Molecular mechanism of formation and destruction of a pseudo­capsule in clear cell renal cell carcinoma.

The process and molecular mechanisms underlying the formation and destruction of a pseudo-capsule (PC) in clear cell renal cell carcinoma (ccRCC) are poorly understood. In the present study, the PCs of surgical specimens from primary tumors and metastatic lesions in 169 patients with ccRCC, and carcinogen-induced ccRCC rat models were semi-quantified using the invasion of PC (i-Cap) score system. This was based on the relationship among the tumor, PC and adjacent normal tissue (NT) as follows: i-Cap 0, tumor has no PC and does not invade NT; i-Cap 1, tumor has a complete PC and does not invade into the PC; i-Cap 2, tumor with focal absences in the PC, which partially invades the PC but not completely through the PC; i-Cap 3, tumor crosses the PC and invades the NT; i-Cap 4, tumor directly invades the NT without a PC. The study suggested that PC formation was not observed without physical compression, and also revealed that tumor invasion into the PC was a prognostic factor for postoperative oncological outcomes. Higher i-Cap, Fuhrman grade and tumor size were independent poor prognostic factors for postoperative disease-free survival. mRNA expression arrays generated from carcinogen-induced ccRCC rat models were used to explore genes potentially associated with the formation and destruction of a PC. Subsequently, human ccRCC specimens were validated for four genes identified via expression array; the results revealed that collagen type 4A2, matrix metalloproteinase-7 and l-selectin were upregulated alongside the progression of i-Cap score. Conversely, endoglin was downregulated. In conclusion, the present study provides insights into the formation and destruction of a PC, and the results may aid the treatment and management of patients with ccRCC.

Treatment patterns and prognosis in patients with Bacillus Calmette-Guérin-exposed high-risk non-muscle invasive bladder cancer: a real-world data analysis.

PURPOSE: The International Bladder Cancer Group designated the subgroup that is resistant to Bacillus Calmette-Guérin (BCG) but does not meet the criteria for BCG-unresponsive NMIBC as "BCG-exposed high-risk NMIBC" to guide optimal trial design. We aimed to investigate the treatment patterns and prognoses of patients with BCG-exposed NMIBC. METHODS: We conducted a retrospective chart review of 3283 patients who received intravesical BCG therapy for NMIBC at 14 participating institutions between January 2000 and December 2019. Patients meeting the criteria for BCG-exposed and BCG-unresponsive NMIBC, as defined by the Food and Drug Administration and International Bladder Cancer Group, were selected. To compare treatment patterns and outcomes, high-risk recurrence occurring more than 24 months after the last dose of BCG was defined as "BCG-treated NMIBC." In addition, we compared prognoses between BCG rechallenge and early cystectomy in patients with BCG-exposed NMIBC. RESULTS: Of 3283 patients, 108 (3.3%), 150 (4.6%), and 391 (11.9%) were classified as having BCG-exposed, unresponsive, and treated NMIBC, respectively. BCG-exposed NMIBC demonstrated intermediate survival curves for intravesical recurrence-free and progression-free survival, falling between those of BCG-unresponsive and treated NMIBC. Among patients with BCG-exposed NMIBC, 48 (44.4%) received BCG rechallenge, which was the most commonly performed treatment, and 19 (17.6%) underwent early cystectomy. No significant differences were observed between BCG rechallenge and early cystectomy in patients with BCG-exposed NMIBC. CONCLUSIONS: The newly proposed definition of BCG-exposed NMIBC may serve as a valuable disease subgroup for distinguishing significant gray areas, except in cases of BCG-unresponsive NMIBC.

[Efficacy of Recombinant Thrombomodulin for Sepsis-Associated Disseminated Intravascular Coagulation Caused by Urinary Tract Infections].

Severe urinary tract infections occasionally cause sepsis and disseminated intravascular coagulation (DIC). We examined the efficacy of recombinant thrombomodulin (rTM) for treating DIC caused by urosepsis. We enrolled 40 patients who were diagnosed with DIC caused by urosepsis at our hospital between April 2018 and May 2022. Twenty-six patients were treated with rTM (rTM group), while 14 patients did not receive rTM (non-rTM group). The DIC score before treatment in the rTM group was significantly higher than that in the non-rTM group (P＜0.01). There was no significant difference in disease-specific survival between the two groups. There was a significant improvement in DIC scores on days 1-3 after administering rTM. However, the duration of DIC in the rTM group was significantly longer than that in the non-rTM group (P＝0.038). The administration of rTM may have benefits in patients with DIC caused by urosepsis.

