Neoadjuvant Nivolumab Plus Gemcitabine/Cisplatin Chemotherapy in Muscle-Invasive Urothelial Carcinoma of the Bladder / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#The activity and safety of neoadjuvant nivolumab plus gemcitabine/cisplatin (N+GC) were tested in patients with muscle-invasive bladder urothelial carcinoma (MIBC). @*Materials and Methods@#In a prospective phase II trial, patients with cT2-T4a N0 MIBC who were eligible for cisplatin and medically appropriate to undergo radical cystectomy (RC) were enrolled. Treatment with nivolumab 3 mg/kg on days 1 and 15 plus GC (cisplatin 70 mg/m2 on day 1, and gemcitabine 1,000 mg/m2 on days 1, 8, and 15) was repeated every 28 days up to 3 or 4 cycles, depending on the surgery schedules. The primary endpoint was pathologic complete response (pCR, ypT0). Secondary endpoints included pathologic downstaging (≤ ypT1), disease-free survival (DFS), and safety. @*Results@#Between September 2019 and October 2020, 51 patients were enrolled. Neoadjuvant N+GC was well tolerated. Among 49 patients who completed neoadjuvant N+GC, clinical complete response (cCR) was achieved in 59% of intent-to-treat (ITT) population. RC was performed in 34 (69%) patients. pCR was achieved in 24% (12/49) of ITT population and 35% (12/34) of RC patients. Median DFS was not reached. Over a median follow-up of 24 months, 12 patients experienced disease recurrence and were treated with palliative therapy or surgery. Although 12 patients declined surgery and were treated with concurrent chemoradiotherapy, DFS was longer in patients with cCR after neoadjuvant therapy than those without. Preoperative programmed death-ligand 1 (PD-L1) did not correlate with pCR or pathologic downstaging rates. @*Conclusion@#Neoadjuvant N+GC was feasible and provided meaningful pathologic responses in patients with MIBC, regardless of baseline PD-L1 expression (ONO-4538-X41; CRIS.nih.go.kr, KCT0003804).

Clinical Utility of Combining Prostate Health Index and PI-RADS Version 2 to Improve Detection of Clinically Significant Prostate Cancer

Purpose@#To evaluate the performance of combining prostate health index (PHI) and Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) for detection of clinically significant prostate cancer (csPCa). @*Materials and Methods@#We retrospectively reviewed patients who underwent prostate biopsy for elevated prostate-specific antigen (PSA) ≥2.5 ng/mL and/or abnormal digital rectal examination. Serum markers for PSA, free PSA (fPSA), and [-2] proPSA (p2PSA) were measured, and PHI was calculated as ([p2PSA/fPSA]×[PSA]1/2). Multiparametric magnetic resonance imaging was performed using a 3.0T scanner and scored using PI-RADSv2. csPCa was defined as either grade group (GG) ≥2 disease or GG1 cancer detected in >2 cores or >50% of positive on biopsy. Univariable and multivariable logistic regression modelling, along with receiver-operating characteristic (ROC) curve analysis was used to predict the probability of csPCa. @*Results@#Of the total 358 patients, 159 (44.4%) were diagnosed with csPCa. On univariable analysis, age, PSA density (PSAD), PHI and PI-RADSv2 were associated with csPCa. The area under the ROC curve (AUC) of baseline model incorporating age and PSAD was 0.663. The AUC of combining PHI and PI-RADSv2 to baseline model was higher than that of PHI alone to baseline model (0.884 vs. 0.807, p<0.0001) and PI-RADSv2 alone to baseline model (0.884 vs. 0.846, p=0.0002), respectively. If biopsy was restricted to patients with PI-RADS 5 as well as PI-RADS 3 or 4 and PHI ≥27, 36.0% of unnecessary biopsy could be avoided at the cost of missing 4.7% of csPCa. @*Conclusions@#The combination of PHI and PI-RADSv2 to baseline model incorporating age and PSAD had higher accuracy for detection of csPCa compared with PHI or PI-RADSv2 alone.

