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Background/Aim: Several studies have reported on the relationship between HOXB13 variants and an increased prostate cancer (PC) risk. To our knowledge there are not many studies on HOXB13 mutations in Japanese patients with prostate cancer, and there many issues remain uninvestigated. We herein clarified the association between HOXB13 genetic variants and PC risk in a Japanese population. Patients and Methods: PC patients were diagnosed at the Gunma University Hospital and affiliated hospitals from 1994 to 2016. Sanger sequencing was performed on the coding regions of the HOXB13 gene in 152 familial PC (FPC) patients. Genotyping was performed on single nucleotide variants (SNVs) found in Sanger sequencing in 230 FPC patients from 152 pedigrees and 197 sporadic PC (SPC) patients and 144 controls. Allelic frequency and clinical data for each variant were studied in cases and controls. Results: G132E and F127C were identified in FPC patients. The frequencies of G132E and F127C were significantly higher compared to the control group (p=0.039). In three families, seven PC patients shared the G132E variant, within second-to-third-degree relatives. It was not possible to clarify to pathogenicity of each SNV alone. Conclusion: We found two significant variants of the HOXB13 gene, G132E, F127C by analyzing and comparing gene samples from PC and non-PC patients. Furthermore, the HOXB13 G132E variant was found significantly increased in the FPC group.

Supplementary Data from High-Density Lipoprotein Induces Proliferation and Migration of Human Prostate Androgen–Independent Cancer Cells by an ABCA1-Dependent Mechanism

Background One of the growth mechanisms of castration-resistant prostate cancer (CRPC) is de novo androgen synthesis from intracellular cholesterol, and statins may be able to inhibit this mechanism. In addition, statins have been reported to suppress the expression of androgen receptors (ARs) in prostate cancer cell lines. In this study, we investigated a combination therapy of novel AR antagonists and statin, simvastatin, for CRPC. Methods LNCaP, 22Rv1, and PC-3 human prostate cancer cell lines were used. We developed androgen-independent LNCaP cells (LNCaP-LA). Microarray analysis was performed, followed by pathway analysis, and mRNA and protein expression was evaluated by quantitative real-time polymerase chain reaction and Western blot analysis, respectively. Cell viability was determined by MTS assay and cell counts. All evaluations were performed on cells treated with simvastatin and with or without AR antagonists (enzalutamide, apalutamide, and darolutamide). Results The combination of darolutamide and simvastatin most significantly suppressed proliferation in LNCaP-LA and 22Rv1 cells. In a 22Rv1-derived mouse xenograft model, the combination of darolutamide and simvastatin enhanced the inhibition of cell proliferation. In LNCaP-LA cells, the combination of darolutamide and simvastatin led to reduction in the mRNA expression of the androgen-stimulated genes, KLK2 and PSA; however, this reduction in expression did not occur in 22Rv1 cells. The microarray data and pathway analyses showed that the number of differentially expressed genes in the darolutamide and simvastatin-treated 22Rv1 cells was the highest in the pathway termed "role of cell cycle." Consequently, we focused our efforts on the cell cycle regulator polo-like kinase 1 (PLK1), cyclin-dependent kinase 2 (CDK2), and cell cycle division 25C (CDC25C). In 22Rv1 cells, the combination of darolutamide and simvastatin suppressed the mRNA and protein expression of these three genes. In addition, in PC-3 cells (which lack AR expression), the combination of simvastatin and darolutamide enhanced the suppression of cell proliferation and expression of these genes. Conclusions Simvastatin alters the expression of many genes involved in the cell cycle in CRPC cells. Thus, the combination of novel AR antagonists (darolutamide) and simvastatin can potentially affect CRPC growth through both androgen-dependent and androgen-independent mechanisms.

