Optimal sequential therapy using tyrosine kinase inhibitors as the first-line treatment in patients with metastatic renal cell carcinoma: A nationwide multicenter study.

Objective: The purpose of the study was to identify the best sequence of therapy beginning with a tyrosine kinase inhibitor (TKI) as the first-line therapy for patients with metastatic renal cell carcinoma (mRCC) in terms of overall survival (OS), progression-free survival (PFS), and rates of discontinuation and adverse effects during the treatment period. Methods: This is a retrospective, nationwide multicenter study of patients with mRCC after diagnosis at 10 different tertiary medical centers in Korea from January 1992 to December 2017. We focused on patients at either "favorable" or "intermediate" risk according to the International mRCC Database Consortium criteria, and they were followed up (median 335 days). Finally, a total of 1409 patients were selected as the study population. We generated a Cox proportional hazard model adjusted for covariates, and the different therapy schemes were statistically tested in terms of OS as well as PFS. In addition, frequencies of discontinuation and adverse events were compared among the therapy schemes. Results: Of the primary patterns of treatment sequences (24 sequences), "sunitinib-pazopanib" and "sunitinib-everolimus-immunotherapy" showed the most beneficial results in both OS and PFS with significantly lower hazards than "sunitinib", which is the most commonly treated agent in Korea. Considering that the "TKI-TKI" structure showed relatively higher discontinuation rates with higher adverse effects, the overall beneficial sequence would be "sunitinib-everolimus-immunotherapy". Conclusion: Among several sequential therapy starting with TKIs, "sunitinib-everolimus- immunotherapy" was found to be the best scheme for mRCC patients with "favorable" or "intermediate" risks.

Survival pattern of metastatic renal cell carcinoma patients according to WHO/ISUP grade: a long-term multi-institutional study.

The World Health Organization/International Society of Urological Pathology (WHO/ISUP) grading of renal cell carcinoma (RCC) is classified from grade 1-4, regardless of subtype. The National Comprehensive Cancer Network (NCCN) guidelines (2022) state that if there is an adverse pathological feature, such as grade 3 or higher RCC in stage 1 patients, more rigorous follow-up imaging is recommended. However, the RCC guidelines do not provide specific treatment or follow-up policies by tumor grade. Therefore, this study attempted to find out whether tumor grade affects survival rates in patients with metastatic RCC. The Korean Renal Cancer Study Group (KRoCS) database includes 3108 patients diagnosed with metastatic RCC between September 1992 and February 2017, with treatment methods, progression, and survival data collected from 11 tertiary hospitals. To obtain information on survival rates or causes of death, we utilized the Korea National Statistical Office database and institutional medical records. Data were accessed for research purpose on June, 2023. We then reviewed these sources to gather comprehensive and reliable data on the outcomes of our study cohort. This database was retrospectively analyzed, and out of 3108 metastatic RCC patients, 911 had been identified as WHO/ISUP grade. Grades were classified into either a low-grade (WHO/ISUP grade 1-2) or a high-grade group (WHO/ISUP grade 3-4). The patients were then analyzed related to progression and overall survival (OS). In metastatic clear cell RCC patients, the 1-year OS rate was 69.4% and the median OS was 17.0 months (15.5-18.5) followed up to 203.6 months. When comparing the patient groups, 119 low-grade and 873 high-grade cases were identified. No baseline difference was observed between the two groups, except that the high-grade group had a higher ECOG 1 ratio of 50.4% compared with 34.5% for the low-grade group (p = 0.009). There was a significant difference in OS between high-grade and low-grade groups. OS was 16.0 months (14.6-17.4) in the high-grade group and 28.0 months (21.1-34.9) in the low-grade group (p < 0.001). However, there was no difference in progression-free survival (PFS) rates with 9.0 months (8.0-10.0) for the high-grade group and 10.0 months (6.8-13.2) for the low-grade group (p = 0.377) in first-line treatment. In multivariable analysis, WHO/ISUP grade was a risk factor (HR = 1.511[1.135-2.013], p = 0.005) that influenced the OS. In conclusion, WHO/ISUP grade is a major data source that can be used as a ubiquitous marker of metastatic RCC in pre-IO era. Depending on whether the RCC is high or low grade, the follow-up schedule will need to be tailored according to grade, with higher-grade patients needing more active treatment as it can not only affect the OS in the previously known localized/locoregional recurrence but also the metastatic RCC patient.