Predictive Factors for Acute Urinary Retention After Transperineal Template-Guided Mapping Biopsy

Purpose@#We investigated the predictive factors for acute urinary retention (AUR) after transperineal template-guided mapping biopsy (TTMB). @*Materials and Methods@#We retrospectively reviewed the records of 459 patients who had undergone TTMB between May 2017 and July 2020. Overall complications after TTMB were analyzed and categorized according to the Clavien-Dindo classification. Factors that were likely to affect AUR were analyzed using a logistic regression model. @*Results@#Overall complications after TTMB were observed in 95 of the 459 patients (20.7%), of which AUR was the most commonly reported (17.4%, n=80), followed by hematuria (3.1%, n=14). Hematuria in one patient was categorized as Clavien-Dindo grade IIIa. All remaining complications were Clavien-Dindo grade I. In the multivariate regression model, age ≥65 (odds ratio, 2.44; 95% confidence interval [CI], 1.42–4.17; p=0.001), prostate volume ≥30 mL (odds ratio, 3.72; 95% CI, 1.19–11.62; p<0.02), and number of biopsy cores ≥30 (odds ratio, 2.89; 95% CI, 1.29–6.43; p=0.01) were identified as the predictors for AUR after TTMB. @*Conclusions@#AUR is the most common complication after TTMB. Age ≥65 years, prostate volume ≥30 mL, and number of biopsy cores ≥30 were significant predictors of AUR following TTMB.

Perioperative and Oncological Outcomes of 1,002 Consecutive Patients With Localized Renal Cell Carcinoma Treated by Robotic Partial Nephrectomy at a Single Center

Purpose@#To analyze and compare the results of robotic partial nephrectomy (RPN) at a single center with the previous large-scale studies in terms of perioperative and oncological outcomes. @*Materials and Methods@#We retrospectively evaluated 1,013 cases of RPN in our center database from December 2008 to August 2018. Total 11 cases were excluded in final analysis. We evaluated perioperative outcomes as the Trifecta achievement, which is defined as no positive surgical margin (PSM), no perioperative complications greater than Clavien-Dindo classification I and a warm ischemia time of <25 minutes. In addition, we analyzed pathological and oncological outcomes; recurrence, metastasis, all-cause deaths, cancer-specific deaths, and 5-year survival rates. @*Results@#In 1,002 cases, the Trifecta achievement was 61.1% (n=612). The postoperative complication was 18.4% (n=184) but most were grade 2 or less (14.9%, n=145). Ninety-three cases (9.28%) had benign and 907 cases (90.5%) had malignant pathologies. A local recurrence were 14 cases (1.54%) and distant metastasis were 20 cases (2.2%) during follow-up periods. Allcause death rate was 1.2% (n=11) and cancer-specific death rate was 0.2% (n=2). The median follow-up period was 39 months. A 5-year recurrence-free survival rate, cancer-specific survival rate, and overall survival rate were 95.2%, 99.7%, and 98.4%. @*Conclusions@#In summary, our data shows comparable perioperative outcomes to other largescale studies of RPN in terms of the Trifecta achievement with similar baseline characteristics. In terms of oncological outcomes, there was lower rate of PSM and similar recurrence free survival rate.

Effects of Complete Bladder Cuff Removal on Oncological Outcomes Following Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#This study aimed to evaluate the effects of bladder cuff method on oncological outcomes in patients who underwent radical nephroureterectomy (RNU) for upper tract urothelial carcinoma. @*Materials and Methods@#The records of 1,095 patients treated with RNU performed at our hospital between 1994 and 2018 were retrospectively reviewed; 856 patients with no bladder tumor history were enrolled in the present study. The management of bladder cuff was divided into two categories: extravesical ligation (EL) or transvesical resection (TR). Survival was analyzed using the Kaplan-Meier method and Cox regression analyses were performed to determine which factors were associated with intravesical recurrence (IVR)–free survival (IVRFS), cancer-specific survival (CSS), and overall survival (OS). @*Results@#The mean patient age was 64.8 years and the median follow-up was 37.7 months. Among the 865 patients, 477 (55.7%) underwent the TR and 379 (44.3%) the EL. Significantly higher IVRFS (p=0.001) and OS (p=0.013) were observed in the TR group. In multivariable analysis, IVR, CSS, and OS were independently associated with the EL. Among 379 patients treated with the EL, eight underwent remnant ureterectomy. Based on radical cystectomy–free survival, significant difference was not observed between the two groups. However, significantly higher IVRFS was observed in the TR group when the tumor was located in the renal pelvis. @*Conclusion@#Intramural complete excision of the distal ureter during RNU should be the gold standard approach compared with EL for the management of distal ureter in terms of oncological outcomes.