[Adrenal Hemangiomatous Endothelial Cyst That was Difficult to Differentiate from Adrenal Malignant Tumor: A Case Report].

A 65-year-old woman was referred to our hospital for fever and diagnosed with pyelonephritis. Abdominal computed tomography showed a right adrenal tumor incidentally, that was 6.5 cm in diameter. We could not rule out malignant disease by magnetic resonance imaging examination and performed resection of the right adrenal tumor. The histopathological examination revealed an adrenal hemangiomatous endothelial cyst, and there was no evidence of malignancy. It was difficult to differentiate between adrenal cyst and adrenal cancer in preoperative diagnostic imaging because the tumor contained hemorrhage and necrotic tissue.

Composite pheochromocytoma associated with neurofibromatosis type 1.

Introduction: Composite pheochromocytoma is a rare tumor, occurring in only 3% of pheochromocytomas. We report a case of composite pheochromocytoma with neurofibromatosis type 1. Case presentation: A 42-year-old man was referred to our department for further evaluation of an incidentally detected right adrenal tumor. He was a patient at another hospital for neurofibromatosis type 1. The serum and urinary catecholamine levels exceeded the normal range. Abdominal computed tomography and magnetic resonance imaging showed a 2.8 cm diameter right adrenal tumor, and 123I-metaiodobenzyguanidine scintigraphy showed radioisotope uptake. He was diagnosed with pheochromocytoma and underwent a right laparoscopic adrenalectomy. Histopathological examination revealed that the tumor consisted of a pheochromocytoma and ganglioneuroma. The final diagnosis was composite pheochromocytoma-ganglioneuroma. Five years after surgery, no recurrence was observed. Conclusion: Preoperative diagnosis of composite pheochromocytoma-ganglioneuroma is difficult; therefore, histopathological examination is necessary for a definitive diagnosis. Pheochromocytoma management requires lifelong follow-up.

Subsequent Upper Urinary Tract Carcinoma Related to Worse Survival in Patients Treated with BCG.

Upper urinary tract urothelial carcinoma (UTUC) after intravesical bacillus Calmette-Guerin (BCG) therapy is rare, and its incidence, clinical impact, and risk factors are not fully understood. To elucidate the clinical implications of UTUC after intravesical BCG therapy, this retrospective cohort study used data collected between January 2000 and December 2019. A total of 3226 patients diagnosed with non-muscle-invasive bladder cancer (NMIBC) and treated with intravesical BCG therapy were enrolled (JUOG-UC 1901). UTUC impact was evaluated by comparing intravesical recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) rates. The predictors of UTUC after BCG treatment were assessed. Of these patients, 2873 with a medical history that checked UTUC were analyzed. UTUC was detected in 175 patients (6.1%) during the follow-up period. Patients with UTUC had worse survival rates than those without UTUC. Multivariate analyses revealed that tumor multiplicity (odds ratio [OR], 1.681; 95% confidence interval [CI], 1.005-2.812; p = 0.048), Connaught strain (OR, 2.211; 95% CI, 1.380-3.543; p = 0.001), and intravesical recurrence (OR, 5.097; 95% CI, 3.225-8.056; p < 0.001) were associated with UTUC after BCG therapy. In conclusion, patients with subsequent UTUC had worse RFS, CSS, and OS than those without UTUC. Multiple bladder tumors, treatment for Connaught strain, and intravesical recurrence after BCG therapy may be predictive factors for subsequent UTUC diagnosis.

C-reactive protein as a prognostic predictor for non-muscle invasive bladder cancer after intravesical bacillus Calmette-Guérin therapy: A Japan Urological Oncology Group study analysis.

