Urological cancer statistics on incidence from 1975 to 2019 and mortality from 1958 to 2022 in Japan.

BACKGROUND: In Japan, comprehensive cancer statistics are collected through cancer registries. However, data on urological cancers are rarely summarized or published in research papers. METHODS: This retrospective study was performed using publicly available statistical data on urological cancers (prostate cancer [PCa], bladder cancer [BCa], and cancers of kidney and urinary tract [except urinary bladder]) in Japan, including a summary of the Ministry's mortality statistics, cancer incidence statistics from the Regional Cancer Registries through 2015, and the National Cancer Registry statistics from 2016. We examined the incidence and mortality rates of urological cancers stratified by age groups. RESULTS: The number of new cases of PCa, BCa, and cancers of kidney and urinary tract (except urinary bladder) in 2019 was 94,748, 23,383, and 30,458, respectively, and the number of deaths in 2022 was 13,439, 9,598, and 9,795, respectively. The incidence and mortality rates of urological cancers have consistently increased. Since 2000, there has been a noteworthy increase in the mortality rate of urological cancers among individuals aged > 85 years. The incidence and mortality rates of BCa and cancers of kidney and urinary tract (except urinary bladder) were significantly higher in males than in females. CONCLUSIONS: Urological cancers in very elderly patients (> 85 years) will become increasingly important in the future.

Purine-Rich Element Binding Protein Alpha, a Nuclear Matrix Protein, Has a Role in Prostate Cancer Progression.

Solid tumors as well as leukemias and lymphomas show striking changes in nuclear structure including nuclear size and shape, the number and size of nucleoli, and chromatin texture. These alterations have been used in cancer diagnosis and might be related to the altered functional properties of cancer cells. The nuclear matrix (NM) represents the structural composition of the nucleus and consists of nuclear lamins and pore complexes, an internal ribonucleic protein network, and residual nucleoli. In the nuclear microenvironment, the NM is associated with multi-protein complexes, such as basal transcription factors, signaling proteins, histone-modifying factors, and chromatin remodeling machinery directly or indirectly through scaffolding proteins. Therefore, alterations in the composition of NM could result in altered DNA topology and changes in the interaction of various genes, which could then participate in a cascade of the cancer process. Using an androgen-sensitive prostate cancer cell line, LNCaP, and its androgen-independent derivative, LN96, conventional 2D-proteomic analysis of the NM proteins revealed that purine-rich element binding protein alpha (PURα) was detected in the NM proteins and differentially expressed between the cell lines. In this article, we will review the potential role of the molecule in prostate cancer.

Japanese clinical practice guidelines for prostate cancer 2023.

This fourth edition of the Japanese Clinical Practice Guidelines for Prostate Cancer 2023 is compiled. It was revised under the leadership of the Japanese Urological Association, with members selected from multiple academic societies and related organizations (Japan Radiological Society, Japanese Society for Radiation Oncology, the Department of EBM and guidelines, Japan Council for Quality Health Care (Minds), Japanese Society of Pathology, and the patient group (NPO Prostate Cancer Patients Association)), in accordance with the Minds Manual for Guideline Development (2020 ver. 3.0). The most important feature of this revision is the adoption of systematic reviews (SRs) in determining recommendations for 14 clinical questions (CQs). Qualitative SRs for these questions were conducted, and the final recommendations were made based on the results through the votes of 24 members of the guideline development group. Five algorithms based on these results were also created. Contents not covered by the SRs, which are considered textbook material, have been described in the general statement. In the general statement, a literature search for 14 areas was conducted; then, based on the general statement and CQs of the Japanese Clinical Practice Guidelines for Prostate Cancer 2016, the findings revealed after the 2016 guidelines were mainly described. This article provides an overview of these guidelines.

Cribriform pattern 4/intraductal carcinoma of the prostate and persistent prostate-specific antigen after radical prostatectomy.