Background Recently, presepsin has been reported to be a useful biomarker for early diagnosis of sepsis and evaluation of prognosis in septic patients. However, few reports have evaluated its usefulness in patients with urinary tract infections (UTI). This study aimed to evaluate whether presepsin could be a valuable marker for detecting severe sepsis, and whether it could predict the therapeutic course in patients with UTI compared with markers already used: procalcitonin (PCT) and C-reactive protein (CRP). Methods From April 2014 to December 2016, a total of 50 patients with urinary tract infections admitted to Gunma university hospital were enrolled in this study. Vital signs, presepsin, PCT, CRP, white blood cell (WBC) count, causative agents of urinary-tract infections, and other data were evaluated on the enrollment, third, and fifth days. The patients were divided into two groups: with (n = 11) or without (n = 39) septic shock on the enrollment day, and with (n = 7) or without (n = 43) sepsis on the fifth day, respectively. Presepsin was evaluated as a biomarker for systemic inflammatory response syndrome (SIRS) or septic shock. Results Regarding the enrollment day, there was no significant difference of presepsin between the SIRS and non-SIRS groups (p = 0.276). The median value of presepsin (pg/mL) was significantly higher in the septic shock group (p p = 0.007). ROC curve for diagnosing septic shock indicated an area under the curve (AUC) of 0.881 for presepsin (vs. 0.690, 0.583, and 0.527 for PCT, CRP and WBC, respectively). Regarding the 5th day after admission, the median presepsin value on the enrollment day was significantly higher in the SIRS groups than in the non-SIRS groups (p = 0.006). On the other hand, PCT (≥ 2 ng/ml) on the enrollment day was an independent risk factor for SIRS. ROC curve for diagnosing sepsis on the fifth day indicated an AUC of 0.837 for PCT (vs. 0.817, 0.811, and 0.802 for presepsin, CRP, and WBC, respectively). Conclusions This study showed that presepsin may be a good marker for diagnosing septic shock based on admission data in patients with UTI.

Background Urothelial carcinoma arises from the inner urothelial membrane of the renal pelvis, ureter, and bladder and often causes macrohematuria. Here, we report a rare case in which the patient developed non-symptomatic urothelial carcinoma anatomically outside the bladder wall 17 years after bladder diverticulectomy. Case presentation An 82-year-old male patient previously underwent gastrectomy for stomach cancer and partial hepatectomy for intrahepatic cholangiocarcinoma. Follow-up computed tomography revealed a tumor in the retroperitoneal space, where a bladder diverticulum was removed 17 years earlier. Multiparametric magnetic resonance imaging suggested that the tumor was malignant with rectal invasion. Subsequent computed tomography-guided percutaneous biopsy revealed that the tumor was urothelial carcinoma. The patient underwent two courses of neoadjuvant chemotherapy followed by pelvic exenteration with pelvic lymph node dissection. He is currently receiving adjuvant therapy with an immune checkpoint inhibitor and has had no recurrence for 3 months. Conclusions Multiparametric magnetic resonance imaging is a helpful tool for predicting both tumor malignancy and invasion before a pathologically confirmed diagnosis. Although this case is rare, urologists should be aware of the occurrence of urothelial carcinoma after bladder diverticulectomy in cases of incomplete resection of the diverticulum.

Background/Aim: Several studies have reported on the relationship between HOXB13 variants and an increased prostate cancer (PC) risk. To our knowledge there are not many studies on HOXB13 mutations in Japanese patients with prostate cancer, and there many issues remain uninvestigated. We herein clarified the association between HOXB13 genetic variants and PC risk in a Japanese population. Patients and Methods: PC patients were diagnosed at the Gunma University Hospital and affiliated hospitals from 1994 to 2016. Sanger sequencing was performed on the coding regions of the HOXB13 gene in 152 familial PC (FPC) patients. Genotyping was performed on single nucleotide variants (SNVs) found in Sanger sequencing in 230 FPC patients from 152 pedigrees and 197 sporadic PC (SPC) patients and 144 controls. Allelic frequency and clinical data for each variant were studied in cases and controls. Results: G132E and F127C were identified in FPC patients. The frequencies of G132E and F127C were significantly higher compared to the control group (p=0.039). In three families, seven PC patients shared the G132E variant, within second-to-third-degree relatives. It was not possible to clarify to pathogenicity of each SNV alone. Conclusion: We found two significant variants of the HOXB13 gene, G132E, F127C by analyzing and comparing gene samples from PC and non-PC patients. Furthermore, the HOXB13 G132E variant was found significantly increased in the FPC group.

