Real world evidence of enfortumab vedotin in patients with advanced urothelial cancer: A multicenter observational study.

OBJECTIVES: To explore the characteristics of patients and assess the effectiveness of enfortumab vedotin (EV) in those with treatment-resistant advanced urothelial cancer in a real-world setting. PATIENTS AND METHODS: A multicenter observational study was conducted on 103 evaluable patients with advanced urothelial cancer who received EV. Outcomes were assessed by radiographic response, progression-free survival (PFS), and overall survival (OS), with treatment-related adverse events (trAEs). Radiographic response was assessed using Response Evaluation Criteria in Solid Tumors version 1.1, while trAEs were studied in line with Common Terminology Criteria for Adverse Events version 5.0. RESULTS: The median follow-up was 8.9 months (range, 0.1-16.4). The observed objective response rate was 50.5%. The median PFS was 6.0 months (95% CI: 4.7-9.8), and the median OS was 14.5 months (95% CI: 12.4-not reached). Out of the 103 patients, 19 (18.4%) had an Eastern Cooperative Oncology Group performance status of 2 or more, 14 (14.7%) had an non-urothelial carcinoma histology, and 40 (38.3%) had at least one pre-existing comorbidity. There were 26 (25.2%) patients who reported 49 trAEs, with 9 (18.3%) being grade 3 or higher. The most common trAEs included rash, occurring in 18.4%. CONCLUSIONS: This study describes the characteristics and outcomes of patients with previously treated advanced urothelial cancer receiving EV. The findings demonstrate that EV showed robust anti-tumor activity and had manageable safety profiles outside the clinical trial setting.

Predicting Objective Response of Pembrolizumab in Platinum-Refractory Urothelial Carcinoma Based on NLR Fluctuation and Liver Metastases.

BACKGROUND AND PURPOSE: It is well known that patients with objective response to pembrolizumab have a durable duration of response leading to favorable survival outcomes. We investigated the possibility of predicting the objective response with concise indicators obtained from daily clinical practice. Methods In our multi-institutional cohort, 220 platinum-refractory metastatic urothelial carcinomas (mUC) treated with pembrolizumab for at least six weeks with complete information of objective response were investigated. Results The median follow-up was 7.3 months, and 119 patients deceased during the follow-up. A multivariate logistic regression analysis exhibited two independent variables predicting the objective response, including the neutrophil-lymphocyte ratio (NLR) change at six weeks of treatment and liver metastasis. We proposed a risk group using these two indicators. Patients with no predictive indicators / one of those were assigned to favorable (42%) / intermittent (47%) risk groups. Patients with both indicators were assigned to poor risk (11%). Notably, the objective response rate was well delineated in 41%, 25%, and 0% for favorable, intermediate, and poor risk groups, respectively (p<0.001). Distinct overall survival (OS) between the risk groups was also confirmed with the median OS of 14.1, 11.7, and 4.2 months in favorable, intermediate, and poor risk groups, respectively. CONCLUSIONS: At the six weeks of the pembrolizumab treatment, our risk model predicts the objective response rate precisely. Notably, those classified as 'poor risk'-marked by liver metastasis and a heightened NLR-should be considered for alternative therapy with a different mode of action, highlighting a critical decision point in treatment optimization.

Nephron-sparing ureteroscopic surgery vs. radical nephroureterectomy: comparable survival-outcomes in upper tract urothelial carcinoma.

PURPOSE: This study investigates the utility of ureteroscopic surgery (URS) as an alternative to radical nephroureterectomy (RNU) in managing upper tract urothelial carcinoma (UTUC), with a focus on survival outcomes and re-evaluation of current the European Association of Urology guidelines criteria. METHODS: We conducted a retrospective, multi-institutional review of 143 UTUC patients treated with URS (n = 35) or RNU (n = 108). Clinicopathological factors were analyzed, and survival outcomes were assessed using Kaplan-Meier analysis and Cox proportional-hazards models. RESULTS: The median follow-up period was 27 months. Overall survival (OS) and radiographic progression-free survival (rPFS) were comparable between the URS and RNU groups (OS: HR 2.42, 95% CI 0.63-9.28, P = 0.0579; rPFS: HR 1.82, 95% CI 0.60-5.47, P = 0.1641). URS conferred superior renal function preservation. In patients characterized by factors such as radiographically invisible lesions, negative cytology, pTa stage, low-grade tumors, and multiple lesions, the OS outcomes with URS were comparable to those with RNU as follows: radiographically invisible lesions (P = 0.5768), negative cytology (P = 0.7626), pTa stage (P = 0.6694), low-grade tumors (P = 0.9870), and multiple lesions (P = 0.8586). CONCLUSION: URS offers survival outcomes similar to RNU, along with better renal function preservation, especially in low-risk UTUC patients. These findings underscore the urgency of re-evaluating the current EAU guidelines and encourage further research into determining the ideal patient selection for URS in UTUC treatment.

