PURPOSE: Immune checkpoint inhibitor (ICI)-based combination therapy is a standard first-line treatment for metastatic renal cell carcinoma (mRCC), with combinations such as nivolumab plus cabozantinib (Nivo + Cabo) and pembrolizumab plus lenvatinib (Pem + Len) demonstrating favorable oncologic outcomes. However, no direct comparisons between these two regimens have been conducted. This study aimed to compare the safety and oncologic outcomes of Nivo + Cabo and Pem + Len in patients with mRCC. METHODS: This retrospective study included 185 patients with mRCC treated with Nivo + Cabo (n = 81) or Pem + Len (n = 104) between January 2018 and June 2025 across multiple institutions. The primary outcome was a comparison of treatment-related adverse events (TrAEs). Oncologic outcomes, including objective response rate (ORR), progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS), were compared using one-to-one propensity score matching. RESULTS: Any-grade TrAEs occurred in 90% of patients in the Nivo + Cabo group and 92% in the Pem + Len group (p = 0.6). Severe TrAEs (grade ≥ 3) were more frequent in the Pem + Len group (44%) than in the Nivo + Cabo group (30%, p = 0.048). Tyrosine kinase inhibitor dose reduction and treatment discontinuation rates were similar between groups. In the matched cohort (Nivo + Cabo: n = 74; Pem + Len: n = 74), ORRs were comparable (66% vs. 71%, p = 0.6). With a median follow-up of 17 months, no significant differences were observed in PFS (p = 0.4), CSS (p = 0.9), or OS (p = 0.5). CONCLUSIONS: Nivo + Cabo and Pem + Len demonstrated similar oncologic efficacy as first-line treatments for mRCC. However, Pem + Len was associated with more severe TrAEs. Careful toxicity management and shared decision-making are essential when selecting ICI-based combinations.

Few studies have investigated the efficacy of immuno-oncology (IO) combinations at different metastatic sites in renal cell carcinoma (RCC). We evaluated the differential efficacy of IO-IO and IO-tyrosine kinase inhibitor (TKI) combinations by metastatic site in metastatic RCC (mRCC). This retrospective multicenter study by the JK-FOOT Study Group included 579 patients with intermediate- or poor-risk mRCC (per International Metastatic RCC Database Consortium criteria) treated with first-line IO combinations between September 2018 and December 2024. Metastatic sites were lymph nodes, lungs, bones, liver, brain, and others. The primary endpoints were progression-free survival (PFS) and overall survival (OS); the secondary endpoint was objective response rate. Efficacy was compared between IO-IO and IO-TKI for each site. For lymph node (n = 36), lung (n = 132), or brain (n = 16) metastases, OS or PFS was not significantly different between IO-IO and IO-TKI. In bone metastases (n = 80), OS tended to favor IO-TKI (P = 0.053). In liver metastases (n = 22), OS was significantly longer with IO-TKI (P = 0.011). IO-TKI may be a more appropriate first-line option than IO-IO for mRCC with bone or liver metastases, while efficacy is similar for other sites.

BASCKGROUND: Immune checkpoint inhibitor (ICI)-based combination therapies have become the standard first-line treatment for metastatic renal cell carcinoma (mRCC). Proton-pump inhibitors (PPIs), frequently used to treat gastrointestinal conditions, have been implicated in modulating ICI efficacy, potentially through gut microbiome dysbiosis. However, the impact of PPIs on ICI-based therapies for mRCC remains unclear. METHODS: This multicenter retrospective cohort study analyzed 427 patients with mRCC classified as intermediate or poor risk according to the IMDC criteria treated with first-line IO-IO (ipilimumab plus nivolumab) or IO-TKI (ICI plus tyrosine kinase inhibitor) therapies. Patients were stratified by PPI use during the 30 days before and including the day of ICI initiation. Overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) were compared between PPI users and nonusers. RESULTS: PPI use was significantly associated with shorter OS in patients receiving IO-IO therapy (median OS, 23.34 months vs. not reached; P = .002), but not in those receiving IO-TKI therapy (P = .909). Multivariate analysis confirmed PPIs as an independent prognostic factor for OS in the IO-IO group (HR, 1.647; 95% CI, 1.007-2.693; P = .046). No significant differences in PFS or ORR were observed between PPI users and nonusers in either group, although the complete response rate was notably lower in PPI users treated with IO-IO (1.6% vs. 10.3%; P = .025). CONCLUSIONS: PPI use was associated with inferior survival in mRCC patients receiving IO-IO therapy, potentially through microbiome modulation and other immunologic or clinical mechanisms; however, these findings are based on retrospective data and should be regarded as hypothesis-generating. Caution is advised when prescribing PPIs to patients undergoing ICI-based therapy, particularly IO-IO regimens, and prospective studies are needed to confirm whether avoiding unnecessary PPI use can improve clinical outcomes.