OBJECTIVE: To investigate the involvement of pretreatment C-reactive protein (CRP) and neutrophil-to-lymphocyte ratio (NLR) in the prognosis of patients who underwent intravesical bacillus Calmette-Guérin (BCG) therapy for non-muscle invasive bladder cancer (NMIBC). METHODS: The clinicopathological data of 1709 patients with NMIBC who underwent initial intravesical BCG therapy after transurethral resection of bladder tumor were retrospectively analyzed to evaluate the outcome of intravesical BCG therapy in a multicenter study conducted by the Japan Urological Oncology Group. The prognoses of these patients were analyzed to determine whether the biomarkers (CRP and NLR) could predict the efficacy of intravesical BCG therapy. Patients were divided into two groups according to the pretreatment CRP and NLR, with cutoff values defined as CRP ≥ 0.5 mg/dl and NLR ≥ 2.5, based on several previous reports. RESULTS: In the univariable analysis, CRP ≥ 0.5 mg/dl was significantly associated with intravesical recurrence, cancer-specific survival, and bladder cancer (BC) progression, while NLR ≥ 2.5 was not significantly associated with patient prognosis. In the multivariable analysis, CRP ≥ 0.5 mg/dl was significantly associated with intravesical recurrence and BC progression. The concordance index was used to examine the accuracy in predicting recurrence and progression events. While CRP was slightly, though not statistically significant, inferior to the European Association of Urology risk classification, the combination of them showed improved predictive accuracy. CONCLUSION: This study suggests that CRP can be a prognostic factor after intravesical BCG therapy and may provide useful data for determining treatment and follow-up strategies for patients with NMIBC.

Probiotics enhances anti-tumor immune response induced by gemcitabine plus cisplatin chemotherapy for urothelial cancer.

Chemotherapy drugs, such as gemcitabine and cisplatin (GC), are frequently administered to patients with advanced urothelial carcinoma, however the influence of the gut microbiota on their action is unclear. Thus, we investigated the effects of GC on the gut microbiome and determined whether oral supplementation with a probiotics mixture of Lactobacillus casei Shirota and Bifidobacterium breve enhanced the anti-tumor immune response. After subcutaneous inoculation with MBT2 murine bladder cancer cells, syngenic C3H mice were randomly allocated into eight groups. The gut microbiome cluster pattern was altered in both the GC and oral probiotics groups (p = 0.025). Both tumor-bearing conditions (no treatment) and GC chemotherapy influenced Pseudoclostridium, Robinsoniella, Merdimonas, and Phocea in the gut. Furthermore, comparison of the GC-treated and GC + probiotics groups revealed an association of four methyltransferase family enzymes and two short-change fatty acid-related enzymes with oral probiotics use. A significant difference in tumor volume was observed between the GC and GC + probiotics groups at week 2 of treatment. Additionally, decreased recruitment of cancer-associated fibroblasts and regulatory T cells, and activation of CD8+ T cells and dendritic cells were observed in the tumor microenvironment. Our findings reveal the positive effects of a probiotics mixture of Lactobacillus and Bifidobacterium in enhancing anti-tumor effects through the gut-tumor immune response axis. Future clinical trials are needed to evaluate the full benefits of this novel supplement with oral probiotics in patients with advanced urothelial carcinoma.

5­Aminolevurinic acid inhibits the proliferation of bladder cancer cells by activating heme synthesis.

Iron is an essential nutrient that facilitates cell proliferation and growth, and it can contribute to tumor growth. Although iron chelators have shown great potential in preclinical cancer models, they can cause adverse side­effects. The aim of the present study was to determine whether treatment with 5­aminolevurinic acid (5­ALA) has antitumor effects in bladder cancer, by reduction of mitochondrial iron without using an iron chelator, through activation of heme synthesis. T24 and MGH­U3 cells were treated with 5­ALA. Ferrochelatase uses iron to convert protoporphyrin IX into heme, thus additional groups of T24 and MGH­U3 cells were transfected with synthesized ferrochelatase small interfering RNA (siRNA) either to silence ferrochelatase or to provide a negative siRNA control group, and then cell viability, apoptosis, mitochondrial Fe2+, the cell cycle, and ferritin expression were analyzed in all groups and compared. As an in vivo assessment, mice with orthotopic bladder cancer induced using N­butyl­N­(4­hydro­oxybutyl) were treated with 5­ALA. Bladder weight and pathological findings were evaluated, and immunohistochemical analysis was performed for ferritin and proliferating cell nuclear antigen (PCNA). In the cells treated with 5­ALA, proliferation was decreased compared with the controls, and apoptosis was not detected. In addition, the expression of Fe2+ in mitochondria was decreased by 5­ALA, expression of ferritin was also reduced by 5­ALA, and the percentage of cells in the S phase of the cell cycle was significantly increased by 5­ALA. In T24 and MGH­U3 cells with silenced ferrochelatase, the inhibition of cell proliferation, decreased expression of Fe2+ in mitochondria, reduced expression of ferritin, and increased percentage of cells in the S phase by treatment with 5­ALA were weakened. In vivo, no mouse treated with 5­ALA developed muscle­invasive bladder cancer. The expression of ferritin was weaker in mice treated with 5­ALA and that of PCNA was higher than that in mice treated without 5­ALA. It was concluded that 5­ALA inhibited proliferation of bladder cancer cells by activating heme synthesis.