Objectives: The objective of this study is to identify the effect of cribriform pattern 4 carcinoma/intraductal carcinoma of the prostate (CC/IDCP) on persistent prostate-specific antigen (PSA) levels after robot-assisted radical prostatectomy (RARP) in patients with localized prostate cancer (PCa). Patients and Methods: This retrospective study included 730 consecutive patients with localized PCa who underwent RARP at Mie University (n = 392) and Aichi Medical University (n = 338) between 2015 and 2021. Patients with clinically metastatic PCa (cN1 and cM1) and those who received neoadjuvant and/or adjuvant therapy before biochemical recurrence were excluded. We evaluated the effects of CC/IDCP on persistent PSA levels after RARP. Persistent PSA was defined as PSA level ≥0.2 ng/mL at 1 month postoperatively and consecutively thereafter. Using factors from logistic regression analysis, models were developed to predict persistent PSA levels. Results: Approximately 6.3% (n = 46) of the patients had persistent PSA levels. Patients with biopsy CC/IDCP (bCC/IDCP) and pathological CC/IDCP (pCC/IDCP) based on RARP specimens were 11.6% (85/730) and 36.5% (267/730), respectively. Multivariate analysis of the prediction of persistent PSA levels using preoperative factors revealed that PSA density, percentage of positive cancer cores, biopsy grade group and bCC/IDCP were independent prognostic factors. Furthermore, multivariate analysis of the prediction of persistent PSA levels using postoperative factors, excluding pN1, revealed that pathological grade group, pCC/IDCP, seminal vesicle invasion and lymphovascular invasion were independent prognostic factors. In the receiver operating characteristic curve analysis for predicting persistent PSA after RARP, areas under the receiver operating characteristic curve for the model with preoperative factors, postoperative factors, including pN1, and postoperative factors, excluding pN1, were 0.827, 0.833 and 0.834, respectively. Conclusions: bCC/IDCP predicted persistent PSA after RARP in the overall population, while pCC/IDCP predicted persistent PSA only when the pN1 population was excluded. This may be useful for predicting susceptible patients with worse outcomes.

A simple risk stratification model for prostate cancer using histopathologic findings of radical prostatectomy.

OBJECTIVES: To develop a simple postoperative risk stratification based on histopathologic findings from radical prostatectomy specimens. METHODS: This study included 3 cohorts of patients with a preoperative diagnosis of clinically localized prostate cancer: 1 derivation cohort (n = 432) and 2 validation cohorts (n = 506 and n = 720). First, a postoperative risk stratification model was developed in the derivation cohort using the factors extraprostatic extension, surgical margin status, seminal vesicle invasion, and lymph node involvement. Each of the first 3 factors was assigned 0 or 1 point for negative or positive results, respectively, and the sum of the points, ranging from 0 to 3, was scored. pN1 was not scored but was analyzed separately. Validation cohorts were then used to evaluate the predictive accuracy of the model. Additionally, we compared the model with the Cancer of the Prostate Risk Assessment (CAPRA) score. RESULTS: Because the log-rank test showed no statistically significant differences between scores 1 vs 2 or score 3 vs pN1 in the derivation cohort, the following 3-level risk stratification was created: low risk (score 0), intermediate risk (score 1-2), and high risk (score 3 or pN1). There were statistically significant differences in recurrence-free survival between any of 2 groups of 3-level risk stratification. This model similarly worked in both validation cohorts. The C indexes for the model were higher than those for the CAPRA score. CONCLUSIONS: This simple postoperative risk stratification model, based on radical prostatectomy findings, has a prognostic impact that has been validated in a multicenter population.

Psoas mass index at the level of the third lumbar vertebra on computed tomography is a prognostic predictor for metastatic castration-sensitive prostate cancer.