Comparison of Short-Term Outcomes and Safety Profiles between Androgen Deprivation Therapy+Abiraterone/Prednisone and Androgen Deprivation Therapy+Docetaxel in Patients with De Novo Metastatic Hormone-Sensitive Prostate Cancer.

PURPOSE: This study aimed to compare the short-term outcomes and safety profiles of androgen-deprivation therapy (ADT)+abiraterone/prednisone with those of ADT+docetaxel in patients with de novo metastatic hormone-sensitive prostate cancer (mHSPC). MATERIALS AND METHODS: A web-based database system was established to collect prospective cohort data for patients with mHSPC in Korea. From May 2019 to November 2022, 928 patients with mHSPC from 15 institutions were enrolled. Among these patients, data from 122 patients who received ADT+abiraterone/prednisone or ADT+docetaxel as the primary systemic treatment for mHSPC were collected. The patients were divided into two groups: ADT+abiraterone/prednisone group (n=102) and ADT+docetaxel group (n=20). We compared the demographic characteristics, medical histories, baseline cancer status, initial laboratory tests, metastatic burden, oncological outcomes for mHSPC, progression after mHSPC treatment, adverse effects, follow-up, and survival data between the two groups. RESULTS: No significant differences in the demographic characteristics, medical histories, metastatic burden, and baseline cancer status were observed between the two groups. The ADT+abiraterone/prednisone group had a lower prostate-specific antigen (PSA) progression rate (7.8% vs. 30.0%; p=0.011) and lower systemic treatment discontinuation rate (22.5% vs. 45.0%; p=0.037). No significant differences in adverse effects, oncological outcomes, and total follow-up period were observed between the two groups. CONCLUSIONS: ADT+abiraterone/prednisone had lower PSA progression and systemic treatment discontinuation rates than ADT+docetaxel. In conclusion, further studies involving larger, double-blinded randomized trials with extended follow-up periods are necessary.

Effect of Diabetes Mellitus on Symptomatic Improvement After Surgery for Benign Prostatic Hyperplasia in Patients With Lower Urinary Tract Symptom and its Relations With Prostatic Urethral Angulation.

PURPOSE: To compare improvement of lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia in diabetic versus nondiabetic patients after transurethral resection of the prostate (TURP) or holmium laser enucleation of the prostate (HoLEP). METHODS: The medical records of 437 patients who underwent TURP or HoLEP at a tertiary referral center from January 2006 to January 2022 were retrospectively analyzed. Among them, 71 patients had type 2 diabetes. Patients in the diabetic mellitus (DM) and non-DM groups were matched 1:1 according to age, baseline International Prostate Symptom Score (IPSS), and ultrasound measured prostate volume. Changes in LUTS were assessed at 3 months after surgery using IPSS and evaluated by categorizing patients according to prostatic urethral angulation (PUA; <50° vs. ≥50°). Medication-free survival after surgery was also investigated. RESULTS: No significant differences were noted between the DM and non-DM groups in baseline characteristics except for comorbidities (i.e., hypertension, cerebrovascular disease, and ischemic heart disease, P=0.021, P=0.002, and P=0.017, respectively) and postvoid residual urine volume (115±98 mL vs. 76±105 mL, P=0.028). Non-DM patients showed significant symptomatic improvement regardless of PUA, while DM patients demonstrated improvement in obstructive symptoms only in those with large PUA (≥51°). Among patients with small PUA, DM patients had worse medication-free survival after surgery compared to controls (P=0.044) and DM was an independent predictor of medication reuse (hazard ratio, 1.422; 95% confidence interval, 1.285-2.373; P=0.038). CONCLUSION: DM patients experienced symptomatic improvement after surgery only in those with large PUA. Among patients with small PUA, DM patients were more likely to reuse medication after surgery.

Risk analysis of metformin use in prostate cancer: a national population-based study.