OBJECTIVES: We aimed to evaluate overall survival (OS) and determine the optimal timing of cytoreductive nephrectomy (CN) in patients with metastatic renal cell carcinoma (mRCC) receiving immune checkpoint inhibitor (ICI)-based therapy. METHODS: This retrospective study reviewed medical records of 447 patients with mRCC treated with ICI at multiple Japanese institutions between January 2018 and August 2023. From this cohort, 178 patients with lymph node or distant metastases received either cytoreductive nephrectomy (CN group; n = 72) or ICI therapy without cytoreductive nephrectomy (non-CN group; n = 106) as first-line treatment. RESULTS: Median progression-free survival was 15.7 months, and median overall survival was 58.1 months. CN significantly improved OS, with the CN group's median OS not reached, compared to 29.6 months in the non-CN group (p = 0.01). Deferred CN also showed improved survival outcomes. Poor prognostic factors for immediate CN included International Metastatic Renal Cell Carcinoma Database Consortium poor risk, sarcomatoid differentiation, and a high neutrophil-to-lymphocyte ratio. CONCLUSIONS: We developed a prognostic model to guide patient selection for CN, emphasizing the need for personalized treatment strategies.

BACKGROUND: Despite durable benefits of ipilimumab and nivolumab in metastatic renal cell carcinoma (mRCC), early progressive disease (PD), defined as disease progression within 3 months, occurs, and its predictors remain unclear. We aimed to investigate the clinical factors associated with early PD in patients with mRCC treated with this regimen. METHODS: A retrospective analysis of a multi-institutional database identified 193 patients with mRCC treated with ipilimumab plus nivolumab. Logistic regression analyses assessed associations between clinical factors and early PD. RESULTS: During a median follow-up of 17 months, patients had median overall (OS) and progression-free survival (PFS) of 35 and 14 months, respectively. Objective response and PD rates were 49.9% and 24.9%, respectively. Patients with early PD had significantly worse OS than those with non-early PD (10 vs. 42 months; P = 0.0002). Multivariate analyses identified bone metastasis and performance status (PS) as independent indicators of early PD (P = 0.03 and 0.01, respectively). Early PD rates varied by metastatic site (lung, 19.3%; bone, 31.2%; brain, 10%; and liver, 30%). Patients with clear-cell RCC had a median OS of 48 months and PFS of 22 months. The identified variables of early PD were consistent across all patient populations evaluated. CONCLUSIONS: Bone metastasis and PS predict early PD in patients with mRCC treated with ipilimumab plus nivolumab, with antitumor effect of the regimen varying by metastatic site. Clarifying the characteristics of early PD may guide clinical decision-making in treatment selection.

BACKGROUND/AIM: Immune-related adverse events (irAEs) are associated with improved clinical outcomes in patients with metastatic renal cell carcinoma (mRCC) treated with immuno-oncology therapy. However, various irAEs occur during such therapy. In this study, we analyzed the association between irAEs and prognosis of patients with mRCC treated with nivolumab and ipilimumab. PATIENTS AND METHODS: We retrospectively collected data from 193 patients with mRCC who were treated with nivolumab and ipilimumab as first-line treatment between September 2018 and February 2023 at multiple institutions. We performed Cox proportional hazards analysis for progression-free (PFS) and overall (OS) survival to identify specific irAEs associated with prognosis. RESULTS: Among the 153 eligible patients (median age=68 years; range=27-86 years, the median PFS was 7.8 months (95% confidence interval=6.0-12.5 months), and the median OS was 34.0 months (95% confidence interval=23.9 months - not reached). The most common irAEs were endocrine disorder (28.8%), rash (18.3%), pulmonary disorder (10.5%), and liver dysfunction (9.8%). In the multivariate analysis, endocrine disorder-related irAEs were identified as prognostic factors for significantly better PFS and OS. Additionally, rash-related irAEs were significant prognostic factors, specifically for better OS (p<0.05). CONCLUSION: Both rash and endocrine disorder-related irAEs were predictors of survival outcomes in patients with mRCC treated with nivolumab and ipilimumab. Optimal management of these irAEs is essential for improving prognosis.

