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Real-world data on health-related quality of life (HRQoL) in advanced urothelial carcinoma (aUC) receiving immune checkpoint inhibitors (ICIs) are limited. This study included 42 patients with aUC who received second-line or later pembrolizumab (n = 19), maintenance avelumab followed by first-line chemotherapy (n = 13), or adjuvant nivolumab after radical surgery (n = 10). Time-course changes in the domains and scales related to HRQoL were evaluated using the EORTC QLQ-C30, FACT-G, and SF-8 questionnaires during ICI therapy. Anchor-based approaches for minimally important differences were determined as 'improved', 'stable', and 'deteriorated'. We found significant improvements after the start of pembrolizumab treatment on many scales. Almost none of the scales changed significantly in the avelumab and nivolumab groups. Approximately 80% of the pembrolizumab group had deteriorated social/family well-being in FACT-G. Approximately 60% of the patients in the avelumab group had deteriorated general health and vitality in SF-8. In the nivolumab group, none of the scales deteriorated in > 50% of the patients. Deterioration of physical function in the SF-8 was associated with occurrence of treatment-related adverse events ≥ grade 2 during ICI therapy (P = 0.013). Our findings demonstrated that majority of patients with aUC who received ICI therapy had a stable HRQoL, which was consistent with evidence from clinical trials. [ABSTRACT FROM AUTHOR]

Background. Photodynamic diagnosis‐assisted transurethral resection of bladder tumors (PDD‐TURBT) enhances detection of elusive lesions compared to standard white light‐transurethral resection of bladder tumors (WL‐TURBT). If minimal light exposure during PDD‐TURBT induces the accumulation of reactive oxygen species (ROS), potentially resulting in phototoxicity in small lesions, apoptosis may be triggered in residual small tumors, allowing them to escape resection. We investigated the hypothesis of a potential photodynamic therapeutic effect during PDD‐TURBT. Methods and Materials. Our study, conducted between January 2016 and December 2020 at Nara Medical University Hospital, focused on a specific emphasis on ROS production. Immunohistochemical analysis for thymidine glycol and Nε‐hexanoyl‐lysine was performed on 69 patients who underwent 5‐aminolevulinic acid‐mediated PDD‐TURBT and 28 patients who underwent WL‐TURBT. Additionally, we incrementally applied the minimal irradiation energy to T24 and UM‐UC‐3 cells treated with 5‐aminolevulinic acid using instruments similar to those used in PDD‐TURBT and evaluated intracellular ROS production and phototoxicity. Results. Immunohistochemical analysis revealed a significant increase in production of thymidine glycol and Nε‐hexanoyl‐lysine within the PDD‐TURBT group. In T24 and UM‐UC‐3 cells treated with 5‐aminolevulinic acid and light exposure, immunofluorescent staining demonstrated a dose‐dependent increase in intracellular ROS production. In addition, higher irradiation energy levels were associated with a greater increase in ROS production and phototoxicity, as well as more significant decrease in mitochondrial membrane potential. Conclusion. Although the irradiation energy used in PDD‐TURBT did not reach the levels commonly used in photodynamic therapy, our findings support the presence of a potential cytotoxic effect on bladder lesions during PDD‐TURBT. [ABSTRACT FROM AUTHOR]

Background. Although routine surveillance imaging to examine upper urinary tract urothelial cancer recurrence during follow‐up of nonmuscle invasive bladder cancer is recommended, its necessity remains invalidated. A single‐institute long‐term follow‐up cohort study to evaluate the clinical impact of routine surveillance imaging and identify risk factors for upper urinary tract urothelial cancer recurrence after nonmuscle invasive bladder cancer treatment was conducted. Methods and Materials. A retrospective chart review of 864 patients with primary nonmuscle invasive bladder cancer who underwent initial transurethral resection of bladder tumor between 1980 and 2020 was conducted. The opportunities to diagnose its recurrence were examined. Moreover, oncological outcomes included upper urinary tract urothelial cancer recurrence‐free survival and overall survival. Results. Of 864 patients, 19 (2.2%) experienced upper urinary tract urothelial cancer recurrence. Among 19 patients, recurrence was detected through routine imaging in 12 (63.2%), cystoscopy in 2 (10.5%), urine cytology in 2 (10.5%), and presence of gross hematuria in 1 (5.3%). All patients had high‐ or highest‐risk NMIBC at diagnosis of primary nonmuscle invasive bladder cancer. On multivariate Fine‐Gray proportional regression analyses, a tumor size of ≥30 mm and carcinoma in situ were independently associated with short upper urinary tract urothelial cancer recurrence‐free survival (P = 0.040 and 0.0089, respectively). Conclusion. Most patients experiencing upper urinary tract urothelial cancer recurrence were diagnosed by routine surveillance imaging, suggesting its clinical importance, especially for patients with nonmuscle invasive bladder cancer accompanied by a tumor size of ≥30 mm and carcinoma in situ. [ABSTRACT FROM AUTHOR]