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.

Real-world treatment patterns and oncological outcomes in early relapse and refractory disease after bacillus Calmette-Guérin failure in non-muscle-invasive bladder cancer.

OBJECTIVE: To assess real-world oncological outcomes between the radical cystectomy (RC) group and non-RC group for early relapse and refractory disease. METHODS: We retrospectively analyzed 953 patients with recurrent non-muscle-invasive bladder cancer (NMIBC) who received bacillus Calmette-Guérin (BCG) at 31 affiliated hospitals from 2000 to 2019. Patients with missing data on the timing of failure were excluded and 871 patients remained eligible, of whom 447, 357, and 67 were classified as early relapse/refractory disease, intermediate/late relapse disease, and intolerant disease, respectively. For early relapse/refractory disease, patients were divided into two salvage treatment groups: RC and non-RC. The clinicopathological variables of each group were examined using Kaplan-Meier plots and proportional Cox hazard ratios with matched score analyses to compare oncological outcomes between the two groups. RESULTS: Significantly worse progression-free survival and cancer-specific survival (CSS) were confirmed in the early relapse/refractory disease group compared to the intermediate/late relapse group. Of the 88 salvage patients in the RC group with early relapse/refractory disease, ≤pT1 was observed in 47, pT2 in 11, and ≥pT3 in 28 (two patients with unknown pT category). In early relapse/refractory disease, the RC group showed significantly high-risk tumor compared to the non-RC group. However, no significant difference was observed in CSS after matched score analyses (p = 0.45) between the RC and non-RC groups. CONCLUSIONS: This study found that the RC group showed no significant superiority compared to the non-RC group in CSS for early relapse/refractory disease in terms of first salvage therapy.

Association of Increased Age With Decreased Response to Intravesical Instillation of Bacille Calmette-Guérin in Patients With High-Risk Non-Muscle Invasive Bladder Cancer: Retrospective Multi-Institute Results From the Japanese Urological Oncology Research Group JUOG-UC-1901-BCG.

OBJECTIVE: To compare the therapeutic effect of Bacille Calmette-Guérin (BCG) intravesical instillation in older and younger patients with high-risk non-muscle-invasive bladder cancer. The comparison was performed with propensity score matching (PSM) without terminating the death of the older patients using relatively large-scale retrospective data from multiple institutes in Japan. MATERIALS AND METHODS: Overall, 3283 patients diagnosed with non-muscle-invasive bladder cancer treated with intravesical BCG instillation during 2000-2018 in 31 institutes were examined; 1437 and 602 patients with high-grade T1 and Tis tumors were divided into those aged ≥75 and <75 years. Multivariate analysis using the Fine-Gray competing risks regression model before PSM and survival analysis using the cumulative incidence method after PSM were performed. RESULTS: In the pre-PSM series of high-grade T1 tumors, age ≥75 years was an independent prognostic factor for both recurrence and progression in multivariate analysis (P = .015 and P = .013). In the pre-PSM series with Tis tumor, no variables to predict recurrence and progression was found. In the post-PSM series of 870 high-grade T1 tumors, cumulative probability of recurrence after BCG intravesical instillation were significantly higher in patients aged ≥75 years than in those aged <75 years (P = .008). The frequency of discontinuation of BCG instillation in patients aged ≥75 years with high-grade T1 and Tis was not significantly different from those in patients aged <75 years (P = .564 and P = .869). CONCLUSION: The cumulative probability of recurrence after intravesical BCG instillation was significantly higher in older than in younger patients with high-grade T1 bladder cancer.

Impact of carcinoma in situ on the outcome of intravesical Bacillus Calmette-Guérin therapy for non-muscle-invasive bladder cancer: a comparative analysis of large real-world data.