INTRODUCTION: Various approaches are required to prevent and treat heterogeneity-based prostate cancer. Here, we analyzed the anticancer effects of metformin, which has a good toxicity profile and is inexpensive. METHOD: From January 2010 to December 2019, analysis was conducted retrospectively in a cohort from the National Health Insurance Service database. The wash-out period was set for cancer diagnosis in 2010 and 2011, and subjects (105,279) diagnosed with prostate cancer (ICD C61) from 2012 to 2014 were excluded The final subjects (105,216) were defined as the metformin administration group when they took metformin for 180 days or more from January 2012 to December 2019. The non-metformin group was defined as those who took less than 180 days from January 2012 to December 2019. The prevalence of prostate cancer according to metformin administration and the risk according to the cumulative duration of metformin were analyzed. RESULTS: A total of 105,216 people were included in this study, with 59,844 in the metformin group and 45,372 in the metformin non-administration group. When calculating HRs (Hazard Rate) according to the cumulative period of metformin administration, metformin administration period length was inversely associated with prostate cancer risk (Q2 HR = 0.791 95% CI: 0.773-0.81, Q3 HR = 0.634 95% CI: 0.62-0.649, Q4 HR = 0.571 95% CI: 0.558-0.585). HRs tended to decrease with the cumulative duration of metformin administration. CONCLUSION: This study confirmed that prostate cancer risk decreased with increasing duration of metformin administration. Metformin should be considered as a new strategy in the treatment and prevention of prostate cancer characterized by heterogeneity.

Association between Psychological Suffering and Suicidal Thinking in Patients with Urologic Cancer Using Real-World Data.

Cancer is a leading cause of death in Korea, and depression and suicide are major psychiatric problems in cancer patients. This study aimed to explore the correlation between anxiety, depression, social support, cancer state, and suicidality among urologic cancer patients. Sixty patients with urologic cancer were admitted to a university hospital between October 2019 and February 2020. The patients were evaluated using the Patient Health Questionnaire-9, Generalized Anxiety Disorder 7-item scale, Suicidality module of the Mini International Neuropsychiatric Interview (MINI), and the Lubben Social Network scales (LSNS). To determine which psychological or demographic factors affected suicide risk, Fisher's exact test, Wilcoxon rank-sum test, regression, and logistic regression were conducted. It was found that the greater the depressive symptoms, the higher the suicidal risk (OR = 1.32, 95% CI = 1.08-1.61). Furthermore, anxiety symptoms and the duration of cancer after diagnosis significantly increased depressive symptoms (p = 0.032). Clinicians should be able to identify the risk factors for suicide in patients with cancer, one of which is depression. To assess the risk of suicide, we must evaluate not only depressive symptoms but also the related anxiety and duration of the disease. Prevention and intervention efforts are needed to improve depressive moods and anxiety after cancer diagnosis.

Clinical significance of prostate volume and testosterone reduction on lower urinary tract symptoms in patients with prostate cancer undergoing androgen deprivation therapy.

To investigate the effect of both prostate volume and serum testosterone changes on lower urinary tract symptoms in patients with prostate cancer undergoing androgen deprivation therapy. A total of 167 patients who received androgen deprivation therapy for prostate cancer treatment from January 2010 to August 2020 were enrolled in this retrospective study. Changes in the International Prostate Symptom Score (IPSS) in the patient groups stratified by prostate volume and the amount of testosterone reduction were assessed every 4 weeks until 12 weeks after androgen deprivation therapy initiation. Longitudinal mixed models were used to assess the adjusted effects of prostate volume and testosterone reduction on IPSS change. All mean values of IPSS-total score (IPSS-total), voiding subscore (IPSS-vs), and storage subscore (IPSS-ss) significantly decreased from baseline to week 12 in both patients with small (< 33 mL) and large (≥ 33 mL) prostates. The mean values of IPSS-total, IPSS-vs, and IPSS-ss similarly decreased in patients with large prostate with a baseline IPSS-total of ≥ 13. However, in those with small prostate, IPSS-ss specifically remained unchanged, while IPSS-total and IPSS-vs significantly decreased. In addition, only in patients with small prostate (< 33 mL), patients with lesser testosterone reduction (< Δ400 ng/dL) showed greater improvement in IPSS-ss by 7.5% compared with those with greater testosterone reduction (≥ Δ400 ng/dL). In conclusion, although androgen deprivation therapy generally improves lower urinary tract symptoms, it may worsen specifically storage symptoms in patients with relatively small prostate and greater testosterone reduction. Our finding suggests that testosterone may influence lower urinary tract symptoms in these patients.

