Cisplatin-based neoadjuvant chemotherapy (NAC) improves outcomes in muscle-invasive bladder cancer (MIBC), whereas the efficacy of carboplatin-based or suboptimal regimens remains unclear. We retrospectively reviewed 265 patients who underwent radical cystectomy, including 164 with MIBC. Among them, 21 received ≥3 cycles of gemcitabine/cisplatin (optimal NAC), 44 received ≤2 cycles of cisplatin-based NAC, 36 received gemcitabine/carboplatin (GCarb) NAC, and 63 underwent cystectomy alone. Propensity score matching was applied to compare the GCarb and no-NAC cohorts based on clinical stage, performance status, and renal function. The pathological complete response rate did not differ between the groups. Disease-free survival tended to be worse in the GCarb cohort (P = .07). Importantly, the median time-to-cystectomy from diagnosis with MIBC was significantly longer with GCarb than no-NAC cohort (3.1 vs. 1.5 months). These findings suggest that GCarb-based NAC may be detrimental by delaying surgery without providing oncological benefit, reinforcing guideline recommendations against its use in MIBC.

BACKGROUND/AIM:Clear cell renal cell carcinoma (ccRCC) exhibits marked intratumoral heterogeneity, reflected in its macroscopic color variation. As limited tissue sampling often underrepresents aggressive tumor components, macroscopic appearance may serve as an accessible, integrative indicator of intratumoral heterogeneity. However, its oncologic relevance has not been systematically investigated. This study evaluated a macroscopic color scoring system and its correlation with pathological prognostic factors and histological parameters linked to therapeutic response-related gene signatures. PATIENTS AND METHODS:Macroscopic color in 309 surgically treated ccRCC cases was retrospectively analyzed and scored as 1 (golden yellow), 2 (yellow/pale tan), or 3 (grey/white). Correlations with pathological prognostic factors, histological features (cytological phenotype/vascularity-based architectural classification/immunophenotype), and recurrence-free survival (RFS) were evaluated. Survival analyses were performed using the Kaplan-Meier method with log-rank tests and Cox proportional hazards regression models. RESULTS:Macroscopic color score was significantly correlated with TNM stage (p=0.009), tumor size (p=0.001), and histological parameters, including World Health Organization (WHO)/International Society of Urologic Pathology (ISUP) nucleolar grade, sarcomatoid/rhabdoid features, tumor-type necrosis, cytological phenotype, vascularity-based architectural classification, and immunophenotype (p<0.001). Higher scores were associated with adverse histological parameters, decreased vascularity, and increased immune infiltration. The strongest correlations were observed with WHO/ISUP grade and vascularity-based architectural classification. Although its C-index was lower than that of histological parameters, macroscopic color score effectively stratified RFS into three distinct groups [hazard ratio (HR)=2.69; p=0.022 for score 2; HR=6.53; p<0.001 for score 3]. CONCLUSION:Macroscopic intratumoral heterogeneity in ccRCC may offer a readily accessible surrogate for biological diversity and tumor microenvironmental features linked to therapeutic response. Systemic gross evaluation may improve tissue sampling, reduce pathological underestimation, and support personalized treatment strategies.

BACKGROUND/AIM:To re-evaluate established recurrence risk models for clear cell renal cell carcinoma (ccRCC) using the tumor, node, metastasis (TNM) 2017 classification and the World Health Organization/International Society of Urological Pathology (WHO/ISUP) grading system, and to perform an exploratory analysis of whether these updates improve the predictive accuracy of recurrence risk models. PATIENTS AND METHODS:We retrospectively analyzed 295 patients who underwent surgery for non-metastatic ccRCC at Osaka Metropolitan University Hospital between 2013 and 2020. Pathological features were re-evaluated using both the TNM 2009 and TNM 2017 classifications, as well as the Fuhrman and WHO/ISUP grading systems. We examined the frequency of pathological upstaging to pT3a and compared recurrence predictions across grading systems. In addition, we assessed recurrence risk stratification using the Leibovich 2003 and 2018 models with updated pathological classifications. Recurrence-free survival (RFS) was assessed using Kaplan-Meier analysis, and prognostic accuracy was evaluated using Harrell's concordance index (C-index). RESULTS:Among cT1 cases, pathological upstaging to pT3a occurred more frequently according to TNM 2017 (18.9%) than TNM 2009 (16.0%). TNM 2017 showed superior prognostic performance for predicting recurrence in cT1 tumors (C-index, 0.748 vs. 0.726). The WHO/ISUP grade demonstrated greater predictive accuracy than the Fuhrman grade (C-index, 0.817 vs. 0.737). The C-index of the Leibovich 2003 model improved from 0.812 (TNM 2009 plus Fuhrman classification) to 0.834 (TNM 2017 plus the WHO/ISUP classification). The highest predictive accuracy was achieved using the Leibovich 2018 model (C-index, 0.870). CONCLUSION:Re-evaluation using TNM 2017 and WHO/ISUP grading was associated with improved predictive accuracy of recurrence risk models for localized ccRCC and may aid postoperative risk stratification.