BACKGROUND: This study investigated the clinical impact of carcinoma in situ (CIS) in intravesical Bacillus Calmette-Guérin (BCG) therapy for patients with non-muscle-invasive bladder cancer (NMIBC). METHODS: This study retrospectively evaluated 3035 patients who were diagnosed with NMIBC and treated by intravesical BCG therapy between 2000 and 2019 at 31 institutions. Patients were divided into six groups according to the presence of CIS as follows: low-grade Ta without concomitant CIS, high-grade Ta without concomitant CIS, high-grade Ta with concomitant CIS, high-grade T1 without concomitant CIS, high-grade T1 with concomitant CIS, and pure CIS (without any papillary lesion). The endpoints were recurrence- and progression-free survival after the initiation of BCG therapy. We analyzed to identify factors associated with recurrence and progression. RESULTS: At a median follow-up of 44.4 months, recurrence and progression were observed in 955 (31.5%) and 316 (10.4%) patients, respectively. Comparison of six groups using univariate and multivariate analysis showed no significant association of CIS. However, CIS in the prostatic urethra was an independent factors associated with progression. CONCLUSION: Concomitant CIS did not show a significant impact in the analysis of Ta and T1 tumors which were treated using intravesical BCG. Concomitant CIS in the prostatic urethra was associated with high risk of progression. Alternative treatment approaches such as radical cystectomy should be considered for patients with NMIBC who have a risk of progression.

Prognostication in Japanese patients with bacillus Calmette-Guérin-unresponsive non-muscle-invasive bladder cancer undergoing early radical cystectomy.

OBJECTIVES: The US Food and Drug Administration recently defined the clinical term "bacillus Calmette-Guérin-unresponsive non-muscle-invasive bladder cancer" as a disease state resistant to adequate bacillus Calmette-Guérin therapy. There is a significant lack of prognostication for this disease even in patients who have undergone early radical cystectomy. This study aimed to identify the clinical outcomes and prognostic factors in Japanese patients with bacillus Calmette-Guérin-unresponsive non-muscle-invasive bladder cancer who underwent early radical cystectomy. METHODS: Data from a large-scale multicenter retrospective study included 2879 patients with highest-risk or high-risk non-muscle-invasive bladder cancer who received intravesical bacillus Calmette-Guérin induction therapy between January 2000 and December 2019. A total of 141 patients (4.3%) met the criteria for bacillus Calmette-Guérin-unresponsive disease, of whom 47 (33.3%) underwent early radical cystectomy. Prognostic factors for three clinical endpoints, namely, unresectable lesion-free survival, cancer-specific survival, and overall survival, were identified. RESULTS: The highest-risk status at induction bacillus Calmette-Guérin was associated with short unresectable lesion-free survival (hazard ratio 7.85; P < 0.05), cancer-specific survival (hazard ratio 12.24; P < 0.05), and overall survival (hazard ratio 9.25; P < 0.01). Moreover, extravesical tumors (pathological T3 or T4) on the radical cystectomy specimens were associated with poor prognosis and were found at a higher rate in patients with the highest-risk status at induction bacillus Calmette-Guérin than in those with high-risk status (35.7% vs 21.2%). CONCLUSIONS: The highest-risk status among the pre-bacillus Calmette-Guérin factors was associated with upstaging to extravesical tumors and poor prognosis despite early radical cystectomy procedures. Appropriate decision-making and the correct timing of radical cystectomy are vital to avoid treatment delays and improve outcomes.

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.

Intravesical Bacillus Calmette-Guérin Treatment for T1 High-Grade Non-Muscle Invasive Bladder Cancer with Divergent Differentiation or Variant Morphologies.

The 2016 World Health Organization classification newly described infiltrating urothelial carcinoma (UC) with divergent differentiation (DD) or variant morphologies (VMs). Data comparing oncological outcomes after bladder-preservation therapy using intravesical Bacillus Calmette-Guérin (BCG) treatment among T1 bladder pure UC (pUC), UC with DD (UC-DD), and UC with VMs (UC-VM) are limited. We evaluated 1490 patients with T1 high-grade bladder UC who received intravesical BCG during 2000-2019. They were classified into three groups: 93.6% with pUC, 4.4% with UC-DD, and 2.0% with UC-VM. Recurrence-free, progression-free, and cancer-specific survival following intravesical BCG were compared among the groups using multivariate Cox regression analysis, also used to estimate inverse probability of treatment weighting-adjusted hazard ratio and 95% confidence interval for the outcomes. Glandular differentiation and micropapillary variant were the most common forms in the UC-DD and UC-VM groups, respectively. Of 1490 patients, 31% and 13% experienced recurrence and progression, respectively, and 5.0% died of bladder cancer. Survival analyses revealed the impact of concomitant VMs was significant for cancer-specific survival, but not recurrence-free and progression-free survival compared with that of pUC. Our analysis clearly demonstrated that concomitant VMs were associated with aggressive behavior in contrast to concomitant DD in patients treated with intravesical BCG.