Effects of Complete Bladder Cuff Removal on Oncological Outcomes Following Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#This study aimed to evaluate the effects of bladder cuff method on oncological outcomes in patients who underwent radical nephroureterectomy (RNU) for upper tract urothelial carcinoma. @*Materials and Methods@#The records of 1,095 patients treated with RNU performed at our hospital between 1994 and 2018 were retrospectively reviewed; 856 patients with no bladder tumor history were enrolled in the present study. The management of bladder cuff was divided into two categories: extravesical ligation (EL) or transvesical resection (TR). Survival was analyzed using the Kaplan-Meier method and Cox regression analyses were performed to determine which factors were associated with intravesical recurrence (IVR)–free survival (IVRFS), cancer-specific survival (CSS), and overall survival (OS). @*Results@#The mean patient age was 64.8 years and the median follow-up was 37.7 months. Among the 865 patients, 477 (55.7%) underwent the TR and 379 (44.3%) the EL. Significantly higher IVRFS (p=0.001) and OS (p=0.013) were observed in the TR group. In multivariable analysis, IVR, CSS, and OS were independently associated with the EL. Among 379 patients treated with the EL, eight underwent remnant ureterectomy. Based on radical cystectomy–free survival, significant difference was not observed between the two groups. However, significantly higher IVRFS was observed in the TR group when the tumor was located in the renal pelvis. @*Conclusion@#Intramural complete excision of the distal ureter during RNU should be the gold standard approach compared with EL for the management of distal ureter in terms of oncological outcomes.

Predictive Factors for Acute Urinary Retention After Transperineal Template-Guided Mapping Biopsy

Purpose@#We investigated the predictive factors for acute urinary retention (AUR) after transperineal template-guided mapping biopsy (TTMB). @*Materials and Methods@#We retrospectively reviewed the records of 459 patients who had undergone TTMB between May 2017 and July 2020. Overall complications after TTMB were analyzed and categorized according to the Clavien-Dindo classification. Factors that were likely to affect AUR were analyzed using a logistic regression model. @*Results@#Overall complications after TTMB were observed in 95 of the 459 patients (20.7%), of which AUR was the most commonly reported (17.4%, n=80), followed by hematuria (3.1%, n=14). Hematuria in one patient was categorized as Clavien-Dindo grade IIIa. All remaining complications were Clavien-Dindo grade I. In the multivariate regression model, age ≥65 (odds ratio, 2.44; 95% confidence interval [CI], 1.42–4.17; p=0.001), prostate volume ≥30 mL (odds ratio, 3.72; 95% CI, 1.19–11.62; p<0.02), and number of biopsy cores ≥30 (odds ratio, 2.89; 95% CI, 1.29–6.43; p=0.01) were identified as the predictors for AUR after TTMB. @*Conclusions@#AUR is the most common complication after TTMB. Age ≥65 years, prostate volume ≥30 mL, and number of biopsy cores ≥30 were significant predictors of AUR following TTMB.

Perioperative and Oncological Outcomes of 1,002 Consecutive Patients With Localized Renal Cell Carcinoma Treated by Robotic Partial Nephrectomy at a Single Center

Purpose@#To analyze and compare the results of robotic partial nephrectomy (RPN) at a single center with the previous large-scale studies in terms of perioperative and oncological outcomes. @*Materials and Methods@#We retrospectively evaluated 1,013 cases of RPN in our center database from December 2008 to August 2018. Total 11 cases were excluded in final analysis. We evaluated perioperative outcomes as the Trifecta achievement, which is defined as no positive surgical margin (PSM), no perioperative complications greater than Clavien-Dindo classification I and a warm ischemia time of <25 minutes. In addition, we analyzed pathological and oncological outcomes; recurrence, metastasis, all-cause deaths, cancer-specific deaths, and 5-year survival rates. @*Results@#In 1,002 cases, the Trifecta achievement was 61.1% (n=612). The postoperative complication was 18.4% (n=184) but most were grade 2 or less (14.9%, n=145). Ninety-three cases (9.28%) had benign and 907 cases (90.5%) had malignant pathologies. A local recurrence were 14 cases (1.54%) and distant metastasis were 20 cases (2.2%) during follow-up periods. Allcause death rate was 1.2% (n=11) and cancer-specific death rate was 0.2% (n=2). The median follow-up period was 39 months. A 5-year recurrence-free survival rate, cancer-specific survival rate, and overall survival rate were 95.2%, 99.7%, and 98.4%. @*Conclusions@#In summary, our data shows comparable perioperative outcomes to other largescale studies of RPN in terms of the Trifecta achievement with similar baseline characteristics. In terms of oncological outcomes, there was lower rate of PSM and similar recurrence free survival rate.