OBJECTIVES:To evaluate the feasibility, safety, and short-term oncological and functional outcomes of repeat robot-assisted partial nephrectomy (RAPN) for ipsilateral local recurrence of renal cell carcinoma after partial nephrectomy (PN) and describe the relevant surgical strategies. METHODS:We retrospectively evaluated eight consecutive patients who underwent repeat RAPN between April 2019 and January 2026. Patient characteristics, perioperative outcomes, renal function, pathological findings, and adhesion severity were analyzed. Intraoperative adhesions were graded as minor or severe based on the surgeon's assessment. RESULTS:Eleven ipsilateral recurrent tumors were analyzed in eight patients. Repeat RAPN was successfully performed in all patients without conversion to open surgery or radical nephrectomy. The median operative time, warm ischemia time, and estimated blood loss were 157 min, 15 min, and 50 mL, respectively. No major (Clavien-Dindo grade ≥ III) complications occurred. All malignant tumors were pT1a with negative surgical margins. At the median follow-up of 17.5 months, no local recurrence or distant metastasis was observed. The median eGFR values at 1 and 3 months were 57.1 and 55.7 mL/min/1.73 m2, respectively. Severe adhesions were more common among patients who did not receive anti-adhesion agents during initial surgery. CONCLUSIONS:Repeat RAPN may be a feasible and safe salvage option for ipsilateral recurrence after PN, with acceptable early oncological and functional outcomes. Our findings suggest that anti-adhesion agent use during the initial PN may be associated with reduced adhesion-related difficulty during subsequent reoperations, although further validation is needed.

BACKGROUND/AIM:Immune checkpoint inhibitors are widely used in treating metastatic urothelial carcinoma and metastatic renal cell carcinoma. However, the incidence, timing, and clinical impact of immune-related adverse events in real-world practice remain unclear. This study aimed to investigate their onset patterns and outcomes. PATIENTS AND METHODS:We retrospectively analyzed 210 patients with metastatic urothelial carcinoma (n=127) or metastatic renal cell carcinoma (n=83) treated with immune checkpoint inhibitors between 2017 and 2023 at a single academic institution. Events were graded using Common Terminology Criteria for Adverse Events version 5.0. Associations with progression-free and overall survival were assessed. We also evaluated cumulative incidence, corticosteroid or immunosuppressant use, and outcomes after rechallenge. RESULTS:Immune-related adverse events occurred in 78 patients (37.1%), more frequently in metastatic renal cell carcinoma (47.0%) than in metastatic urothelial carcinoma (30.9%). Overall, grade ≥3 events occurred in 22.0% of patients, with higher incidence in renal cell carcinoma (27.7%) than in urothelial carcinoma (17.3%). In metastatic urothelial carcinoma, their presence was linked to longer survival; no difference was seen in metastatic renal cell carcinoma. Most events developed within six months; only 3.4% occurred after one year. High-dose corticosteroids were administered in 13.8% of patients, and 72.4% of them successfully completed tapering. Immunosuppressants were used in 1.4%. Eleven patients underwent rechallenge, of whom two experienced recurrence. CONCLUSION:Immune-related adverse events showed distinct incidence and prognostic relevance between urothelial and renal cell carcinoma. These findings underscore the need for treatment-specific monitoring and provide practical insights into managing toxicities and decisions regarding immunotherapy rechallenge.