Clinical value of minimum apparent diffusion coefficient for prediction of clinically significant prostate cancer in the transition zone.

BACKGROUND: This study investigated the association between apparent diffusion coefficients in Prostate Imaging Reporting and Data System 4/5 lesions and clinically significant prostate cancer in the transition zone. METHODS: We included 102 patients who underwent transperineal cognitive fusion targeted biopsy for Prostate Imaging Reporting and Data System 4/5 lesions in the transition zone between 2016 and 2020. The association between apparent diffusion coefficients and prostate cancers in the transition zone was analyzed. RESULTS: The detection rate of prostate cancer was 49% (50/102), including clinically significant prostate cancer in 37.3% (38/102) of patients. The minimum apparent diffusion coefficients in patients with clinically significant prostate cancer were 494.5 ± 133.6 µm2/s, which was significantly lower than 653.8 ± 172.5 µm2/s in patients with benign histology or clinically insignificant prostate cancer. Age, prostate volume, transition zone volume, and mean and minimum apparent diffusion coefficients were associated with clinically significant prostate cancer. Multivariate analysis demonstrated that only the minimum apparent diffusion coefficient value (odds ratio: 0.994; p < 0.001) was an independent predictor of clinically significant prostate cancer. When the cutoff value of the minimum apparent diffusion coefficient was less than 595 µm2/s, indicating the presence of prostate cancer in the transition zone, the detection rate increased to 59.2% (29/49) in this cohort. CONCLUSION: The minimum apparent diffusion coefficient provided additional value to indicate the presence of clinically significant prostate cancer in the transition zone. It may help consider the need for subsequent biopsies in patients with Prostate Imaging Reporting and Data System 4/5 lesions and an initial negative targeted biopsy.

Diagnostic performance of Oncuria™, a urinalysis test for bladder cancer.

BACKGROUND: Due to insufficient accuracy, urine-based assays currently have a limited role in the management of patients with bladder cancer. The identification of multiplex molecular signatures associated with disease has the potential to address this deficiency and to assist with accurate, non-invasive diagnosis and monitoring. METHODS: To evaluate the performance of Oncuria™, a multiplex immunoassay for bladder detection in voided urine samples. The test was evaluated in a multi-institutional cohort of 362 prospectively collected subjects presenting for bladder cancer evaluation. The parallel measurement of 10 biomarkers (A1AT, APOE, ANG, CA9, IL8, MMP9, MMP10, PAI1, SDC1 and VEGFA) was performed in an independent clinical laboratory. The ability of the test to identify patients harboring bladder cancer was assessed. Bladder cancer status was confirmed by cystoscopy and tissue biopsy. The association of biomarkers and demographic factors was evaluated using linear discriminant analysis (LDA) and predictive models were derived using supervised learning and cross-validation analyses. Diagnostic performance was assessed using ROC curves. RESULTS: The combination of the 10 biomarkers provided an AUROC 0.93 [95% CI 0.87-0.98], outperforming any single biomarker. The addition of demographic data (age, sex, and race) into a hybrid signature improved the diagnostic performance AUROC 0.95 [95% CI 0.90-1.00]. The hybrid signature achieved an overall sensitivity of 0.93, specificity of 0.93, PPV of 0.65 and NPV of 0.99 for bladder cancer classification. Sensitivity values of the diagnostic panel for high-grade bladder cancer, low-grade bladder cancer, MIBC and NMIBC were 0.94, 0.89, 0.97 and 0.93, respectively. CONCLUSIONS: Urinary levels of a biomarker panel enabled the accurate discrimination of bladder cancer patients and controls. The multiplex Oncuria™ test can achieve the efficient and accurate detection and monitoring of bladder cancer in a non-invasive patient setting.

Prognostic significance of the presence of tertiary Gleason grade 5 in robot-assisted radical prostatectomy specimens in Japanese patients with clinically localized prostate cancer.