The Relationships between Abnormal Serum Lipid Levels, Depression, and Suicidal Ideation According to Sex.

(1) Background: Serum lipid levels affect not only nutritional status but also emotional state. The purpose of this study was to examine the effects of various socio-demographic characteristics, abnormal cholesterol levels, and BMI indicators on depressive symptoms and suicidal ideation in the Korean population. (2) Methods: A total of 23,692 people were surveyed using data from the Korea National Health and Nutrition Examination Survey (KNHNES) 2014, 2016, and 2018. Data from 11,653 patients were analyzed. Age, sex, chronic disease, smoking, alcohol consumption, total cholesterol (HDL, triglycerides), BMI, depression, and suicidal ideation were measured. (3) Results: According to sex, low HDL, high triglycerides, and suicidal ideation were significant, along with low education level, smoking, binge drinking, and high BMI. High triglyceride level was shown to significantly increase the risk of depression in males (OR = 1.535, 95% CI = 1.098-2.147). Factors affecting suicidal ideation in males were age, binge drinking, and depression, while blood lipid factors were not significant. (4) Conclusions: Of the types of serum lipid factors affecting depression and suicidal ideation, high triglycerides were found to be a risk factor for depression in men. Serum lipids can be used as biomarkers to reflect depressive symptoms in men depending on cholesterol level.

Efficacy of phosphodiesterase type 5 inhibitors in patients with erectile dysfunction after nerve-sparing radical prostatectomy: a systematic review and meta-analysis.

Background: Nerve-sparing radical prostatectomy (NSRP) had to be performed because approximately 94% of patients are diagnosed with localized prostate cancer (PCa). Although NSRP is generally done to improve functional outcomes, erectile dysfunction (ED) is one of the most prevailing complications after radical prostatectomy (RP). Phosphodiesterase type 5 inhibitors (PDE5-Is) are the most well-known treatment agent for postoperative ED. This study aimed to assess the efficacy of PDE5-Is in patients with ED after NSRP. Methods: In this systematic literature review, randomized controlled trials on the efficacy and safety of PDE5-Is in patients who underwent NSRP were searched in MEDLINE, EMBASE, and the Cochrane Controlled Trials Register using the OVID platform. This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Cochrane Review Methods. The quality of the evidence of the outcome data was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. Results: A total of 14 trials involving 2,822 patients were included. Significant improvements in the International Index of Erectile Function-Erectile Function (IIEF) domain score [mean difference (MD) =4.93; 95% confidence interval (CI): 4.14-5.71; P<0.00001] and erectile function recovery events [odds ratio (OR) =2.06; 95% CI: 1.45-2.94; P<0.0001] were observed after PDE5-I treatment. A higher positive response to Sexual Encounter Profile (SEP) question 2 (OR =2.27; 95% CI: 1.80-2.86; P<0.00001) and question 3 (OR =2.78; 95% CI: 1.97-3.91; P<0.00001) was also found after PDE5-I treatment. However, the incidence of treatment-emergent adverse events (TEAEs) was higher after PDE5-I treatment than after placebo treatment (OR =2.91; 95% CI: 1.84-4.61). Furthermore, the incidence of headache (OR =3.38; 95% CI: 2.40-4.75) and flushing (OR =9.44; 95% CI: 4.30-20.70) was also significantly higher after PDE5-I treatment (P<0.00001). In terms of the quality of the evidence of the outcome data, inconsistency problems were detected in all outcomes and imprecision problems in most outcomes. Discussion: PDE5-I treatment was more effective to placebo treatment in patients with ED after NSRP. No clinically serious complications were found in spite of the incidence of TEAEs being higher after PDE5-I treatment.

