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Purpose: The aim of this study was to investigate the association between angiolymphatic invasion (ALI) and bladder cancer in patients who underwent radical cystectomy (RC).Materials and Methods: Multicenter retrospective data from 495 bladder cancer patients who underwent RC between 2007 and 2019 were enrolled in this study. Patients were stratified into 2 groups according to the presence of ALI. The effect of ALI was analyzed by the Kaplan-Meier method and Cox regression hazard models for patients’ cancer-specific survival (CSS), overall survival (OS), and recurrence-free survival (RFS).Results: The median age of the 495 patients in the study was 65 years, with median and mean follow-up durations of 23.3 months and 37.1 months, respectively. ALI was present in 182 patients (36.8%). ALI was significantly associated with worse RFS as well as CSS and OS (p

Even with advances in perioperative medical care, anesthetic management, and surgical techniques, radical cystectomy (RC) which remains the gold standard therapy for the treatment of muscle-invasive bladder cancer, yet is still associated with a high morbidity rate as well as a prolonged length of hospitalization (LOH). Recently, there has been a great deal of interest in developing multimodal and multidisciplinary strategies that might aid in the acceleration postoperative convalescence by decreasing variance in perioperative care for patients having complex operations. Many patient series have shown that Enhanced Recovery After Surgery (ERAS) protocols can improve outcomes in patients having RC by reducing the incidence of gastrointestinal complications and the LOH without increasing readmissions or overall morbidity. Many studies are going to evaluate and incorporate scientific data in ERAS program to modify as many of the variables leading to RC morbidity, as well as to enhance how patients are cared for before and after operation. In this review, we offer a summary of the preoperative, intraoperative, and postoperative key components of undergoing an ERAS protocol for patients undergoing RC, as well as future research prospects.

Radical cystectomy (RC) is the gold standard treatment option for muscle invasive bladder cancer (MIBC). However, up to 25% of patients who undergo RC show metastatic lymph node deposits during the procedure. In such cases, the 5-year survival rate is reported to be 25%–30%. Pelvic lymph node dissection (PLND) can also provide useful prognostic information, including data regarding the disease burden, lymph node density, and extracapsular extension of metastatic lymph nodes. Accordingly, the National Comprehensive Cancer Network guidelines recommend that PLND that includes the common iliac lymph node should be performed at the time of RC to allow reliable staging of MIBC. In addition to its diagnostic role, many studies have reported the potential therapeutic role of PLND. Data from clinical trials indicate a substantial oncological advantage in PLND cohorts compared to non-PLND cohorts, regardless of pathological nodal status, as a result of removal of metastatic and micrometastatic tumor cells nested in lymph nodes. As such, despite the diagnostic and therapeutic role of PLND in MIBC, the optimal PLND template remains controversial. Currently, extended PLND (E-PLND) is recommended for diagnostic purposes, however, E-PLND did not show therapeutic effectiveness in some recent preliminary randomized controlled trials. In this review, we will discuss the appropriate range of PLND for RC in terms of its diagnostic and therapeutic importance, and propose an appropriate range of PLNDs based on the evidence and randomized trials so far.

Purpose: This study aimed to determine the prognostic roles of several immune-related laboratory parameters in patients with metastatic kidney and bladder cancer treated with immune checkpoint inhibitors (ICIs).Materials and Methods: Overall, 36 patients with either metastatic bladder (N=18) or kidney cancer (N=18) were enrolled retrospectively. Progression-free survival (PFS) and overall survival according to the pretherapeutic serum De Ritis ratio (DRR), neutrophil-to-lymphocyte ratio (NLR), and albumin level after ICI treatment, were analyzed. Treatment duration was adjusted using Contal and O’Quigley’s method to explore the cutoff and maximize the log-rank test statistic. Cox proportional hazards model was used to analyze the laboratory parameters.Results: A total of 9 patients received a combination therapy of multiple ICIs (N=9) and targeted agents (N=7). The median NLR, DRR, and albumin level at baseline were 1.7, 1.2, and 4.2 mg/dL, respectively. In the univariable analysis, combination of immunotherapies, total ICI cycles, baseline DRR, and albumin level were significant for PFS. Sex ratio, total ICI cycles, and baseline NLR and DRR were significant for cancer-specific survival (CSS). DRR and albumin levels, which were measured for up to 10 cycles, were significant in PFS and CSS. NLR was additionally significant in CSS. After adjusting total ICI cycles, DRR was significant in PFS and CSS, albumin level was significant only in PFS, and NLR was significant only in CSS in the multivariable analysis.Conclusions: NLR, DRR, and albumin level are significant factors associated with the survival of patients with metastatic kidney and bladder cancer treated with ICI.

Background Ureteral reconstruction is required after surgical resection of the tumor invading the urinary tract in ovarian cancer with low incidence. There are no currently reported surgical outcomes of ureteral reconstruction during cytoreductive surgery. The aim of the study is to investigate the clinical features and surgical outcomes of ureteral reconstruction during primary, interval and secondary cytoreductive surgery for ovarian cancer. Methods A total of 3226 patients who underwent primary, interval or secondary cytoreductive surgery for ovarian cancer between January 2000 and May 2021 were reviewed. Fifty-six patients who underwent ureteral reconstruction during cytoreductive surgery were included in the analysis. Results Ureteral reconstruction was required in 1.7% (56/3226) of ovarian cancer patients. Of the 56 patients who underwent ureteral reconstruction during cytoreductive surgery, 35 (62.5%) had primary ovarian cancer, and 21 (37.5%) had recurrent ovarian cancer. The median tumor size invading the lower urinary tract was 2.0 cm (range, 0.4–9.5 cm). Ureteroneocystostomy with direct implantation (51.8%) and psoas hitch (8.9%), transureteroureterostomy (7.1%), and ureteroureterostomy (32.1%) were required as part of cytoreductive surgery. Complete cytoreduction with ureteral reconstruction was achieved in 83.9% (47/56) and the rest of the patient population (16.1%) achieved a gross residual tumor size of less than 1 cm. All complications, including hydronephrosis (33.9%), were managed, none resulting in long-term sequelae. In primary ovarian cancer, the 5-year disease-free survival and overall survival were 50.0% and 89.5%, respectively. In patients with recurrent ovarian cancer, the 5-year disease-free survival and overall survival were 23.6% and 64.0%, respectively. Conclusions Ureteral reconstruction as a part of cytoreductive surgery for ovarian cancer could be performed with acceptable morbidities. Complete cytoreduction by a multidisciplinary surgical team, including urologic oncologists, should be pursued for the surgical management of ovarian cancer. Trial registration Retrospectively registered.