BACKGROUND: The aim of this study was to study the prognostic significance of tertiary Gleason grade (TGG) 5 in patients with clinically localized prostate cancer treated with robot-assisted radical prostatectomy (RARP). METHODS: A total of 600 Japanese patients who underwent RARP for clinical stage T1-3N0M0 prostate cancer were evaluated. TGG5 was evaluated according to the International Society of Urological Pathology criterion. Cox hazard regression was used to evaluate the prognostic significance of prostate-specific antigen and pathological features in RARP specimens. RESULTS: Of the 600 RARP specimens, 92 (15%) had TGG5. TGG5 component was found in 30 (10%) of 287 cases with Gleason score (GS) 3 + 4, 55 (37%) of 149 cases with GS 4 + 3 and 7 (17%) of 40 cases with GS 4 + 4. There were no significant differences in pathological stage and surgical margin status between GS 3 + 4 with and without TGG5, as well as between GS 4 + 4 with and without TGG5. Of the 600 patients, 92 (15%) patients had biochemical recurrence (BCR) after surgery, with a median follow-up period of 42 (3-104) months. There were no differences in 5-year BCR-free survival rates between patients with GS 3 + 4 with and without TGG5 (92 vs. 100%, P = 0.16), as well as between patients with GS 4 + 3 with and without TGG5 (79 vs. 71%, P = 0.30). Similarly, there were no differences in 3-year BCRFS rates between patients with GS 4 + 4 with and without TGG5 (80 vs. 71%, P = 0.38). CONCLUSIONS: In our population, the presence of TGG5 in RARP specimens had no strong impact on pathological and prognostic outcomes.

Salvage radiation therapy for prostate cancer patients after prostatectomy.

OBJECTIVES: The aim of this study was to identify risk factors to predict a biochemical recurrence (BCR) in patients treated with salvage radiation therapy (SRT) after radical prostatectomy (RP). METHODS: We retrospectively reviewed 122 Japanese patients who received SRT for BCR after RP. Using uni- and multivariate Cox proportional hazard models, we identified the predictive factors of BCR after SRT. RESULTS: With a median follow-up of 61.3 months, 45.9% of the patients showed BCR after SRT, with 61.5 and 41.8% of non-BCR rates at the second and fifth years. Univariate proportional hazards analysis demonstrated that extraprostatic disease (P = 0.029), seminal vesicle invasion (P = 0.005), microvascular invasion (P = 0.001), postoperative Gleason score (P = 0.008) and pre-SRT prostate-specific antigen (PSA) (P = 0.005) were significantly associated with BCR after SRT. However, only the presence of microvascular invasion and a higher pre-SRT PSA were significant predictors in the multivariate analysis. The non-BCR rate in the second year after SRT for 15 patients with microvascular invasion and pre-SRT PSA > 1.2 ng/ml was only 21% compared to 72.5% of 72 patients with negative microvascular invasion and a pre-SRT PSA of <1.2 ng/ml (P = 0.000031). CONCLUSIONS: While SRT is the most important secondary treatment option for patients with BCR after RP, the effectiveness of SRT may not be uniform. The combination of risk factors such as microvascular invasion in RP specimens and pre-SRT PSA may provide a better way to stratify the risk of BCR after SRT.

Age and prostate volume are risk factors for transient urinary incontinence after transurethral enucleation with bipolar for benign prostatic hyperplasia.

OBJECTIVES: To investigate the predictive factors for transient urinary incontinence after transurethral enucleation with bipolar. METHODS: We retrospectively analyzed the data of 584 patients who underwent transurethral enucleation with bipolar between December 2011 and September 2016 operated by a single surgeon. Urinary incontinence after transurethral enucleation with bipolar was defined as involuntary leakage of urine that required the use of pads. It was evaluated at 1 week, and 1, 3, 6, 12 and 24 months after transurethral enucleation with bipolar. We defined transient urinary incontinence as urinary incontinence persisting up to 1 month after transurethral enucleation with bipolar. Based on independent risk factors identified by a multivariate stepwise logistic regression analysis, a nomogram to predict transient urinary incontinence was developed. RESULTS: Of the 584 patients, 17.3%, 13.5%, 3.1%, 0.41%, and 0% patients had urinary incontinence at 1 week, 1, 3, 6 and 12 months after transurethral enucleation with bipolar, respectively. The mean (±standard error) age was 69.6 ± 0.26 years, estimated prostate volume was 54.7 ± 0.91 cm3 , operative time was 58.0 ± 1.1 min and the prostate specimen weight was 30.6 ± 0.69 g. On univariate analysis, age, prostate volume estimated by transrectal ultrasonography, prostate-specific antigen, prostate specimen weight, operative time, prostate specimen weight/prostate volume and prostate specimen weight/operative time were significant predictive factors for transient urinary incontinence after transurethral enucleation with bipolar. On multivariate analysis, age (hazard ratio 1.07, P-value = 0.0034) and prostate volume (hazard ratio 1.03, P-value < 0.0001) were independent risk factors for transient urinary incontinence after transurethral enucleation with bipolar. CONCLUSIONS: Age and prostate volume estimated by transrectal ultrasonography seem to represent significant independent risk factors for transient urinary incontinence after transurethral enucleation with bipolar. This should be well discussed with the patient before surgery.