242 Background: Prostate health index (phi) using -2proPSA (p2PSA), which is a precursor of PSA, has been reported to be useful as a marker for predicting the presence of cancer in the gray zone with a PSA value of 4-10 ng/ml. There is no detailed report on the biology of p2PSA in castration resistant prostate cancer (CRPC) patients and it is unknown. We retrospectively investigated the biology of p2PSA and its usefulness as a marker using CRPC patient's samples. Methods: The study was performed using samples from a prospective study of CRPC patients treated with enzalutamide. We examined 98 pre-enzalutamide treatment serum samples that can measure p2PSA. The samples were collectively measured by Beckman Coulter (Tokyo, Japan). We also examined the correlation between the measurement results of p2PSA and the prognosis of phi and CRPC patients calculated accordingly. This study was approved by the IRB of Gunma University Hospital (IRB 2021-092, 1983). Results: The study population of 98 patients had a median age of 73 years. The median PSA before administration of enzalutamide was 23.8 ng/ml, the median p2PSA was 208.8 pg/ml, and the median phi was 188.0. The median values of each parameter were divided into two groups, and the PSA progression free survival (PSA-PFS) and overall survival (OS) rate were compared by the Kaplan-Meier method. In the study of PSA-PFS, PSA, p2PSA, and phi could not be significant markers. In the OS study, the median OS of the PSA low group was NYR (not yet reached), the high group was 26.8 months, the p2PSA low group was NYR, the high group was 26.8 months, the phi low group was NYR, and the high group was 26.8 months. The OS was significantly better in the low- value group for each parameter (p-values 0.024, 0.034, 0.018, respectively). Conclusions: The biology of p2PSA in CRPC patients has been clarified. Although we couldn't find a clear advantage over PSA, we would like to add a study based on the data of this study.

BACKGROUND Recent studies have shown that an early prostate-specific antigen (PSA) response to androgen receptor-targeting agents in metastatic castration-resistant prostate cancer (mCRPC) is associated with a better prognosis. We analyzed the early PSA response to enzalutamide (ENZ) by measuring the PSA doubling time (PSADT) and PSA velocity (PSAV) while monitoring oncologic outcomes and survival in Japanese patients. METHODS We analyzed a total of 241 patients with mCRPC who were treated with ENZ. The patients' median age was 75 ± 7.9 years (range, 53-93 years). There were 171 (71%) predocetaxel cases, and 70 (29%) post docetaxel cases. PSA-progression-free survival (PFS) and overall survival (OS) were assessed according to Prostate Cancer Working Group 2 criteria. This study was approved by the Institutional Review Board of Gunma University Hospital (No. 1595). RESULTS We observed 77 good response (GR; case in which PSA remained low after treatment) cases (31.9%), 125 acquired resistance (AR; decline in PSA after treatment followed by progression) cases (51.9%), and 39 primary resistance (PR; lack of decline in PSA) cases (16.2%). Predocetaxel, PSA-PFS, and OS were significantly higher compared with post docetaxel (PSA-PFS: 47.0 vs 13.4 weeks, P

Objectives: The microsurgical approach is considered the most reliable procedure in varicocelectomy. However, as there are difficulties in identifying the spermatic artery at the peripheral level, we had introduced intraoperative indocyanine green angiography (ICGA) for identification of arteries. In this study, we further investigated the usefulness of intraoperative ICGA in combination with an ordinary Doppler detector in microsurgical subinguinal varicocelectomy. Methods: A total of 140 men who underwent microsurgical subinguinal varicocelectomy at Gunma University Hospital were included. An operating microscope equipped with a near-infrared charge-coupled device was used for intraoperative ICGA. After exposing the vessels, arteries were identified using endoscopic vision only or with assistance of Doppler detector or ICGA, or of both. The number of preserved arteries was compared among the groups. Results: ICGA clearly visualized the internal spermatic arteries in all cases, allowing the surgeon to perform real-time identification and isolation of the spermatic artery intraoperatively. The use of ICGA or Doppler detector significantly increased the number of preserved arteries compared to the microscope-only operation from 1.11 to 1.75 (p < 0.05) and 1.57 (p < 0.05), respectively. The additional use of ICGA with Doppler detector further increased the number of preserved arteries to 2.41 (p < 0.05). Conclusions: Intraoperative ICGA facilitated safe and quick microsurgical subinguinal varicocelectomy by enabling visualization of thin spermatic cord blood vessels. Improved preservation of thin arteries, which is essential for patients with infertility, can be achieved with the combined use of ICGA and ordinary Doppler detector.