Simple Summary: The clinical utility of urine nectins in bladder cancer (BCa) is unclear. We investigated the potential diagnostic and prognostic values of Nectin-2 and Nectin-4. This study included 122 patients with BCa, including 78 with non-muscle-invasive BCa, 44 with muscle-invasive BCa, and ten healthy controls. The detection sensitivities of urine Nectin-2, urine Nectin-4, NMP-22, and cytology were 84%, 98%, 52%, and 47%, respectively. Their specificities were 40%, 80%, 100%, and 100%, respectively. Urine Nectin-2 and Nectin-4, but not NMP-22, were significantly more sensitive than cytology alone. A four-titer grouping based on levels of urine Nectin-2/Nectin-4 had a high capability for discriminating between NMIBC and MIBC. Urine levels correlated with tumor expression and serum levels in the Nectin-4 analysis. Urine nectins are potential diagnostic biomarkers for BCa. The clinical utility of urine nectins in bladder cancer (BCa) is unclear. We investigated the potential diagnostic and prognostic values of urine Nectin-2 and Nectin-4. Levels of urine Nectin-2, Nectin-4, and NMP-22 were quantified using an enzyme-linked immunosorbent assay in 122 patients with BCa, consisting of 78 with non-muscle-invasive BCa (NMIBC) and 44 with muscle-invasive BCa (MIBC), and ten healthy controls. Tumor nectin expression in MIBC was evaluated with immunohistochemical staining of transurethral resection specimens. The level of urine Nectin-4 (mean: 18.3 ng/mL) was much higher than that of urine Nectin-2 (mean: 0.40 ng/mL). The sensitivities of Nectin-2, Nectin-4, NMP-22, and cytology assays were 84%, 98%, 52%, and 47%, respectively; their specificities were 40%, 80%, 100%, and 100%, respectively. Both urine Nectin-2 and Nectin-4, though not NMP-22, were found to be significantly more sensitive than cytology. A four-titer grouping based on levels of urine Nectin-2/Nectin-4 (low/high, high/high, low/low, and high/low) showed a high capability for discriminating between NMIBC and MIBC. Neither urine Nectin-2 nor Nectin-4 levels had a significant prognostic value in NMIBC or MIBC. Urine levels correlated with tumor expression and serum levels in the Nectin-4 analysis, but not in the Nectin-2 analysis. Urine nectins are potential diagnostic biomarkers for BCa. [ABSTRACT FROM AUTHOR]

Enfortumab vedotin (EV), a nectin-4-directed antibody conjugated to monomethyl auristatin E (MMAE), has been approved for patients with advanced urothelial carcinoma (aUC) previously treated with platinum-based chemotherapy and immune inhibitors. Taxane agents and MMAE share antitumor mechanisms through microtubule disruption, thus raising a notable concern regarding cross-resistance between these drugs. This case report describes two patients with taxane-based chemotherapy-refractory aUC who responded well to EV. A 71-year-old man (case 1) with pT3N0M0 renal pelvic UC showed a partial response to EV in metastatic lesions of the bilateral lungs and right pelvic lymph nodes after three cycles of paclitaxel plus gemcitabine chemotherapy. A 53-year-old man (case 2) with cT3bN2M0 bladder UC underwent platinum-based neoadjuvant chemotherapy and the following radial cystectomy (ypTis ypN0). He developed bilateral lung metastases and showed a complete response to EV in the metastatic lesions after 20 cycles of paclitaxel plus nedaplatin chemotherapy. Our experience of two cases demonstrated that tumor response to EV can be expected in patients with taxane-refractory aUC. [ABSTRACT FROM AUTHOR]