CYLD destabilizes NoxO1 protein by promoting ubiquitination and regulates prostate cancer progression.

The NADPH oxidase (Nox) family of enzymes is solely dedicated in the generation of reactive oxygen species (ROS). ROS generated by Nox are involved in multiple signaling cascades and a myriad of pathophysiological conditions including cancer. As such, ROS seem to have both detrimental and beneficial roles in a number of cellular functions, including cell signaling, growth, apoptosis and proliferation. Regulatory mechanisms are required to control the activity of Nox enzymes in order to maintain ROS balance within the cell. Here, we performed genome-wide screening for deubiquitinating enzymes (DUBs) regulating Nox organizer 1 (NoxO1) protein expression using a CRISPR/Cas9-mediated DUB-knockout library. We identified cylindromatosis (CYLD) as a binding partner regulating NoxO1 protein expression. We demonstrated that the overexpression of CYLD promotes ubiquitination of NoxO1 protein and reduces the NoxO1 protein half-life. The destabilization of NoxO1 protein by CYLD suppressed excessive ROS generation. Additionally, CRISPR/Cas9-mediated knockout of CYLD in PC-3 cells promoted cell proliferation, migration, colony formation and invasion in vitro. In xenografted mice, injection of CYLD-depleted cells consistently led to tumor development with increased weight and volume. Taken together, these results indicate that CYLD acts as a destabilizer of NoxO1 protein and could be a potential tumor suppressor target for cancer therapeutics.

The association between family history of prostate cancer and development of prostate cancer among Korean population: A prospective cohort study using KoGES data.

ABSTRACT: This study aimed to assess the impact of family history (FH) on prostate cancer (PCa) development among a general Korean population. We conducted a prospective cohort study based on the registry records of 211,789 participants in the database of the Korean Genome and Epidemiology Study from 2001 to 2013. A total of 69,693 men with appropriate records were evaluated by being categorizing into 2 groups; a PCa group (100) and control group (69,593). FH of PCa was also categorized as FH of total, father, or brother. Odds ratios (ORs) of PCa development were calculated by using stratified logistic regression models. The adjusted OR of PCa history of father was 27.7 (95% confidence interval [CI] = 9.7-79.2, P < .001) in PCa patients compared to control, and that of PCa history of brother was 15.8 (95% CI = 3.6-69.6, P < .001). Among the adjusted variables, age (OR, 1.17; 95% CI, 1.14-1.21; P < .001), and hyperlipidemia (OR, 2.25; CI, 1.32-3.84; P = .003) were also identified as significant predictors of PCa development. There was no difference in the impact of FH on PCa development between different age groups at PCa diagnosis (<60 vs ≥60 years). To our knowledge, this study represents the first prospective cohort study based on the registry data of a Korean population showing the significance of FH on PCa development. Additionally, the effect of FH on the early onset of PCa has not been confirmed in our analysis.

A Novel Kinase Inhibitor AX-0085 Inhibits Interferon-γ-Mediated Induction of PD-L1 Expression and Promotes Immune Reaction to Lung Adenocarcinoma Cells.

In this study, we describe a novel kinase inhibitor AX-0085 which can suppress the induction of PD-L1 expression by Interferon-γ (IFN-γ) in lung adenocarcinoma (LUAD) cells. AX-0085 effectively blocks JAK2/STAT1 signaling initiated by IFN-γ treatment and prevents nuclear localization of STAT1. Importantly, we demonstrate that AX-0085 reverses the IFN-γ-mediated repression of T cell activation in vitro and enhances the anti-tumor activity of anti-PD-1 antibody in vivo when used in combination. Finally, transcriptomic analyses indicated that AX-0085 is highly specific in targeting the IFN-γ-pathway, thereby raising the possibility of applying this reagent in combination therapy with checkpoint inhibitor antibodies. It may be particularly relevant in cases in which PD-L1-mediated T cell exhaustion leads to immunoevasive phenotypes.

Intravenous Iron Isomaltoside 1000 Reduces Postoperative Anemia in Patients Undergoing Elective Urologic Surgery and Those with Urosepsis.