Background Enzalutamide (ENZ) is used to treat patients with castration-resistant prostate cancer (CRPC). However, the kinetics of serum androgens before and after ENZ treatment are unknown. Objective To elucidate the kinetics of serum androgens and explore the possibility of identifying a useful marker for predicting the effects of ENZ. Design, setting, and participants We conducted a prospective study from 2014 to 2018 at Gunma University Hospital and related facilities. Data were analyzed for 104 patients with CRPC treated with ENZ. Outcome measurements and statistical analysis We measured serum androgen levels using liquid chromatography-tandem mass spectrometry. Relationships with outcomes were assessed using multivariable Cox regression and log-rank analyses. Results and limitations The median age of the patients was 73 yr. Median serum testosterone, dihydrotestosterone (DHT), androstenedione, and dehydroepiandrosterone sulfate levels were 49.0, 5.8, 222.2, and 326.3 pg/ml, respectively. We performed multivariate analysis using Cox regression to predict prostate-specific antigen progression–free survival (PSA-PFS) and overall survival (OS). Hemoglobin level (≥12.5 vs, Take Home Message The effect of enzalutamide was significantly better for cases with high blood androgen levels before treatment. In addition, the incidence of adverse events of anorexia, malaise, and fatigue tended to be low. These results suggest that serum androgen levels before enzalutamide treatment may be useful for predicting efficacy, prognosis, and the incidence of adverse events.

Background Recently, presepsin is reported to be a biomarker for early diagnosis of sepsis and evaluation of prognosis in septic patients, but there are few reports about urinary-tract infections. The objective of this study is to evaluate whether presepsin is a recent marker for detecting severe sepsis, and whether it can predict the therapeutic course in UTI when compared with procalcitonin (PCT) and C-reactive protein (CRP), already used markers.Methods From April 2014 to December 2016, a total of 50 patients, who were admitted into Gunma university hospital with urinary-tract infections, were enrolled in this study. Vital signs, presepsin, PCT, CRP, white blood cell (WBC), causative diseases of urinary-tract infections and other data were evaluated at the enrollment, third and fifth days. The patients were divided into two groups; with (n=11) or without (n=39) septic shock at the enrollment day, and with (n=7) or without (n=43) sepsis at the fifth day, respectively. Presepsin was evaluated for systemic inflammatory response syndrome (SIRS) or septic shock. Results Concerning the enrollment day, there was no significant difference of presepsin between SIRS and non-SIRS groups (p=0.276). The median presepsin (pg/mL) was significantly higher in the septic shock group (pConclusions This study shows that presepsin may be a good marker for diagnosis of severe patients who need vasopressor therapy at the data of admission, and PCT may be a good marker for predicting hard-to-treat cases in UTI.

Castration-resistant prostate cancer shows resistance to not only androgen deprivation therapy (ADT) but also X-ray therapy. On the other hand, carbon ion beams have a high biological effect and are used for various cancers showing resistance to X-ray therapy. The purposes of this study are to clarify the difference in the sensitivity of Castration-resistant prostate cancer to X-ray and carbon ion beams and to elucidate the mechanism. The androgen-insensitive prostate cancer cell line LNCaP-LA established by culturing the androgen-sensitive prostate cancer cell line LNCaP for 2 years in androgen-free medium was used for this study. First, colony formation assays were performed to investigate its sensitivity to X-ray and carbon ion beams. Next, DNA mutation analysis on 409 cancer-related genes and comprehensive transcriptome analysis (RNA-seq) were performed with a next-generation sequencer. Lethal dose 50 values of X-rays for LNCaP and LNCaP-LA were 1.4 Gy and 2.8 Gy, respectively (P