Purpose: The treatment landscape for advanced, unresectable, or metastatic urothelial carcinoma (aUC) has shifted substantially since the advent of immune checkpoint inhibitors (ICIs). We investigated the extent to which pembrolizumab therapy is superior to conventional chemotherapy as a second-line treatment. Patients and Methods: A multicenter-derived database registered 454 patients diagnosed with aUC between 2008 and 2020. Of these, 94 patients (21%) who received second-line pembrolizumab and 75 (17%) who received second-line chemotherapy but never received third-line or later ICI therapy were included. We compared overall survival (OS) from the initial date of first-line chemotherapy between two groups by adjusting for prognostic factors through propensity score matching (PSM) and inverse probability of treatment weighting (IPTW). The IPTW-adjusted hazard ratio and 95% confidence interval were estimated using a multivariate Cox regression analysis. To identify patients who were more likely to benefit from second-line pembrolizumab than from chemotherapy, we performed a subgroup analysis for OS with an IPTW-adjusted model. Results: The PSM-adjusted comparison showed a significant improvement in the prognosis with second-line pembrolizumab use (P = 0.01). The OS benefit with the advent of pembrolizumab was 8 months (18 months vs 26 months). Multivariable analyses using IPTW adjustment demonstrated that lymph node metastasis (P = 0.001), lung metastasis (P = 0.013), and bone metastasis (P = 0.003) were poor independent prognostic factors, and pembrolizumab use (P = 0.021) was a favorable independent prognostic factor. Subgroup analyses revealed that pembrolizumab was associated with survival benefits over chemotherapy in all subgroups, including young patients (age < 70 years), those who received radical surgery, and those without visceral metastasis. Conclusion: We demonstrated a significant improvement in prognosis after the advent of pembrolizumab for patients with aUC. ICIs should not be restricted based on patient characteristics. [ABSTRACT FROM AUTHOR]

Purpose: We investigated sleep parameters and patient-reported outcomes before, during, and after induction Bacillus Calmette-Guerin therapy using questionnaires and actigraphy in patients with non-muscle invasive bladder cancer. Methods: We investigated 10 patients who received Bacillus Calmette-Guerin therapy once weekly for 8 weeks. The International Prostate Symptom Score, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30, Functional Assessment of Cancer Therapy-Bladder, and multi-item Short Form-8 tools were used to assess patient-reported outcomes. Participants completed all questionnaires before (baseline), at the 4th and 8th doses, and 1 month after the last Bacillus Calmette-Guerin dose. The MotionWatch8 was fastened to patients' waist throughout the study. Composite sleep quality was determined based on sleep duration, efficiency, and fragmentation. Results: We observed a transient increase in frequency/nocturia subscores and the insomnia subscore. The number of patients with poor sleep quality increased from 0 (0%) at baseline to 7 (70%) at the 4th dose and to 6 (60%) patients at the 8th dose. Among 10 patients, 6 (60%) were assigned to the sleep deterioration group and 4 (40%) to the non-deterioration group. Sleep quality was restored to baseline levels in 5 of 6 patients (83%) within 1 month after the last dose in the sleep deterioration group, and the nocturia subscore of the International Prostate Symptom Score was significantly increased only in this group (P=0.03). Conclusions: This is the first study that confirms intravesical Bacillus Calmette-Guerin-induced sleep quality deterioration based on a questionnaire survey and actigraphy. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the diagnostic performance of fluorescent voided urine cytology (FVUC) using a novel automated detection technology to screen for primary bladder cancer and for surveillance of recurrent bladder tumour. Patients and Methods: We created a rapid, objective, automated, and high‐throughput detection device for hexylaminolevulinate‐mediated FVUC, named the cellular fluorescence analysis unit‐II (CFAU‐II). Two different cohorts were used in this study: (i) screening test for primary bladder cancer (165 patients with bladder cancer and 52 controls), and (ii) surveillance test for detecting intravesical recurrent tumour (192 patients with treated non‐muscle‐invasive bladder cancer and 15 with post‐nephroureterectomy upper urinary tract cancer). Voided urine samples were subjected to urine analysis, conventional VUC (cVUC), and FVUC. Diagnostic performance was compared between cVUC, FVUC, and a combination of the two. Results: A total of 614 urine samples were successfully collected, processed, and analysed. Comparative analysis of the screening test cohort demonstrated that the overall sensitivity of FVUC (63%, P < 0.001) and combination testing (72%, P < 0.001) was significantly higher than that of cVUC (29%). FVUC was found to be superior in most of the subgroups, especially in low‐grade, Ta, and small tumours. Analysis of the surveillance test cohort showed that combination testing achieved a sensitivity of 82% and a negative predictive value of 98%, whereas those of cVUC were 39% and 96%, respectively. According to the pathological finding of recurrent tumours presenting false‐negative result in the FVUC, the majority of the overlooked recurrent diseases were Ta low‐grade tumours. Logistic regression analysis suggested an association between the risk of false‐positive results and high density of urine white blood cells and alkaluria. Conclusion: The present findings clearly demonstrate that FVUC using the newly developed automation technology has superior sensitivity to cVUC for both screening for primary bladder cancer and recurrent tumour detection. It is essential to confirm the clinical usefulness of this method via further large‐scale studies, in addition to ensuring its affordability and availability. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 committee 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. [ABSTRACT FROM AUTHOR]