Efficacy and Safety of Naftopidil in Patients With Neurogenic Lower Urinary Tract Dysfunction: An 8-Week, Active-Controlled, Stratified-Randomized, Double-Blind, Double-Dummy, Parallel Group, Noninferiority, Multicenter Design / 대한배뇨장애요실금학회지

Purpose@#The aim of this study was to evaluate the efficacy and safety of naftopidil compared with tamsulosin in patients with neurogenic lower urinary tract dysfunction (LUTD). @*Methods@#This study was conducted as an 8-week, active-controlled, stratified-randomized, double-blind, double-dummy, parallel group, noninferiority, and multicenter clinical trial. After 2 weeks of screening, eligible subjects were randomly assigned to receive naftopidil (25 mg for 1 week followed by 75 mg for 7 weeks) or tamsulosin (0.2 mg for 8 weeks). Primary endpoint was a change of International Prostatic Symptom Score (IPSS) total score after 8 weeks of treatment. @*Results@#One hundred ninety-four subjects with neurogenic LUTD were included into this trial. There were no differences between the 2 groups in baseline characteristics, including urodynamic study results, subtype of LUTD, pretreatment and concomitant medication, and causes of neurogenic bladder. The medication compliance rate was 94.0% (naftopidil, 93.6%; tamsulosin, 94.4%). There was a statistically significant decrease of IPSS total score at 8 weeks versus baseline in both the naftopidil (-5.64±0.66) and tamsulosin (-6.53±0.65) groups (P<0.0001 each). The mean difference between both groups was 0.89 (upper limit of 95% confidential interval, 2.72), which was lower than the noninferiority limit of 3 points. A subgroup analysis of neurologic lesions and sex found no mean difference of IPSS total score in each group. There was also no difference in safety profiles, including treatment emergent adverse events. @*Conclusions@#Naftopidil was not inferior to tamsulosin as a therapeutic drug for patients with neurogenic LUTD and had a similar safety profile.

Strategy for Prostate Cancer Patients with Low Prostate Specific Antigen Level (2.5 to 4.0 ng/mL)

Background@#To evaluate the strategy for detection of prostate cancer (PCa) with low prostate specific antigen (PSA) level (2.5–4.0 ng/mL), prostate biopsy patients with low PSA were assessed. We evaluated the risk of low PSA PCa and the strategy for screening low-PSA patients. @*Methods@#We retrospectively analyzed the patients who underwent prostate biopsy with low PSA level. Baseline characteristics, PSA level before prostate biopsy, prostate volume, prostate specific antigen density (PSAD), and pathological data were assessed. @*Results@#Among the 1986 patients, 24.97% were diagnosed with PCa. The PSAD was 0.12 ± 0.04 ng/mL2 in the PCa-diagnosed group and 0.10 ± 0.04 ng/mL2 in non-cancer-diagnosed group (P < 0.001). Of the 496 patients diagnosed with PCa, 302 (60.89%) were in the intermediate- or high-risk group. PSAD was 0.13 ± 0.04 ng/mL2 in the intermediate- or highrisk group and 0.11 ± 0.03 ng/mL2 in the very low- and low-risk group (P < 0.001). Of 330 patients who underwent radical prostatectomy, 85.15% were diagnosed as having significant cancer. There was significant correlation between PSAD and PCa (r = 0.294, P < 0.001).PSAD with a specificity of 80.00% of a clinically significant cancer diagnosis was assessed at 0.1226 ng/mL2 . @*Conclusion@#The PCa detection rate in the low-PSA group was not lower than that of previous studies of patients with PSA from 4.0 to 10.0 ng/mL. Further, it may be helpful to define a strategy for PCa detection using PSAD in the low-PSA group.