PURPOSE: Postoperative anemia is associated with increased morbidity and mortality in patients undergoing surgery. Anemia is also a common feature during sepsis. Therefore, here, we aimed to investigate the safety and efficacy of intravenous iron isomaltoside 1000 (Monofer®) in patients undergoing elective urologic surgery and in those with urosepsis. MATERIALS AND METHODS: This multicenter study was conducted through the review of the medical records of patients with postoperative anemia undergoing elective urologic surgery or with urosepsis in a multicenter hospital. Patients received a single intravenous iron isomaltoside (IIM), and their hemoglobin (Hb) level was evaluated before and after administration of IIM. Safety data included adverse effects and hypersensitivity reactions. In addition, the patients were divided into three groups (200 mg, 400 mg, and 600 mg IIM) to compare Hb changes before and after the administration of IIM. RESULTS: The study analyzed 52 men and 30 women with a mean age of 67 years. There was a significant difference between pre-treatment Hb and post-treatment Hb according to the type of the surgery after administration (p=0.01) of IIM in patients with postoperative anemia, and the mean preoperative Hb before IIM administration was 8.5 g/dL and that after IIM administration was 9.9 g/dL (p=0.006) in patients with urosepsis. The mean preoperative Hb changed from 10 g/dL to 11 g/dL after administration (p<0.001) of IIM in the whole cohort. There were no side effects due to the administration of intravenous IIM. CONCLUSION: A single perioperative intravenous injection of IIM 1000 significantly increased the Hb level in patients with anemia who underwent urologic elective surgery. Moreover, this treatment can be considered to have potential clinical benefits for anemia caused by sepsis.

Do Lifestyle Factors Affect Lower Urinary Tract Symptoms? Results from the Korean Community Health Survey.

PURPOSE: To evaluate the relationships between lower urinary tract symptoms (LUTS) and lifestyle factors (physical activity, smoking, alcohol consumption, body mass index, and stress) in Korean men. METHODS: We analyzed the survey results of South Korean men (n=64,439) who were 40 years of age or older among whom interviews were conducted using questionnaires. Trained interviewers performed face-to-face surveys using computer-assisted personal interviewing, the International Prostate Symptom Score (IPSS), and standard questions. We assessed the relationships of lifestyle factors (physical activity, cigarette smoking, alcohol intake, height, weight, and stress) with LUTS. RESULTS: We observed higher IPSS scores in participants who engaged in no exercise (n=46,008 [71.7%], IPSS=3.19±5.36) than in those who engaged in vigorous physical activity (n=10,657 [17.6%], IPSS=2.28±4.15). Former smokers showed higher total, storage, and voiding symptom IPSS scores than current smokers and nonsmokers. Nondrinkers had higher IPSS scores than current alcohol drinkers. In multivariable logistic regression analysis, we detected no relationship between LUTS and current alcohol drinking in the moderate and severe LUTS groups, using the mild LUTS group as a reference (moderate: 0.91; 95% confidence interval [CI], 0.91-0.91; P<0.001, severe: 0.78; 95% CI, 0.78-0.78; P<0.001). Participants with moderate to severe stress showed higher total IPSS scores than those with no or mild stress (3.38±5.77 vs. 2.88±4.90), with significant relationships between stress and LUTS found in the moderate and severe LUTS groups. In logistic regression analysis, stronger relationships were found for storage and voiding symptoms in the moderate and severe stress groups compared to the mild stress group. CONCLUSION: A history of smoking, low levels of physical activity, low body mass index, and moderate to severe stress were associated with a greater severity of LUTS. Moderate to severe stress was also related to voiding symptoms. However, there was no association between alcohol intake and LUTS severity.

Correction: A genetic variant in SLC28A3, rs56350726, is associated with progression to castration-resistant prostate cancer in a Korean population with metastatic prostate cancer.

[This corrects the article DOI: 10.18632/oncotarget.18298.].

Effect of highly concentrated hyaluronic acid/chondroitin sulphate instillation on ureteric stent-induced discomfort after ureteroscopic lithotripsy: a multicentre randomised controlled pilot study.

