Second-line Pembrolizumab for Metastatic Urothelial Carcinoma: Differences in Treatment Outcomes According to the Primary Site.

BACKGROUND/AIM: To evaluate the difference in the clinical efficacy and safety of pembrolizumab between patients with metastatic upper tract urothelial carcinoma (UTUC), which includes renal pelvic urothelial carcinoma (UC) and ureteral UC, and those with metastatic lower tract urothelial carcinoma (LTUC). PATIENTS AND METHODS: A total of 752 patients who received pembrolizumab for the treatment of chemoresistant UC were retrospectively analyzed. We compared progression-free survival (PFS), overall survival (OS) and adverse events (AEs) in patients with renal pelvic UC, ureteral UC, and LTUC. RESULTS: The median follow-up period was 42.5 [interquartile range (IQR)=35.1-47.4] months. The primary tumor site was in the upper tract in 362 (48.1%) patients [renal pelvis, n=219 (60.5%); ureter, n=143 (39.5%)] and in the lower tract in 390 (51.9%) patients. The estimated glomerular filtration rate before pembrolizumab treatment in the UTUC group was significantly lower than that in the LTUC group (p<0.001). The median PFS in the UTUC and LTUC groups was 3.4 months, respectively (p=0.271). The median OS in the UTUC and LTUC groups was 10.1 months and 11.7 months, respectively (p=0.195). In an analysis of UTUC divided into renal pelvic UC, ureteral UC, and LTUC, patients with renal pelvic UC had a significantly poorer prognosis in comparison to the other two groups (p=0.041). The incidence of any-grade AEs (51.7% vs. 47.9%, p=0.343) and grade ≥3 AEs (12.2% vs. 12.8%, p=0.826) in the two groups was not statistically significantly different. CONCLUSION: No significant differences were found between the UTUC and LTUC groups with regard to the oncological outcomes and safety of pembrolizumab. Patients with renal pelvic UC had a significantly poorer prognosis than those with other ureteral UCs and LTUCs.

[A Case of Chromophobe Renal Cell Carcinoma Producing Interleukin-6 with Stauffer Syndrome].

A 41-year-old male consulted a local doctor with fever and left flank pain. He was introduced to our hospital for a left renal mass detected by ultrasonography. Blood analysis revealed elevated white blood cell count, C-reactive protein, bilirubin and aspartate transaminase. Computed tomography demonstrated a left renal mass (expansive growth), which was 11 cm in maximum diameter and enhanced moderately at the corticomedullary phase. Neither distant metastasis, infectious findings nor hepatobiliary abnormalities were observed. The patient underwent laparoscopic radical nephrectomy with a clinical diagnosis of non-clear cell renal cell carcinoma cT2bN0M0 with Stauffer syndrome. The surgery required 186 minutes of insufflation, and estimated blood loss and specimen weight were 44 ml and 695 g, respectively. There were no complications. Histopathological diagnosis was chromophobe renal cell carcinoma-classic pattern (ChRCC-C), which was producing interleukin-6 in the tumor cytoplasm immunohistochemically. Postoperatively, there was early defervescence with complete resolution of the Stauffer syndrome. No relapse or liver dysfunction has occurred at 5 years after operation. To our knowledge, this is the first reported case in the literature of ChRCC accompanied by Stauffer syndrome.

Site-specific Risk Stratification Models for Postoperative Recurrence and Survival Prediction in Patients with Upper Tract Urothelial Carcinoma Undergoing Radical Nephroureterectomy: Better Stratification for Adjuvant Therapy.