Prostate-specific antigen screening impacts on biochemical recurrence in patients with clinically localized prostate cancer.

OBJECTIVE: To clarify the impact of prostate-specific antigen screening on surgical outcomes of prostate cancer. METHODS: Patients who underwent radical prostatectomy were divided into two groups according to prostate-specific antigen testing opportunity (group 1, prostate-specific antigen screening; group 2, non-prostate-specific antigen screening). Perioperative clinical characteristics were compared using the Wilcoxon rank-sum and χ2 -tests. Cox proportional hazards models were used to identify independent predictors of postoperative biochemical recurrence-free survival. RESULTS: In total, 798 patients (63.2%) and 464 patients (36.8%) were categorized into groups 1 and 2, respectively. Group 2 patients were more likely to have a higher prostate-specific antigen level and age at diagnosis and larger prostate volume. Clinical T stage, percentage of positive cores and pathological Gleason score did not differ between the groups. The 5-year biochemical recurrence-free survival rate was 83.9% for group 1 and 71.0% for group 2 (P < 0.001). On multivariate analysis, prostate-specific antigen testing opportunity (hazard ratio 2.530; P < 0.001) was an independent predictive factor for biochemical recurrence after surgery, as well as pathological T stage, pathological Gleason score, positive surgical margin and lymphovascular invasion. Additional analyses showed that prostate-specific antigen screening had a greater impact on biochemical recurrence in a younger patients, patients with a high prostate-specific antigen level, large prostate volume and D'Amico high risk, and patients meeting the exclusion criteria of the Prostate Cancer Research International Active Surveillance study. CONCLUSIONS: Detection by screening results in favorable outcomes after surgery. Prostate-specific antigen screening might contribute to reducing biochemical recurrence in patients with localized prostate cancer.

No clinical significance of the time interval between biopsy and robotic-assisted radical prostatectomy for patients with clinically localized prostate cancer on biochemical recurrence: a propensity score matching analysis.

PURPOSE: To investigate the impact of the time interval (TI) between prostate biopsy and robot-assisted radical prostatectomy (RARP) on the risk of biochemical recurrence (BCR). METHODS: We retrospectively reviewed the medical records of 793 consecutive patients who were treated with RARP at our institution. Patients were divided into three groups, according to TI, to compare BCR-free survival (BCRFS) rates: Group 1 (n = 196), TI < 3 months; Group 2 (n = 513), 3 ≤ TI < 6 months; Group 3 (n = 84), TI ≥ 6 months. Eighty-three patients with TI ≥ 6 months were matched with an equal number of patients with TI < 6 months based on propensity scores by using four preoperative factors: prostate-specific antigen (PSA), primary (pGS) and secondary (sGS) Gleason score and positive prostate biopsy. RESULTS: The 5-year BCRFS rates for TI Groups 1, 2, and 3 were 76%, 80.7% and 82.6% (P = 0.99), respectively. The multivariate analysis revealed that PSA, pGS, sGS and a positive prostate biopsy were independent preoperative risk factors for BCR. The propensity adjusted 5-year BCRFS for patients with TI ≥ 6 months was 84.0%. This was not worse than that of patients with TI < 6 months (71.0%, P = 0.18). CONCLUSIONS: In our cohorts, a delay in the time from biopsy to RARP did not significantly affect recurrence. Therefore, hasty treatment decisions are unnecessary for at least 6 months after diagnosis of early prostate cancer.

Impact of Surgeon and Hospital Volume on the Safety of Robot-Assisted Radical Prostatectomy: A Multi-Institutional Study Based on a National Database.

INTRODUCTION: We aimed to perform a multi-institutional study using a national database led by the Japanese Society of Endourology to investigate the effect of surgeon or hospital volume on the safety of robot-assisted radical prostatectomy (RARP). MATERIALS AND METHODS: Clinical data of 3,214 patients who underwent RARP for the treatment of clinically localized prostate cancer between April 2012 and March 2013 in Japan were evaluated. Surgical outcomes and all intra- and perioperative complications were collected. RESULTS: The intraoperative complication rate was 0.56%. In a total number of 241 patients, 261 perioperative complications were observed. The following percentages of patients presented the Clavien-graded complications: 7.2%, grades 1-2; 0.84%, grade 3; and 0.093%, grade 4a. No cases of multiple organ dysfunction or death (grades 4b and 5) were found. Multivariable logistic regression analysis showed that the hospital volume (OR 3.6; p = 0.010) for intraoperative complications and surgeon volume (OR 0.19; p < 0.0001) and extended lymph node discectomy (OR 3.9; p < 0.0001) for perioperative complications were significant independent risk factors. CONCLUSIONS: Hospital volume for intraoperative complications and surgeon volume and extended lymph node dissection for perioperative complications were significantly associated with increased risk of each complication in RARP.