Objective: The present study evaluated the clinical relevance of an integrative preoperative assessment of inflammation-, nutrition-, and muscle-based markers for patients with muscle-invasive bladder cancer (MIBC) undergoing curative radical cystectomy (RC). Methods: The analysis enrolled 117 patients and the variables included age, body mass index (BMI), neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, platelet-to-lymphocyte ratio, modified Glasgow Prognostic Score (mGPS), prognostic nutritional index (PNI), Controlling Nutritional Status score, psoas muscle index (PMI), and peak expiratory flow (PEF). The correlations among the variables were evaluated and their prognostic values after RC were tested. Results: Three inflammation markers (ratios of blood cell counts) were positively correlated (p < 0.0001). The PNI and the BMI were positively correlated (p = 0.04), although they were inversely correlated with the three inflammation markers (p < 0.0001). Age was not significantly correlated with the inflammation markers and PMI, although older age was associated with lower PNI and lower PEF. The disease-specific survival was independently predicted by T4 tumor, positive N status, and decreased PNI. Overall survival was independently predicted by T4 tumor, mGPS, and pretreatment sarcopenia status. Conclusions: The inflammation-, nutrition-, and muscle-based markers would be useful risk assessment tools for MIBC. [ABSTRACT FROM AUTHOR]

Background: Although the significance of preoperative nutritional status has been investigated, there is no report regarding the relationship of their postoperative changes on outcomes in patients who underwent radical cystectomy for bladder cancer. Here, we report the clinical impact of the change, from baseline, in nutritional status and volume of abdominal skeletal muscle mass and adipose tissue after radical cystetomy.Methods: A retrospective analysis of 89 patients with bladder cancer, who underwent curative radical cystectomy, was conducted to assess the time course of change, from baseline, in body composition and nutritional status at 1, 3, 6, 12, and 24 months, after surgery. Skeletal muscle mass and abdominal adipose tissue mass were quantified by unenhanced computed tomography images. Two different nutritional indices, the Prognostic Nutritional Index and the Controlling Nutritional Status score were calculated from laboratory blood tests. We evaluated the prognostic value of the rate of change in the body composition and nutritional status after radical cystectomy.Results: The cross-sectional area at the level of the third lumbar vertebra of the psoas major muscle and nutritional indices showed a transient deterioration at 1 and 3 months after radical cystectomy, with a return to baseline values from 6 to 24 months. A ≤ -10% loss in the area of the psoas muscle was associated with a shorter overall survival, compared to those with a > -10 change [hazard ratio (HR) 2.2, P = 0.02]. Multivariate analyzes identified sarcopenia status at baseline (HR 2.2, P = 0.03) and a ≤ -10% loss in the psoas muscle (HR 2.4, P = 0.02) were identified as independent prognostic factors for overall survival. A subanalysis of patients without sarcopenia identified a worse survival outcome for patients with a ≤ -10% loss in the psoas muscle (HR 2.6, P = 0.03) and ≤ - 5 change in the Prognostic Nutritional Index (HR 3.6, P = 0.01).Conclusion: Further research is required to establish appropriate rehabilitation protocols and nutritional interventions after radical cystectomy for maintaining skeletal muscle mass and nutrition status which could counteract physical deterioration and improve outcomes. [ABSTRACT FROM AUTHOR]

Clinical evidence regarding risk reduction of repeated bladder recurrence after initial photodynamic diagnosis (PDD)-assisted transurethral resection of bladder tumor (TURBT) is still limited in patients with non-muscle-invasive bladder cancer (NMIBC). We analyzed patients with primary NMIBC undergoing TURBT without any adjuvant treatment to compare the risk of cumulative recurrence between the conventional white-light (WL)-TURBT and PDD-TURBT. Out of 430 patients diagnosed with primary NMIBC from 2010 to 2019, 40 undergoing WL-TURBT and 60 undergoing PDD-TURBT were eligible. Multivariate Cox regression analysis for time to the first recurrence demonstrated that PDD assistance was an independent prognostic factor with better outcome (p = 0.038, hazard ratio = 0.39, and 95% confidence interval 0.16–0.95). While no patient experienced more than one recurrence within 1000 postoperative days in the PDD-TURBT group, five out of 40 patients treated by WL-TURBT experienced repeated recurrence. The comparison of cumulative incidence per 10,000 person-days between the two groups revealed that PDD assistance decreased by 6.6 recurrences per 10,000 person-days (exact p = 0.011; incidence rate ratio 0.37, Clopper–Pearson confidence interval 0.15–0.82). This is the first study addressing PDD assistance-induced risk reduction of repeated bladder recurrence using the person-time method. Our findings could support clinical decision making, especially on adjuvant therapy after TURBT. [ABSTRACT FROM AUTHOR]