Background: Site-specific postoperative risk models for localized upper tract urothelial carcinoma (UTUC) are unavailable. Objective: To create specific risk models for renal pelvic urothelial carcinoma (RPUC) and ureteral urothelial carcinoma (UUC), and to compare the predictive accuracy with the overall UTUC risk model. Design setting and participants: A multi-institutional database retrospective study of 1917 UTUC patients who underwent radical nephroureterectomy (RNU) between 2000 and 2018 was conducted. Outcome measurements and statistical analysis: A multivariate hazard model was used to identify the prognostic factors for extraurinary tract recurrence (EUTR), cancer-specific death (CSD), and intravesical recurrence (IVR) after RNU. Patients were stratified into low-, intermediate-, high-, and highest-risk groups. External validation was performed to estimate a concordance index of the created risk models. We investigated whether our risk models could aid decision-making regarding adjuvant chemotherapy (AC) after RNU. Results and limitations: The UTUC risk models could stratify the risk of cumulative incidence of three endpoints. The RPUC- and UUC-specific risk models showed better stratification than the overall UTUC risk model for all the three endpoints, EUTR, CSD, and IVR (RPUC: concordance index, 0.719 vs 0.770, 0.714 vs 0.794, and 0.538 vs 0.569, respectively; UUC: 0.716 vs 0.767, 0.766 vs 0.809, and 0.553 vs 0.594, respectively). The UUC-specific risk model can identify the high- and highest-risk patients likely to benefit from AC after RNU. A major limitation was the potential selection bias owing to the retrospective nature of this study. Conclusions: We recommend using site-specific risk models instead of the overall UTUC risk model for better risk stratification and decision-making for AC after RNU. Patient summary: Upper tract urothelial carcinoma comprises renal pelvic and ureteral carcinomas. We recommend using site-specific risk models instead of the overall upper tract urothelial carcinoma risk model in risk prediction and decision-making for adjuvant therapy after radical surgery.

Efficacy of combined androgen blockade therapy in patients with metastatic hormone-sensitive prostate cancer stratified by tumor burden.

OBJECTIVE: To determine the effect of combined androgen blockade with a first-generation anti-androgen on the prognoses of metastatic hormone-sensitive prostate cancer patients stratified by tumor burden. METHODS: We retrospectively analyzed the cases of metastatic hormone-sensitive prostate cancer patients who were treated with androgen deprivation therapy in 2008-2017 at 30 institutions in Japan. To compare the overall survival and progression-free survival rates of the patients treated with castration monotherapy and combined androgen blockade, we carried out a Cox proportional hazards regression analysis using both inverse probability of treatment weighting and instrumental variables methods. High-burden disease was defined as the presence of four or more bone metastases and/or visceral metastasis. RESULTS: Of 2048 patients, 702 (34.3%) and 1346 (65.7%) patients were classified as the low- and high-burden groups, respectively. In each group, >80% of the patients were treated with combined androgen blockade. Although there was no significant between-group difference in the overall survival according to the androgen deprivation therapy method, in the high-burden group the progression-free survival of the combined androgen blockade-treated patients was significantly better than that of patients treated with castration monotherapy: inverse probability of treatment weighting method, hazard ratio 0.49, 95% confidence interval 0.34-0.71; instrumental variables method, hazard ratio 0.80, 95% confidence interval 0.60-0.98. CONCLUSION: In the high-burden group, combined androgen blockade with a first-generation anti-androgen resulted in superior progression-free survival compared with castration monotherapy. For well-selected metastatic hormone-sensitive prostate cancer patients, the use of combined androgen blockade might still have some suitable scenarios.

Impact of histological variants on outcomes in patients with urothelial carcinoma treated with pembrolizumab: a propensity score matching analysis.

OBJECTIVES: To assess the impact of histological variants on survival and response to treatment with pembrolizumab in patients with chemo-resistant urothelial carcinoma (UC). PATIENTS AND METHODS: The medical records of 755 patients with advanced UC who received pembrolizumab were reviewed retrospectively. Patients were classified into pure UC (PUC) and each variant. Best overall response (BOR) and overall survival (OS) were compared between the groups using a propensity score matching (PSM). RESULTS: Overall, 147 (19.5%) patients harboured any histological variant UC (VUC). After PSM, there were no significant differences in the objective response rate (ORR, 24.5% vs 17.3%, P = 0.098) or disease control rate (DCR, 36.7% vs 30.2%, P = 0.195) when comparing patients with any VUC and PUC. Furthermore, any VUC, as compared with PUC, was associated with a similar risk of death (hazard ratio [HR] 0.90, 95% confidence interval [CI] 0.68-1.20; P = 0.482). Squamous VUC, which was the most frequent variant in the cohort, had a comparable ORR, DCR and OS as compared with PUC or non-squamous VUC. The patients with sarcomatoid VUC (n = 19) had significantly better ORR (36.8%, P = 0.031), DCR (52.6%, P = 0.032), and OS (HR 0.37, 95% CI 0.15-0.90; P = 0.023) compared to patients with PUC. CONCLUSIONS: The presence of variant histology did not seem to affect BOR or OS after pembrolizumab administration in patients with chemo-resistant UC. The patients with sarcomatoid VUC achieved favourable responses and survival rates compared to PUC.