Introduction and Objectives: Metastatic castration resistance prostate cancer is a lethal disease. New AR-axis-targeted agent are available, but they will eventually become ineffective. Brefeldin A, an endoplasmic reticulum (ER) protein transport inhibitor, has been shown to cause ER stress. Navitoclax is a BH3 mimetic drug that targets anti-apoptotic proteins (BCL2 and BCLXL) and induces apoptosis in some solid tumors. Here, we investigated the efficacy of Brefeldin A combined with navitoclax on prostate cancer cells. Materials and Methods: We assessed the effect of combination therapy for prostate cancer cells using MTS assay, qRT-PCR, luciferase assay, and western blot. Results: Combination therapy with Brefeldin A and navitoclax synergistically decreased cell viability in prostate cancer cells. Mechanistically, Brefeldin A induced MCL1 degradation and, combined with navitoclax, drove apoptosis. Further, integrated stress response was at least in part involved in Brefeldin A-induced MCL1 degradation. Conclusions: Combination therapy with Brefeldin A and navitoclax shows synergistic anti-tumor effects in prostate cancer cells. These results suggest that Brefeldin A might still be effective in prostate cancer if used with navitoclax. Citation Format: Akira Ohtsu, Seiji Arai, Tatsuhiro Sawada, Yoshiyuki Miyazawa, Yoshitaka Sekine, Kazuhiro Suzuki. Brefeldin A mediates integrated stress response and in combination with Navitoclax induces apoptosis in prostate cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5655.

Background/Aim: There are several treatment options for metastatic hormone-sensitive prostate cancer (mHSPC) in the world. In recent years, the use of docetaxel, abiraterone, enzalutamide, and apalutamide has been used for mHSPC, but combined androgen blockade (CAB) therapy using first-generation antiandrogens has been widely used in Japan. There is a background. We performed a consecutive study of patients who received combined androgen blockade (CAB) at a single institute to determine the prognostic factors for mHSPC. Patients and Methods: We conducted a consecutive study of 237 mHSPC patients treated with CAB from 2003 to 2017 at the Gunma University Hospital. Prostate-specific antigen progression-free survival (PSA-PFS) and overall survival (OS) were estimated by the Kaplan-Meier method. The associations between pre-treatment risk factors and the PSA response 3 months after starting CAB, PSA-PFS, and OS were evaluated by the Cox proportional hazards model. Results: Among the 237 cases, the median PSA-PFS and OS times were 63.0 and 91.4 months, respectively. The median PSA-PFS and OS times of M1 cases (174 cases, 73.4% of all 237 cases) were 36.1 and 75.9 months, respectively. The Eastern Cooperative Oncology Group performance status (ECOG PS) score, hemoglobin (Hb), lactate dehydrogenase, extent of disease, visceral metastasis (no vs. yes), and PSA response after 3 months were significant predictors of OS according to Cox regression analysis of prognostic factors in M1 patients. The ECOG PS, Hb, visceral metastasis (no vs. yes), and PSA response after 3 months predicted OS high-risk patients in LATITUDE criteria. The OS was 92.1 months in the low-risk group (0-1 risk factors), 48.2 months in the intermediate-risk group (2 risk factors), and 16.9 months in the high-risk group (3-4 risk factors). Conclusion: CAB should be considered as a treatment option for strictly selected patients with mHSPC, even though novel treatments are available.

Background/aim The purpose of the present study was to clarify whether treatment with YM155, a novel small-molecule inhibitor of survivin, reversed cabazitaxel resistance in castration-resistant prostate cancer (CRPC). Materials and methods Cabazitaxel resistance was induced in the castration-resistant prostate cancer cell line, 22Rv1-CR. In vitro and in vivo models were used to test the efficacy of YM155 and cabazitaxel. Results Survivin gene expression was significantly higher in 22Rv1-CR than its parent cells (22Rv1). In 22Rv1-CR cells, YM155 significantly reduced expression of the survivin gene in a concentration-dependent manner. YM155 alone was poorly effective; however, it significantly enhanced the anticancer effects of cabazitaxel on 22Rv1-CR in vitro and in vivo. Conclusion Inhibition of survivin by YM155 overcomes cabazitaxel resistance in CRPC cells.