Immune checkpoint inhibitors (ICIs) are a key component of first-line treatment for metastatic renal cell carcinoma (mRCC). However, predicting treatment-related adverse events (TRAEs) remains challenging. This study investigated the utility of eosinophil-related biomarkers as predictors of Common Terminology Criteria for Adverse Events grade ≥ 3 TRAEs in mRCC patients undergoing ICI combination therapy. In this retrospective analysis across 21 hospitals in Japan, we examined 180 patients treated with ICI/ICI therapy and 216 patients treated with ICI/tyrosine kinase inhibitor (TKI) therapy. Grade ≥ 3 TRAEs occurred in 39.4% and 31.9% of patients in the ICI/ICI and ICI/TKI groups, respectively. An elevated eosinophil proportion of ≥ 2.0% (odds ratio [OR]: 2.36; 95% CI [confidence interval] 1.23-4.54, p = 0.01) and a low neutrophil/eosinophil ratio (NER) of ≤ 40.0 (OR: 2.78, 95% CI 1.39-5.53, p = 0.004) were significant predictors of severe TRAEs in the ICI/ICI group. However, no significant associations were found in the ICI/TKI group. These findings may help identify patients who suffer from grade ≥ 3 TRAEs and help determine individualized treatment strategies in patients with mRCC.

Radiotherapy (RT) for prostate cancer increases the risk of bladder cancer. The genomic landscape of bladder cancer following RT for prostate cancer and its differentiation from bladder cancers that develop without a history of pelvic RT remains unclear. We examined gene mutations in bladder cancers that developed following RT and those that developed without prior RT. Fourteen patients who developed primary bladder cancer following brachytherapy were categorized into radiation-associated bladder tumor (RA-BT) group, whereas 33 patients diagnosed with primary bladder cancer without a history of pelvic RT were classified into the bladder tumor (BT) group. The frequency of TERT promoter mutations was 35.7% and 63.6% in the RA-BT and BT groups, respectively (p = 0.112). Among the other characteristic mutations, FGFR3 and TP53 were frequently observed in both groups (FGFR3: RA-BT vs. BT, 14.3 vs. 42.4%; TP53: RA-BT vs. BT, 50 vs. 33.3%). Rare mutations in bladder cancer were more frequently observed in the RA-BT group, including ADGRB3 (28.6%), CBL (21.4%), TGM7 (21.4%), and BTK (14.3%). There were significantly more C → T substitutions in the RA-BT group than in the BT group. In our study, the genetic mutations in the RA-BT group had distinct features from those in the BT group.

PURPOSE: The purpose of this study is to determine the utility of the CANLPH score as a predictive biomarker for patients with advanced and metastatic renal cell carcinoma (a/mRCC). By validating its prognostic value, this study aims to contribute to more personalized treatment strategies for a/mRCC. METHODS: In a multicenter retrospective study by the JK-FOOT consortium, we analyzed data from 309 a/mRCC patients undergoing ICI-based therapy. The CANLPH score-a composite marker of C-reactive protein to albumin ratio (CAR), neutrophil to lymphocyte ratio (NLR), and platelet to hemoglobin ratio (PHR)-for its prognostic accuracy in predicting cancer-specific survival (CSS). Advanced statistical methods, including receiver operating characteristic (ROC) curve analysis, Cox proportional-hazard regression, and Harrell's concordance index (C-index), were employed to assess its predictive capacity against established factors. RESULTS: The median follow-up period was 17 months, revealing two-year and five-year overall survival rates of 76.8% and 62.4%, respectively, with CSS rates at 78.3% and 66.2%. The CANLPH score well stratified survival outcomes of ICI-based treatment for RCC patients (HR 5.71; P < 0.0001). C-index analysis demonstrated that the CANLPH score had the highest predictive potency for CSS among models, including IMDC score. Multivariate analysis confirmed the CANLPH score (HR, 5.59; P = 0.0007) and Karnofsky performance status (HR, 2.59; P = 0.0032) as independent prognostic factors for CSS. CONCLUSIONS: The CANLPH score emerges as a critical tool in the a/mRCC therapeutic landscape, enabling precise prediction of patient outcomes with ICI-based therapies. Limitations include the retrospective design and the single national cohort. Prospective validation studies are warranted.