Impact of prior intravesical bacillus Calmette-Guerin therapy on the effectiveness of pembrolizumab for patients with metastatic urothelial carcinoma.

OBJECTIVE: The aim of this study was to determine whether a history of treatment for non-muscle invasive bladder cancer (NMIBC), including intravesical bacillus Calmette-Guerin (BCG) therapy, affects the treatment outcomes of pembrolizumab in patients with metastatic, chemo-resistant urothelial carcinoma (UC). MATERIALS AND METHODS: The clinicopathological data of 755 patients with metastatic, chemo-resistant UC who received pembrolizumab were retrospectively reviewed. Best overall response and overall survival (OS) from the initiation of pembrolizumab were analyzed with regard to the history of NMIBC treatment and BCG usage using propensity score matching (PSM). RESULTS: A total of 155 (20.5%) patients had a history of NMIBC treatment, of which 97 (12.8%) had received intravesical BCG therapy. When compared to patients without a NMIBC history (median 10.0 months), the OS from the initiation of pembrolizumab for patients with a NMIBC history (13.3 months, HR [95% CI] 0.79 [0.62-1.02], P = 0.073), those with a NMIBC history and BCG (12.1 months, HR 0.87 [0.64-1.17], P = 0.356), or those with a NMIBC history but not BCG (14.5 months, HR 0.68 [0.45-1.12], P = 0.061) were not significantly different. This tendency was robust after 1:1 or 1:2 PSMs. The objective response rate (ORR, 24.5% vs. 31.0%, P = 0.222) and disease control rate (DCR, 56.1% vs. 52.1%, P = 0.501) of the 155 patients with an NMIBC history did not differ from those of 155 matched patients without an NMIBC history. Among those with an NMIBC history, the prior use of BCG did not affect OS (with vs. without BCG, 12.1 vs. 14.5 months, HR 1.29 [0.80-2.09], P = 0.295), ORR (24.5% vs. 34.0%, P = 0.298) or DCR (57.1% vs. 56.0%, P = 0.908). The ORR in BCG-treated patients was significantly lower than that in those without a NMIBC history (19.8% vs. 33.3%, P = 0.042), whereas DCR between the 2 groups did not differ significantly (55.8% vs. 54.4%, P = 0.855). CONCLUSIONS: Our risk-adjusted analyses revealed that a history of prior NMIBC treatment, including intravesical BCG therapy, did not affect the treatment outcomes of pembrolizumab in metastatic UC patients.

Bacillus Calmette-Guérin-unresponsive non-muscle invasive bladder cancer outcomes in patients without radical cystectomy.

BACKGROUND: Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) is a newly defined subtype that is unlikely to benefit from BCG rechallenge. Radical cystectomy is currently recommended for BCG-unresponsive NMIBC; however, a certain proportion of these patients can be managed with treatments other than that. Herein, we conducted a multicenter retrospective study to analyze the clinical outcomes of BCG-unresponsive NMIBC patients who did not receive radical cystectomy. METHODS: Of the 141 BCG-unresponsive NMIBC patients, 94 (66.7%) received treatment except radical cystectomy. Survival outcomes were calculated from the date of diagnosis using the Kaplan-Meier method and compared using the log-rank test. Prognostic factors were identified using the multivariate Cox regression model. This group was further classified into three groups according to the number of risk factors, and survival outcomes were compared. RESULTS: Multivariate analyses identified low estimated glomerular filtration rate (< 45 ml/min/1.73 m2) and large tumor size (≥ 30 mm) before BCG induction as independent poor prognostic factors for progression-free survival and overall survival, while the latter was also an independent factor for cancer-specific survival. The presence of variant histology was an independent poor prognostic factor for overall survival. The high-risk non-cystectomy group showed a significantly poor prognosis for progression-free survival (hazard ratio: 7.61, 95% confidence interval: 2.11-27.5), cancer-specific survival (10.4, 0.54-70.02), and overall survival (8.28, 1.82-37.7). CONCLUSIONS: Our findings suggest that patients with renal impairment and large tumors should undergo radical cystectomy if the complications and intentions of the patients allow so.

Novel metastatic burden-stratified risk model in de novo metastatic hormone-sensitive prostate cancer.