Clinical significance of preoperative renal function and gross hematuria for intravesical recurrence after radical nephroureterectomy for upper tract urothelial carcinoma.

OBJECTIVES: To investigate the predictive values of perioperative factors and to develop a nomogram for intravesical recurrence after radical nephroureterectomy in patients with upper urinary tract urothelial carcinoma. METHODS: A retrospective analysis of 144 patients who underwent radical nephroureterectomy from 1996 to 2014 was carried out. The actuarial probabilities of the intravesical recurrence-free survival rate were calculated using the Kaplan-Meier method. Prognostic indicators for intravesical recurrence were identified using competing-risks regression analyses. RESULTS: Intravesical recurrence occurred in 63 patients during the follow-up period. The intravesical recurrence-free survival rates at 1, 3, and 5 years were 65.7%, 50.6% and 47.1%, respectively. In univariate analysis, the presence of gross hematuria (P = 0.028) and the preoperative serum creatinine level (P = 0.033) were significantly associated with intravesical recurrence. In multivariate analysis, the presence of gross hematuria (subdistribution hazard ratio 2.03, 95% CI 1.145-3.496; P = 0.013) and the preoperative serum creatinine level (subdistribution hazard ratio 3.15, 95% CI 1.161-3.534; P = 0.021) were independent predictors for intravesical recurrence after radical nephroureterectomy. Accordingly, a nomogram based on the model was developed. The concordance index of this model was 0.632. CONCLUSION: The presence of gross hematuria and preoperative serum creatinine levels seem to be independent predictors for intravesical recurrence after radical nephroureterectomy. Our nomogram developed based on these factors might aid in appropriate patient selection for clinical trials of novel therapeutic interventions, including administration of intravesical chemotherapy.

Sarcopenia as a Novel Preoperative Prognostic Predictor for Survival in Patients with Bladder Cancer Undergoing Radical Cystectomy.

PURPOSE: To investigate the prognostic significance of sarcopenia on long-term outcomes in patients with bladder cancer after radical cystectomy (RC). METHODS: We retrospectively reviewed 136 patients undergoing RC for urothelial carcinoma at our institution. Prognostic impact of the preoperative clinical, laboratory, and radiologic parameters were evaluated by Cox proportional hazard model analyses, and a nomogram was developed to predict cancer-specific survival (CSS) after RC. RESULTS: The mean follow-up was 46.7 months. Patients with sarcopenia had a significantly shorter CSS than those without sarcopenia. On univariate Cox analysis, clinical T stage, histology of transurethral resection of bladder tumor (TURBT) specimen, pretreatment hemoglobin, pretreatment neutrophil-to-lymphocyte ratio (NLR), pretreatment serum C-reactive protein level, pretreatment serum albumin level, presence of hydronephrosis, and presence of sarcopenia were associated with significantly worse CSS. On multivariate Cox stepwise analysis, sarcopenia (hazard rate [HR] = 2.3, p = 0.015), clinical T stage (cT4: HR = 5.3; p = 0.0096), presence of hydronephrosis (HR = 2.0; p = 0.033), histology of TURBT specimen (HR = 2.2, p = 0.044), and NLR (HR = 1.3; p = 0.0048) were significant independent predictors of an unfavorable prognosis Based on the results of the multivariate analysis, we developed a nomogram to predict 1-, 3-, and 5-year CSS after RC. CONCLUSIONS: Sarcopenia, clinical T stage, presence of hydronephrosis, histology of TURBT specimen, and NLR are novel preoperative prognostic factors even after adjustment for other known preoperative predictors in patients undergoing RC for bladder cancer.

Impact of a preoperatively estimated prostate volume using transrectal ultrasonography on surgical and oncological outcomes in a single surgeon's experience with robot-assisted radical prostatectomy.