Intravesical mitomycin-C is recommended immediately after transurethral resection of bladder tumor for nonmuscle-invasive bladder cancer. However, a lack of compliance occurs due to the associated complications. Here, we aimed to assess the efficacy and safety of intravesical mitomycin-C before transurethral resection of bladder tumor in patients with nonmuscle-invasive bladder cancer.This was a single-center, open-label, parallel-arm, randomized phase II clinical trial in patients with suspected nonmuscle-invasive bladder cancer before transurethral resection of bladder tumor. Participants were randomly assigned (1:1) to receive 2 doses of intravesical mitomycin-C (40 mg/20 mL) 1 day and 4 hours before transurethral resection of bladder tumor (n = 49) or no treatment (n = 50) with block randomization (size 2 and 4), stratified by Bacillus Calmette-Guérin/intravesical mitomycin-C. The primary endpoint was recurrence-free survival and secondary endpoints were progression-free survival and adverse events in the per-protocol analysis.Seventy-one patients (33, intervention; 38, control) were well matched for baseline characteristics. Sixty-one had been followed without recurrence for at least 10.4 months; 3 and 8 patients showed recurrence in the intervention and control groups, respectively. The 1-year recurrence-free survival rate was 97% and 89% for the intervention and control groups, respectively. Neoadjuvant intravesical mitomycin-C resulted in a reduction (63%) in the relative recurrence risk (hazard ratio, 0.37; 80% 1-sided confidence interval, -∞-0.65,Two doses of neoadjuvant intravesical mitomycin-C are safe and effective in reducing nonmuscle-invasive bladder cancer recurrence and progression after transurethral resection of bladder tumor.

Summary Background Standard treatment for high-risk non-muscle-invasive bladder cancer is transurethral resection of bladder tumour followed by intravesical BCG immunotherapy. However, despite high initial responses rates, up to 50% of patients have recurrence or become BCG-unresponsive. PD-1 pathway activation is implicated in BCG resistance. In the KEYNOTE-057 study, we evaluated pembrolizumab, a PD-1 inhibitor, in BCG-unresponsive non-muscle-invasive bladder cancer. Methods We did this open-label, single-arm, multicentre, phase 2 study in 54 sites (hospitals and cancer centres) in 14 countries. In cohort A of the trial, adults aged 18 years or older with histologically confirmed BCG-unresponsive carcinoma in situ of the bladder, with or without papillary tumours, with an Eastern Cooperative Oncology Group performance status of 0–2, and who were ineligible for or declined radical cystectomy were enrolled. All enrolled patients were assigned to receive pembrolizumab 200 mg intravenously every 3 weeks for up to 24 months or until centrally confirmed disease persistence, recurrence, or progression; unacceptable toxic effects; or withdrawal of consent. The primary endpoint was clinical complete response rate (absence of high-risk non-muscle-invasive bladder cancer or progressive disease), assessed by cystoscopy and urine cytology approximately 3 months after the first dose of study drug. Patient follow-ups were done every 3 months for the first 2 years and every 6 months thereafter for up to 5 years. Efficacy was assessed in all patients who received at least one dose of the study drug and met BCG-unresponsive criteria. Safety was assessed in all patients who received at least one dose of the study drug. This trial is registered with ClinicalTrials.gov number, NCT02625961 , and is ongoing. Findings Between Dec 9, 2015, and April 1, 2018, we screened 334 patients for inclusion. 186 patients did not meet inclusion criteria, and 47 patients were assigned to cohort B (patients with BCG-unresponsive high grade Ta or any grade T1 papillary disease without carcinoma in situ; results will be reported separately). 101 eligible patients were enrolled and assigned to receive pembrolizumab. All 101 patients received at least one dose of the study drug and were included in the safety analysis. Five patients had disease that did not meet the US Food and Drug Administration definition of BCG-unresponsive non-muscle-invasive bladder cancer and were therefore not included in the efficacy analysis (n=96). Median follow-up was 36·4 months (IQR 32·0–40·7). 39 (41%; 95% CI 30·7–51·1) of 96 patients with BCG-unresponsive carcinoma in situ of the bladder with or without papillary tumours had a complete response at 3 months. Grade 3 or 4 treatment-related adverse events occurred in 13 (13%) patients; the most common were arthralgia (in two [2%] patients) and hyponatraemia (in three [3%] patients). Serious treatment-related adverse events occurred in eight (8%) patients. There were no deaths that were considered treatment related. Interpretation Pembrolizumab monotherapy was tolerable and showed promising antitumour activity in patients with BCG-unresponsive non-muscle-invasive bladder cancer who declined or were ineligible for radical cystectomy and should be considered a a clinically active non-surgical treatment option in this difficult-to-treat population. Funding Merck Sharp & Dohme.

This study was performed to compare clinical outcomes of lymphatic n-butyl cyanoacrylate (NBCA) embolization and ethanol sclerotherapy in patients with symptomatic postoperative pelvic lymphoceles. This prospective, open-label, randomized, and controlled trial took place at two medical centers in Korea. Patients ≥18 years old with symptomatic postoperative pelvic lymphoceles were randomly assigned (1:1) to one of two study arms: lymphatic embolization or sclerotherapy. A target of 44 patients was set for each group to assess clinical outcomes. The trial began in August 2018 but ended as a pilot study in February 2020. Problematic patient enrollment precluded full population recruitment, only 11 patients (lymphatic embolization, 5; sclerotherapy, 6) eventually participating. Clinical success and drainage tube removal rates were 100% in both arms. To achieve clinical success, significantly more procedures were needed in the sclerotherapy group than in the lymphatic embolization group (4.5±1.23 vs 2.0±1.00; pp=0.267). No significant adverse events or recurring symptomatic lymphoceles were evident at 3-month follow-up visits. Both lymphatic NBCA embolization and ethanol sclerotherapy might be safe and effective in treating symptomatic postoperative pelvic lymphoceles, showing no significant difference in clinical outcomes. In a future randomized prospective study, it is essential to establish better inclusion criteria to selectively include intractable lymphoceles to find out the difference in the outcome between the two treatments.