Combination therapy with enfortumab vedotin (EV) and pembrolizumab has shown superior overall survival (OS) compared to platinum-based chemotherapy in advanced urothelial carcinoma (UC). Given the expanding landscape of first-line treatments, understanding site-specific effectiveness is vital for developing individualized strategies. We conducted a retrospective analysis of 225 patients with advanced UC treated between April 2009 and August 2024. Systemic therapy efficacy was assessed in relation to metastatic site, focusing on site-specific responses. Patients were classified into three treatment periods (chemotherapy period [April 2009–June 2017; P1], pembrolizumab period [July 2017–December 2020; P2], and avelumab and EV period [January 2021–August 2024; P3]). Within each period, patients were stratified by metastatic pattern—lymph node-only, liver, or other—and OS was analyzed accordingly. The objective response rates for chemotherapy, pembrolizumab, avelumab, and EV were 41

OBJECTIVES:Non-renorrhaphy technique during partial nephrectomy has not been sufficiently studied. This study aimed to evaluate the surgical outcomes of the non-renorrhaphy technique in robot-assisted partial nephrectomy (RAPN) for tumors with RENAL scores of 10-12. METHODS:We retrospectively analyzed 51 consecutive patients who underwent RAPN with or without renorrhaphy for RENAL score 10-12 tumors at Osaka Metropolitan University Hospital between March 2015 and December 2023. Perioperative outcomes were compared between 16 patients in the nonrenorrhaphy group and 35 patients in the renorrhaphy group. Univariate and multivariate linear regression analyses were conducted to identify predictors of renal function and renal parenchymal volume preservation. RESULTS:Patient demographics and preoperative tumor characteristics exhibited no significant differences between the two groups. Operative time was significantly shorter in the nonrenorrhaphy group (185 vs. 217 min, p = 0.0016). The preservation rate of renal parenchymal volume was significantly higher in the nonrenorrhaphy group (86.7 vs. 74.2%, p = 0.0016), but there was no significant difference in the preservation rate of estimated glomerular filtration rate (p = 0.6380). No significant difference was observed in the incidence of major complications (Clavien-Dindo grade ≥ 3) between the two groups. Urinary leakage occurred in both groups (p = 0.9399). In univariate and multivariate analyses, renorrhaphy and clinical tumor size were identified as significant predictors of renal parenchymal volume preservation. CONCLUSIONS:Even in cases with RENAL scores of 10-12, the non-renorrhaphy technique appears to be a feasible and safe approach, and may be associated with better preservation of renal parenchymal volume.

[Background] Clear cell renal cell carcinoma (ccRCC) exhibits heterogeneous macroscopic colors, ranging from golden yellow to pale tan or white, demonstrating intratumoral heterogeneity in cellular composition. This study aimed to establish a macroscopic color scoring system for ccRCC and evaluate its correlation with pathological prognostic factors and previously reported histological parameters linked to treatment response-related gene signatures. [Methods] We retrospectively analyzed macroscopic color variation in 309 localized ccRCC cases, categorizing it into three levels: score 1 (golden yellow), score 2 (yellow to pale tan), and score 3 (grey to white). The prognostic significance of macroscopic color scores and their associations with pathological prognostic features were evaluated. [Results] Macroscopic color score was significantly correlated with TNM stage (p = 0.009), tumor size (p = 0.001), World Health Organization (WHO)/International Society of Urologic Pathology (ISUP) grade, sarcomatoid/rhabdoid features, tumor-type necrosis, cytological phenotype, vascularity-based architectural classification, and immunophenotype (p < 0.001). Higher scores were associated with adverse histological parameters, decreased vascularity, and increased immune infiltration, with the strongest correlations observed for WHO/ISUP grade and vascularity-based architectural classification. Although the C-index, a measure of predictive accuracy, of macroscopic score was lower than that of histological parameters, it effectively stratified recurrence-free survival into three distinct groups (hazard ratio, 2.69; p = 0.022 for score 2; hazard ratio, 6.53; p < 0.001 for score 3). [Conclusion] Macroscopic color variation in ccRCC may reflect underlying morphological and molecular heterogeneity. The macroscopic color scoring system may be valuable for guiding tissue sampling and risk stratification, potentially informing treatment strategies and diagnostic imaging approaches.

Resectable renal cell carcinoma (RCC) with colon invasion is extremely rare and is usually managed by open surgery. To our knowledge, this is the first case report documenting the management of a patient with robot-assisted laparoscopic radical nephrectomy (RARN) with colon resection and inferior vena cava thrombotectomy. The procedure was completed without conversion to open surgery or major peri- and post-operative complications, confirming the technical feasibility of RARN in this challenging setting. However, given the complexity and high morbidity risk, this approach should be reserved for experienced surgeons in high-volume centers, and further evidence is required to define its role.