The metastatic burden is a critical factor for decision-making in the treatment of metastatic hormone-sensitive prostate cancer (HSPC). This study aimed to develop and validate a novel risk model for survival in patients with de novo low- and high-burden metastatic HSPC. The retrospective observational study included men with de novo metastatic prostate cancer who were treated with primary androgen-deprivation therapy at 30 institutions across Japan between 2008 and 2017. We created a risk model for overall survival (OS) in the discovery cohort (n = 1449) stratified by the metastatic burden (low vs high) and validated its predictive ability in a separate cohort (n = 951). Based on multivariate analyses, lower hemoglobin levels, higher Gleason grades, and higher clinical T-stage were associated with poor OS in low-burden disease. Meanwhile, lower hemoglobin levels, higher Gleason grade group, liver metastasis, and higher extent of disease scores in bone were associated with poor OS in patients with high-burden disease. In the discovery and validation cohorts, the risk model using the aforementioned parameters exhibited excellent discriminatory ability for progression-free survival and OS. The predictive ability of this risk model was superior to that of previous risk models. Our novel metastatic burden-stratified risk model exhibited excellent predictive ability for OS, and it is expected to have several clinical uses, such as precise prognostic estimation.

Risk stratification for the prognosis of patients with chemoresistant urothelial cancer treated with pembrolizumab.

The use of immune checkpoint inhibitors to treat urothelial carcinoma (UC) is increasing rapidly without clear guidance for validated risk stratification. This multicenter retrospective study collected clinicopathological information on 463 patients, and 11 predefined variables were analyzed to develop a multivariate model predicting overall survival (OS). The model was validated using an independent dataset of 292 patients. Patient characteristics and outcomes were well balanced between the discovery and validation cohorts, which had median OS times of 10.2 and 12.5 mo, respectively. The final validated multivariate model was defined by risk scores based on the hazard ratios (HRs) of independent prognostic factors including performance status, site of metastasis, hemoglobin levels, and the neutrophil-to-lymphocyte ratio. The median OS times (95% confidence intervals [CIs]) for the low-, intermediate-, and high-risk groups (discovery cohort) were not yet reached (NYR) (NYR-19.1), 6.8 mo (5.8-8.9), and 2.3 mo (1.2-2.6), respectively. The HRs (95% CI) for OS in the low- and intermediate-risk groups vs the high-risk group were 0.07 (0.04-0.11) and 0.23 (0.15-0.37), respectively. The objective response rates for in the low-, intermediate-, and high-risk groups were 48.3%, 28.8%, and 10.5%, respectively. These differential outcomes were well reproduced in the validation cohort and in patients who received pembrolizumab after perioperative or first-line chemotherapy (N = 584). In conclusion, the present study developed and validated a simple prognostic model predicting the oncological outcomes of pembrolizumab-treated patients with chemoresistant UC. The model provides useful information for external validation, patient counseling, and clinical trial design.

Differential prognostic factors in low- and high-burden de novo metastatic hormone-sensitive prostate cancer patients.

Metastatic burden is a critical factor for therapy decision-making in metastatic hormone-sensitive prostate cancer. The present study aimed to identify prognostic factors in men with high- or low-metastatic burden treated with primary androgen-deprivation therapy. The study included 2450 men with de novo metastatic prostate cancer who were treated with primary androgen-deprivation therapy at 30 institutions across Japan between 2008 and 2017. We investigated the prognostic value of various clinicopathological parameters for progression-free survival (PFS) and overall survival (OS) in patients stratified by low- or high-metastatic burden. Among the 2450 men, 841 (34.3%) and 1609 (65.7%) were classified as having low- and high-metastatic burden, respectively. Median PFS of the low- and high-burden groups were 44.5 and 16.1 months, respectively, and the median OS was 103.2 and 62.7 months, respectively. Percentage of biopsy-positive core, biopsy Gleason grade group, T-stage, and N-stage were identified to be differentially prognostic. M1a was associated with worse PFS than was M1b in the low-burden group, whereas lung metastasis was associated with better PFS and OS than was M1b in the high-burden group. Differential prognostic factors were identified for patients with low- and high-burden metastatic prostate cancer. These results may assist in decision-making to select the optimal therapeutic strategies for patients with different metastatic burdens.

Oncological outcomes of a multicenter cohort treated with axitinib for metastatic renal cell carcinoma.