LBA442 Background: Although most pts with HR NMIBC respond to BCG, pts whose cancer does not respond or who relapse within 12 mo have poor prognosis and require radical cystectomy (RC). The single-arm, multicohort phase 2 KEYNOTE-057 trial (NCT02625961) was designed to investigate the safety and efficacy of pembro monotherapy for pts with BCG-unresponsive HR NMIBC (per FDA) who were ineligible or declined to undergo RC. Results from cohort A (carcinoma in situ [CIS] ± papillary tumors) showed a clinical complete response rate of 41% at 3 mo and led to approval of pembro monotherapy for such pts in the United States. We describe the results from cohort B (papillary tumors without CIS). Methods: Pts were aged ≥18 y with BCG-unresponsive HR NMIBC with papillary tumors only (high-grade Ta or any-grade T1) at baseline and ECOG PS 0-2. Pts received pembro 200 mg every 3 wk (Q3W) for ≤35 cycles (~2 y). Cancer was assessed at 12 wk and Q12W thereafter if no recurrent HR NMIBC or progression was observed; CT urography was done Q24W. Primary end points for cohort B were 12-mo disease-free survival (DFS) rate of HR NMIBC as assessed by central pathology/radiology review and safety, assuming a 12-mo DFS of >20% for HR NMIBC. Secondary efficacy end points were 12-mo DFS rate of any disease; progression-free survival (PFS) to worsening of grade, stage, or death; PFS to muscle invasion, metastasis, or death; and overall survival (OS). Results: Overall, 132 pts received pembro for a median of 9.5 cycles (range, 1.0-35.0). Median age was 72 y (range, 37-87); 57 pts (43.2%) had T1 stage; all pts (100%) had urothelial histology; 104 pts (78.8%) were male; pts received a median of 10 (range, 6-33) prior BCG instillations. Median follow-up was 45.4 mo (range, 14.9-77.1). Efficacy data are shown in Table. Thirty-one pts (23.5%) had RC after stopping pembro. Treatment-related AEs occurred in 97 pts (73.5%); 19 (14.4%) had a grade 3/4 treatment-related AE and 14 pts (10.6%) discontinued due to a treatment-related AE. No deaths from treatment-related AEs occurred. Conclusions: Pembro showed notable antitumor activity in pts with BCG-unresponsive non-CIS papillary HR NMIBC after ~45 mo of follow-up. Toxicity was manageable and consistent with that in cohort A, with no new safety signals. Results suggest pts with non-CIS papillary HR NMIBC unresponsive to BCG who declined or were ineligible to undergo RC may also benefit from pembro monotherapy. Clinical trial information: NCT02625961 . [Table: see text]

In the surgical oncology field, the change from a past radical surgery to an organ preserving surgery is a big trend. In muscle-invasive bladder cancer treatment, neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) is the standard of care for muscle-invasive bladder cancer (MIBC) patients eligible for cisplatin. There is a growing interest in bladder preserving strategies after NAC because good oncologic outcome has been reported for pathologic complete response (pCR) patients after NAC, and many studies have continued to discuss whether bladder preservation treatment is possible for these patients. However, in actual clinical practice, decision-making should be determined according to clinical staging and there is a gap that cannot be ignored between clinical complete response (cCR) and pCR. Currently, there is a lack in a uniform approach to post-NAC restaging of MIBC and a standardized cCR definition. In this review, we clarify the gap between cCR and pCR at the current situation and focus on emerging strategies in bladder preservation in selected patients with MIBC who achieve cCR following NAC.

Purpose The lower incidence of bladder cancer among women has led to a lack of information on female radical cystectomy (RC). This study aimed to analyze the characteristics related with female RC in a cohort from multiple academic institutions. Materials and methods This was a retrospective review of 384 female patients who underwent RC for bladder cancer. Epidemiologic, perioperative variables including urologic referral periodwith consequent pathologic stage distributions were assessed. The changes in surgical techniques over time were illustrated. Also, we evaluated recurrence-free survival (RFS) at 2 and 5 years and overall survival (OS) at 5 years with stage-specific analyses using the Kaplan-Meier method. Results The mean follow-up time was 35 months (interquartile rage [IQR], 9 to 55). The average time to urologic referral with initial symptoms was 5.5 (IQR, 1 to 6) months and over 20% of patients visited clinics after 6 months. In subsequent stage distributions according to referral period, T2 or higher stage distributions were abruptly increased after 1 year. Overall 2-year/5-year RFS rates were 0.72/0.57 and 5-year OS was 0.61. Notable surgical descriptions were as follows: 91% of patients underwent open RC; 80% of patients underwent an ileal conduit; and 83% of patients received anterior exenteration. However, the proportions of robotic surgery, orthotopic neobladder and organ sparing cystectomy have increased recen-tly. Conclusion We identified the general characteristics and changes in pattern of female RC. Our results also suggest that women are susceptible to delays in referral to an urologist and are at greater risk for worse prognosis.

Purpose The purpose of this study was to determine whether histologic inflammation (HI) in initial and repeat prostate biopsy specimens was significantly associated with the detection of prostate cancer. Materials and Methods Between 2005 and 2017, the clinicopathological records of patients with high prostatespecific antigen (PSA) levels who underwent initial and repeat prostate biopsies were retrospectively reviewed. The presence of HI and its degree in each biopsied specimen were interpreted by one uropathologist with 20 years of experience. The association between HI and cancer diagnosis was statistically assessed, with p < 0.05 considered significant, and the cancer and non-cancer groups were compared. Results Among the 522 patients with a median PSA levels of 6.5 ng/dL, including 258 (49.4%) whose cancer was diagnosed following repeat biopsy, the median degrees of HI in the initial and repeat biopsies were 25.0% and 41.7%, respectively. Furthermore, 211 (40.4%) and 247 (47.3%) patients had HI (> 0%) on biopsied specimens, respectively. Comparison of the cancer and noncancer groups revealed that a greater rate of HI specimens in the initial biopsy was associated with fewer prostate cancer diagnoses following repeat biopsy (p < 0.001). Other comparisons between the cancer and non-cancer groups showed that the cancer group had a significantly higher rate of hypertension, whereas those non-cancer group had a significantly higher rate of benign prostatic hyperplasia and prostatitis (p < 0.05). Conclusion A finding of a lesser degree of HI in the initial and a greater degree of HI in the repeat biopsied specimens was associated with the higher probability of cancer diagnosis in patients with high PSA levels.