Background To investigate the association between androgen deprivation therapy (ADT) and changes in the estimated glomerular filtration rate (eGFR) in male Japanese prostate cancer patients, based on post-hoc analysis of data from a previous prospective study.Methods From among 103 prostate cancer patients in whom renal function changes were tracked over 5 years, 88 were divided into a group who completed ADT within 3 years (short ADT group; n = 47) and a group who continued with ADT for more than 5 years (continuous ADT group; n = 41). We compared the groups in terms of the eGFR, calculated based on age and serum creatinine (mg/dL), before ADT initiation and every other year over the next 5 years. This study was approved by the Ethics Committee for Clinical Studies of Gunma University Hospital (Approval No: 8 − 5).Results The eGFR decreased by 4.91 and 2.89 ml/min in the short and continuous ATD groups, respectively, over the 5-year period following ADT initiation. The respective decreases in the eGFR were 0.98 and 0.58 ml/min/year. No significant difference in the eGFR was observed between the two groups at any measurement point.Conclusions ADT patients showed a decrease in the eGFR of 0.58–0.98 ml/min/y over a 5-year period, which is about twice as high as that of normal Japanese males. No significant difference in the eGFR by ADT duration was observed.

INTRODUCTION AND OBJECTIVE:Urinary-tract infections are common diseases, and sometimes progress to sepsis or septic shock which can be lethal. Therefore, the diagnosis and severity of sepsis are im...

79 Background: Enzalutamide (ENZ) is used to treat patients with castration-resistant prostate cancer (CRPC). Quality of life (QOL) during ENZ treatment for CRPC patients is very important, but the markers that predict QOL are unknown. We investigated the relationship between serum testosterone (T) levels before ENZ and QOL changes in CRPC patients. Methods: We conducted a prospective study from 2014 to 2018 at Gunma University Hospital and related facilities. We analyzed 95 patients who were able to evaluate QOL by FACT-P before, 4 weeks, and 12 weeks after ENZ administration. We measured serum T levels using liquid chromatography-tandem mass spectrometry (LC-MS/MS). This study was approved by the institutional review board of Gunma University Hospital (No.1177). Results: The study population of 95 patients had a median age of 72 years and median PSA of 21.6 ng/ml. The median overall survival from the time of ENZ administration in 95 cases was 26.8 months. The median serum T levels before ENZ treatment was 50.0 pg/ml. The mean total FACT-P score before ENZ administration, 4 weeks and 12 weeks later were 95.8, 91.7, and 90.1, respectively. 95 patients were divided into two groups, a high T levels (T-High) group and a low T (Low-T) group, and changes in FACT-P were examined. The mean FCAT-P values in the High-T and Low-T groups were 98.5 and 84.6 after 4 weeks and 96.4 and 82.2 after 12 weeks, which were significantly higher in the High-T group (p < 0.05, respectively). In the Low-T group, the mean FACT-P value after 12 weeks was significantly lower than that before administration (p < 0.05). Conclusions: It was suggested that the serum T levels of CRPC patients before ENZ treatment may be useful for predicting marker of QOL changes after ENZ treatment.

236 Background: We mainly perform Robotic-Assisted laparoscopic Radical Prostatectomy (RARP) and Carbon Ion Radiotherapy (CIRT) as curative treatment for prostate cancer. Several factors such as cancer control and quality of life after treatment are considered to be important, but there are few reports comparing sexual function changes before and after treatment between RARP and CIRT. We performed retrospective study comparing the evaluation of sexual function after RARP and CIRT cases using the propensity score matching method. Methods: 127 patients treated by RARP from 2014 to 2018 and 190 patients treated by CIRT monotherapy from 2010 to 2019 were evaluated. We evaluated Expanded Prostate Cancer Index Composite (EPIC) score before and after treatment. The EPIC was compared before, 12 months, and 24 months after treatment. Propensity score matching was performed using the age at treatment, PSA value, T stage, and pretreatment EPIC comprehensive score of sexual function as covariates. A cohort of 101 patients in each group was prepared and examined. This study was approved by the Institutional Review Board of Gunma University Hospital (No. IRB2020-050, 1839). Results: The mean ± standard deviation of each of the RARP and CIRT groups were age; 65.1 ± 5.9, 65.3 ± 6.5 years, PSA value; 6.31 ± 2.07, 6.34 ± 2.46 ng/ ml, pretreatment EPIC sexual function overall score; 46.4 ± 15.6, 48.2 ± 16.2. In both groups, T1N0M0 was 16%, T2N0M0 was 83%, and T3N0M0 was 1%. The total EPIC sexual function scores before, 12 months, and 24 months after treatment were 46.4, 27.9, 28.2 in the RARP group, and 48.2, 41.4, 41.6 in the CIRT group, respectively. In both groups, there was a significant decrease in score after 12 months and 24 months compared to before treatment (p < 0.05). At 12 and 24 months, the total EPIC sexual function score in the CIRT group was significantly higher than RARP group (p < 0.001). Conclusions: In prostate cancer cases adjusted by propensity score matching, the decrease in EPIC sexual function score was significantly smaller in the CIRT group than RARP group. The results of this study seemed to be useful information for decision making with patients.