The present study aimed to evaluate the efficacy of the real-world use of axitinib and to develop a prognostic model for stratifying patients who could derive long-term benefit from axitinib. This was a retrospective, descriptive study evaluating the efficacy of axitinib in patients with metastatic renal cell carcinoma that had been treated with 1 or 2 systemic antiangiogenic therapy regimens at 1 of 36 hospitals belonging to the Japan Urologic Oncology Group between January 2012 and February 2019. The primary outcome was overall survival (OS). Using a split-sample method, candidate variables that exhibited significant relationships with OS were chosen to create a model. The new model was validated using the rest of the cohort. In total, 485 patients were enrolled. The median OS was 34 months in the entire study population, whereas it was not reached, 27 months, and 14 months in the favorable, intermediate, and poor risk groups, respectively, according to the new risk classification model. The following 4 variables were included in the final risk model: the disease stage at diagnosis, number of metastatic sites at the start of axitinib therapy, serum albumin level, and neutrophil : lymphocyte ratio. The adjusted area under the curve values of the new model at 12, 36, and 60 months were 0.77, 0.82, and 0.82, respectively. The efficacy of axitinib in routine practice is comparable or even superior to that reported previously. The patients in the new model's favorable risk group might derive a long-term survival benefit from axitinib treatment.

Tumor Location Based Segmentation in Upper-Tract Urothelial Carcinoma Impacts on the Urothelial Recurrence-Free Survival: A Multi-Institutional Database Study.

INTRODUCTION AND OBJECTIVES: The predictive impact of primary tumor location for patients with upper-tract urothelial carcinoma (UTUC) in the presence of concomitant urothelial bladder cancer, along with urothelial recurrence after the curative treatment is still contentious. We evaluated the association between precise tumor location and concomitant presence of urothelial bladder cancer and urothelial recurrence-free survival in patients with UTUC treated by radical nephroureterectomy with a bladder cuff. METHODS: A total of 1,349 patients with localized UTUC (Ta-4N0M0) from a retrospective multi-institutional cohort were studied. We queried four UTUC databases. This retrospective clinical series was of patients with localized UTUC managed by nephroureter-ectomy with a bladder cuff, for whom data were from the Nishinihon Uro-Oncology Collaborative Group registries. Patients with a history of chemotherapy or radiotherapy were excluded from the study. Associations between the location of the tumor and subsequent outcome following nephroureterectomy were assessed using COX multivariate analysis. The location of the tumor was verified by pathological samples. Urothelial recurrence was defined as tumor relapse in any local urothelium, and coded apart from distant metastasis. The median follow-up was 34 months. RESULTS: A total of 887 patients had an evaluation of the tumor location in which 475 patients had pelvic tumors (53.6%), 96 had ureteral tumors in the U1 segment (10.8%), 87 in the U2 segment (9.8%), and 176 in the U3 segment (19.8%). There were 52 patients who had multifocal tumors (5.9%) as follows: 8 (0.9%) in the pelvis and ureter, 11 (1.2%) in U1 + U2, 1 (0.1%) in U1 + U3, 27 (3.0 %) in U2 + U3, and 6 (0.7%) in U1 + U2 + U3. In all, 145 (16.3%) had concomitant bladder tumors. Logistic regression analysis of gender, age, hydronephrosis, cytology, performance status, grade, lymphovascular invasion, pT, pN, and tumor focality showed that tumor location was associated with the presence of concomitant bladder cancer (p = 0.004, HR = 1.265). When the tumor location was stratified into 8 segments, including multifocal tumors, only the U3 segment remained as a predictor for the presence of concomitant bladder cancer (p = 0.002, HR = 2.872). Kaplan-Meier analysis for unifocal disease showed that lower ureter tumors (a combination of U2 and U3) had a worse prognosis for urothelial recurrence than pelvic tumors or upper ureteral tumors (U1) (p < 0.001 for lower ureteral tumors versus pelvic tumors, p = 0.322 for upper ureteral tumor versus pelvic tumor by log rank). Multivariate analysis showed that lower ureter remained as a prognostic factor for urothelial recurrence after adjusting for gender, age, hydronephrosis, urine cytology, lymphovascular invasion, pT, and pN (p < 0.001, HR = 1.469), and a similar tendency was found when the analysis was run for patients without concomitant bladder tumors (p = 0.003, HR = 1.446). Patients with lower ureteral tumors had a higher prevalence of deaths (HR = 2.227) compared to patients with upper ureter tumors. CONCLUSIONS: This multi-institutional study showed that the primary tumor locations were independently associated with the presence of concomitant bladder tumors and subsequent urothelial recurrence.