Node-Positive Bladder Cancer After Neoadjuvant Chemotherapy Followed by Radical Cystectomy: A Single-Center Retrospective Study

Purpose@#There remains a lot of unmet need to increase understanding of node-positive (ypN+) muscle invasive bladder cancer (MIBC) after neoadjuvant chemotherapy and radical cystectomy to decide the appropriate therapeutics. @*Materials and Methods@#In a retrospective study using the center cancer chemotherapy registry, we found 113 MIBC patients who were treated with neoadjuvant chemotherapy involving gemcitabine and cisplatin (GP) followed by radical cystectomy between 2010 and 2014. Disease-free survival (DFS) and overall survival (OS) were compared according to the pathologic node positivity (ypN- vs. ypN+). Among a total of 165 patients with MIBC who received neoadjuvant chemotherapy involving GP, 118 underwent radical cystectomy. In 46 patients with ypN+ disease, DFS and OS were evaluated according to administration of adjuvant GP. @*Results@#After neoadjuvant chemotherapy and radical cystectomy, 41% of patients had ypN+ disease, which showed significantly shorter DFS (median, 7.4 months; 95% confidence interval [CI], 5.3–9.6 months) and OS (median, 20.0 months; 95% CI, 13.4–26.6 months) compared to those with ypN- disease. The patients with ypN+ disease had a high risk of recurrence or death, regardless of the administration of adjuvant chemotherapy or adjuvant regimen. @*Conclusions@#Within the limitations of this retrospective study, MIBC patients with ypN+ disease despite neoadjuvant chemotherapy and radical cystectomy had a poor prognosis. Further studies involving novel, effective adjuvant treatment including immunotherapy agents are needed to reduce the high risk of recurrence or death in these patients.

Node-Positive Bladder Cancer After Neoadjuvant Chemotherapy Followed by Radical Cystectomy: A Single-Center Retrospective Study

Purpose@#There remains a lot of unmet need to increase understanding of node-positive (ypN+) muscle invasive bladder cancer (MIBC) after neoadjuvant chemotherapy and radical cystectomy to decide the appropriate therapeutics. @*Materials and Methods@#In a retrospective study using the center cancer chemotherapy registry, we found 113 MIBC patients who were treated with neoadjuvant chemotherapy involving gemcitabine and cisplatin (GP) followed by radical cystectomy between 2010 and 2014. Disease-free survival (DFS) and overall survival (OS) were compared according to the pathologic node positivity (ypN- vs. ypN+). Among a total of 165 patients with MIBC who received neoadjuvant chemotherapy involving GP, 118 underwent radical cystectomy. In 46 patients with ypN+ disease, DFS and OS were evaluated according to administration of adjuvant GP. @*Results@#After neoadjuvant chemotherapy and radical cystectomy, 41% of patients had ypN+ disease, which showed significantly shorter DFS (median, 7.4 months; 95% confidence interval [CI], 5.3–9.6 months) and OS (median, 20.0 months; 95% CI, 13.4–26.6 months) compared to those with ypN- disease. The patients with ypN+ disease had a high risk of recurrence or death, regardless of the administration of adjuvant chemotherapy or adjuvant regimen. @*Conclusions@#Within the limitations of this retrospective study, MIBC patients with ypN+ disease despite neoadjuvant chemotherapy and radical cystectomy had a poor prognosis. Further studies involving novel, effective adjuvant treatment including immunotherapy agents are needed to reduce the high risk of recurrence or death in these patients.

Atezolizumab in Patients with Pretreated Urothelial Cancer: a Korean Single-Center, Retrospective Study / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Treatment targeting immune checkpoint with programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors has demonstrated efficacy and tolerability in the treatment of metastatic urothelial carcinoma (mUC). We investigated the efficacy and safety of atezolizumab in mUC patients who failed platinum-based chemotherapy. MATERIALS AND METHODS: A retrospective study using the Samsung Medical Center cancer chemotherapy registry was performed on 50 consecutive patients with mUC treated with atezolizumab, regardless of their PD-L1(SP142) status, as salvage therapy after chemotherapy failure between May 2017 and June 2018. Endpoints included overall response rate (RR), progression-free survival (PFS), and safety. RESULTS: Among 50 patients, men constituted 76% and the median age was 68 years (range, 46 to 82 years). Twenty-three patients (46%) received atezolizumab as second-line therapy. PD-L1 (SP142) status IC0/1 and IC2/3 were found in 21 (42%) and 21 (42%) of patients, respectively; in eight patients (16%), PD-L1 (SP142) expression was not available. Atezolizumab was generally well tolerated, with pruritus and fatigue being the most commonly observed toxicities. As a result, partial response was noted in 20 patients (40%), with 12 (24%) stable diseases. RRwas higherin IC2/3 (62%) than in IC0/1 patients (24%, p=0.013). The median PFS was 7.4 months (95% confidence interval, 3.4 to 11.4 months). As expected, PFS also was significantly longer in IC2/3 patients than in IC0/1 (median, 12.7 vs. 2.1 months; p=0.005). PFS was not significantly influenced by age, sex, performance status, number of previous chemotherapy, site of metastases, or any of the baseline laboratory parameters. CONCLUSION: In this retrospective study, atezolizumab demonstrated clinically efficacy and tolerability in unselected mUC patients who failed platinum-based chemotherapy.