BACKGROUND: To assess the impact of preoperatively estimated prostate volume (PV) using transrectal ultrasonography (TRUS) on surgical and oncological outcomes in robot-assisted radical prostatectomy (RARP). METHODS: We analyzed the experience of a single surgeon at our hospital who performed 436 RARPs without neoadjuvant hormone therapy between August 2006 and December 2013. Patients were divided into three groups according to their preoperative PV calculated using TRUS (PV ≤ 20 cm(3): group 1, n = 61; 20 < PV < 50 cm(3): group 2, n = 303; PV ≥ 50 cm(3): group 3, n = 72). RESULTS: Blood loss was significantly higher in group 3 than in group 1 and group 2. In stage pT2 patients, the rate of positive surgical margin (PSM) was significantly lower in group 3 than in group 1. In addition, perioperative complications significantly increased with increasing PV, while the extraprostatic extension (EPE) rate significantly decreased with increasing PV. The preoperative biopsy Gleason score, prostate-specific antigen (PSA) density, and clinical T2 stage were inversely correlated with increasing PV. Biochemical recurrence-free survival after RARP was significantly lower in group 1 than in groups 2 and 3. CONCLUSIONS: A large prostate size was significantly associated with increased blood loss and a higher rate of perioperative complications. A small prostate size was associated with a higher PSM rate, PSA density, Gleason score, EPE rate, and biochemical recurrence rate. These results suggest that RARP was technically challenging in patients with large prostates, whereas small prostates were associated with unfavorable oncological outcomes.

Laparoendoscopic single-site adrenalectomy versus conventional laparoscopic adrenalectomy: a comparison of surgical outcomes and an analysis of a single surgeon's learning curve.

BACKGROUND: Conventional laparoscopic adrenalectomy (LA) is the gold standard procedure for benign adrenal tumors. Laparoendoscopic single-site adrenalectomy (LESS-A) has been developed as an extension of standard laparoscopic minimally invasive procedures. METHODS: This retrospective study compared the first experience of one surgeon with 70 LESS-A to 140 LA cases with respect to evaluating the influence of the inexperience on surgical outcomes and to assess this surgeon's learning curve for LESS-A. RESULTS: Age, gender, BMI, percentage of patients with prior abdominal surgery, tumor laterality, and tumor size were all comparable between the two groups. There were no statistically significant differences in any surgical outcomes, including mean operative time, pneumoperitoneum time, estimated blood loss, transfusion requirements, hemoglobin decrease at postoperative day 1, analgesic requirements, postoperative day of oral intake, conversion rate, or morbidity between the two groups. The one exception was hospital stay. There were no mortalities or reoperations in either group. The morbidity rates in the LESS-A group and LA group were 4.2 and 6.4%, respectively (p = 0.528). LESS-A appears to have a steep learning curve and the operative time of the initial 70 cases decreased markedly and remained stable when the experience level exceeded 12 cases. There was no morbidity or conversion in these first 12 LESS-A cases. Multiple regression analysis revealed that surgeon experience (p = 0.008) and tumor size (p = 0.001) were independent predictors of prolonged operative time. CONCLUSIONS: Surgical outcomes of LESS-A were equivalent to those of LA without compromising safety. The introduction of LESS-A at our hospital was smooth and safe. While the indication for LESS-A has been controversial, LESS-A was a useful procedure, especially for cases in which cosmesis is of paramount importance.

Comparison of Postoperative Stress Urinary Incontinence between Anteroposterior Dissection and Modified Gilling Method in Holmium Laser Enucleation of the Prostate.

PURPOSE: Few studies have evaluated the usefulness of anteroposterior dissection holmium laser enucleation of the prostate (HoLEP). Thus, this study investigated the incidence of stress urinary incontinence (SUI) after HoLEP and usefulness of anteroposterior dissection HoLEP in preventing postoperative SUI. MATERIALS AND METHODS: In total, 288 patients who underwent HoLEP performed by a single experienced surgeon between May 2014 and September 2021 were enrolled. Furthermore, 134 patients underwent retrograde dissection using the modified Gilling method (surgery 1) and 154 patients underwent anteroposterior dissection HoLEP (surgery 2). The risk factors for SUI, as well as the rates of SUI improvement for the two surgical procedures, were evaluated. RESULTS: Postoperative SUI was observed in 58 (20.1%) of 288 patients, of whom, 48 (82.8%) recovered continence within 6 months. Ten patients (17.2%) required more than 6 months to recover continence. SUI incidence 1 month after HoLEP was 29.9% (40/134 patients) for surgery 1 and 11.7% (18/154 patients) for surgery 2; a statistically significant difference was observed between the two groups (odds ratio [OR], 0.311; 95% confidence interval [CI], 0.168-0.575; p < 0.001). In addition, surgery 2 was significantly associated with early recovery from SUI compared with surgery 1 (stratified hazard ratio, 0.782; 95% CI, 0.615------0.995; p < 0.001). The multivariable analysis demonstrated that only surgical procedure (OR, 0.350; 95%CI, 0.168-0.732; p=0.005) was an independent predictor of SUI.- Conclusion: We reaffirmed that anteroposterior dissection HoLEP is a useful procedure for reducing the risk of postoperative SUI and early recovery of urinary continence.