BACKGROUND: Computed tomography-defined low skeletal muscle mass is associated with oncological outcomes in patients with prostate cancer. However, its association with the outcomes of hormone-treated metastatic castration-sensitive prostate cancer remains unclear. We aimed to determine the association between metastatic castration-sensitive prostate cancer and psoas muscle parameters. METHODS: We retrospectively reviewed 121 patients with N1 and/or M1 metastatic castration-sensitive prostate cancer who underwent primary androgen deprivation therapy between 2005 and 2021, either by administration of luteinizing hormone-releasing hormone agonist/antagonist or by surgical castration accompanied by bicalutamide, a first-generation antiandrogen. Before treatment administration, the psoas muscle index at the level of the third lumbar vertebra (psoas muscle area [cm2]/height2 [m2]) and the mean Hounsfield units of the psoas muscle were evaluated using non-contrast computed tomography and in relation to oncological outcomes. RESULTS: The median follow-up was 56.9 months. Furthermore, during follow-up, 82 (67.7%) and 53 (43.8%) patients progressed to castration-resistant prostate cancer and died, respectively. Multivariate analysis of castration-resistant prostate cancer-free survival and overall survival showed significant differences in the Gleason score, clinical N-stage, and psoas muscle index (median cutoff: 3.044 cm2/m2). CONCLUSIONS: Pretreatment psoas muscle index is an independent predictor of poor castration-resistant prostate cancer-free survival and overall survival in patients with N1 and/or M1 metastatic castration-sensitive prostate cancer.

Lipoma Arising in the Eustachian Tube.

Lipomas are among the most common soft tissue tumors. Surgical removal of lipoma is considered if the patient has symptoms or cosmetic challenges. Lipomas that develop from any fat tissue in the body and involve the eustachian tube are extremely rare. Herein, we report the case of a patient with a lipoma arising in the eustachian tube. We also summarized the literature on tumors originating from the eustachian tubes. A 62-year-old female presented to our department with a five-year history of left nasal congestion. Nasal endoscopy revealed a tumor in the left eustachian tube. The tumor was considered a lipoma on computed tomography (CT) and magnetic resonance imaging (MRI) and was removed using a transnasal endoscopic approach. Nasal endoscopy and radiologic imaging can be used to detect tumors in the nasopharynx, including the eustachian tubes. Magnetic resonance imaging is particularly useful for the diagnosis of lipomas. A lipoma in the eustachian tube can cause nasal congestion and aural fullness, and the transnasal endoscopic approach is useful for tumor removal.

Stage at diagnosis of colorectal cancer through diagnostic route: Who should be screened?

BACKGROUND: Colorectal cancer (CRC) is a global health concern, with advanced-stage diagnoses contributing to poor prognoses. The efficacy of CRC screening has been well-established; nevertheless, a significant proportion of patients remain unscreened, with > 70% of cases diagnosed outside screening. Although identifying specific subgroups for whom CRC screening should be particularly recommended is crucial owing to limited resources, the association between the diagnostic routes and identification of these subgroups has been less appreciated. In the Japanese cancer registry, the diagnostic routes for groups discovered outside of screening are primarily categorized into those with comorbidities found during hospital visits and those with CRC-related symptoms. AIM: To clarify the stage at CRC diagnosis based on diagnostic routes. METHODS: We conducted a retrospective observational study using a cancer registry of patients with CRC between January 2016 and December 2019 at two hospitals. The diagnostic routes were primarily classified into three groups: Cancer screening, follow-up, and symptomatic. The early-stage was defined as Stages 0 or I. Multivariate and univariate logistic regressions were exploited to determine the odds of early-stage diagnosis in the symptomatic and cancer screening groups, referencing the follow-up group. The adjusted covariates were age, sex, and tumor location. RESULTS: Of the 2083 patients, 715 (34.4%), 1064 (51.1%), and 304 (14.6%) belonged to the follow-up, symptomatic, and cancer screening groups, respectively. Among the 2083 patients, CRCs diagnosed at an early stage were 57.3% (410 of 715), 23.9% (254 of 1064), and 59.5% (181 of 304) in the follow-up, symptomatic, and cancer screening groups, respectively. The symptomatic group exhibited a lower likelihood of early-stage diagnosis than the follow-up group [P < 0.001, adjusted odds ratio (aOR), 0.23; 95% confidence interval (95%CI): 0.19-0.29]. The likelihood of diagnosis at an early stage was similar between the follow-up and cancer screening groups (P = 0.493, aOR for early-stage diagnosis in the cancer screening group vs follow-up group = 1.11; 95%CI = 0.82-1.49). CONCLUSION: CRCs detected during hospital visits for comorbidities were diagnosed earlier, similar to cancer screening. CRC screening should be recommended, particularly for patients without periodical hospital visits for comorbidities.