Early Experiences with Nivolumab in Patients with Metastatic Renal Cell Carcinoma and Failed Target Therapy

PURPOSE: The efficacy of nivolumab in metastatic renal cell carcinoma (mRCC) has been proven. However, the nivolumab experience in Korean patients with mRCC is still poorly reported. We report initial experiences with the efficacy and safety of nivolumab in patients with mRCC. MATERIALS AND METHODS: We retrospectively reviewed records for 25 patients with mRCC who had failed targeted therapy and were treated by nivolumab (2 mg/kg, every 2 weeks) at a single institution. The primary endpoint was objective response rate (ORR), and secondary endpoints were progression-free survival (PFS), safety profiles, and ORR in a programmed cell death receptor ligand 1 (PD-L1) expression subgroup. RESULTS: The median age was 60 years and 16 patients (64%) were male. Objective responses were achieved in 8 patients (32.0%) (complete response, 1; partial response, 7). Median PFS was 3.0 months (95% confidence interval, 1.46–4.53). Treatment-related adverse events (AEs) of any grade were observed in 19 patients (76.0%) with 6 (24.0%) experiencing grade 3 to 4 treatment-related AEs. In subgroups by PD-L1 expression levels classified as 1% or greater and less than 1%, ORR was 50% and 0%, respectively. CONCLUSIONS: This study showed the efficacy and safety of initial experiences with nivolumab in Korean patients with mRCC who had failed targeted therapy. Our results were comparable to recent clinical trials on nivolumab in mRCC.

Persistent Erectile Dysfunction after Discontinuation of 5-Alpha Reductase Inhibitor Therapy in Rats Depending on the Duration of Treatment

PURPOSE: The current study is aimed to assess whether a longer duration of 5α-reductase inhibitor (5α-RI) exposure was associated with higher rate of permanent erectile dysfunction (ED) in a rat model. MATERIALS AND METHODS: Male Sprague-Dawley rats (n=76) were assigned to five groups: (i) normal control group; (ii) dutasteride (0.5 mg/rat/d) for 4-weeks group; (iii) dutasteride for 4-weeks plus 2-weeks of resting group; (iv) dutasteride for 8-weeks group; and (v) dutasteride for 8-weeks plus 2-weeks of resting group. In vivo erectile responses to electrical stimulation, and changes of fibrotic factors and smooth muscle/collagen contents in the corpus cavernosum were evaluated in each group. RESULTS: Dutasteride administration for 4 and 8 weeks significantly decreased erectile parameters compared with the control group. Reduced erectile responses were recovered during 2 weeks of drug-free time in the 4-week treatment group, but were not in the 8-week group. Protein levels of fibrosis-related factors transforming growth factor (TGF)-β1, TGF-β2, and p-Smad/Smad (Smad 2/3) in the corpus cavernosum showed no significant change after 4 weeks of dutasteride oral administration, but were enhanced after 8 weeks. Dutasteride markedly decreased smooth muscle content and increased collagen after 4 and 8 weeks of use, but no nuclear size changes; however, neither group showed significant improvement in the smooth muscle to collagen ratio after the rest period. CONCLUSIONS: Our study showed that recovery from ED depended on the duration of medication, and administration of dutasteride for more than 8-weeks in rats could result in irreversible ED even after discontinuation of medication.