A 79-year-old woman underwent radical cystectomy after neoadjuvant chemotherapy for urothelial carcinoma of bladder (high grade, pT3aN0M0). Six months later, a computed tomography scan revealed multiple lung metastases. Salvage treatment with chemotherapy and pembrolizumab was administered, and a complete response was achieved. Two years after surgery, however, a left adrenal mass appeared, and positron emission tomography／computed tomography showed significant solitary uptake in the left adrenal gland. She underwent left adrenalectomy and histological findings revealed that the adrenal tumor was a metastatic urothelial carcinoma. No new lesion was observed over one year after surgery. Surgical resection should be considered in cases with solitary metastasis who responded systemic treatment.

606 Background: New approaches involving immune checkpoint inhibitors (ICIs) and antibody-drug conjugates prolong overall survival (OS) in patients with metastatic urothelial carcinoma (mUC). However, the access to such systemic therapy in clinical practice is suboptimal, and whether these agents improve OS in patients with mUC over time remains unclear. In the present study, we investigated the OS trend from the initiation of first-line therapy with these agents to identify changes due to the medication and time of treatment initiation. Methods: We retrospectively evaluated 195 patients who received platinum-based chemotherapy as a first line treatment. The patients were treated with chemotherapy, pembrolizumab, avelumab, or enfortumab vedotin (EV) sequentially and were divided into the following three groups: chemotherapy period (April 2009–June 2017; P1), pembrolizumab period (July 2017–December 2020; P2), and avelumab and EV period (January 2021–August 2022; P3) based on the regulatory approval. Data cutoff was set at July 31, 2023. Results: OS was prolonged over time by the new therapeutic agents, and median OS was 11, 25, not reached, and 35.5 months for patients who were treated with chemotherapy, pembrolizumab, avelumab, or EV, respectively. However, median OS was 14, 18 months, and not reached in P1, P2 and P3, respectively. Analysis by periods showed that OS was significantly longer in P2 than in P1 (HR = 0.62, 95% CI: 0.43–0.89, P = 0.009) and in P3 than in P1 (HR = 0.47, 95% CI: 0.28–0.78, P = 0.015). No difference was observed in OS between P2 and P3 (HR = 0.66, 95% CI: 0.36–1.20, P = 0.21). Overall, the proportion of patients who received ICIs increased over time, as indicated by the fact that 77 and 95 patients received ICIs (pembrolizumab or avelumab) in P2 and P3, respectively. However, the prevalence of the treatment with EV was only 24%, and 43% of patients who received pembrolizumab received best supportive care. Conclusions: This study showed an improvement in OS over time in patients with mUC in real-world practice and may indicate the importance of not missing the appropriate opportunity to receive sequential treatments.

New approaches involving immune checkpoint inhibitors and antibody-drug conjugates prolong overall survival in patients with metastatic urothelial carcinoma. However, the access to such systemic therapy in clinical practice is suboptimal, and whether these agents improve overall survival in patients with metastatic urothelial carcinoma over time remains unclear. Hence, we investigated the overall survival trend from the initiation of first-line therapy with these agents to identify changes due to the medication and time of treatment initiation. We retrospectively evaluated 195 patients from a single center. They were treated with chemotherapy, pembrolizumab, or avelumab or enfortumab vedotin. The treatment was categorized into chemotherapy, pembrolizumab or avelumab/enfortumab vedotin period. The new agents prolonged overall survival from the start of first-line therapy. Furthermore, sequential treatment with these agents in real-world clinical practice has been reported to prolong overall survival. These study results will have major implications when a new first-line therapy is approved in the future.

Background and Objectives: Our aim was to clarify the oncological outcomes of the two different approaches to laparoscopic nephroureterectomies (LNUs) in Japan, and to examine whether there were any significant differences between the transperitoneal approach and the retroperitoneal approach. Materials and Methods: We retrospectively evaluated patients who underwent an LNU for upper tract urothelial carcinoma (UTUC) from January 2013 to December 2022. We identified 52 patients who underwent a transperitoneal LNU (tLNU) and 93 who underwent a retroperitoneal LNU (rLNU). We adopted age, smoking, and pT-stage matching, and 43 patients were classified in each group. We investigated the time from surgery to recurrence (RFS: recurrence-free survival), the time to death (OS: overall survival), and the time to non-urothelial-tract recurrence-free survival (NUTRFS). A Cox regression analysis was performed to evaluate the risk factors that influenced recurrence. Results: There were no significant differences in the RFS, OS, and NUTRFS between the two matched groups. In the multivariate Cox regression analysis, the pT stage (pT3≥ vs. pT2≤) had an HR = 2.09 and a p = 0.01, and was an independent prognostic risk factor regarding cancer recurrence. Conclusions: There were no significant differences in the oncological outcomes between the tLNU and rLNU groups. It is suggested that the transperitoneal approach should be selected for LNUs.