PURPOSE: Immune checkpoint inhibitor (ICI)-based combination therapy is a standard systemic treatment for metastatic renal cell carcinoma (mRCC). Although differential pharmacologic action between ICI+ICI and ICI+tyrosine kinase inhibitor (TKI) combinations may affect outcomes, comparative studies using real-world data are few. METHODS: We retrospectively analyzed the records of 447 mRCC patients treated with 1st-line ICI-based combinations at multiple institutions between January 2018 and August 2023, and selected 320 patients diagnosed with clear cell RCC (ccRCC) for further study. Cohorts were matched using one-to-one propensity scores based on IMDC risk classification. Overall survival (OS), progression-free survival (PFS), objective response rates (ORRs), and treatment-related adverse events (TrAE) were compared. RESULTS: The matching process yielded 228 metastatic ccRCC patients treated with ICI+ICI (n = 114) or ICI+TKI (n = 114). Median OS was 53 months (95%CI: 33-NA) in patients treated with ICI+ICI and was not reached (95%CI: 43-NA) with ICI+TKI (P = 0.24). Median PFS was significantly shorter for ICI+ICI (13 months, 95%CI: 7-25) than for ICI+TKI (25 months, 95%CI: 13-NA) (P = 0.047). There were no differences in second-line PFS for sequential therapy after 1st-line combinations of ICI+ICI or ICI+TKI (6 vs. 8 months, P = 0.6). There were no differences in ORR between the 2 groups (ICI+ICI: 51% vs. ICI+TKI: 55%, P = 0.8); the progressive disease (PD) rate was significantly higher in patients treated with the ICI+ICI combination (24% vs. 11%, P = 0.029). The rate of any grade TrAE was significantly higher in patients treated with ICI+TKI (71% vs. 85%, P = 0.016), but we found no differences in severe TrAE between the 2 groups (39% vs. 36%, P = 0.8). CONCLUSIONS: In a matched cohort of real-world data, we confirmed comparable OS benefits between ICI+ICI and ICI+TKI combinations. However, differential clinical behaviors in terms of PFS, PD rates, and TrAE between ICI-based combinations may enrich clinical decision-making.

INTRODUCTION: Inflammatory myofibroblastic tumors are borderline malignant soft tissue tumors primarily affecting the lungs and pelvic organs. This report presents a rare case of an inflammatory myofibroblastic tumor originating from the prostate gland in a young male. CASE PRESENTATION: A 20-year-old man developed gross hematuria and dysuria, revealing a prostatic mass. Pathological examination of a biopsy displayed spindle-shaped myofibroblast proliferation and an infiltrate of inflammatory cells, leading to a diagnosis of inflammatory myofibroblastic tumor. Following fertility preservation measures, the patient underwent a robot-assisted laparoscopic total prostatectomy with bilateral nerve sparing, resulting in a postoperative diagnosis of inflammatory myofibroblastic tumor. No recurrence was observed in subsequent imaging, and urinary continence was maintained. CONCLUSION: Surgical resection appears effective in managing inflammatory myofibroblastic tumors of the prostate. This case underscores the importance of complete tumor resection due to the significant recurrence risk associated with inflammatory myofibroblastic tumors. Radical total prostatectomy emerges as a potential treatment strategy for prostate originating inflammatory myofibroblastic tumors.

BACKGROUND/AIM: Radium-223 treatment reduces the risk of death in patients with metastatic castration-resistant prostate cancer (CRPC). This study analyzed the prognostic factors in patients treated with radium-223 dichloride. PATIENTS AND METHODS: Patients who received radium-223 dichloride were retrospectively analyzed. Prostate-specific antigen (PSA) response and alkaline phosphatase (ALP) decline rates were analyzed. Overall survival (OS) was evaluated using Kaplan-Meier curves, and prognostic factors for OS were assessed using Cox proportional hazards analysis. RESULTS: Fifty-six patients were included in the study. The five-year OS rate in patients after diagnosis of CRPC was 62.2% [95% confidence interval (CI)=27.55-112.45], while the five-year OS rate in patients at the initiation of radium-223 treatment was 21.3% (95%CI=17.20-36.79). Six patients (11.1%) had a >50% PSA decline rate, and 10 (17.9%) had a >50% ALP decline rate. Cox proportional hazards analysis showed that PSA levels at the initiation of radium-223 treatment [hazard ratio (HR)=1.00; 95%CI=1.00-1.00; p=0.0054] and Gleason Pattern (GP) 5 (HR=5.42; 95%CI=1.08-27.27; p=0.0400) were associated with OS. Patients with GP 5 had a significantly poorer prognosis compared with patients with a GP ≤4. Early administration of radium-223 as a first- or second-line treatment was not associated with OS compared with late administration of radium-223 as a third-line or later treatment. CONCLUSION: GP 5 and high PSA levels at radium-223 initiation were associated with worse OS. Radium-223 as first- or second-line treatment was not associated with OS. Therefore, a treatment strategy for CRPC based on GP 5 is needed.