Risk stratification by means of biological age-related factors better predicts cancer-specific survival than chronological age in patients with upper tract urothelial carcinoma: a multi-institutional database study.

BACKGROUND: Chronological age is an important factor in determining the treatment options and clinical response of patients with upper tract urothelial carcinoma (UTUC). Much evidence suggests that chronological age alone is an inadequate indicator to predict the clinical response to radical nephroureterectomy (RNU). PATIENTS AND METHODS: We retrospectively reviewed the data from 1510 patients with UTUC (Ta-4) treated by surgery. White blood cell (WBC) count, neutrophil-to-lymphocyte ratio, hemoglobin (Hb), platelets, albumin, alkaline phosphatase, lactate dehydrogenase, creatinine, and corrected calcium were tested by the Spearman correlation to indicate the direction of association with chronological age, which yielded significant, negative associations of Hb (p < 0.001) and WBC (p = 0.010) with chronological age. For scoring, we assigned points for these categories as follows; point '0' for Hb >14 (reference) and 13-13.9 [odds ratio (OR): 1.533], point '1' for 12-12.9 (OR: 2.391), point '2' for 11-11.9 (OR: 3.015), and point '3' for <11 (OR: 3.584). For WBC, point '1' was assigned for >9200 (OR: 2.541) and '0' was assigned for the rest; 9200-8500 (reference), 8499-6000 (OR: 0.873), 5999-4500 (OR: 0.772), 4499-3200 (OR: 0.486), and <3200 (OR: 1.277). RESULTS: The 10-year cancer-specific survival (CSS) in the higher risk group with scores of 4 or higher in patients age <60 years was worse than a score of 0, or 1 in age >80 years [mean estimated survival 69.7 months, confidence interval (CI): 33.3-106 versus 103.5. CI: 91-115.9]. The concordance index between biological age scoring and chronological age was 0.704 for CSS and 0.798 for recurrence-free survival. The limitation of the present study is the retrospective nature of the cohort included. CONCLUSIONS: The biological age scoring developed for patients with UTUC undergoing RNU. It was applicable to those with localized disease and performed well in diverse age populations.

General anesthesia with propofol for ovarian teratoma excision associated with anti-N-methyl-D-aspartate receptor encephalitis.

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune disorder caused by production of anti-NMDAR antibodies that is often associated with ovarian teratoma and exhibits various manifestations including psychiatric symptoms, seizures, hypoventilation, and autonomic nerve instability. Patients with this disorder who receive early surgical tumor resection along with immunotherapy have better outcome than the rest of the patients. To establish an anesthetic plan, it is important to understand the pharmacological interaction between the anesthetic agents and the disabled NMDAR, because NMDAR is one of the major sites of action for commonly-used anesthetic agents. Herein, we describe two young female patients with anti-NMDAR encephalitis who required surgical resection of ovarian teratoma under general anesthesia using propofol, remifentanil, and fentanyl. In both of these anesthetic courses, neither psychoneuronal modification nor autonomic instability by propofol was evident. Furthermore, propofol has been reported to suppress the effects of ketamine on the posterior cingulate cortices, which is the area of the brain concerned with psychotomimetic activity and neural damage of NMDAR antagonists. Our cases imply that propofol is safely used in patients with anti-NMDAR encephalitis, although it has some pharmacological effects on NMDAR.

Outcomes of subsequent non-muscle-invasive bladder cancer treated with intravesical Bacillus Calmette-Guérin after radical nephroureterectomy for upper urinary tract urothelial carcinoma.