Comparison of the efficacy of enfortumab vedotin between patients with metastatic urothelial carcinoma who were treated with avelumab or pembrolizumab: real-world data from a multi-institutional study in Japan.

OBJECTIVES: Enfortumab vedotin (EV) is a novel antibody-drug conjugate approved for metastatic urothelial carcinoma (UC) refractory to prior treatment with immune checkpoint inhibitors (ICIs). However, the difference in efficacy of EV after each ICIs and prognostic factors are not well known. We aimed to compare the efficacy of EV in patients with metastatic UC who were treated with avelumab or pembrolizumab and to identify the prognostic factors. METHODS: The records of 100 patients with advanced metastatic UC who received EV after the administration of either avelumab or pembrolizumab were retrospectively collected from five academic hospitals in Japan. RESULTS: The median follow-up period was 6.7 months. The median overall survival (OS) and progression-free survival (PFS) in the EV after avelumab/pembrolizumab group were not reached/14.7 months (p = 0.17) and 10.4/5.2 months (p = 0.039), respectively. The objective response rates (ORR) were 66.6% and 46.8% in EV after avelumab and EV after pembrolizumab groups, respectively (p = 0.14). Multivariate analysis identified histological variants, liver metastasis, low serum albumin levels, and high serum CRP level as significant poor prognostic factors. The median OS and PFS of cachexia patients with both low serum albumin levels and high serum CRP levels were 6.0 months and 0.93 months, respectively. CONCLUSION: PFS was superior in patients treated with EV after avelumab to EV after pembrolizumab. However, OS showed no significant difference between the two groups. Because the prognosis of patients with cachexia is extremely poor, the initiation of EV should be discussed in these patients.

Prognostic Impact of Immune-Related Adverse Events as First-Line Therapy for Metastatic Renal Cell Carcinoma Treated With Nivolumab Plus Ipilimumab: A Multicenter Retrospective Study.

BACKGROUND: Immune checkpoint inhibitors can cause various immune-related adverse events (irAEs). This study aimed to evaluate the association between the incidence of irAEs and oncological outcomes of metastatic renal cell carcinoma (mRCC) treated with nivolumab plus ipilimumab as first-line therapy. PATIENTS AND METHODS: We retrospectively analyzed data from 69 patients with mRCC treated with nivolumab plus ipilimumab as first-line therapy between September 2018 and September 2021 at 4 institutions. Cox regression analyses were performed to investigate the important factors affecting overall survival (OS) in patients with mRCC treated with nivolumab plus ipilimumab as first-line therapy. RESULTS: During observation with a median follow-up of 9.1 months, the median OS was not reached, while the median progression-free survival was 6.0 months. Patients with irAEs had significantly prolonged OS and progression-free survival than those without irAEs (p = .012 and .002, respectively). Multivariate analysis showed that 3 independent factors, including C-reactive protein (CRP), irAEs, and performance status (PS), were significantly associated with OS (p = .04, .02, and .01, respectively). The patients were subsequently divided into 3 groups as follows: group 1, 20 patients with all 3 independent OS predictors; group 2, 18 patients with irAE predictors alone or 2 positive independent OS predictors (irAEs + CRP or irAEs + PS); group 3, 31 patients with 3 negative independent S predictors. OS varied significantly among the 3 groups (p = .004). CONCLUSION: The appearance of irAEs could predict OS in patients with mRCC treated with nivolumab plus ipilimumab as the first-line therapy.

C-Reactive Protein-Albumin Ratio Predicts Objective Response to Enfortumab Vedotin in Metastatic Urothelial Carcinoma.