Combined approach for predicting the efficacy of nivolumab in head and neck carcinoma by tissue and soluble expressions of PD-L1 and PD-L2.

BACKGROUND: Predictive biomarkers for nivolumab in recurrent or metastatic head and neck squamous cell carcinoma (RMHNSCC) have not yet been established. METHODS: The tumor proportion score (TPS), combined positive score (CPS), and soluble forms of programmed cell death ligand-1 (PD-L1) and programmed cell death ligand-2 (PD-L2) were retrospectively analyzed in patients with RMHNSCC treated with nivolumab. RESULTS: The positivity rates for TPS (PD-L1), CPS (PD-L1), TPS (PD-L2), and CPS (PD-L2) were 73.8%, 78.2%, 56.4%, and 78.2%, respectively. Patients with high TPS (PD-L1), CPS (PD-L1), or CPS (PD-L1 and PD-L2) showed significantly prolonged progression-free survival. Favorable overall survival was associated with high CPS (PD-L1 and PD-L2) and low soluble PD-L1 and PD-L2 levels. The expressions of tissue and soluble PD-L1/2 were not correlated. CONCLUSIONS: Our study revealed that compared to PD-L1 expression alone, dual expression of PD-L1 and PD-L2 in tissue or soluble form could be feasible biomarkers in patients with RMHNSCC who received nivolumab.

[Role of Bone Scan Index (BSI) in the Prognosis and Treatment Efficacy in Castration-Sensitive Prostate Cancer Patients with Bone Metastasis].

Bone is the most common metastatic site in prostate cancer (PCa). Although the extent of disease (EOD) grade is used for evaluating burden of bone metastasis, the accuracy of bone metastasis classification needs improvement. Bone scan index (BSI) was developed as a quantitative tool to enhance the interpretability and clinical relevance of the bone scan. This study aimed to explore the role of BSI using BONENAVI® software in determining the prognosis and treatment efficacy in castration-sensitive PCa (mCSPC) patients with bone metastasis. We retrospectively reviewed 61 mCSPC patients with bone metastasis who had received primary androgen deprivation therapy (PADT) at our institution. All patients received PADT with luteinizing hormone-releasing hormone agonist or surgical castration accompanied by first-generation antiandrogen, bicalutamide. Bone scans were performed with 99[m]Tc-MDP. BSI (%) was divided into two groups (＜1.0 and ≧1.0), and BSI response rates(change at 0 months to after 6 months) were determined using thresholds of 45% decline. Castration-resistant prostate cancer (CRPC) -free survival (CRPC-FS) and Overall survival (OS) rates were analyzed using the Kaplan-Meier method. The median follow-up was 41. 9 months. Overall, 16 patients (26. 2%) died. Multivariate analysis on pretreatment factors revealed that hemoglobin (P＝0.03) and BSI (P＝0.04) were independent prognostic factors for OS. The 5-year OS rates in patients with low BSI and high BSI were 84.6% and 39.2%, respectively (P＝0.02). In 40 patients who had a bone scan before and after PADT, OS rates in patients with a good response (≧45%) were significantly higher than those with a poor response (＜45%) (P＝0.001). Nadir PSA titers within 6 months after the start of treatment (P＝0.005), Hb (P＝0.003), and BSI change (P＝0.014) were independent prognostic factors for OS. In mCSPC patients with bone metastases, BSI at diagnosis was an important predictor of CRPC progression and OS as a pre-treatment factor, and BSI change rate and PSA nadir as post-treatment factors.