IntroductionUrinary fistula is a rare complication following robot‐assisted partial nephrectomy. For cases refractory to conservative treatment, only ureteral stent placement and percutaneous drainage are the established treatment alternatives.Case presentationA 44‐year‐old man presented with urinary fistula 3 weeks after robot‐assisted partial nephrectomy for right renal cell carcinoma. Follow‐up observations were conducted for 2 weeks; however, no improvements were observed. Additionally, the patient did not improve following percutaneous drainage and ureteral stent insertion. Subsequently, the patient received percutaneous injections of fibrin glue, with the urinary fistula showing significant improvements on the following day.ConclusionOur findings indicated that percutaneous fibrin glue injection can effectively treat refractory urinary fistula following partial nephrectomy.

A 74-year-old man visited the urology clinic with the chief complaint of urinary retention in December 2014. Serum level of initial prostate specific antigen (PSA) was 50 ng/ml and he was diagnosed with Gleason Score 4＋4 prostate adenocarcinoma with regional lymphadenopathy (cT3aN1M0). PSA level had declined after the treatment with combined androgen blockade. In November 2018, he was diagnosed with castration resistant prostate cancer (CRPC) as local progression was detected by computed tomography (CT) while PSA level did not increase. Since local symptoms worsened, resulting in repeated hematuria after the treatment with enzalutamide, palliative radiation therapy to the prostate (45 Gy) was performed. Five months later, follow-up CT showed multiple metastasis in bilateral lung and left testicle. Serum level of neuron-specific enolase (NSE) was 24.4 ng/ml without an elevated in serum PSA level. He received rebiopsy of the prostate, but no malignant findings were observed. Consequently, bilateral orchiectomy was performed for diagnosis of left testicular tumor. Pathological examination revealed metastasis of neuroendocrine prostate cancer (NEPC). Chemotherapy using cisplatin and irinotecan was administered after orchiectomy. Complete response of lung lesions was achieved and serum level of NSE decreased within normal range. No recurrence has been confirmed for 4 years after the completion of chemotherapy.

OBJECTIVE:Adjuvant nivolumab prolonged disease-free survival compared with placebo in patients at high risk of recurrence following radical cystectomy or radical nephroureterectomy in the CheckMate 274 trial. However, the ideal eligibility criteria for adjuvant therapy in real-world clinical practice remain controversial.METHODS:We retrospectively analyzed clinical data of 409 patients who underwent radical cystectomy (n = 252) or radical nephroureterectomy (n = 157) and validated the risk of recurrence based on the classification used in the CheckMate 274 trial. We also investigated the impact of perioperative chemotherapy, lymph node dissection and pathological factors on prognosis.RESULTS:The median follow-up time was 37.5 and 32.1 months in bladder cancer and upper tract urothelial carcinoma, respectively. Among the high-risk patients based on CheckMate 274 trial, disease-free survival was considerably shorter for bladder cancer and upper tract urothelial carcinoma patients than for low-risk patients (hazard ratios: 4.132 and 7.101, respectively). The prevalence of adjuvant chemotherapy in high-risk patients was low (24 and 38% for bladder cancer and upper tract urothelial carcinoma, respectively). The extent of lymph node dissection in bladder cancer and presence of lymph node dissection in upper tract urothelial carcinoma did not affect prognosis. Cox proportional multivariate analysis revealed CheckMate 274-high-risk as a poor prognostic factor in bladder cancer and upper tract urothelial carcinoma.CONCLUSIONS:This study validated the risk classification for recurrence following radical cystectomy and radical nephroureterectomy using the CheckMate 274 criteria in real-world practice. Further research would help assess the degree of benefit obtained from adjuvant nivolumab.