To verify the validity of our antimicrobial prophylaxis regimen for transperineal prostate biopsies, we investigated the rate of infectious complications in this procedure. We retrospectively investigated the infectious complications in 485 patients who underwent a transperineal prostate biopsy between 2014 and 2016 at our hospital. In the clinic, we use cefazolin (CEZ) for antimicrobial prophylaxis. Infectious complications were assessed up to postoperative day (POD) 30. Patients with infectious complications were further investigated to determine the site of infection, outbreak day, and type of pathogenic bacteria. The rate of infectious complications was 0.82% (4 out of 485 patients). Three patients developed prostatitis, 1 progressed into septic shock, and 1 patient developed epididymitis. The pathogenic bacteria identified were Pseudomonas aeruginosa (1 of 4), Enterococcus faecalis (1 of 4) and Escherichia coli that harbour extended-spectrum beta lactamase (ESBL-productive E. coli) (2 of 4). The earliest outbreak was POD 2 and the latest was POD 14. Infectious complications tended to increase in patients in whom an indwelling urethral catheter was inserted (p = 0.0567). However, there were no statistically significant relationships between any risk factor and the occurrence of infectious complications. We concluded that CEZ is adequate for the prevention of perioperative infectious complications in transperineal prostate biopsies. Furthermore, we reaffirmed the importance of correct perioperative management, including preoperative assessment.

Androgen is beneficial for the prostate with normal functions but creates a risk for prostate cancer progression. How androgen receptor (AR) mediates these various actions of androgen remains elusive. AR conserves a phosphorylation motif within its ligand-binding domain throughout species. Here, we have found AR phosphorylated at Ser815 (P-AR) is expressed in normal tissues of both human and mouse prostates. P-AR begins being expressed in association with prostatic development and decreases its expression levels by castration in the mouse prostate. Functional analysis of AR in the prostate cancer PC-3 cells showed ligand-induced AR nuclear translocation and transactivation were disturbed by its phosphorylation at Ser815. Moreover, P-AR suppressed oncogenic AKT signaling suggesting AR has a suppression function for prostate cancer development. In fact, AR phosphorylation levels progressively decrease in human prostates as cancer worsens. These findings showed androgen might utilize P-AR to self-antagonize oncogenic signals and cancer progression believed to be regulated by non-phosphorylated AR (NonP-AR). By differing its target genes and signal regulations from those of NonP-AR, P-AR co-expression with NonP-AR may be the molecular basis for androgen to balance its actions and to control disease developments.

Antitumor effect mechanism of statin in prostate cancer cells focusing on autophagy Background:Statins have recently been studied for their proapoptotic and antimetastatic effects. However, the exact mechanisms of their anticancer actions remain unclear. We have studied the novel castration resistant prostate cancer (CRPC) treatment with statins. Using microarrays, we discovered up-regulation of ATG4B (Autophagy related 4 homolog B) in PC-3 cells after simvastatin treatment. In this study, we evaluated the effects of simvastatin focusing on androgen-independent prostate cancer cells. Methods:PC-3, LNCaP-LA, 22RV-1-LA (taht were derived from LNCaP and 22RV1 cells and cultured in 10% charcoal-stripped fetal bovine serum for 3 months), and DU145 human prostate cancer cell lines were used. Microarrays were performed using PC-3 untreated or administered with simvastatin (0 uM versus 5 uM). Proliferation, migration, and invasion were evaluated using MTS assay, Migration assay, and Invasion assay, respectively. The increases of autophagy were detected by western blot using microtubule associated protein 1 light chain 3 (LC-3) antibody and confirmed by a fluorescence microscope with staining autophagosomes by autophagy detection kit (abcam, Cambridge, UK). Results:Using microarrays, we discovered up-regulation of ATG4B in PC-3 cells after simvastatin treatment. Simvastatin inhibited the proliferation, migration, and invasion of PC-3, LNCaP-LA, 22RV1-LA and DU145 cells. The expression level of LC-3 was up-regulated by simvastatin in PC-3, LNCaP-LA, 22RV1-LA and DU145 cells. In PC-3 cells treated with statin, a significant increase in autophagosomes was confirmed by fluorescence microscopy. The expression of LC-3 and autophagosomes were increased in a concentration-dependent manner. Conclusions:It was found that statin administration enhances autophagy induction in a prostate cell line. We plan to study the combined effect with other drugs that induce autophagy. We would like to develop CRPC treatment by inducing autophagy cell death. Citation Format: Yoshiyuki Miyazawa, Daisuke Oka, Hiroshi Nakayama, Yoshitaka Sekine, Seiji Arai, Kazuhiro Suzuki. Antitumor effect mechanism of statin in PCa cells focusing on autophagy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1935.