Purpose The purpose of this study was to compare oncologic outcomes between open nephroureterectomy (ONU) and laparoscopic nephroureterectomy (LNU) in patients with upper tract urothelial carcinoma. Materials and Methods The medical records of consecutive ONU and LNU cases from five tertiary institutions were retrospectively analyzed between 2000 and 2012. The propensity-score matching methodology was used to compare the two surgical approaches in terms of age, body mass index, American Society of Anesthesiologists score, tumor location, grade, pathologic T and N categories, the presence of lymphovascular invasion, and follow-up duration. The Kaplan-Meier with log-rank tests and clustered Cox regression were used to compare the estimated rates of survival for each surgical approach and to investigate the effect of the surgical approach on each prognostic outcome. Results Six hundred thirty-eight propensity-score matching pairs (n=1,276) were compared; LNU was significantly better than ONU in all types of survival, including intravesical recurrence-free survival (IVRFS), disease-free survival, overall survival (OS), and cancer-specific survival (CSS) (p < 0.05). The 3-year OS and CSS rates were significantly higher with LNU than with ONU (p < 0.05). Compared with ONU, LNU had significantly better 3-year OS and CSS rates (82.9% and 86.2% vs. 78.3% and 81.8%); there were no differences at 5 years. In subgroup analysis of the early-staged group, advanced-stage group, lymph node–positive group, and lymph node–negative group, the two approaches did not significantly affect prognostic outcomes, except LNU improved the IVRFS in the lymph node–negative or no history of previous bladder cancer group. Conclusion LNU had a significantly better prognostic outcome than ONU after propensity-score matching.

Background In this study, we aimed to propose a validated prediction model for disease‐free survival (DFS) after radical nephroureterectomy (RNU) in a Korean population with upper urinary tract urothelial carcinoma (UTUC). Methods We performed a retrospective review of 1561 cases of UTUC who underwent either open RNU (ONU, n = 906) or laparoscopic RNU (LNU, n = 615) from five tertiary Korean institutions between January 2000 and December 2012. Data were used to develop a prediction model using the Cox proportional hazards model. Prognostic factors were selected using the backward variable selection method. The prediction model performance was investigated using Harrell's concordance index (C‐index) and Hosmer‐Lemeshow type 2 statistics. Internal validation was performed using a bootstrap approach, and the National Cancer Center data set (n = 128) was used for external validation. Results A best‐fitting prediction model with seven significant factors was developed. The C‐index and two Hosmer‐Lemeshow type statistics of the prediction model were 0.785 (95% CI, 0.755‐0.815), 4.810 (P = 0.8506), and 5.285 (P = 0.8088). The optimism‐corrected estimate through the internal validation was 0.774 (95% CI, 0.744‐0.804) and the optimism‐corrected calibration curve was close to the ideal line with mean absolute error = 0.012. In external validation, the discrimination was 0.657 (95% CI, 0.560‐0.755) and the two calibration statistics were 0.790 (P = 0.9397) and 3.103 (P = 0.5408), respectively. Conclusion A validated prediction model based on a large Korean RNU cohort was developed with acceptable performance to estimate DFS in patients with UTUC.

BACKGROUND: Limited data compare first-line carboplatin-based chemotherapy and immune checkpoint blockade in cisplatin-ineligible metastatic urothelial carcinoma (mUC) patients. The primary evidence guiding treatment decisions was a recent Food and Drug Administration/European Medicines Agency safety alert based on emerging data from two ongoing phase III trials, reporting shorter survival in programmed death-ligand 1 (PD-L1) negative patients receiving immunotherapy. Final results from these trials are unknown. OBJECTIVE: To compare survival in cisplatin-ineligible mUC patients receiving first-line immunotherapy versus carboplatin-based chemotherapy. DESIGN, SETTING, AND PARTICIPANTS: We conducted a retrospective cohort study of 2,017 mUC patients receiving first-line carboplatin-based chemotherapy (n=1,530) or immunotherapy (n=487) from January 1, 2011 to May 18, 2018 using the Flatiron Health electronic health record-derived database. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was overall survival (OS), comparing 12- and 36-month OS, and hazard ratios before and after 12 months. Propensity score-based inverse probability of treatment weighting (IPTW) was used to address confounding in Kaplan-Meier and Cox regression model estimates of comparative effectiveness. RESULTS AND LIMITATIONS: IPTW-adjusted OS rates in the immunotherapy group were lower at 12 months (39.6% [95% CI 34.0-45.3%] versus 46.1% [95% CI 43.4-48.8%]) but higher at 36 months (28.3% [95% CI 21.8-34.7%] versus 13.3% [95% CI 11.1-15.5%]) relative to the chemotherapy group. Immunotherapy treatment demonstrated inferior OS during the first 12 months relative to carboplatin-based chemotherapy (IPTW-adjusted HR 1.37, 95% CI 1.15-1.62), but superior OS beyond 12 months (IPTW-adjusted HR 0.50, 95% CI 0.30-0.85). Limitations include retrospective design and potential unmeasured confounding. CONCLUSIONS: In the setting of mUC, clinicians and patients should carefully consider how to balance the short-term benefit of chemotherapy against the long-term benefit of immunotherapy. PATIENT SUMMARY: To determine the optimal first-line therapy for metastatic bladder cancer patients who are unfit for cisplatin, we compared carboplatin-based chemotherapy versus immunotherapy using real-world data. Survival in the first year of treatment was lower with immunotherapy relative to chemotherapy, but for patients surviving beyond the first year, immunotherapy was superior.