Impact of Radical Nephrectomy and Partial Nephrectomy on Actual Estimated Overall Survival Compared to Life Expectancy in Patients with Renal Cell Carcinoma.

PURPOSE: Reports suggest that partial nephrectomy provides no significant benefit in terms of cancer-specific and overall survival (OS) compared to radical nephrectomy. Here, we focused on survival in terms of life expectancy and investigated the significance of partial nephrectomy for localized renal cell carcinoma (RCC) patients. PATIENTS AND METHODS: Our retrospective study included 937 patients (median age 63 years) with localized RCC who underwent partial nephrectomy or radical nephrectomy. Various predictive factors were explored, and the association between actual OS and life expectancy was analyzed. RESULTS: Performance status (PS) ≥1 and tumor size ≥40 mm were identified as independent poor prognostic factors for cancer-specific survival. Age ≥60, male sex, PS ≥1, C-reactive protein elevation, pT1b stage, and radical nephrectomy were identified as independent poor prognostic factors for OS. OS and life expectancy did not differ in the partial nephrectomy group (P=0.11). OS was significantly shorter than life expectancy in the radical nephrectomy group (P<0.0001). In PS0 or pT1a patients, there was a significant difference between actual OS and life expectancy in the radical nephrectomy group (P<0.0001), but not in the partial nephrectomy group (P=0.15). In patients with a life expectancy ≥10 years, PS0, and pTa, OS and life expectancy differed in the radical nephrectomy group, but not in the partial nephrectomy group. CONCLUSION: Partial nephrectomy can improve actual OS, and notably, PS and tumor size are crucial factors that determine the choice of surgical procedure. Further research is needed to establish appropriate treatment strategies and criteria for clinical practice.

Non-maintenance intravesical Bacillus Calmette-Guérin induction therapy with eight doses in patients with high- or highest-risk non-muscle invasive bladder cancer: a retrospective non-randomized comparative study.

BACKGROUND: To explore possible solutions to overcome chronic Bacillus Calmette-Guérin (BCG) shortage affecting seriously the management of non-muscle invasive bladder cancer (NMIBC) in Europe and throughout the world, we investigated whether non-maintenance eight-dose induction BCG (iBCG) was comparable to six-dose iBCG plus maintenance BCG (mBCG). METHODS: This observational study evaluated 2669 patients with high- or highest-risk NMIBC who treated with iBCG with or without mBCG during 2000-2019. The patients were classified into five groups according to treatment pattern: 874 (33%) received non-maintenance six-dose iBCG (Group A), 405 (15%) received six-dose iBCG plus mBCG (Group B), 1189 (44%) received non-maintenance seven-/eight-dose iBCG (Group C), 60 (2.2%) received seven-/eight-dose iBCG plus mBCG, and 141 (5.3%) received only ≤5-dose iBCG. Recurrence-free survival (RFS), progression-free survival, and cancer-specific survival were estimated and compared using Kaplan-Meier analysis and the log-rank test, respectively. Propensity score-based one-to-one matching was performed using a multivariable logistic regression model based on covariates to obtain balanced groups. To eliminate possible immortal bias, 6-, 12-, 18-, and 24-month conditional landmark analyses of RFS were performed. RESULTS: RFS comparison confirmed that mBCG yielded significant benefit following six-dose iBCG (Group B) in recurrence risk reduction compared to iBCG alone (groups A and C) before (P < 0.001 and P = 0.0016, respectively) and after propensity score matching (P = 0.001 and P = 0.0074, respectively). Propensity score-matched sequential landmark analyses revealed no significant differences between groups B and C at 12, 18, and 24 months, whereas landmark analyses at 6 and 12 months showed a benefit of mBCG following six-dose iBCG compared to non-maintenance six-dose iBCG (P = 0.0055 and P = 0.032, respectively). There were no significant differences in the risks of progression and cancer-specific death in all comparisons of the matched cohorts. CONCLUSIONS: Although non-maintenance eight-dose iBCG was inferior to six-dose iBCG plus mBCG, the former might be an alternative remedy in the BCG shortage era. To overcome this challenge, further investigation is warranted to confirm the real clinical value of non-maintenance eight-dose iBCG.