A 67-year-old man underwent open radical left nephrectomy for left renal cell carcinoma [pT4N0M1 (right lower lobe of lung)] and thoracoscopic partial right lung resection for lung metastasis. The patient subsequently developed a solitary lung metastasis at 10 months and then at 26 months postoperatively. He underwent partial lung resection on each occasion. During the 28 months postoperatively, he was found to have a 12 mm middle mediastinal lymph node metastasis and a 30 mm splenic metastasis, which gradually increased in size. Three months after discovery, sunitinib was initiated at 37.5 mg 2 weeks on/1 week off. Twelve days later, the patient presented with complaints of fever. A gas-producing splenic abscess was diagnosed and he was admitted on the same day. His condition improved with antibiotics and splenic drainage. On day 35 of hospitalization, he underwent laparoscopic splenectomy. The patient's postoperative clinical course was uneventful and he was discharged 7 days after the surgery.

We compared sexual function by the expanded prostate cancer index composite (sexual domains of EPIC), health-related quality of life (SF-8), and International Prostate Symptom Score (I-PSS) inpatients using tadalafil after prostate brachytherapy (PB). Forty-five patients who underwent PB between April 2011 and January 2014 were included in this study. Patients were divided into the tadalafil (20 mg,once/week or once/two weeks) treated and non-treated (NT) groups. Sexual function was assessed prior to PB treatment and followed up to 24 weeks after PB. SF-8, sexual domains of EPIC, IPSS and subjective symptoms were assessed pre-PB and at 4, 8, 16, and 24 weeks post-PB. Patients in the tadalafil group achieved higher sexual function scores compared to NT group at all time points. For SF8, the patients in the tadalafil group significantly improved in mental health by the eighth week, and significantly worsened in the NT group (8 w ; p = 0.04). The voiding domains of EPIC score were found to worsen significantly after 4 weeks from PB in both groups, but the score tended to improve over 24 weeks. There was no significant difference between two groups. The I-PSS total score was found to worsen significantly in both groups post-PB, but the tadalafil group had a tendency to worsen less. PB treatment of localized prostate cancer is preferred for the preservation of sexual function. Management of sexual dysfunction with tadalafil after PB does not worsen sexual functions. We concluded that tadalafil might be applicable to mental health care in the treatment of patients with a high interest in sexual function before PB.

The aim of our study was to identify risk factors that may influence outcomes for patients presenting with Fournier gangrene. Twelve patients hospitalized and treated between August 2007 and August 2013 were included in this study. Distinct features were noted after one or two weeks of hospitalization. We did not observe a significant correlation between death risk and the extent of necrosis in this patient set. However, the extent of necrosis tended to correlate with the duration of hospitalization in the survivors. We also compared the results of blood biochemical analyses between the surviving and non-surviving groups. A significant difference was noted in the levels of glucose (Glu) after two weeks. In the non-surviving group, Glu levels were increased. These findings suggest a relationship between glycemic control after the initiation of therapy and death. We also examined the results of blood biochemical analyses according to the duration of hospitalization. The lactate dehydrogenase (LDH) levels at admission and LDH levels after two weeks were significantly higher in the patients with a duration of hospitalization longer than the median duration of 61.5 days. These findings suggest a relationship between the duration of hospitalization and the extent of necrosis at diagnosis.

We report a case of a patient with a fistula between the right ureter and external iliac artery. The patient was a 75-year-old woman who had undergone abdominal radical hysterectomy for uterine cancer, and whole pelvis radiotherapy for right external iliac lymph node metastasis. Her post-operative course was complicated by hydronephrosis of the right kidney, which was treated by the insertion of a double-J stent. While removing the frequently obstructed double-J stent after percutaneous nephrostomy, arterial hemorrhage occurred from the external urethral meatus. Computed tomographic scan demonstrated right ureteral external iliac artery fistula formation located adjacent to the pseudoaneurysm. The patient was treated successfully with endovascular stent grafting and has showed no episode of hematuria since then.