ObjectiveTo investigate the association between antibiotic therapy and the efficacy of intravesical BCG therapy in patients with high-risk non-muscle invasive bladder cancer (NMIBC).MethodsThis study involved the retrospective review of medical records of patients who underwent transurethral resection of bladder tumors for high-risk NMIBC followed by intravesical BCG therapy between 2008 and 2017. Patients were categorized as none, short- (2-6 days), and long-course use (≥7 days) based on the duration of antibiotic treatment concurrent with or initiated ≤30 days before BCG therapy. Oncologic outcomes, including recurrence-free survival and progression-free survival, were analyzed.ResultsOf the 276 patients enrolled in the study, 162 (58.7%) had pathologic T1 disease and 206 (80.2%) had high-grade disease. Concurrently with or prior to BCG therapy, 114 patients had (41.3%) received short-course antibiotic therapy, and 96 (34.8%) patients had received long-course antibiotics. The 5-year recurrence-free survival (62.2% vs 26.9%; log rank, p ConclusionLong-course antibiotic treatment concurrently with or prior to intravesical BCG adversely influenced disease recurrence and progression outcomes in patients with high-risk NMIBC. Careful use of antibiotics may be required to enhance the efficacy of intravesical BCG therapy. Further mechanistic and prospective studies are warranted.

Purpose: To investigate programmed cell death-ligand 1 (PD-L1) expression status and the clinical and pathological factors related to its expression in urothelial carcinoma (UC) patients.Materials and Methods: Data from 761 UC patients who underwent testing for PD-L1 expression using the VENTANA (SP-142 immunohistochemistry assay) for measuring PD-L1 expression according to the manufacturer's protocol between February 2016 and July 2019 were retrospectively reviewed. Patients were categorized into three groups based on the percentage of tumor area covered by PD-L1-expressing tumor-infiltrating immune cells (ICs) as follows: IC0 (

INTRODUCTION AND OBJECTIVE:Incontinence after radical prostatectomy is poorly understood. Preoperative factors such as age and membranous urethral length (MUL) have been shown to correlate with pos...

INTRODUCTION AND OBJECTIVE:Preoperative chronic kidney disease (CKD) status may affect disease outcomes in patients with upper tract urothelial carcinoma (UTUC). We evaluated the impact of preopera...

Background: Sarcomatoid urothelial carcinoma with chondrosarcomatous differentiation (SUCCD) in the ureter has a poor prognosis and is a rare histological variant of ureteral cancer. The majority of ureteral cancers are urothelial carcinomas. Clinical case: We present a case of well-controlled metastatic SUCCD treated with an immune checkpoint inhibitor after radical surgery and failed adjuvant chemotherapy. The patient was a 68-year-old male with previous cure history of cT1 staged esophageal squamous cell carcinoma referred to the urology department for a right hydronephroureterosis complicating an intraureteral enhancing mass. After ureteroscopic biopsy and intraureteral urine cytology, atypical pleomorphic cell nests and chondroid tissue consistent with sarcomatoid urothelial carcinoma were observed. The patient underwent a successful radical right nephroureterectomy with bladder cuffing. The final diagnosis was a pT3N0 sarcomatoid urothelial carcinoma (heterologous component: chondrosarcoma > 95%) located at the right distal ureter and right renal calyx with infiltration of the periureteric fat and renal parenchyma of the renal capsule. On the postoperative one-month follow-up computed tomography scan, multiple enlarged lymph nodes and metastatic lung nodules were detected. The initiated three cycles of gemcitabine-carboplatin therapy was marked by disease progression; thus, second-line therapy with atezolizumab was used for treatment. After five cycles of atezolizumab, the tumors showed a partial response without any grade 3 complications. Conclusion: The recurrent metastatic SUCCD showed good response to the immune checkpoint inhibitor after unsuccessful therapy with radical surgery and first line chemotherapy despite the unfavorable outcome of the pathology.

Clear cell papillary renal cell carcinoma (ccpRCC) was recently established as a distinct type of epithelial neoplasm by the International Society of Urological Pathology Vancouver Classification of Renal Neoplasia. Here, we report a case of partial nephrectomy for a ccpRCC detected during the routine follow-up of a previously treated liposarcoma in a 70-year-old male patient. The patient was referred to the urology department for a right-sided renal mass (size: 2 cm) detected during routine annual imaging follow-up for a malignant right inguinal fibrous histocytoma and liposarcoma that had been diagnosed 6 and 4 years earlier, respectively, and treated with surgery and adjuvant radiation therapy. Following partial nephrectomy, the renal mass was pathologically diagnosed as ccpRCC, and immunohistochemistry revealed carbonic anhydrase 9 (CA9) expression. No recurrences or metastases were detected on follow-up imaging for 6 months. This is the first report of partial nephrectomy for incidentally discovered CA9-positive ccpRCC.

Urothelial bladder cancer (UBC) is one of the most prevalent and aggressive malignancies. Recent evidence indicates that the tumor microenvironment (TME), including a variety of immune cells, is a critical modulator of tumor initiation, progression, evolution, and treatment resistance. Mast cells (MCs) in UBC are possibly involved in tumor angiogenesis, tissue remodeling, and immunomodulation. Moreover, tumor-infiltration by MCs has been reported in early-stage UBC patients. This infiltration is linked with a favorable or unfavorable prognosis depending on the tumor type and location. Despite the discrepancy of MC function in tumor progression, MCs can modify the TME to regulate the immunity and infiltration of tumors by producing an array of mediators. Nonetheless, the precise role of MCs in UBC tumor progression and evolution remains unknown. Thus, this review discusses some critical roles of MCs in UBC. Patients with UBC are treated at both early and late stages by immunotherapeutic methods, including intravenous bacillus Calmette–Guérin instillation and immune checkpoint blockade. An understanding of the patient response and resistance mechanisms in UBC is required to unlock the complete potential of immunotherapy. Since MCs are pivotal to understand the underlying processes and predictors of therapeutic responses in UBC, our review also focuses on possible immunotherapeutic treatments that involve MCs.

Locally advanced or metastatic urothelial bladder cancer (a/m UBC) is currently treated using platinum-based combination chemotherapy. Immune checkpoint inhibitors (ICIs) are the preferred second-line treatment options for cisplatin-eligible a/m UBC patients and as first-line options in cisplatin-ineligible settings. However, the response rates for ICI monotherapy are modest (~20%), which necessitates the exploration of alternative strategies. Dysregulated activation of fibroblast growth factor receptor (FGFR) signaling enhances tumor proliferation, survival, invasion, angiogenesis, and immune evasion. The recent U.S. Food and Drug Administration approval of erdafitinib and the emergence of other potent and selective FGFR inhibitors (FGFRis) have shifted the treatment paradigm for patients with a/m UBC harboring actionable FGFR2 or FGFR3 genomic alterations, who often have a minimal-to-modest response to ICIs. FGFRi–ICI combinations are therefore worth exploring, and their preliminary response rates and safety profiles are promising. In the present review, we summarize the impact of altered FGFR signaling on a/m UBC tumor evolution, the clinical development of FGFRis, the rationale for FGFRi–ICI combinations, current trials, and prospective research directions.