OBJECTIVES: To describe the clinicopathological characteristics and prognosis of subsequent non-muscle-invasive bladder cancer (NMIBC) after radical nephroureterectomy (RNU) for upper urinary tract urothelial carcinoma (UTUC), and particularly its response to intravesical Bacillus Calmette-Guérin (BCG). PATIENTS AND METHODS: An observational study was conducted in 1463 patients with UTUC who had undergone RNU and in 1555 patients with primary NMIBC. Of the 1463 patients with UTUC, 256 (17%) subsequently developed NMIBC (UTUC-NMIBC group) and were available for the analysis. The clinicopathological background and outcomes, including intravesical recurrence-free survival and bladder progression-free survival, were compared between the patients with UTUC-NMIBC and the patients with primary NMIBC treated with intravesical BCG. Propensity score matching was performed to adjust for the potential differences in the backgrounds of the two groups. To validate the utility of the CUETO scoring model in the UTUC-NMIBC group, risk scores were calculated and compared with the published probabilities for recurrence and progression. RESULTS: Compared with the unadjusted primary NMIBC group (n = 352), the UTUC-NMIBC group (n = 75) were found to have a worse prognosis for intravesical recurrence and progression, before propensity score matching. After propensity score matching for potential confounding factors, however, a worse prognosis was observed only for intravesical recurrence. The validation test of the CUETO scoring model for the UTUC-NMIBC group showed a significant difference in the rate of intravesical recurrence and progression for the 0-4 and 5-6 score groups between the UTUC-NMIBC group and the CUETO risk table reference data. CONCLUSION: Compared with the primary NMIBC group, the UTUC-NMIBC group had a worse prognosis after intravesical BCG, especially with regard to intravesical recurrence. This suggests that patients with UTUC-NMIBC are inherently poor responders to BCG exposure. An optimal treatment strategy and risk scoring model to select patients for adjuvant intravesical BCG, chemotherapy or immediate radical cystectomy should be established.

Biological Behavior and Long-Term Outcomes of Carcinoma In Situ in Upper Urinary Tract Managed by Radical Nephroureterectomy.

PURPOSE: In patients with urothelial carcinoma CIS (carcinoma in situ) generally has a poor prognosis. However, to our knowledge the outcomes of pure/primary CIS and the behavior of CIS concomitant with pTa-pT4 upper tract urothelial carcinoma managed by nephroureterectomy have not been previously specified. We explored the biological and prognostic features of concomitant CIS compared with those of pure/primary CIS. MATERIALS AND METHODS: We queried a multicenter upper tract urothelial carcinoma database. Data from NUOG (Nishinihon Uro-Oncology Group) were analyzed, including patient gender, age, presence of bladder cancer and pT stage. Clinicopathological features were compared between the different subtypes. Cancer specific and overall survival, and the relative excess risk of death were estimated by CIS subtype. RESULTS: We identified 163 patients with CIS in the upper urinary tract, of whom pure/primary CIS was noted in 24.5%. In the concomitant CIS cohort the pathological diagnosis of the nonCIS region was pTa, pT1, pT2, pT3 and pT4 in 4.9%, 22.8%, 25.2%, 44.7% and 1.6% of patients, respectively. The sensitivity of a selective urine cytology test was higher in the pure/primary CIS group than in the concomitant CIS group (60.0% vs 37.4%). At a median followup of 32 months 10-year estimated mean cancer specific survival was 92.4 months (range 83.7 to 101.0) in the overall CIS cohort. Ten-year estimated mean cancer specific survival in patients with pure/primary CIS was significantly longer than in patients with concomitant carcinoma in situ (111.8 months, range 101.0 to 122.6 vs 85.89, range 75.3 to 96.5, log rank p = 0.007). CONCLUSIONS: Patients presenting with concomitant CIS have a worse outcome than those who present with pure/primary CIS, suggesting a need to differentiate these 2 entities in the treatment decision process.

[Laparoscopic Pyelolithotomy in a Horseshoe Kidney : A Case Report and Review of the Literature].

A 76-year-old man was introduced to our department with a right kidney stone. On the basis of further examination, he was diagnosed with a 23 mm right kidney stone accompanied with a horseshoe kidney. Retrograde pyelography and diuretic renogram revealed a non-obstructed right ureteropelvic junction. Finally, we chose laparoscopic pyelolithotomy via peritoneal approach because the stone was large and accompanied with a horseshoe kidney. The surgery took 165 minutes and the estimated blood loss was 25 ml. There were no minor or major complications. Because horseshoe kidney has anatomical abnormalities, it seems to be necessary to consider a different treatment strategy from that of an upper urinary tract stone in a healthy kidney. We assume that laparoscopic pyelolithotomy is an effective and safe procedure for renal pelvic stones in the case of a horseshoe kidney.