Exploring Immunological Effects and Novel Immune Adjuvants in Immunotherapy for Salivary Gland Cancers.

Salivary gland cancer (SGC) is rare and comprises over 20 histological subtypes. Recently, clinical experience regarding immunotherapies for SGCs has been accumulating, yet their efficacy remains controversial. Understanding the tumor microenvironment (TME), including the expression of immune checkpoint molecules in SGC, is crucial to optimizing immunotherapy. In this review, we demonstrate that high-grade mucoepidermoid carcinoma and salivary duct carcinoma generally exhibit immune-hot TME with high immune cell infiltration, frequent genetic mutations, and robust immune checkpoint molecule expression. In contrast, adenoid cystic carcinomas exhibit an immune-cold TME. While the reported efficacy of immune checkpoint inhibitors (ICIs) for SGCs is generally poor, several studies showed promising clinical efficacy of ICIs, with an objective response rate ranging from 20.0-33.3%, indicating that ICIs might be beneficial for a specific population of SGC. Molecule-targeted therapies including anti-human epidermal growth factor receptor 2 and anti-androgen receptor therapies have shown promising clinical efficacy against SGC. Recent evidence indicates that these molecules could be targets for antigen-specific immunotherapies including chimeric antigen receptor-T therapy and cancer vaccines. This review discusses the current understanding and future directions of immunotherapies for SGCs, including ongoing clinical trials.

Prognostic factors among patients with pathological Grade Group 5 prostate cancer based on robot-associated radical prostatectomy specimens from a large Japanese cohort (MSUG94).

PURPOSE: There are no definitive prognostic factors for patients with pathological Grade Group 5 (pGG 5) prostate cancer (PCa) undergoing robot-associated radical prostatectomy (RARP). This study aimed to explore the prognostic factors among patients with pGG 5 PCa in a large Japanese cohort (MSUG94). METHODS: This retrospective, multi-institutional cohort study was conducted between 2012 and 2021 at ten centers in Japan and included 3195 patients. Patients with clinically metastatic PCa (cN1 or cM1) and those receiving neoadjuvant and/or adjuvant therapy were excluded. Finally, 217 patients with pGG5 PCa were analyzed. RESULTS: The median follow-up period was 28.0 months. The 3- and 5-year biochemical recurrence-free survival (BCRFS) rates of the overall population were 66.1% and 57.7%, respectively. The optimal threshold value (47.2%) for the percentage of positive cancer cores (PPCC) with any GG by systematic biopsy was chosen based on receiver operating characteristic curve analysis. Univariate analysis revealed that the prostate-specific antigen level at diagnosis, pT, pN, positive surgical margins (PSMs), lymphovascular invasion, and PPCC were independent prognostic factors for BCRFS. A multivariate analysis revealed that PSMs and PPCC were independent prognostic factors for BCRFS. Using these two predictors, we stratified BCRFS, metastasis-free survival (MFS), and castration-resistant PCa-free survival (CRPC-FS) among patients with pGG 5 PCa. CONCLUSION: The combination of PSMs and PPCC may be an important predictor of BCRFS, MFS, and CRPC-FS in patients with pGG 5 PCa undergoing RARP.

Postoperative complications and determinant of selecting non intracorporeal urinary diversion in patients undergoing robot-assisted radical cystectomy: an initial experience.

