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Purpose@#The aim of this retrospective study was to evaluate the efficacy of adjuvant cisplatin-based chemotherapy in patients with locally advanced upper tract urothelial carcinoma (UTUC), administered following radical nephroureterectomy. @*Materials and Methods@#Patients with UTUC, arising from renal pelvis or ureter, staged pT3/T4 or N+ were treated with adjuvant chemotherapy following surgery. The chemotherapy consisted of gemcitabine 1,000 mg/m2 on days 1 and 8, cisplatin 70 mg/m2 on day 1. Treatment was repeated every 3 weeks for up to 4 cycles. Endpoints included disease-free survival (DFS), metastasis-free survival (MFS), and safety. @*Results@#Among 89 eligible patients, 85 (95.5%) completed at least 3 cycles of adjuvant chemotherapy. Chemotherapy was well tolerated, the main toxicities being mild-to-moderate gastrointestinal toxic effects and pruritus. With a median follow-up of 37 months, median DFS was 30 months (95% confidence interval, 22 to 39), and the median MFS was not reached. The 3-year DFS and MFS were 44% and 56%, respectively. Multivariate analyses revealed that the main factor associated with DFS and MFS was the lymph node involvement, whereas age, T category, grade, or the primary site of UTUC were not significantly associated with DFS or MFS. @*Conclusion@#Adjuvant cisplatin-based chemotherapy after radical surgery of pT3/T4 or N+ UTUC was feasible and may demonstrate benefits in DFS and MFS. Whether novel agents added to the chemotherapy regimen, as a concurrent combination or maintenance, impacts on survival or reduces the development of metastases remains to be studied.
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Purpose@#We aimed to assess the effectiveness of early single intravesical administration of epirubicin in preventing intravesical recurrence after radical nephroureterectomy for upper tract urothelial carcinoma. @*Materials and Methods@#Patients with upper tract urothelial carcinoma who underwent radical nephroureterectomy between November 2018 and May 2022 were retrospectively reviewed. Intravesical epirubicin was administered within 48 hours if no evidence of leakage was observed. Epirubicin (50 mg) in 50 mL normal saline solution was introduced into the bladder via a catheter and maintained for 60 minutes. The severity of adverse events was graded using the Clavien-Dindo classification. We compared intravesical recurrence rate between the two groups. Multivariate analyses were performed to identify the independent predictors of bladder recurrence following radical nephroureterectomy. @*Results@#Epirubicin (n=55) and control (n=116) groups were included in the analysis. No grade 1 or higher bladder symptoms have been reported. A statistically significant difference in the intravesical recurrence rate was observed between the two groups (11.8% at 1 year in the epirubicin group vs. 28.4% at 1 year in the control group; log-rank p=0.039). In multivariate analysis, epirubicin instillation (hazard ratio [HR], 0.43; 95% confidence interval [CI], 0.20 to 0.93; p=0.033) and adjuvant chemotherapy (HR, 0.29; 95% CI, 0.13 to 0.65; p=0.003) were independently predictive of a reduced incidence of bladder recurrence. @*Conclusion@#This retrospective review revealed that a single immediate intravesical instillation of epirubicin is safe and can reduce the incidence of intravesical recurrence after radical nephroureterectomy. However, further prospective trials are required to confirm these findings.
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Purpose@#Bladder preservation chemoradiotherapy (CRT) in patients with a clinical complete response (cCR) following cisplatin-based neoadjuvant chemotherapy (NAC) is a promising treatment strategy for muscle-invasive bladder urothelial carcinoma (MIBC). A combined analysis of raw data from two prospective phase II studies was performed to better evaluate the feasibility of selective bladder preservation CRT. @*Materials and Methods@#The analysis was based on primary efficacy data from two independent studies, including 76 MIBC patients receiving NAC followed by bladder preservation CRT. The efficacy data included metastasis-free survival (MFS) and disease-free survival (DFS). For the present analysis, starting point of survival was defined as the date of commencing CRT. @*Results@#Among 76 patients, 66 had a cCR following NAC. Sixty-four patients received gemcitabine and cisplatin (GC) combination chemotherapy in neoadjuvant setting, and 12 received nivolumab plus GC. Bladder preservation CRT following NAC was generally well-tolerated, with low urinary tract symptoms being the most common late complication. With a median follow-up of 64 months, recurrence was recorded in 43 patients (57%): intravesical only (n=20), metastatic only (n=16), and both (n=7). In 27 patients with intravesical recurrence, transurethral resection, and Bacillus Calmette-Guerin treatment was given to 17 patients. Salvage cystectomy was performed in 10 patients. Median DFS was 46.3 (95% confidence interval [CI], 25.1 to 67.5) months, and the median MFS was not reached. Neither DFS nor MFS appeared to be affected by any of the baseline characteristics. However, DFS was significantly longer in patients with a cCR than in those without (hazard ratio, 0.465; 95% CI, 0.222 to 0.976). @*Conclusion@#The strategy of NAC followed by selective bladder preservation CRT based on the cCR is feasible in the treatment of MIBC. A standardized definition of cCR is needed to better assess disease status post-NAC.
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Background@#This study assessed the comparative effectiveness of sextant and extended 12-core systematic biopsy within combined biopsy for the detection of prostate cancer. @*Methods@#Patients who underwent combined biopsy targeting lesions with a Prostate Imaging Reporting and Data System (PI-RADS) score of 3–5 were assessed. Two specialists performed all combined cognitive biopsies. Both specialists performed target biopsies with five or more cores. One performed sextant systematic biopsies, and the other performed extended 12-core systematic biopsies. A total of 550 patients were analyzed. @*Results@#Cases requiring systematic biopsy in combined biopsy exhibited a significant association with age ≥ 65 years (odds ratio [OR], 2.32; 95% confidence interval [CI], 1.25– 4.32; P = 0.008), PI-RADS score (OR, 2.32; 95% CI, 1.25–4.32; P = 0.008), and the number of systematic biopsy cores (OR, 3.69; 95% CI, 2.11–6.44; P < 0.001). In patients with an index lesion of PI-RADS 4, an extended 12-core systematic biopsy was required (target-negative/ systematic-positive or a greater Gleason score in the systematic biopsy than in the targeted biopsy) (P < 0.001). @*Conclusion@#During combined biopsy for prostate cancer in patients with PI-RADS 3 or 5, sextant systematic biopsy should be recommended over extended 12-core systematic biopsy when an effective targeted biopsy is performed.
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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).
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
Subject(s)
Animals , Humans , Male , Rats , 5-alpha Reductase Inhibitors , Administration, Oral , Collagen , Dutasteride , Electric Stimulation , Erectile Dysfunction , Finasteride , Models, Animal , Muscle, Smooth , Oxidoreductases , Rats, Sprague-Dawley , Transforming Growth FactorsABSTRACT
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.
Subject(s)
Humans , Male , Disease-Free Survival , Drug Therapy , Fatigue , Neoplasm Metastasis , Pruritus , Retrospective Studies , Salvage TherapyABSTRACT
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.
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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.