OBJECTIVE: To investigate the effectiveness and safety of instilling highly concentrated hyaluronic acid (HA)/chondroitin sulphate (CS) on ureteric stent-related pain, urinary symptoms, and quality of life (QoL) of patients who underwent ureteroscopic lithotripsy for ureteric stones followed by ureteric stent placement. PATIENTS AND METHODS: Eligible patients were randomly allocated to receive intravesical instillation with HA/CS or normal saline just after ureteric stent placement. Just before stent removal on postoperative day 7, the patients completed the Ureteric Stent Symptom Questionnaire (USSQ), International Prostate Symptom Score (IPSS) QoL question, and a pain visual analogue scale (VAS). RESULTS: In total, 92 patients (46 each in the treatment and control arms) completed the study. The groups did not differ in terms of age or stent indwelling time. Compared with the control group, the treatment group had significantly lower USSQ urinary symptom domain scores (24.6 vs 32.5; P < 0.001), better IPSS QoL scores (3.5 vs 4.4, P = 0.018), and lower VAS pain scores (2.0 vs 3.2; P < 0.001). They also had lower total body pain subscores (16.7 vs 22.0; P = 0.01) and lower additional pain subscores due to urinary tract infections (2.1 vs. 3.2; P = 0.01) in the USSQ. CONCLUSIONS: Highly concentrated HA/CS effectively improved urinary symptoms and pain, and reduced the need for additional medication or procedures after ureteric stent placement.

Do additional cores from cancer-suspicious lesions on transrectal ultrasound improve prostate cancer detection including index tumors over 12-core systematic biopsy?

OBJECTIVE: The efficacy of additional cores from cancer-suspicious lesions by transrectal ultrasound (TRUS) for the detection of prostate cancer (PCa) was assessed. MATERIALS AND METHODS: Data were collected from 4144 men who underwent systematic 12-core biopsy with no cancer-suspicious lesions (Group A: 3256 cases) or 13- or more-core (systematic 12 core + additional cores) biopsy with cancer-suspicious lesions (Group B: 888 cases) on TRUS-guided biopsy. The effect of additional biopsy cores on the cancer detection rate was investigated. RESULTS: PCa was detected in 1006 (30.9%) cases in Group A and 485 (54.6%) cases in Group B (p < 0.001). In 370/485 (76.3%) patients in Group B, cancer was detected from the additional cores from TRUS suspicious lesions. Logistic regression analysis showed that the number of biopsy cores was the most significant factor for cancer detection (hazards ratio: 2.6 [2.221-3.043], p < 0.001]. Additional core biopsies did not increase the detection rate of index tumors (p < 0.001). However, the Gleason score of index tumors was higher than that of systematic cores (p < 0.001). Kaplan-Meier analysis showed no significant differences in survival according to biopsy number and location of index tumors (log-rank test: p = 0.583, p = 0.165, respectively). CONCLUSION: Although additional core biopsies can increase the cancer detection rate, they do not increase the detection rate of index tumors. Biopsy core number and the location of index tumors had no effect on biochemical outcomes.

Effect of Starting Penile Rehabilitation with Sildenafil Immediately after Robot-Assisted Laparoscopic Radical Prostatectomy on Erectile Function Recovery: A Prospective Randomized Trial.

PURPOSE: It has not been clearly proved in real practice whether early rehabilitation with phosphodiesterase type 5 inhibitors starting immediately after radical prostatectomy improves erectile function recovery more effectively than delayed treatment with the same regimen. We performed a prospective randomized trial to identify this. MATERIALS AND METHODS: Patients with prostate cancer and an IIEF-5 (International Index of Erectile Function-5) preoperative score of 17 or greater were randomly assigned to receive sildenafil 100 mg regularly twice per week for 3 months immediately after urethral catheter removal as the early group or only 3 months after nerve sparing robot-assisted laparoscopic radical prostatectomy as the delayed group. The study primary end point was the full erectile function recovery rate, defined as an IIEF-5 score of 17 or greater, during the 12 months. RESULTS: Of the 120 randomized patients the proportion who achieved full recovery was significantly higher during the 12 months in the early group than in the delayed group (ß = 0.356, p <0.001, generalized estimating equation). After 9 months postoperatively the proportion of patients who achieved full recovery steadily increased to 41.4% at 12 months in the early group while patients in the delayed group showed no further improvement. Thus, full recovery was achieved in only 17.7% of patients at 12 months. Only early sildenafil treatment independently improved full recovery at 12 months (HR 2.943, p = 0.034). CONCLUSIONS: Our trial provides clinical data to suggest that earlier rehabilitation with phosphodiesterase type 5 inhibitors can contribute to the recovery of erectile function after radical prostatectomy in the clinical setting.