Objective: Often a sick or an anxious person can experience pain or anxiety relief if another person holds his or her hand. In this study, we conducted investigations to determine whether hand-holding during cystoscopy decreases patient anxiety, pain, and dissatisfaction while at the same time increasing patient comfort and tolerance during the procedure. Patients and Methods: Eighty-six male patients who underwent flexible cystoscopy between November 2015 and March 2017 were randomized as follows: hand-holding (group I, n = 43) or non-hand-holding (group II, n = 43) during the procedure. Before flexible cystoscopy, lidocaine gel was instilled in the urethra. Patients’ anxiety levels were quantified using the State-Trait Anxiety Inventory. A visual analog scale (0–10) was used for self-assessment of satisfaction, discomfort, and willingness to undergo repeat cystoscopy. Results: Demographic characteristics, mean age, procedure duration, procedure indications, and preprocedural analyses did not differ significantly between the 2 groups. In group I, the postprocedural mean anxiety level, pain score, heart rate, and systolic blood pressure were significantly lower compared with those in group II (p = 0.009, p = 0.003, p = 0.022, and p = 0.014, respectively). In group I, postprocedural mean satisfaction score were higher, and patients were more likely to undergo a repeat cystoscopy, compared with those in group II (p = 0.001 and p = 0.004, respectively). Conclusions: Hand-holding during cystoscopy significantly reduced patients’ feelings of anxiety, pain, discomfort, and dissatisfaction. Hand-holding served as a simple, inexpensive, and effective adjunct to sedation during cystoscopy.

Objective The present study aimed to determine the effect of an increasing number of predisposing atheroembolic risk factors on the development of chronic kidney disease (CKD) after partial nephrectomy (PN) in patients with T1-stage renal cell carcinoma (RCC). Methods The study included 147 patients with T1-stage RCC with a normal contralateral kidney and without preoperative CKD, who underwent open (OPN, N = 83, 56.5%) or laparoscopic PN (LPN, N = 64, 43.5%) between 2003 and 2014. Postoperative CKD was defined as an estimated glomerular filtration rate

In the present study we examined the effect of the Prognostic Nutritional Index (PNI) on the overall survival (OS) and progression-free survival (PFS) of patients with metastatic renal cell carcinoma (RCC) treated with targeted therapy.The study included 125 patients with metastatic RCC. Pretreatment PNI was calculated as 10 × serum albumin (g/dL) + 0.005 × total lymphocyte count (per mmThe median follow-up time was 45.3 months (interquartile range, 23.7-77.3 months). Decreased PNI was significantly associated with older female patients, poor Eastern Cooperative Oncology Group performance status, types of initial drug, and increased Memorial Sloan Kettering Cancer Center (MSKCC) and Heng risk score (P .05). An increase in the PNI of 1 unit was associated with a 10% decrease in the risk of death from RCC (hazard ratio, 0.90; P .001). In the multivariable analysis, the PNI was an independent prognostic factor for OS (P .001). In intermediate-risk patients according to MSKCC and Heng risk criteria, OS was better in the high PNI group than in the low PNI group (P = .0136 and P = .0009, respectively).PNI is an independent prognostic factor in patients with metastatic RCC treated with targeted therapy. When used as an adjunct, it increases the prognostic accuracy of established factors and could be a valuable tool for tailoring surveillance, patient counseling, and clinical trial design.

Background Docetaxel is the preferred chemotherapeutic agent for hormone-refractory prostate cancer (PC) patients. However, patients eventually develop docetaxel resistance, and no effective treatment options are available for them. Objective We aimed to establish docetaxel resistance in castration-resistant prostate cancer (CRPC) cell lines (DU145/TXR, PC-3/TXR, and CWR22/TXR) and characterized transcriptional changes upon acquiring resistance to the docetaxel. Methods Human PC cells (DU145, PC-3, CWR22) and all docetaxel-resistant cells were maintained in Roswell Park Memorial Institute Medium (RPMI) 1640 media supplemented with 10% fetal bovine serum and 1% penicillin/streptomycin. ABCB1 was detected by using both parental and docetaxel-resistant CRPCs prepared for flow cytometry. For the evaluation of tumor-suppressive effects under each chemotherapeutic agent, subcutaneous xenografts of DU145 or DU145/TXR were implanted at the mouse flank. Results The P-glycoprotein-encoding gene ABCB1 was distinctively upregulated in the resistant cells, and its overexpression played an essential role in docetaxel resistance in CRPC. When tested for the cytotoxicity of gemcitabine, another option for chemotherapy, the docetaxel-resistant cells were shown to become sensitive to the drug, implying additional phenotypic transformation in the docetaxel-resistant cells. Studies using xenograft animal models demonstrated that the growth of tumors composed of both docetaxel-sensitive and docetaxel-resistant cells was deterred most profoundly when docetaxel and gemcitabine were administered together. Conclusion This study suggests that when a drug develops therapeutic resistance, sensitivity tests could be another option, ultimately providing insight into a novel alternative clinical strategy.

Background The differences in progression-free survival (PFS) and cancer-specific survival (CSS) of metastatic renal cell carcinoma (mRCC) patients according to treatment, type of metastasis, and Heng criteria risk are unclear. In this study, we compared survival according to various such parameters. Methods Between 2000 to 2014, 214 mRCC patients, of whom 171 (79.9%) were intermediate-risk and 43 (20.1%) were poor-risk, were retrospectively selected; 126 (58.9%) patients were treated with immunotherapy (IT) and 88 (41.1%) with targeted therapy (TT). Moreover, 144 patients had synchronous mRCCs (67.3%, SM) and 70 had metachronous mRCCs (32.7%, MM). The Kaplan-Meier method and log-rank test were used to compare progression-free survival (PFS) and CSS. Results During a median 4.2 (1.0–70.4) months of systemic treatment and 98.3 (4.8–147.6) months of follow-up, the median PFS and CSS were 4.7 (95% confidence interval [CI]: 3.8–5.5) and 13.8 (95% CI, 9.8–18.3) months, respectively. The PFS and CSS were significantly better in the MM (5.9 and 21.3 months) and intermediate-risk groups (5.2 and 18.3 months) than those in the SM (4.4 and 9.6 months) and poor-risk groups (2.7 and 5.8 months), respectively (p 0.05). Conclusion Dividing patients into specific subcategories helps to better predict therapeutic outcomes. Electronic supplementary material The online version of this article (10.1186/s12885-019-5900-1) contains supplementary material, which is available to authorized users.