Clinical outcomes after intravesical bacillus Calmette-Guérin for the highest-risk non-muscle-invasive bladder cancer newly defined in the Japanese Urological Association Guidelines 2019.

OBJECTIVE: To assess the clinical outcomes of highest-risk non-muscle-invasive bladder cancer patients treated with intravesical bacillus Calmette-Guérin. METHODS: The medical charts of patients with non-muscle-invasive bladder cancer treated with intravesical bacillus Calmette-Guérin between 2000 and 2018 at a single institution were retrospectively reviewed. Patients were stratified into three groups (intermediate-, high- and highest-risk groups) according to the risk classification of the updated Japanese Urological Association guidelines 2019. Among the three groups, the intravesical recurrence-free survival and progression-free survival were estimated and compared, respectively. Furthermore, the different types of risk factors in the highest-risk group were analyzed. RESULTS: Of the 165 patients, 49 (30%) patients had intravesical recurrence and 23 (14%) patients showed progression to muscle-invasive disease during a median follow-up period of 53 months. Significant differences were not noted in the recurrence-free survival and progression-free survival among the three groups. Multivariable survival analysis of 74 patients in the highest-risk group showed that carcinoma in situ in the prostatic urethra was a significant predictor associated with recurrence (hazard ratio 3.20, P = 0.026) and progression (hazard ratio 4.36, P = 0.013). CONCLUSIONS: Intravesical bacillus Calmette-Guérin can control highest-risk non-muscle-invasive bladder cancer in most patients. Our findings might aid in decision-making regarding the treatment of this subset of patients who require intensive treatment, such as intravesical therapy with bacillus Calmette-Guérin and radical cystectomy.

Photodynamic Diagnosis-Assisted En Bloc Transurethral Resection of Bladder Tumor for Nonmuscle Invasive Bladder Cancer: Short-Term Oncologic and Functional Outcomes.

Background: We describe the oncologic and functional outcomes and the surgical technique of the photodynamic diagnosis (PDD)-assisted en bloc transurethral resection of bladder tumor (EBTUR) using a rectangular cutting loop. Methods: We reviewed 40 patients with carcinoma in situ-free nonmuscle invasive bladder cancer undergoing PDD-TURBT. Of 40 patients, 12 underwent photodynamic diagnosis-assisted en bloc transurethral resection of bladder tumor (PDD-EBTUR) and 28 underwent PDD-assisted conventional TURBT (cTURBT). Two groups were matched in terms of clinicopathologic background and did not include patients treated with intravesical Bacillus Calmette-Guerin. The assessment of postoperative quality of life (QoL) was based on patient-reported outcome measure, including the International Prostate Symptom Score, Functional Assessment of Cancer Therapy-Bladder (FACT-BL), and 8-item Short Form (SF-8™) questionnaires before and 1 month after TUR. This study was approved by the Ethics commitee and all participants provided informed consent. Results: PDD guidance provided substantial help for circumferent demarcation around the bladder tumor, which precedes tumor dissection. One female patient (12%) treated by PDD-EBTUR had grade II bladder perforation requiring prolonged catheterization. Pathologic assessment of horizontal and vertical margins in resected specimens by PDD-EBTUR revealed that all specimens had muscularis propria, and the rate of en bloc resection was 100%. No patient had intravesical recurrence in the PDD-EBTUR group (median follow-up, 11 months), while two patients in the PDD-cTURBT group had Ta low-grade recurrent tumors (8 months). Postoperatively, scores of daytime frequency and nocturia were increased in both groups. QoL assessment using the FACT-BL and SF-8 revealed that postoperative deterioration of bladder-specific subscale and emotional/mental scores was found in the EBTUR group but not in the cTURBT group. Conclusions: Based on the initial experience on 12 patients, we considered that PDD-EBTUR is an acceptable surgical method. Further experience and research are mandatory to determine whether this technique yields better outcomes and has true clinical advantage.