白木 良一

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: Acute uncomplicated cystitis (AUC) is a urinary tract infection and is generally treated using antimicrobial therapy. Escherichia coli is the main causative agent of AUC. Recently, the prevalence of fluoroquinolone (FQ)-resistant-E. coli has demonstrated a noticeable increase. In this study, we aimed to investigate the effectiveness of appropriate antimicrobial treatment in AUC caused by E. coli in real-world clinical settings. METHODS: This retrospective cohort study reviewed the records of patients with AUC treated at the urology department of Minami Cooperative Hospital between April 2016 and December 2020. Effectiveness was defined as clinical improvement. RESULTS: The study cohort of 730 patients had a median age of 65.5 years (interquartile range, 57-78 years) and 23.2% were aged <55 years. E. coli was detected in 73.4% of patients, of whom 26.7% had levofloxacin (LVFX)-resistant strains. LVFX-resistant E. coli was associated with age ≥55 years and recurrent cases. Effectiveness was determined in 75.1% of cases, of which 75% complied with the Japanese or other international guidelines. The overall treatment effectiveness was highest with β-lactam (BL)/β-lactamase inhibitor (BLI) combinations (94.7%). The effectiveness of first- and third-generation cephalosporins (CPs) was 81.1-83.3%, and that of FQs and sulfamethoxazole-trimethoprim (ST) was 82.6-83.8%. For LVFX-resistant E. coli, the treatment effectiveness was highest (100%) with BL/BLI combinations, intermediate (75-81%) with first- and third-generation CPs and ST, and lowest (50%) with FQs. CONCLUSIONS: BL/BLI combinations had the highest effectiveness for the treatment of AUC.

BACKGROUND: The treatment strategy for urothelial carcinoma has advanced with the development of enfortumab vedotin (EV); however, a comparative analysis of its therapeutic efficacy between upper urinary tract urothelial carcinoma (UTUC) and bladder cancer (BCa) has yet to be established. We aimed to compare the effects of EV after pembrolizumab treatment between the patients with UTUC and BCa. METHODS: We included the patients with advanced UC patients who received EV after pembrolizumab in this retrospective study. We investigated the impact of various clinical variables including age, primary site of disease (UTUC vs. BCa), Liver metastasis, lung metastasis, prior number of regimens before EV treatment, and ECOG PS, which influenced on prognosis and efficacy of EV treatment. RESULTS: A total of 63 male and 23 female patients were included in our study. The number of UTUC and BCa patients were 33 and 53, respectively. The UTUC cohort had a significantly older patient population and a greater incidence of lung metastases compared to the BCa group. The prognosis of UTUC patients were not significantly different from BCa patients. However, UTUC was determined as significant factor to predict better overall response rate than BCa in multiple logistic regression analysis. CONCLUSIONS: UTUC patients showed significantly better response to EV treatment than BCa patients.

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.

Although glycosphingolipids (GSLs) and sterol metabolites are known to be involved in many diseases, including neurodegenerative disorders, the quantification of these molecules in humans has been scarcely investigated. Similarly, the effects of age, sex, and statin use have not been sufficiently investigated or reported in the literature. In this study, we measured the levels of human cerebrospinal fluid (CSF) GSLs of various fatty acid acyl chain lengths and sterol metabolites using hydrophilic interaction liquid chromatography and electrospray tandem mass spectrometry in a neurologically normal population. We successfully quantified the presence of glucosylated cholesterol, galactosylated cholesterol, glucosylated sitosterol, glucosylceramide (GlcCer), galactosylceramide, lactosylceramide (LacCer), and galabiosylceramide (Gb2). There were no statistically significant differences in CSF concentrations of these lipids between males and females. We also found no correlation between CSF concentration and age or statin dose, except for GlcCer d18:1-C23:1. Significant positive correlations with age were shown only in males. Our results indicate that, in future studies, age and sex should be taken into consideration when comparing CSF GSL levels in patients with neurological disorders with those in neurologically normal control subjects.

The composition of the distal ileum microbiota and the impact of fecal exposure during intracorporeal urinary diversion (ICUD) on gastrointestinal (GI) complications remain unclear. This study included 146 patients with bladder cancer who underwent ICUD without bowel preparation and received only a single day of antibiotic prophylaxis. Fecal samples were collected directly from the distal ileum during surgery, and ascitic fluid was obtained postoperatively from abdominal drains. Among the patients, 129 (88.3%) had minimal microbial growth in ileal feces, while 17 (11.7%) showed significant colonization. The most commonly identified organisms were Streptococcus, Enterococcus, Enterobacter, Klebsiella, and Candida. The incidence of GI complications was significantly higher in patients with positive ileal fecal cultures compared to those with no detectable growth (39.4% vs. 7.7%, P < 0.001), and even more pronounced in patients with positive ascitic cultures (72.5% vs. 11.3%, P < 0.001). Multivariate analysis identified positive ascitic cultures as an independent predictor of GI complications. Additionally, frailty was significantly associated with the presence of microbial growth in ascitic fluid. These findings suggest that, although the distal ileal microbiota is largely suppressed under short-term antibiotic prophylaxis, the presence of intra-abdominal bacteria or fungi is strongly linked to postoperative GI complications, including ileus. Frailty may contribute to microbial dysbiosis and the persistence of intra-abdominal pathogens, particularly Enterococcus and Enterobacter species.