INTRODUCTION AND OBJECTIVES:Most patients with non-muscle invasive bladder cancer (NMIBC) who receive standard-of-care TURBT and Bacillus Calmette-Guerin (BCG) experience recurrence. For BCG-unresp...

Purpose We aimed to evaluate the efficacy and safety of the use of docetaxel plus androgen deprivation therapy (ADT) for metastatic hormone-sensitive prostate cancer (mHSPC) in Korean patients. Materials and methods This study was conducted retrospectively. In total, 61 Korean patients with mHSPC who used docetaxel plus ADT were identified from medical records. Patients received docetaxel plus ADT at a dose of 75 mg/m2 every 3 weeks for 6 cycles. We evaluated prostate-specific antigen (PSA) response, PSA progression, progression to castration-resistant prostate cancer (CRPC), clinical progression, and adverse events. Results Most of the patients had high volume disease (98.3%) and 83.6% had a Gleason score of 8 or higher. The median PSA level at the start of ADT was 131.4 ng/mL. The percentage of patients whose PSA levels decreased to less than 0.2 ng/mL at 3, 6, and 12 months were 28.3%, 41.0%, and 45.0%, respectively. During a median of 12.0 months after treatment, PSA progression occurred in 13.3% of patients. Clinical progression and progression to CRPC were observed in 15.1% and 14.8%, respectively. Neutropenia grade ≥3 and febrile neutropenia occurred in 63.5% and 11.5%, respectively. Conclusions Comparing our findings with those of the prior chemohormonal therapy versus androgen ablation randomized trial for extensive disease in prostate cancer (CHAARTED) study, in Korean patients, the use of docetaxel plus ADT for mHSPC showed similar results for early oncologic outcomes including PSA response and time to clinical progression. However, we observed a higher rate of adverse events, which should be considered seriously.

451 Background: Pembrolizumab (pembro) was approved in January 2020 for treatment of HR NMIBC based on interim results from 96 patients (pts) in the open-label, single-arm, multicenter, phase II KEYNOTE-057 (NCT02625961) study. Here we present updated efficacy and safety results with extended minimum follow-up of 26.3 mo from KEYNOTE-057 cohort A. Methods: Pts aged ≥18 years with histologically confirmed Bacillus Calmette-Guérin (BCG)–unresponsive HR carcinoma in situ (CIS), with or without papillary tumors, who were ineligible for or declined radical cystectomy (RC) received pembro 200 mg Q3W for up to 24 mo or until disease persistence, recurrence, progression, or unacceptable toxicity. Primary end point: complete response rate (CRR). Key secondary end points: duration of response (DOR) and safety. Results: Overall, 101 pts received pembro and 96 were included in the efficacy analysis (5 patients did not meet BCG-unresponsive criteria). Median age was 73 years (range, 44-92), and pts received a median of 12.0 (range, 7.0-45.0) BCG instillations. Median time from enrollment to data cutoff date of May 25, 2020, was 36.4 mo (range, 26.3-48.5). Of 96 pts, CRR was 40.6% (95% CI, 30.7-51.1) at first evaluable disease assessment, and median DOR was 16.2 mo (range, 0.0+ to 36.2). Of 39 responders, 13 (33.3%) remained in CR ≥18 mo and 9 (23.1%) remained in CR ≥24 mo as of the data cutoff date. No pt progressed to MIBC while on study treatment based on protocol-specified disease assessments. CRR was generally consistent with the primary analysis across protocol-prespecified subgroups, including PD-L1 expression status. Forty pts (41.7%) underwent RC after discontinuation of pembro; 35 pts (88%) had no pathologic upstaging to MIBC, 2 (5%) had no available pathology data, and 3 (8%) had evidence of MIBC (all nonresponders); 1 pt had pT2N0 disease at 60 days after the last pembro dose, 1 pt had pT2N1 disease (involvement of a single perivesical lymph node) at 86 days after the last pembro dose, and 1 pt had pT3N1 disease at 457 days after the last pembro dose. For other subsequent treatments, 30 of 96 pts (31.3%) received additional intravesical therapy (eg, BCG), 27 of 96 (28.1%) underwent local procedures (eg, TURBT), and 10 of 96 (10.4%) received systemic therapy. In 101 pts, treatment-related AEs (TRAEs) occurred in 67 pts (66.3%); most frequent were diarrhea, fatigue, and pruritus (10.9% each). Grade 3/4 TRAEs occurred in 13 pts (12.9%). Twenty-two pts (21.8%) experienced immune-related AEs; 3.0% were grade 3-4. Seven pts (6.9%) discontinued due to TRAEs. There were no grade 5 TRAEs. Conclusions: With extended follow-up, pembro continued to show durable and clinically meaningful activity in pts who had HR BCG-unresponsive CIS with or without papillary tumors and who were ineligible for or declined RC. No new safety risks were identified. Clinical trial information: NCT02625961.

