPHA6) splice variant (EPHA6-001) was overexpressed in LNCaP-SF cells, and knockdown of NONO or EPHA6-001 prevented EPHA6-001 expression and reduced proliferation and invasion by LNCaP-SF cells grown under androgen deprivation conditions. Growth inhibition and differential splicing of EPHA6 mRNA by p54nrb/NONO were confirmed in gene silencing experiments in 22Rv1 PCa cells. Importantly, NONO knockdown in LNCaP-SF cells led to reduced tumor growth in castrated mice. These findings indicate that p54nrb/NONO is amplified and overexpressed in CRPC cells and clinical samples, and facilitates CRPC growth by mediating aberrant EPHA6 splicing. We therefore propose that p54nrb/NONO constitutes a novel and attractive therapeutic target for CRPC.

Chyloretroperitoneum is a rare complication of urological surgery. Here we report a case of chyloretroperitoneum that occurred in a 28-year-old man post living-donor transplantation. Twenty-nine days post transplantation, perirenal fluid collection and hydronephrosis were detected and percutaneous drainage was performed. The fluid was chylous and revealed a very high triglyceride concentration (1,197 mg/dL). Total parenteral nutrition and administration of octreotide were performed, but the leakage did not improve. On the contrary, the drainage fluid gradually increased to 1,600 mL/day, and a laparoscopic fenestration was performed owing to a concern about the adverse effects of massive lymph loss. Ascites temporarily appeared but disappeared 3 months post fenestration. To our knowledge, this is the first case report of pelvic chyloretroperitoneum post living-donor transplantation. Furthermore, if chyloretroperitoneum treatment using diet control or octreotide is ineffective, laparoscopic fenestration can be considered as a treatment option.

Introduction Renal transplantation often causes polyuria, and a Foley catheter is typically placed after transplantation. A urethral stricture often makes it difficult to insert a normal diameter urethral catheter. Case presentation We report on the case of a 16-year-old adolescent male with a history of hypospadias surgery who underwent a cystostomy during renal transplantation. A cystostomy was placed during transplantation because of stricture of the pendulous urethra. Urine leakage into the retroperitoneum occurred after cystostomy catheter removal. An 8-Fr urethral catheter was placed, and urine was aspirated to prevent drainage failure. Voiding cystourethrography performed after 2 weeks showed that there was no leakage. After that, the patient had no trouble with urination. Conclusion A cystostomy may be one strategy for renal transplantation patients with a urethral stricture. Urine leak can occur because of the delay in wound healing caused by immunosuppressive therapy. Therefore, cystostomy management strategies should be considered carefully.

Introduction Decreased libido in middle-aged and elderly men is often difficult to treat, and identifying the risk factors affecting decreased libido is important for the clinical management of decreased libido. However, limited information is available regarding specific risk factors in this population. Aim The present study investigated the risk factors for decreased libido among middle-aged and elderly men. Methods Patients who attended our male andropausal outpatient clinic between 2009 and 2015 were enrolled. All patients completed a self-administered questionnaire, which included the Aging Male Symptoms (AMS) scale, International Prostate Symptom Score (IPSS), and Sexual Health Inventory for Men (SHIM). Information on waist size, body mass index, present illness, present use of any medication, and lifestyle habits were collected by each attending physician. Blood biochemical data such as free testosterone, total cholesterol, triglyceride, high density lipoprotein-cholesterol (HDL-Chol), and hemoglobin A1c values were assessed. Libido was assessed based on AMS scale question 17, and a score of 4 or higher was defined as severely decreased libido (severe group). Main Outcome Measure The clinical factors associated with severely decreased libido were analyzed based on multiple regression analysis. Results A total of 292 subjects were included in the analysis, 111 (38%) of which belonged to the severe group. The mean age of study subjects was 66.2 years, and the mean FT value was 7.1 ± 2.2. Comparisons of each variable among the severe and not severe groups showed significant differences in older age, current cigarette smoking, AMS scale, IPSS, frequency of nocturnal voiding, SHIM score, and HDL-Chol value. Multivariate regression analysis revealed that current cigarette smoking, frequent nocturnal voiding, and a low SHIM score were the independent risk factors for severely decreased libido. Furthermore, the frequency of nocturnal voiding significantly increased with severity of decreased libido. Conclusion Current cigarette smoking, frequent nocturnal voiding, and a low SHIM score were the independent risk factors for a severely low libido. K Shigehara, Y Kato, M Iijima, et al. Risk Factors Affecting Decreased Libido Among Middle-Aged to Elderly Men; Nocturnal Voiding is an Independent Risk Factor of Decreased Libido. Sex Med 2021;9:100426.

Simple Summary The definitions of locally advanced and oligometastatic prostate cancer are ambiguous, and there are no standard treatments for these. Although multidisciplinary treatment combining systemic and local treatment may be effective, there are many unresolved issues such as the choice of local treatment, use of new endocrine agents and chemotherapy, and selection of optimal patients. The present article discusses the definitions, diagnoses, and treatment of very high-risk prostate cancer and oligometastatic prostate cancer. Abstract Despite the significant advances in the treatment of high-risk prostate cancer, patients with very high-risk features such as being locally advanced (clinical stage T3–4 or minimal nodal involvement), having a high Gleason pattern, or with oligometastasis may still have a poor prognosis despite aggressive treatment. Multidisciplinary treatment with both local and systemic therapies is thought to be effective, however, unfortunately, there is still no standard treatment. However, in recent years, local definitive therapy using a combination of radiotherapy and androgen deprivation is being supported by several randomized clinical trials. This study reviews the current literature with a focus on the definition of very high-risk prostate cancer, the role of modern imaging, and its treatment options.