OBJECTIVES: Immune checkpoint inhibitor (ICI)-based combination therapies are first-line treatments for locally advanced or metastatic renal cell carcinoma (mRCC). However, second-line treatment efficacy remains uncertain due to limited large randomized trials. This study evaluated real-world oncological outcomes after second-line treatments in patients who received combination ICIs as first-line treatment. METHODS: Among 467 patients who received ICI combination therapy as first-line treatment for mRCC between January 2018 and January 2024, those who received cabozantinib (Cabo) or axitinib (Axi) as second-line treatment were included in this study. The patient characteristics at the initiation of second-line treatment, progression-free survival (PFS), and overall survival (OS) were compared between the two groups. Prognostic factors associated with OS after the initiation of second-line treatment were evaluated. RESULTS: The Cabo and Axi groups included 87 and 45 patients, respectively. Median OS and PFS after the initiation of secondary treatment were 32 and 9 months in the Cabo group (p = 0.269), and 33 and 12 months in the Axi group (p = 0.399). Multivariable analysis identified serum C-reactive protein (CRP) ≥ 0.6 mg/dL and estimated glomerular filtration rate (eGFR) < 40 mL/min/1.73 m2 at the start of secondary treatment as independent predictors of OS. Stratification by these factors revealed a significant OS difference (p < 0.001). CONCLUSIONS: Oncological outcomes after the initiation of secondary treatment did not differ significantly between the Cabo and Axi groups. An eGFR < 40 mL/min/1.73 m2 and CRP ≥ 0.6 mg/dL at the start of Cabo or Axi treatment were independent OS predictors after secondary treatment.

OBJECTIVES: We aimed to evaluate the long-term oncological and functional outcomes after robot-assisted partial nephrectomy (RAPN) for renal hilar tumors. METHODS: A total of 22 academic hospitals in Japan participated in a prospective, multicenter, single-arm, open-label trial with a 2-year enrollment period. After undergoing RAPN, 105 patients with clinical T1 renal hilar tumors were followed up for 5 years and evaluated. Recurrence-free survival, overall survival, and trends of renal function were set as oncological and functional outcomes. RESULTS: Five-year overall survival and recurrence-free survival were 98.0% and 89.2%, respectively. Mean estimated glomerular filtration rates (eGFRs) were 69.031 mL/min preoperatively, and were 59.374, 58.334, 58.221, 56.975, and 59.602 mL/min at 1, 2, 3, 4, and 5 years after surgery, respectively. While eGFR was significantly lower than the preoperative one at all points (p < 0.001), eGFRs at 1 and 5 years after surgery did not differ significantly (p = 0.793). CONCLUSION: After long-term follow-up, RAPN for clinical T1 renal hilar tumors continues to provide functional and oncological outcomes equivalent to those in the perioperative period. TRIAL REGISTRATION: The study protocol was registered in the Japan Registry of Clinical Trials (jRCT1052190005, UMIN000023968).

BACKGROUND: Enfortumab vedotin (EV), an antibody-drug conjugate (ADC) targeting Nectin-4, has been available as standard care for metastatic urothelial carcinoma (mUC) patients who have progressed after platinum-based chemotherapy and checkpoint inhibitors (CPIs). However, the association between body mass index (BMI) and clinical outcomes for EV remains unknown. METHODS: We analyzed the records of 123 mUC patients who received EV. The cohort was divided into low BMI (< 22, n = 65) and high BMI (≥ 22, n = 58) groups. Propensity score matching was performed to reduce clinical bias between the two groups. RESULTS: In the total cohort (n = 123), the objective response rate (ORR) and disease control rate (DCR) were 46% and 68%, respectively. The ORR was significantly higher in the higher BMI group (62%, n = 58) compared to the lower BMI group (32%, n = 65). Among the pair-matched cohort (n = 100), despite reducing potential bias, the ORR remained significantly higher in the higher BMI group than in the lower BMI group (64% vs. 32%, p = 0.002). Both overall survival (OS) and radiographic progression-free survival (r-PFS) were longer in the higher BMI group compared to the lower BMI group (median OS: not reached vs. 8 months, p = 0.035; median r-PFS: 10 vs. 4 months, p < 0.001). On multivariate analyses, a higher BMI (≥ 22) was an independent predictor for achieving objective response and favorable OS in mUC patients treated with EV. CONCLUSIONS: The findings of this study suggest a potential association between high BMI and improved tumor response to EV in mUC patients with disease progression after platinum-based chemotherapy and CPIs.