Background: Robot-assisted radical cystectomy (RARC) with urinary diversion has become a standard surgical procedure because of its three-dimensional high-definition surgical field of view, flexibility, and stability. However, because of the highly complex steps of surgery, postoperative complications cannot be ignored. Methods: This retrospective, single-center, observational cohort study investigated the postoperative complications following RARC at a non-high-volume center in Japan. From August 2019 to March 2023, 50 consecutive patients who underwent RARC for histologically proven muscle-invasive bladder cancer (MIBC) or high-risk non-MIBC with an indication for radical cystectomy according to the Japanese Urological Association Guideline 2019 were included. Factors correlated with the selection of extracorporeal urinary diversion (ECUD) or cutaneous ureterostomy rather than intracorporeal urinary diversion (ICUD) for urinary diversion were also investigated. Results: In total, 33 (66%) and 31 (62%) patients experienced complications during the first 90 and 30 days after RARC, respectively. Among them, 19 (38%) and 18 (36%) patients developed Clavien-Dindo classification G2 complications, and 12 (24%) and 11 (22%) developed G3 or higher (major) complications during the first 90 and 30 days after RARC, respectively. The most common complications were gastrointestinal complications (26%) and urinary tract infections (22%). Nine patients (18%) underwent surgical intervention within 90 days of undergoing RARC. Higher infusion volume during the operations was significantly correlated with the occurrence of major complications within 90 days (P=0.025) and 30 days (P=0.0158) after RARC. Nineteen patients (38%) underwent non-ICUD. Twelve patients received ECUD as an ileal conduit or neobladder, and among them, three patients received ECUD due to intraabdominal adhesion for previous abdominal surgery or radiation, while four patients received ECUD ileal conduit due to comorbidities and advanced cases (palliative surgery) to shorten the surgery time. Conclusions: Surgical complications related to the initial experience with RARC at a non-high-volume center in Japan cannot be ignored. Although this complicated surgical procedure requires a learning curve to achieve a stable rate of much fewer major complications after RARC, careful assessment of patients' status before surgery and critical postoperative management may reduce complication rates more quickly, even at non-high-volume centers.

Factors affecting the length of hospital stay for total knee arthroplasty in Japan: a retrospective study using the diagnosis procedure combination database.

BACKGROUND: We aimed to evaluate the length of hospital stay following total knee arthroplasty to determine the impact of relevant factors using data from the Diagnosis Procedure Combination database. METHODS: This was a retrospective observational study. The study cohort included 5,831 patients who had osteoarthritis of the knee and had undergone total knee replacement between February 2018 and October 2022 at 38 hospitals. RESULTS: Multivariate analysis showed that the factors influencing the length of stay included: age (p < 0.001), height (p < 0.001), weight (p = 0.049), body mass index (p = 0.008), Barthel index (p < 0.001), method of anesthesia (p < 0.001), bone transplant (p = 0.010), timing of postoperative rehabilitation (p < 0.001), atrial fibrillation (p < 0.001), chronic pain (p < 0.001), and number of institutionally treated cases (p < 0.001) (r = 0.451, p < 0.001). CONCLUSIONS: Shorter or longer hospital stays were found to be associated with the patients' background characteristics and facility-specific factors; these can lead to more accurate estimates of the length of hospital stay and appropriate allocation of resources.

Epigenetic modification of histone acetylation in the sensorimotor cortex after intracerebral hemorrhage.

Epigenetic regulation is involved in post-stroke neuroplasticity. We investigated the effects of intracerebral hemorrhage (ICH) on histone acetylation and gene expression related to neuronal plasticity in the bilateral sensorimotor cortices, which may affect post-stroke sensorimotor function. Wistar rats were randomly divided into the SHAM and ICH groups. We performed ICH surgery stereotaxically based on the microinjection of a collagenase solution in the ICH group. Foot fault and cylinder tests were performed to evaluate motor functions at 4-time points, including pre-ICH surgery. The amount of acetyl histones and the mRNA expression of neurotrophic factors crucial to neuroplasticity in the bilateral sensorimotor cortices were analyzed approximately 2 weeks after ICH surgery. Sensorimotor functions of the ICH group were inferior to those of the SHAM group during 2 weeks post-ICH. ICH increased the acetylation of histone H3 and H4 over the sham level in the ipsilateral and contralateral cortices. ICH increased the mRNA expression of IGF-1, but decreased the expression of BDNF compared with the sham level in the ipsilateral cortex. The present study suggests that histone acetylation levels are enhanced in bilateral sensorimotor cortices after ICH, presenting an altered epigenetic platform for gene expressions related to neuronal plasticity.