The detection of carcinoma in situ (CIS) is essential for the management of high-risk non-muscle invasive bladder cancers. Here, we focused on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) combined with photodynamic diagnosis (PDD) for the detection of CIS. A total of 45 patients undergoing pre-surgical DCE-MRI and PDD-assisted endoscopic surgery accompanied by biopsies of the eight segmentations were analyzed. Immunohistochemical analysis of the biopsies revealed hypervascularity of CIS lesions, a cause of strong submucosal contrast-enhancement. It was found that 56 (16.2%) of 344 biopsies had pathologically proven CIS. In the DCE-MRI, the overall sensitivity and specificity for detecting CIS were 48.2% and 81.9%, respectively. We set out two different combinations of PDD and DCE-MRI for detecting CIS. Combination 1 was positive when either the PDD or DCE-MRI were test-positive. Combination 2 was positive only when both PDD and DCE-MRI were test-positive. The overall sensitivity of combinations 1 and 2 were 75.0% and 37.5%, respectively (McNemar test, vs PDD alone; p = 0.041 and p < 0.001, respectively). However, the specificity was 74.0% and 91.7%, respectively (vs PDD alone; both p < 0.001). Our future goal is to establish 'MRI-PDD fusion transurethral resction of the bladder tumor (TURBT), which could be an effective therapeutic and diagnostic approach in the clinical management of high-risk disease. [ABSTRACT FROM AUTHOR]

Objective To determine the prognostic factors of primary T1 high-grade bladder cancer and to validate the Spanish Urological Club for Oncological Treatment model in Japanese patients with T1 high-grade bladder cancer treated at a single institution. Methods Records of 106 patients with T1 high-grade bladder cancer treated from 1998 to 2013 were retrospectively reviewed. Variables included various clinicopathological parameters, including lymphovascular invasion and tumor growth pattern at the invasion front. Recurrence-free survival and progression-free survival were analyzed. Multivariate Cox proportional regression analysis was used to verify the prognostic significance of the variables. Scores for recurrence and progression were calculated using the Spanish Urological Club for Oncological Treatment model. Results Of 106 patients, 44 (42%) had recurrence and 16 (15%) developed progression after a median (interquartile range) follow-up period of 54 months (range 32-81 months). Non-papillary shape was the only independent predictor for recurrence, while broad-based tumor stalk and infiltrative tumor growth pattern at the invasion front were determined to be independent predictors for progression. Stratification of patients according to the number of progression risk factors yielded hazard ratios of 10.1 and 13.1 in patients having one and two risks, respectively, compared with those without any risks. The Spanish Urological Club for Oncological Treatment model successfully stratified our patients with a trend toward different probabilities of recurrence and progression. Conclusions The results of the present study might be helpful for counseling certain patients towards intensive treatment, such as radical cystectomy and/or platinum-based systemic chemotherapy. In addition, the Spanish Urological Club for Oncological Treatment model might be applicable to Japanese patients with T1 high-grade bladder cancer. [ABSTRACT FROM AUTHOR]

There is limited evidence regarding the tumor expression of nectins and their clinical implications in muscle invasive bladder cancer. Herein, we evaluated expression of Nectins 1–4 in 64 patients with muscle invasive bladder cancer who underwent radical cystectomy using a histochemical scoring method (H-score; immunohistochemical staining intensity multiplied by the percentage of positive-staining cells). The cutoff values were defined based on the median H-scores. Of the 64 patients, 45 (70%) had residual tumors in radical cystectomy specimens, while 13 (20%) had lymph node metastasis. The median (interquartile range) H-scores of Nectin-1, − 2, − 3, and − 4 expression were 0 (0−10), 80 (30−180), 5 (0−30), and 100 (33−160), respectively. The Nectin-4 H-score of the neuroendocrine variant was significantly lower than that of pure urothelial carcinoma (P = 0.015). Post-neoadjuvant chemotherapy pathological response (