Background Radiotherapy (RT) has recently been highlighted as a partner of immune checkpoint inhibitors. The advantages of RT include activation of lymphocytes while it potentially recruits immunosuppressive cells, such as myeloid-derived suppressor cells (MDSCs). This study aimed to investigate the mechanism of overcoming treatment resistance in immunologically cold tumours by combining RT and MDSC-targeted therapy. Methods The abscopal effects of irradiation were evaluated using MB49 and cisplatin-resistant MB49R mouse bladder cancer cells, with a focus on the frequency of immune cells and programmed cell death-ligand 1 (PD-L1) expression in a xenograft model. Results MB49R was immunologically cold compared to parental MB49 as indicated by the fewer CD8 + T cells and lower PD-L1 expression. Polymorphonuclear MDSCs increased in both MB49 and MB49R abscopal tumours, whereas the infiltration of CD8 + T cells increased only in MB49 but not in MB49R tumours. Interestingly, PD-L1 expression was not elevated in abscopal tumours. Finally, blocking MDSC in combination with RT remarkably reduced the growth of both MB49 and MB49R abscopal tumours regardless of the changes in the frequency of infiltrating CD8 + T cells. Conclusions The combination of RT and MDSC-targeted therapy could overcome treatment resistance in immunologically cold tumours.

Background: Recently, switch maintenance with avelumab has been approved for the treatment of advanced or metastatic urothelial carcinoma (UC), with no progression after four to six cycles of first-line platinum-based chemotherapy. However, the optimal number of cycles of platinum-based chemotherapy has not been determined. Objective: To analyze the clinical characteristics of patients with advanced UC who were treated with platinum-based chemotherapy and investigate the association between the number of cycles of the treatment and the patients' overall survival. Methods: A total of 124 patients with advanced UC who were treated with first-line platinum-based chemotherapy at Osaka City University Hospital between April 2009 and January 2020 were retrospectively reviewed. Results: Of the 124 patients, clinical information regarding overall survival was available for 115 patients. The median age was 72 years (range, 43-95 years). Only 59 patients (51.3 %) were treated with gemcitabine and cisplatin, and 52 patients (45.2 %) were treated with gemcitabine and carboplatin. The median number of cycles was three (1-8), and the percentage of patients who discontinued chemotherapy due to progressive disease was 80.3%, 64.0%, and 86.4% in those receiving one to three, four, and five or more cycles, respectively. Moreover, no difference in overall survival was observed between patients who received four cycles and those who received five or more cycles at both univariate and multivariate levels. Conclusions: The present study shows that five or more cycles of first-line platinum-based chemotherapy did not prolong overall survival compared with four cycles, suggesting that four cycles of chemotherapy might be sufficient, considering the new treatment strategy involving switch maintenance with avelumab. (C) 2021 The Author(s). Published by Elsevier Inc.

Cigarette smoking is known to increase the risk of cancer and chronic obstructive pulmonary disease (COPD). In this study, we evaluated the effects of short-term nose-only inhalation exposure to cigarette smoke in mice. Male 10-week-old C57BL mice were exposed to clean air (control) or mainstream cigarette smoke for 1 h/day, 5 days/week, for 2 or 4 weeks. Exposure to cigarette smoke increased the number of inflammatory cells, especially neutrophils, in the bronchoalveolar lavage fluid, increased inflammatory cell infiltration foci, and caused an increase in the thickness of the peripheral bronchial epithelium. Microarray gene expression analysis indicated that smoke exposure induced inflammatory responses, including leukocyte migration and activation of phagocytes and myeloid cells, as early as two weeks after the initiation of exposure. Importantly, chemokine (C-C motif) ligand 17, resistin-like alpha, and lipocalin 2 were upregulated and may serve as useful markers of the toxic effects of exposure to cigarette smoke before pulmonary histological changes become evident.

A 75-year-old woman with a complaint of gross hematuria was referred to our hospital. The patient was diagnosed as having bladder cancer (cT3bN1M0) and received two cycles of chemotherapy with gemcitabine and cisplatin. Radical cystectomy with pelvic lymph node dissection and bilateral ureterostomy was performed after achieving partial response in a lymph node metastasis following chemotherapy. Based on the pathological diagnosis of high-grade (G3) urothelial carcinoma (ypT3aN2), two more cycles of adjuvant chemotherapy with gemcitabine and cisplatin were administered. Four months after completing adjuvant chemotherapy, pulmonary and hepatic metastases appeared, and treatment with pembrolizumab was initiated. The size of the lung metastasis decreased, while that of the liver metastasis increased 2 months after administering pembrolizumab. However, considering treatment beyond progression using checkpoint inhibitors, pembrolizumab was continued, resulting in marked tumor shrinkage of the liver metastasis. After that, pembrolizumab treatment was temporarily discontinued, and radiation therapy was administered for a new lymph node metastasis at the tracheal bifurcation. Eventually, the lymph node metastasis shrank, and the treatment with pembrolizumab was recommenced for 1 year and the metastases remained shrumken.