Female pelvic organ-preserving robot-assisted simple cystectomy and intracorporeal ileal neobladder reconstruction on a young woman with Hunner-type interstitial cystitis.

Introduction: Cystectomy is the last treatment option for Hunner-type interstitial cystitis. However, consensus regarding optimal patient selection or treatment approaches is lacking. Case presentation: A 27-year-old woman presented to a regional hospital with bladder pain and frequent urination. Antimicrobial therapy was administered; however, her symptoms persisted and she was finally diagnosed with HIC. Multiple endoscopic fulgurations of Hunner's lesions with bladder hydrodistension or intravesical therapy were performed; however, the symptoms persisted. A urethral catheter was inserted 1 month before she visited our clinic because of a severely contracted bladder. We performed female pelvic organ-preserving robot-assisted simple cystectomy and intracorporeal ileal neobladder reconstruction. The patient's postoperative course was uneventful and her symptoms resolved. Conclusion: This is the first report of pelvic organ-preserving robot-assisted simple cystectomy and intracorporeal ileal neobladder reconstruction in a young woman with HIC.

Incidence and risk factors of inguinal hernia after robot-assisted radical prostatectomy: a retrospective multicenter cohort study in Japan (the MSUG94 group).

To investigate the incidence and risk factors of inguinal hernia (IH) after robot-assisted radical prostatectomy (RARP) using a multicentric database. The present study used a multicentric database (the MSUG94) containing data on 3,195 Japanese patients undergoing RARP between 2012 and 2021. Surgical procedures utilized for IH prevention were as follows: isolation of the vas deferens, transection of the vas deferens, isolation of the spermatic vessels, and separation of the peritoneum from the internal inguinal ring. The primary and secondary endpoints were IH-free survival and any association between post-RARP IH and clinical covariates. The prophylactic effect of the above procedures were also assessed. IH prevention was attempted in 1,465 (46.4%) patients at five of the nine hospitals. During follow-up (median 24 months), post-RARP IH developed in 243 patients. The post-RARP IH-free survival rates at years 1, 2, and 3 were 94.3%, 91.7%, and 90.5%, respectively. Old age (hazard ratio [HR] 1.037; 95% confidence interval [CI] 1.014-1.061; p = 0.001), low BMI (HR 0.904; 95% CI 0.863-0.946: p < 0.001), and low hospital volume (HR 1.385; 95% CI 1.003-1.902; p = 0.048) were independently associated with IH development. None of the procedures for IH prevention were associated with IH development. Our findings may represent the current, real-world status of post-RARP IH in Japan. The prophylactic effects of the surgical procedures for IH prevention should be further investigated in well-designed, prospective studies to optimize the surgical technique.

Prognostic Importance of Lymphovascular Invasion for Specific Subgroup of Patients with Prostate Cancer After Robot-Assisted Radical Prostatectomy (The MSUG94 Group).

OBJECTIVE: This study aimed to investigate whether lymphovascular invasion (LVI) was associated with oncological outcomes in patients with prostate cancer (PCa) undergoing robotic-assisted radical prostatectomy (RARP). METHODS: This retrospective multicenter cohort study was conducted on 3195 patients with PCa who underwent RARP in nine institutions in Japan. The primary endpoints were the associations between biochemical recurrence (BCR) and LVI and between BCR and clinicopathological covariates, while the secondary endpoints were the association between LVI and the site of clinical recurrence and metastasis-free survival (MFS). RESULTS: In total, 2608 patients met the inclusion criteria. At the end of the follow-up period, 311 patients (11.9%) were diagnosed with BCR and none died of PCa. In patients with pathological stage T2 (pT2) + negative resection margins (RM-), and pT3+ positive RM (RM+), LVI significantly worsened BCR-free survival (BRFS). For patients with PCa who had pT3 and RM+, the 2-year BRFS rate in those with LVI was significantly worse than in those without LVI. Patients with LVI had significantly worse MFS than those without LVI with respect to pT3, RM+, and pathological Gleason grade (pGG). In multivariate analysis, LVI was significantly associated with BRFS in patients with pT3 PCa, and with worse MFS in PCa patients with pT3, RM+, and pGG ≥ 4. CONCLUSIONS: LVI was an independent prognostic factor for recurrence and metastasis after RARP, particularly in patients with pT3 and RM+ PCa. Locally advanced PCa with positive LVI and RM+ requires careful follow-up because of the high likelihood of recurrence.