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.

OBJECTIVE: This study aimed to establish a robust predictive model for biochemical recurrence (BCR) in patients with prostate cancer who underwent robot-Assisted Radical Prostatectomy. MATERIAL AND METHODS: A cohort of 1700 patients who underwent robot-assisted radical prostatectomy (RARP) for prostate cancer between August 2009 and December 2022 was included. BCR was defined as two consecutive PSA levels exceeding 0.2 ng/mL post-radical prostatectomy. Cox proportional hazards regression identified predictive variables for BCR. Subsequently, pathologic T stage, PSA level, positive surgical margin, extraprostatic extension, and seminal vesicle involvement were retained. A nomogram was constructed using R software to predict BCR. The model was evaluated using the C-index and calibration curves. RESULTS: A total of 161 instances of BCR were observed during a median follow-up of 61.0 months (range, 12-162 months). The 5-year BCR-free survival rate for the cohort was 25 %. Univariate analysis demonstrated significant associations between BCR and PSA, clinical T stage, biopsy Gleason score, D'Amico risk classification, pathologic T stage, pathologic Gleason score, extraprostatic extension, seminal vesicle invasion, and positive surgical margins. Multivariate analysis identified high PSA ≥20 ng/mL (HR: 1.93; p = 0.034), pathologic T stage 3-4 (HR: 1.89; p < 0.001), pathologic Gleason score 8-10 (HR: 5.43; p < 0.001), extraprostatic extension (HR: 1.41; p < 0.001), seminal vesicle involvement (HR: 1.92; p = 0.018), and positive surgical margin (HR: 2.73; p < 0.001) as independent predictors of BCR. The new model exhibited a C-index of 0.743 (95 % confidence interval: 0.741-0.745). CONCLUSION: The developed nomogram accurately predicts the likelihood of BCR-free status within 3 years following RARP. This allows for tailored follow-up strategies, optimizing resource allocation, and holds significant clinical utility, warranting broader implementation and further research.

Prostate cancer (PCa) is one of the most common cancers among men worldwide, and robot-assisted radical prostatectomy (RARP) is a widely used treatment for localized PCa. Achieving pentafecta outcomes, which include continence, potency, cancer control, free surgical margins, and no major complications, is a critical measure of surgical success and long-term prognosis. However, predicting these outcomes remains challenging. In this retrospective, single-center study, we analyzed data from 1,752 patients who underwent RARP for localized prostate adenocarcinoma between August 2009 and April 2023. The pentafecta outcome was achieved in 290 patients (16.6%). Multivariate analysis revealed that bilateral nerve sparing significantly increased the likelihood of achieving the pentafecta outcome (odds ratio 10.36, 95% CI: 5.75-18.66; p < 0.001). Preoperative potency and bilateral nerve sparing were also identified as key predictors. Nomograms were developed using preoperative and postoperative variables, including age, PSA level, biopsy Gleason score, clinical stage, pathological tumor stage, tumor grade, nerve sparing, and preoperative potency. Internal validation of the nomograms was performed using bootstrapping methods, demonstrating robust predictive performance. These nomograms provide valuable tools for personalized surgical planning and patient counseling and may be applicable to broader populations, given the inclusion of universally recognized predictive factors and rigorous validation. This study presents the development and validation of nomograms to predict pentafecta outcomes before and after RARP. These nomograms provide valuable tools for clinicians to estimate the likelihood of achieving postoperative pentafecta outcomes. Incorporating these nomograms into clinical practice may improve patient counseling and shared decision-making.

BACKGROUND/AIM: Cancer-induced pain (CIP) exacerbates patient's quality of life. However, it is unknown whether CIP is associated with survival in urothelial carcinoma (UC) patients treated with enfortumab vedotin (EV). This study retrospectively investigated the prognostic significance of CIP in EV-treated UC patients. PATIENTS AND METHODS: We analyzed clinical data from patients with locally advanced or metastatic UC who received EV treatment, assessing various factors such as age, metastasis site, ECOG Performance Status (PS), and CIP status prior to treatment. CIP was determined based on clinical records cancer-related pain or the use of analgesics for pain management. RESULTS: A total of 114 patients (78 males and 36 females) were included in the study. The group with CIP included significantly higher number of patients with bone metastasis. Progression-free survival of the patients with CIP was not significantly different from those without CIP. However, the patients with CIP showed worse overall survival (OS) than those without CIP. Cox proportional regression analysis showed that CIP, liver metastasis, and ECOG PS were significant predictors of poorer OS. CONCLUSION: CIP before the treatment of EV was a significant predictor of reduced OS in patients with UC. Early management of CIP or initiation of EV therapy before CIP development may improve survival outcomes.