BACKGROUND: Enfortumab vedotin (EV), an antibody-drug conjugate that targets Nectin-4, is used for patients with metastatic urothelial carcinoma who have experienced progression on platinum-based chemotherapy and checkpoint inhibitors. Despite the widespread use of the drug, evidence remains scarce regarding clinical indicators that can predict the response to EV treatment. OBJECTIVE: We aimed to explore the predictive value of clinical indicators derived from peripheral blood tests for treatment responses to EV. METHODS: We utilized records of 109 patients with metastatic urothelial carcinoma treated by EV from our multi-institutional dataset. Receiver operating characteristic curve analyses for predicting objective responses including several indicators from blood examinations, such as C-reactive protein-albumin ratio (CAR), hemoglobin, neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, and lactate dehydrogenase, were performed. The optimal cutoff points were determined by the Youden index. Logistic regression analyses for achieving objective responses to EV treatment were performed among these indicators. RESULTS: The median age of the cohort was 74 years, and the median follow-up duration was 10 months for the entire group. Median overall survival and progression-free survival from the initiation of EV were 12 and 6 months, respectively. The objective response rate and disease control rate were 48% and 70%, respectively. The receiver operating characteristic curve analysis aimed at predicting the achievement of an objective response to EV showed that the concordant index for the CAR was 0.774, significantly surpassing other indicators such as hemoglobin level, neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, and serum lactate dehydrogenase. The Youden index identified an optimal cutoff value of 1 for CAR (mg/L for C-reactive protein and g/dL for serum albumin level) in predicting the objective response to EV treatment. Using the cutoff value for the CAR, the cohort was divided into 32 patients (29%) with lower CAR and 77 patients (71%) with higher CAR. The objective response rate was observed to be 84% in the lower CAR group and 32% in the higher CAR group (p < 0.0001). A logistic regression analysis revealed that an Eastern Cooperative Oncology Group Performance Status ≥1 (p = 0.04) and a CAR ≥1 (p < 0.001) were identified as independent predictors for the objective response to EV. CONCLUSIONS: The evaluation of the CAR from a concise blood examination at the initiation of EV could effectively predict the treatment response to EV in patients with metastatic urothelial carcinoma after the progression of platinum-based chemotherapy and checkpoint inhibitors.

Enfortumab vedotin, an antibody-drug conjugate that targets Nectin-4, is currently used for patients with metastatic urothelial carcinoma who no longer respond to checkpoint inhibitors. In the present report, we investigated which clinical indicators can predict achieving an objective response to enfortumab vedotin at the initiation of treatment. Among the blood-based putative indicators, the C-reactive protein-albumin ratio showed the highest value for predicting the treatment response to enfortumab vedotin. As the C-reactive protein-albumin ratio can be easily assessed from blood tests, physicians can consider evaluating it at the start of the EV treatment.

Durable Response to Enfortumab Vedotin Compared to Re-challenging Chemotherapy in Metastatic Urothelial Carcinoma After Checkpoint Inhibitors.

BACKGROUND: Enfortumab vedotin (EV), an antibody-drug conjugate targeting Nectin-4, has been used for patients with metastatic urothelial carcinoma (mUC) after progressing on checkpoint inhibitors (CPIs). Re-challenging chemotherapy with platinum agents and continuing CPIs beyond progressive disease (PD) have often been chosen following PD on CPIs, and several studies indicate favorable treatment effects of re-challenging chemotherapy. There is little evidence for comparing EV and re-challenging chemotherapy in real-world clinical practice. OBJECTIVE: The aim was to reveal the real-world treatment outcomes of EV, re-challenging chemotherapy, and continuing CPIs beyond PD in mUC patients. PATIENTS AND METHODS: A multi-institutional dataset of 350 mUC patients treated with CPIs was utilized. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and duration of response (DOR) were evaluated to compare the treatment arms. RESULTS: One hundred and nine mUC patients were treated with EV with a median follow-up of 6.4 months. The ORR and disease control rate (DCR) were 48% and 70%, respectively. The OS from PD on pembrolizumab exhibited significant differences among the three groups, with a median OS of 8, 14, and 29 months in continuing pembrolizumab beyond PD, re-challenging chemotherapy, and EV, respectively. When comparing the survival outcomes from the initiation of the treatment, there is neither a difference in OS (p = 0.124), PFS (p = 0.936), nor ORR (p = 0.816) between EV and re-challenging chemotherapy. Notably, the DOR in patients who achieved an objective response was significantly longer in the EV group than the re-challenging chemotherapy group (a median of 11 and 5 months, p = 0.049). For OS, the difference was not statistically significant (27 and 11 months in EV and re-challenging chemotherapy, respectively: p = 0.05). CONCLUSIONS: A superior effect of EV on patient survival compared to re-challenging chemotherapy and continuing pembrolizumab beyond PD was observed in our real-world analysis, which is attributed to the durable DOR in EV treatment despite the similar ORR to re-challenging chemotherapy.

Enfortumab vedotin (EV) is an antibody­drug conjugate targeting Nectin-4 and is now utilized for patients with metastatic urothelial carcinoma following treatment with checkpoint inhibitors (CPIs). Until recently, repeating chemotherapy using platinum drugs or continuing CPIs were often the treatments used for these patients. In the present study, we reported real-world treatment outcomes, mainly focusing on EV and repeating chemotherapy. Although the objective responses to the treatments were comparable, the duration of response for patients responding to the treatment was significantly longer in patients treated with EV than in those repeating chemotherapy, resulting in extended survival time with EV treatment.