Prognostic Significance of Systemic Inflammatory Response in Patients with Synchronous and Metachronous Metastatic Renal Cell Carcinoma Receiving First-Line Tyrosine Kinase Inhibitors

PURPOSE@#To determine whether systemic inflammatory response (SIR), particularly platelet-lymphocyte ratio (PLR) and neutrophil-lymphocyte ratio (NLR), has different prognostic role between patients with metastatic renal cell carcinoma (mRCC) receiving first-line tyrosine kinase inhibitors (TKI).@*MATERIALS AND METHODS@#We retrospectively reviewed 547 patients with mRCC who were diagnosed and treated with a first-line TKI between 2007 and 2015. The primary endpoint was overall survival (OS) and secondary endpoint was progression-free survival (PFS). We evaluated differences in survival outcomes according to SIR and identified predictors of OS and PFS.@*RESULTS@#In synchronous mRCC, patients with a higher PLR had significantly worse OS and PFS. Moreover, a higher NLR was also associated with both worse OS and PFS in these patients. However, PLR was not associated with either OS or PFS in metachronous mRCC patients. While metachronous mRCC patients with a higher NLR had worse OS compared to those with lower NLR, there was no difference in PFS according to the status of NLR. On multivariate analysis, PLR was identified as predictive factor for OS (hazard ratio [HR], 1.55) as well as PFS (HR, 1.39) in patients with synchronous mRCC, but not in patients with metachronous mRCC. Additionally, higher NLR was also remained as predictive factor of both OS (HR, 1.83) and PFS (HR, 1.57) in patients with synchronous mRCC.@*CONCLUSIONS@#Our study indicates that simple biomarkers of SIR, particularly PLR and NLR, can be more useful predictors of survival outcomes in patients with synchronous mRCC rather than metachronous mRCC.

Incidence of Pathological Downgrading and Treatment Outcome After Radical Prostatectomy in Patients With Biopsy Confirmed High Gleason Score Prostate Cancer

PURPOSE: High Gleason score (8 to 10) is a poor prognostic factor regardless of treatment. Pathological downgrading sometimes occurs in high grade prostate cancer. The aim of this study is to evaluate treatment outcomes in patients with high grade prostate cancer on biopsy who were pathological downgrading after radical prostatectomy (RP). The impact on outcomes according to changes in the Gleason score after RP was evaluated. MATERIALS AND METHODS: Of 3,236 men who underwent RP between September 1995 and December 2014, 541 patients with biopsy Gleason score 8 to 10 were retrospectively reviewed. We analyzed incidence and biochemical recurrence (BCR) free probability in this downgraded group according to the Gleason grade of cancer in the RP specimen. RESULTS: Of 541 patients had a prostate biopsy Gleason score of 8 to 10. Two hundred ten patients showed pathological downgrading after RP (38.8%). Five-year BCR-free probability of patients who had Gleason score of 7 or less after RP was 46.8%. However, 5-year BCR-free probability of patients who remained Gleason scores 8 to 10 after RP was 28.5%. There was a significantly higher BCR-free probability in pathological downgrading group (p<0.001). On multivariate analysis, biopsy Gleason 8, lower PSA, clinical T2 stage was a significant predictor of downgrading. CONCLUSIONS: In this study, 38.8% of patients with high grade prostate cancer had a Gleason score of 7 or less in the RP specimen. Downgraded prostate cancer had more favorable treatment outcome. Serum PSA, clinical stage and biopsy Gleason score were the predictive factors for pathological downgrading.

Urinary Nerve Growth Factor as a Potential Biomarker of Treatment Outcomes in Overactive Bladder Patients / 대한배뇨장애요실금학회지

PURPOSE: The aim of this study was to investigate urinary nerve growth factor (NGF) as a biomarker of treatment efficacy and recurrence in overactive bladder (OAB) patients. METHODS: We enrolled 189 OAB subjects who visited our outpatient clinic from February 2010 to February 2015. All subjects with OAB received antimuscarinic treatment. A 3-day voiding diary and questionnaire were collected from each patient. Urinary levels of NGF were evaluated at baseline, the beginning of antimuscarinic treatment, and the end of antimuscarinic treatment. Urinary NGF was normalized to urine creatinine (Cr). Between-group comparisons of baseline characteristics were made using the Mann-Whitney U-test. Multivariate logistic regression analyses were used to predict responses to anticholinergic treatment and recurrence. The Wilcoxon signed-rank test with the Bonferroni correction was used for intragroup comparisons. A receiver operating characteristic curve was used to analyze the utility of this biomarker. RESULTS: Urinary levels of NGF/Cr tended to decrease in patients who responded to treatment (n=62), but this was not significant (P=0.260). Urinary NGF levels were higher at baseline in patients who did not experience recurrence than in those who did (P=0.047). In those who did not experience recurrence (n=29), urinary NGF/Cr decreased at the end of treatment compared to baseline, and this reduction was maintained at 12 weeks after the end of treatment (P < 0.05). CONCLUSIONS: Urinary NGF is a potential biomarker for predicting the outcome of antimuscarinic treatment in OAB patients. This may provide useful information when deciding to stop antimuscarinic treatment in responders.