BACKGROUND: Androgen-receptor signaling inhibitors (ARSIs) become the new standard of care for metastatic hormone-sensitive prostate cancer (mHSPC). It is unknown whether time to castration resistance (TTCR), when using the first-line ARSIs, offers predictive value in mHSPC. We sought to assess the clinical outcomes for mHSPC patients treated with first-line ARSIs focusing on the TTCR. METHODS: Data from the ULTRA-Japan study cohort from five academic institutes (496 mHSPC patients) were retrospectively analyzed. RESULTS: The median overall survival (OS) in the total cohort was 80 months with a median follow-up of 18 months. Of 496 patients, 332 (67%), 82 (16.5%), and 82 (16.5%) were treated with first-line abiraterone acetate + prednisone, enzalutamide, and apalutamide, respectively. During the follow-up, a total of 155 (31%) were diagnosed with mCRPC with a median TTCR of 10 months. In those 155 patients, TTCR > 12 months is an independent predictor of longer OS from the first-line ARSIs. Cox regression analysis of the TTCR from initiating first-line ARSI in 496 mHSPC patients revealed three variables as independent predictors of shorter TTCR, including Gleason's score (GS) ≥ 9, the extent of disease (EOD) ≥ 2, and the presence of liver metastasis. CONCLUSION: Our results indicate that mHSPC patients with those three features are likely to have primary resistance to first-line ARSIs (doublet therapy), thus requiring consideration of other options, such as the recent triplet approach.

BACKGROUND: Prostate-specific antigen (PSA) kinetics has been investigated as a prognostic marker in post hoc analyses of clinical trials. This study validated the prognostic value of rapid and deep PSA decline in metastatic hormone-sensitive prostate cancer (mHSPC) using real-world data. METHODS: In total, 1296 patients with mHSPC were retrospectively reviewed. We assessed the prognostic value of a PSA decline to ≤ 0.2 ng/mL after 12 weeks of treatment and investigated several potential risk factors for a poor PSA response. RESULTS: Of 1296 patients, 714 (cohort 1: 55.1%) were treated with conventional hormonal therapy, while 582 (cohort 2: 44.9%) received androgen signaling inhibitors. There were significant differences in progression-free survival and overall survival between patients with PSA decline to ≤ 0.2 ng/mL by 12 weeks of treatment and others (p < 0.001 for each). In addition, patients with an initial PSA ≥ 200 ng/mL, Clinical T4 and Grade Group 5 were less likely to achieve PSA decline to ≤ 0.2 ng/mL by 12 weeks of treatment, with odds ratios of 0.31 (p < 0.001), 0.67 (p = 0.039) and 0.70 (p = 0.043), respectively. CONCLUSION: Our findings suggested that PSA decline to ≤ 0.2 ng/mL by 12 weeks of treatment may be a useful prognostic biomarker for mHSPC in the real-world setting. The prognostic value of this should be further investigated in a prospective cohort, and identification of an optimal cutoff value is necessary for its application in clinical trial design or clinical practice.

BACKGROUND: Metastatic nonclear cell renal cell carcinoma (nccRCC) is a heterogeneous disease with poor prognosis. The clinical characteristics and prognostic factors of immuno-oncology (IO) combination therapy for nccRCC are not well known. This study analyzed patients with metastatic nccRCC treated with IO combination therapy. METHODS: We retrospectively collected data from 447 patients with metastatic RCC treated with IO-based combination therapy as first-line treatment between September 2018 and July 2023 in a Japanese multicenter study. The primary endpoints were objective response rate, progression-free survival (PFS), and overall survival (OS), comparing groups treated with IO-IO and IO-tyrosine kinase inhibitor (TKI) therapies. RESULTS: Seventy-five patients with metastatic nccRCC were eligible for analysis: 39 were classified into the IO-IO group and 36 into the IO-TKI group. Median PFS was 5.4 months (95% CI: 1.6-9.1) for the IO-IO group and 5.6 (95% CI: 3.4-12.0) for the IO + TKI group. Median OS was 24.2 months (95% CI: 7.5-NA) for the IO-IO group and 23.4 (95% CI: 18.8-NA) for the IO + TKI group, with no significant difference. In univariate analysis, International Metastatic Renal Cell Carcinoma Database Consortium scores, Karnofsky performance status, neutrophil-to-lymphocyte ratio, and the presence of liver metastases were significantly associated with OS, whereas in multivariate analysis, only the presence of liver metastases was significantly associated with OS (P = .035). CONCLUSIONS: There was no significant difference in OS or PFS between IO-IO and IO-TKI combination therapy as first-line treatment for patients with nccRCC. Liver metastasis is a poor prognostic factor for such patients.