金沢大学附属病院泌尿器科, Background: Both enzalutamide and abiraterone have demonstrated improved radiographic progression-free and overall survival for castration-resistant prostate cancer (CRPC) compared with placebo controls before docetaxel treatment in phase III studies. These oral agents target androgen and androgen receptor signaling and are thought to be less toxic than chemotherapy. Cross-resistance to these agents was recently reported because of their similar mechanism of action, and it is important to assess which agent is more effective to use initially for CRPC. Methods/design: The present study is a phase III, investigator-initiated, multicenter, head-to-head, randomized controlled trial investigating enzalutamide vs. abiraterone as a first-line treatment for CRPC patients. Patients will be randomly assigned to an enzalutamide or an abiraterone treatment group. The primary endpoint is the time to prostate-specific antigen progression. The target sample size is set at 100 patients per group (total, 200 patients). The study duration is 5 years, and the duration for recruitment is 2 years and 6 months. Discussion: Thus far, there have been no prospective head-to-head studies comparing enzalutamide and abiraterone. This ENABLE study will clarify which agent should be prioritized for CRPC patients and enable clinicians to decide the appropriate treatment before chemotherapy. Trial registration: University hospital Medical Information Network (UMIN) Center identifier UMIN000015529. Registrated 11/1/2014. © 2017 The Author(s).

The present subanalysis of the EARTH study investigates the effects of one year testosterone replacement therapy (TRT) on sleep disturbance among hypogonadal men without obstructive sleep apnea.Sleep disturbance was defined as three or more points in question 4 of the aging males symptoms (AMS) questionnaire. All participants completed the AMS scale, International Prostatic Symptoms Score (IPSS), Sexual Health Inventory for Men (SHIM) and Short Form 36 (SF-36) health survey at baseline and after 12 months. Sexual symptoms were also evaluated based on three AMS subscores (Q15, 16 and 17).We identified 100 patients with sleep disturbance, of whom 48 (24 each in the TRT and control groups) were ultimately included for analysis. All SF-36 categories , AMS scale, IPSS and SHIM score subdomains were significantly worse in patients with sleep disturbance than in those without disturbance. Statistically significant differences in sleep disturbance, erectile symptoms, sexual desire and some domains of the SF-36 were observed between the TRT and control groups after 12 months.Sleep disturbance may be one of the clinical signs for severe hypogonadism. Moreover, TRT improved sleep conditions, sexual function and quality of life among hypogonadal men with sleep disturbance.

Background The present study investigated human papillomavirus (HPV) prevalence in anal and urine samples, and evaluated cytological findings among human immunodeficiency virus (HIV)-infected Japanese men who have sex with men (MSM). Methods A total of 148 patients were enrolled. Anal and urine samples were collected from each participant, and a HPV-DNA test and genotyping were performed using flow-through hybridization. In addition, anal cytology was evaluated based on Papanicolaou staining. Questionnaires regarding lifestyle habits and sexual behavior were obtained. Results The β-globin gene was positive in 131 (88.5%) anal samples and 139 (94.0%) urine samples. Among the β-globin-positive samples, the HPV prevalence in anal and urine samples was 80.9% and 30.9%, respectively. High-risk HPV (HR-HPV) was detected in 57.3% of anal samples and 20.9% of urine samples. Among 122 adequate cytological samples, anal cytological abnormalities were observed in 99 cases (81.1%). Anal cytological tests revealed that atypical squamous cells of an undetermined significance (ASCUS) were detected in 57 (46.7%) patients, followed by low-grade squamous intraepithelial lesions (SIL) in 35 (28.7%), high-grade SIL in five (4.1%), and atypical squamous cells cannot exclude high-grade SIL (ASC-H) in two (1.6%), respectively. The nadir counts of CD4-positive T-lymphocyte less than 200 μL and anal HR-HPV infection were independent risk factors for anal cytological atypia over ASC-H. Conclusions The present study demonstrated high HPV prevalence in the anus and urine, and showed a high incidence of anal cytological atypia associated with HR-HPV infections among HIV-infected MSM patients.

When advanced prostate cancer recurred during hormonal therapy and became the castration-resistant prostate cancer, "vintage hormonal therapy," such as antiandrogen alternating therapy or estrogen-related hormonal therapy, was widely carried out in Japan until 2013. This vintage hormonal therapy controlled the progression of castration-resistant prostate cancer. When castration-resistant prostate cancer relapses during these therapies, chemotherapy using docetaxel has been carried out subsequently. Since new hormonal therapies using abiraterone acetate and enzalutamide, which improve the prognosis of castration-resistant prostate cancer, became available in Japan from 2014, therapeutic options for castration-resistant prostate cancer have increased. Furthermore, the improvement of the further prognosis is promising by using cabazitaxel for docetaxel-resistant castration-resistant prostate cancer and radium-223 for castration-resistant prostate cancer with bone metastasis. An increase in therapeutic options gives rise to many questions, including best timing to use them and the indication. Furthermore, physicians have to consider the treatment for the recurrence after having carried out chemotherapy. We want to argue the difference in hormonal therapy between Japan and Western countries, and problems when carrying out new treatments, and the importance of imaging in the present review article. © 2017 The Japanese Urological Association., Embargo Period 12 months