The effect of onabotulinumtoxinA according to site of injection in patients with overactive bladder: a systematic review and meta-analysis.

PURPOSE: This study assessed the efficacy and safety of onabotulinumtoxinA according to injection site for treatment of overactive bladder. METHODS: A systematic literature review located randomized controlled trials of onabotulinumtoxinA treatment for neurogenic detrusor overactive bladder and idiopathic overactive bladder in adults. We searched MEDLINE, EMBASE, and the Cochrane Controlled Trials Register using the Ovid platform. Meta-analysis was based on Cochrane Review Methods. RESULTS: Eight studies (419 participants) were included. Trigone-including injection demonstrated a significant improvement in symptom score (SMD = - 0.53, 95% CI - 1.04 to - 0.02, P = 0.04, I 2 = 78%), higher complete dryness rates (OR = 2.19 patients, 95% CI 1.32-3.63, P = 0.002, I 2 = 41%), and lower frequency of incontinence episodes (WMD = - 0.85 per day, 95% CI - 1.55 to - 0.16, P = 0.02, I 2 = 87%) in patients. Comparing trigone-including injection to trigone-sparing injection, lower detrusor pressure (WMD = - 2.55 cm H2O, 95% CI - 4.16 to - 0.95, P = 0.002, I 2 = 0%) and higher volume at first desire to void (WMD = 17.54 ml, 95% CI 1.00-34.07, P = 0.04, I 2 = 0%) were observed with trigone-including injection. Between intradetrusor and suburothelial injection sites, there were no differences in efficacy or safety regarding the incidence of vesicoureteral reflux, hematuria, general weakness, bladder discomfort, large post-void residual, and urinary tract infection. CONCLUSION: Trigone-including onabotulinumtoxinA injection has superior efficacy to trigone-sparing injection without increased complications. The depth of injection does not influence the efficacy or safety of onabotulinumtoxinA.

A genetic variant in SLC28A3, rs56350726, is associated with progression to castration-resistant prostate cancer in a Korean population with metastatic prostate cancer.

Background: Genetic variation which related with progression to castration-resistant prostate cancer (CRPC) during androgen-deprivation therapy (ADT) has not been elucidated in patients with metastatic prostate cancer (mPCa). Therefore, we assessed the association between genetic variats in mPCa and progession to CRPC. Results: Analysis of exome genotypes revealed that 42 SNPs were significantly associated with mPCa. The top five polymorphisms were statistically significantly associated with metastatic disease. In addition, one of these SNPs, rs56350726, was significantly associated with time to CRPC in Kaplan-Meier analysis (Log-rank test, p = 0.011). In multivariable Cox regression, rs56350726 was strongly associated with progression to CRPC (HR = 4.172 95% CI = 1.223-14.239, p = 0.023). Materials and Methods: We assessed genetic variation among 1000 patients with PCa with or without metastasis, using 242,221 single nucleotide polymorphisms (SNPs) on the custom HumanExome BeadChip v1.0 (Illuminam Inc.). We analyzed the time to CRPC in 110 of the 1000 patients who were treated with ADT. Genetic data were analyzed using unconditional logistic regression and odds ratios calculated as estimates of relative risk of metastasis. We identified SNPs associated with metastasis and analyzed the relationship between these SNPs and time to CRPC in mPCa. Conclusions: Based on a genetic variation, the five top SNPs were observed to associate with mPCa. And one (SLC28A3, rs56350726) of five SNP was found the association with the progression to CRPC in patients with mPCa.