Potential Biomarkers for Diagnosis of Overactive Bladder Patients: Urinary Nerve Growth Factor, Prostaglandin E2, and Adenosine Triphosphate / 대한배뇨장애요실금학회지

PURPOSE: This study aimed to investigate potential biomarkers for the diagnosis of overactive bladder (OAB). METHODS: A total of 219 subjects were enrolled and divided into 2 groups: OAB subjects (n=189) and controls without OAB symptoms (n=30). Three-day voiding diaries and questionnaires were collected, and urinary levels of nerve growth factor (NGF), prostaglandin E2, and adenosine triphosphate were measured and normalized to urine creatinine (Cr). Baseline characteristics and urinary levels of markers were analyzed. A receiver-operator characteristic (ROC) curve was used to analyze the diagnostic performance of urinary markers. Urinary levels of markers according to subgroup and pathogenesis of OAB were evaluated. Correlation analyses were used to analyze the relationship between urinary levels of markers and voiding diary parameters and questionnaires. RESULTS: There was no difference between the 2 groups with regards to age, sex ratio, or urine Cr (P>0.05). The urinary levels of NGF/Cr were higher in OAB subjects than in controls (P < 0.001). Urinary NGF/Cr was a sensitive biomarker for discriminating OAB patients (area under the curve=0.741; 95% confidence interval, 0.62–0.79; P=0.001) in the ROC curve. The urinary levels of NGF/Cr were significantly higher in OAB subjects than in controls regardless of subgroup or pathogenesis. Correlation analysis demonstrated urinary urgency was significantly related to urinary NGF/Cr level (correlation coefficient, 0.156). Limitations include a relatively wide variation of urinary markers. CONCLUSIONS: Urinary NGF is a potential biomarker that could serve as a basis for adjunct diagnosis of OAB.

Comparison of 5-Year Outcomes of Robot-Assisted Laparoscopic and Laparoscopic Partial Nephrectomy in Patients With Localized Renal Cell Carcinoma

PURPOSE: To compare the 5-year oncologic and functional outcomes of robot-assisted laparoscopic partial nephrectomy (RALPN) and laparoscopic partial nephrectomy (LPN) as treatment for localized renal cell carcinoma (RCC). MATERIALS AND METHODS: We analyzed the records of 181 patients with localized RCC who underwent RALPN (n=97) or LPN (n=84) between 2007 and 2011. Demographic and preoperative data with estimated glomerular filtration rate (eGFR), intraoperative data including warm ischemic time (WIT) and complications, oncologic outcomes (recurrence, metastasis), and rate of eGFR preservation at most recent follow-up were examined. RESULTS: WIT was shorter in the RALPN group (27±9.1 minutes) than the LPN group (31±10 minutes, p=0.019). Intraoperative complication rates were also lower in RALPN patients than LPN patients (4.1% vs. 14.3%). The eGFR preservation rate was higher in the RALPN group (84.6%) than in the LPN group (81.5%, p=0.049). Particularly, a relatively high difference in the eGFR preservation rate was observed in the RALPN group compared with the LPN group according to R.E.N.A.L. score 7–10 values (RALPN, 86.5±12.9 vs. LPN, 76.7±16.0; p=0.003). During the follow-up period, there was no local recurrence in either group and distant metastases only occurred in one patient in the RALPN group and in 2 patients in the LPN group. CONCLUSIONS: RALPN and LPN showed similar 5-year oncologic outcomes, but RALPN was superior to LPN in terms of WIT, intraoperative complications, and long-term eGFR preservation rate, especially in complex cases.