Objectives To investigate the predictive value of various molecular forms of prostate-specific antigen in men with baseline prostate-specific antigen

BACKGROUND The effects of a steroidal antiandrogen (AA) and 5-alpha-reductase inhibitor (5ARI) on prostate tissue hormone content and metabolism are not fully elucidated. The objective of this study is to investigate the hormone content and metabolism of the prostate tissues of patients treated with AA or 5ARI using the ultra-sensitive liquid chromatography–tandem mass spectrometry (LC-MS/MS) method. METHODS Thirty-nine patients with benign prostatic hyperplasia (BPH) undergoing transurethral surgery were included. Serum and prostate tissue hormone and prostate tissue hormone metabolism analyses were performed using LC-MS/MS after 1 month of treatment with chlormadinone acetate (CMA; steroidal AA, 50 mg/day) or dutasteride (DUTA; dual 5ARI, 0.5 mg/day). RESULTS Serum testosterone (T), dihydrotestosterone (DHT), and adrenal androgen levels were lower in the CMA group than the control group. Prostate tissue T and DHT levels were also lower in the CMA group than the control group. In the DUTA group, only serum and prostate DHT concentrations were reduced compared to the control group; in contrast, those of other hormones, especially T and 4-androstene-3,17-dione in the prostate tissue, showed marked elevations up to 70.4- and 11.4-fold normal levels, respectively. Moreover, the hormone metabolism assay confirmed that the conversion of T to DHT was significantly suppressed while that of T to 4-androstene-3,17-dione was significantly accelerated in the prostate tissue of DUTA-treated patients. CONCLUSIONS Although treatment with AA and 5ARI show similar clinical outcomes, their effect on tissue hormone content and metabolism varied greatly. Prostate 9999: XX–XX, 2017. © 2017 Wiley Periodicals, Inc.

Differences in the incidence and mortality rate of prostate cancer between the USA and Japan have been decreasing over time, and were only twofold in 2017. Therefore, countermeasures against prostate cancer could be very important not only in Western countries, but also in developed Asian countries. Screening for prostate cancer in the general population using transrectal ultrasonography, digital rectal examination and/or prostate acid phosphatase began in Japan in the early 1980s, and screening with prostate-specific antigen and digital rectal examination has been widespread in the USA since the late 1980s. Large- and mid-scale randomized controlled trials on screening for prostate cancer began around 1990 in the USA, Canada and Europe. However, most of these studies failed as randomized controlled trials because of high contamination in the control arm, low compliance in the screening arm or insufficient screening setting about screening frequency and/or biopsy indication. The best available level 1 evidence is data from the European Randomized Study of Screening for Prostate Cancer and the Goteborg screening study. However, several non-urological organizations and lay media around the world have mischaracterized the efficacy of prostate-specific antigen screening. To avoid long-term confusion about screening for prostate cancer, leading professional urological organizations, including the Japanese Urological Association, are moving toward the establishment of an optimal screening system that minimizes the drawbacks of overdetection, overtreatment and loss of quality of life due to treatment, and maximizes reductions in the risk of death as a result of prostate cancer and the development of metastatic prostate cancer.