Newly developed preclinical models reveal broad-spectrum CDK inhibitors as potent drugs for CRPC exhibiting primary resistance to enzalutamide.

Androgen-deprivation therapy is a standard treatment for advanced prostate cancer. However, most patients eventually acquire resistance and progress to castration-resistant prostate cancer (CRPC). In this study, we established new CRPC cell lines, AILNCaP14 and AILNCaP15, from LNCaP cells under androgen-deprived conditions. Unlike most pre-existing CRPC cell lines, both cell lines expressed higher levels of androgen receptor (AR) and prostate-specific antigen (PSA) than parental LNCaP cells. Moreover, these cells exhibited primary resistance to enzalutamide. Since AR signaling plays a significant role in the development of CRPC, PSA promoter sequences fused with GFP were introduced into AILNCaP14 cells to conduct GFP fluorescence-based chemical screening. We identified flavopiridol, a broad-spectrum CDK inhibitor, as a candidate drug that could repress AR transactivation of CRPC cells, presumably through the inhibition of phosphorylation of AR on the serine 81 residue (pARSer81 ). Importantly, this broad-spectrum CDK inhibitor inhibited the proliferation of AILNCaP14 cells both in vitro and in vivo. Moreover, a newly developed liver metastatic model using AILNCaP15 cells revealed that the compound attenuated tumor growth of CRPC harboring highly metastatic properties. Finally, we developed a patient-derived xenograft (PDX) model of CRPC and DCaP CR from a patient presenting therapeutic resistance to enzalutamide, abiraterone, and docetaxel. Flavopiridol successfully suppressed the tumor growth of CRPC in this PDX model. Since ARSer81 was found to be phosphorylated in clinical CRPC samples, our data suggested that broad-spectrum CDK inhibitors might be a potent candidate drug for the treatment of CRPC, including those exhibiting primary resistance to enzalutamide.

The Negative Impact of Inflammation-Related Parameters in Prostate Cancer after Robot-Assisted Radical Prostatectomy: A Retrospective Multicenter Cohort Study in Japan (the MSUG94 Group).

Background and Objectives: We aimed to examine the relationship between the inflammation-related parameters, such as the neutrophil-to-lymphocyte ratio (NLR), and the pathological findings and biochemical recurrence (BCR) in patients with prostate cancer (PCa) undergoing robot-assisted radical prostatectomy (RARP). Materials and Methods: A retrospective multicenter cohort study of patients with PCa who underwent RARP at 10 institutes in Japan was conducted. This study enrolled 3195 patients. We focused on patients undergoing RARP who underwent the preoperative measurement of their inflammation-related parameters and who did not receive any neo- or adjuvant therapy. Data on the pre- and postoperative variables for the enrolled patients were obtained. The primary endpoint of this study was the association between BCR and the inflammation-related parameters after RARP. The secondary endpoint was the association between the inflammation-related parameters and the pathological diagnosis of PCa. Results: Data from 2429 patients with PCa who met the study's eligibility criteria were analyzed. The median follow-up period was 25.1 months. The inflammation-related parameters were divided into two groups, and cutoff values were determined based on the receiver operating characteristics. There were no statistically significant differences in biochemical recurrence-free survival for any of the parameters. In the univariate analysis, the NLR was predictive of pathological T3 and lymphovascular invasion; however, there were no significant differences in the multivariate analysis. Conclusions: The inflammation-related parameters did not significantly affect the incidence of BCR, at least among patients with PCa who underwent RARP.