Background: Sarcomatoid urothelial carcinoma with chondrosarcomatous differentiation (SUCCD) in the ureter has a poor prognosis and is a rare histological variant of ureteral cancer. The majority of ureteral cancers are urothelial carcinomas. Clinical case: We present a case of well-controlled metastatic SUCCD treated with an immune checkpoint inhibitor after radical surgery and failed adjuvant chemotherapy. The patient was a 68-year-old male with previous cure history of cT1 staged esophageal squamous cell carcinoma referred to the urology department for a right hydronephroureterosis complicating an intraureteral enhancing mass. After ureteroscopic biopsy and intraureteral urine cytology, atypical pleomorphic cell nests and chondroid tissue consistent with sarcomatoid urothelial carcinoma were observed. The patient underwent a successful radical right nephroureterectomy with bladder cuffing. The final diagnosis was a pT3N0 sarcomatoid urothelial carcinoma (heterologous component: chondrosarcoma > 95%) located at the right distal ureter and right renal calyx with infiltration of the periureteric fat and renal parenchyma of the renal capsule. On the postoperative one-month follow-up computed tomography scan, multiple enlarged lymph nodes and metastatic lung nodules were detected. The initiated adjuvant three cycles of gemcitabine-carboplatin therapy was marked by disease progression; thus, second-line therapy with atezolizumab was used for treatment. After five cycles of atezolizumab, the tumors showed a partial response without any grade 3 complications. Conclusion: The recurrent metastatic SUCCD showed good response to the immune checkpoint inhibitor after unsuccessful therapy with radical surgery and first line chemotherapy despite the unfavorable outcome of the pathology.

5041 Background: Pembro was recently approved for the treatment of HR NMIBC based on results from the phase 2 KEYNOTE-057 (NCT02625961) study. Herein we present safety, efficacy, and posttreatment outcomes with > 2 y follow-up from KEYNOTE-057 cohort A. Methods: Patients with histologically confirmed HR BCG-unresponsive carcinoma in situ (CIS) with or without papillary tumors who received adequate BCG therapy and were ineligible for or opted out of radical cystectomy (RC) received pembro 200 mg Q3W for up to 2 y or until disease recurrence, progression, or unacceptable toxicity. The primary end point was complete response rate (CRR). Key secondary end points were duration of response (DOR) and safety. Results: Overall, 102 patients were initially enrolled, and 96 were included in the efficacy analysis. Median time from enrollment to data cut off was 28.4 months (range, 18.2-40.5). CRR was 40.6% (95% CI, 30.7-51.1), and median DOR was 16.2 months (range, 0+ to 30.4+). Among 39 patients with CR, 18 (46.2%) had a DOR ≥12 months. No patient’s disease progressed to muscle-invasive or metastatic bladder cancer while on study treatment. Median PFS and OS were not reached. At 12 months, PFS was 82.7% and OS was 97.9%. A total of 36 patients (37.5%) underwent RC after discontinuation from study treatment, which included 9 of 22 patients (40.9%) who had recurrence after initial CR and 27 of 57 (47.4%) nonresponders. Of the 36 who underwent RC, 33 (91.6%) had no pathological upstaging to MIBC and 3 (8.3%) had at least pT2 disease at time of RC. For subsequent treatments other than RC, 27 of 96 (28.1%) patients received additional intravesical therapy (eg, BCG, gemcitabine, or mitomycin), 21 of 96 (21.9%) underwent local procedures (eg, TURBT), and 3 of 96 (3.1%) received systemic therapy (eg, pembro). In 102 patients treated with pembro, treatment-related AEs (TRAEs) occurred in 67 (65.7%) patients; most frequently reported TRAEs were fatigue, pruritus, and diarrhea (10.8% each). Grade 3/4 TRAEs occurred in 13 patients (12.7%), and 21 patients (20.6%) experienced immune-mediated AEs. There were no grade 5 TRAEs. Conclusions: After > 2 y of follow-up, durable and clinically meaningful activity of pembro was observed in patients who had HR BCG-unresponsive CIS with or without papillary tumors and who were ineligible for or opted out of RC. Pembro did not seem to limit the opportunity for subsequent therapies, including RC. The safety profile was consistent with what is reported in the literature. Clinical trial information: NCT02625961 .

Purpose: This study aimed to compare progression-free survival (PFS), overall survival (OS), and cancer-specific survival (CSS) in Heng intermediate-risk patients with metastatic renal cell carcinoma (mRCC) treated with first-line immunotherapy (IT) or targeted therapy (TT). Materials and Methods: From 2000 to 2017, a total of 186 intermediate-risk mRCC patients treated with first-line IT (n=64, 34.4%) or TT (n=122, 65.6%) were retrospectively evaluated for PFS, OS, and CSS using the Kaplan–Meier method with log-rank test and Cox proportional hazards models for their risk factors with a p-value for significance of

Background For the expanding population of bladder cancer survivors in Korea, the development of subsequent cancers is a significant concern. Here, we provide the second primary cancer incidence rates and types in Korean patients with bladder cancer. Methods Using population-based data from the Korea Central Cancer Registry from 1993 to 2013, we studied the standardized incidence ratios among 48,875 individuals with an initial diagnosis of bladder cancer. Standardized incidence ratios for second primary cancers were evaluated according to age at diagnosis, latency, diagnostic year, and treatment. Results Over the same period, the overall risk of a second primary cancer was reduced by 6% in patients with bladder cancer compared with the development of a new malignancy in the general population (standardized incidence ratio = 0.94; 95% CI, 0.91–0.97, p

Objective The aim of this study was to predict the discriminating prognostic power of the neutrophil-to-lymphocyte ratio for overall survival in patients with metastatic renal cell carcinoma and to make a new model using the neutrophil-to-lymphocyte ratio. Methods From 2007 to 2014, 190 patients with metastatic renal cell carcinoma treated with either systemic immunotherapy or/and vascular endothelial growth factor-targeted therapy were enroled. A multivariable proportional hazard model was developed to investigate the effects of the neutrophil-to-lymphocyte ratio as predictive prognostic factors for overall survival. This new model was incorporated into the current Heng risk model to validate a modified prognostic classification for overall survival. Results In multivariable analysis, a high neutrophil-to-lymphocyte ratio [hazard ratio (HR) = 1.65] was a significant independent predictor of shorter overall survival (P = 0.005). Additional neutrophil-to-lymphocyte ratio markers improved the discriminating power of the Heng risk classification, as compared to the existing classification model (C-statistic: 0.7198 vs. 0.6943, P = 0.008). The reclassification of patient prognostic categories using the new model showed a total overall net improvement of 61.4% (P < 0.001). Conclusion The neutrophil-to-lymphocyte ratio was a significant prognostic factor of overall survival in metastatic renal cell carcinoma patients treated with systemic therapy. Adding the neutrophil-to-lymphocyte ratio to the Heng model significantly improved the discriminatory power of risk prediction in metastatic renal cell carcinoma.