Metastatic Urothelial Carcinoma With Sarcomatoid Subtype After Robot-Assisted Radical Cystectomy Successfully Treated With Pembrolizumab.

A 76-year-old man who was diagnosed with urothelial carcinoma (UC) in the bladder diverticulum was referred to our institution. The patient was diagnosed with muscle-invasive bladder cancer, which was confirmed by magnetic resonance imaging that showed tumor invasion into the fatty tissue surrounding the diverticulum. After two cycles of neoadjuvant gemcitabine and cisplatin, he underwent robot-assisted radical cystectomy (RARC) with pelvic lymph node dissection followed by intracorporeal ileal conduit. The histopathologic diagnosis of the bladder tumor was UC with squamous differentiation and sarcomatoid subtype and ypT3bN0M0 without positive surgical margins. The patient refused any adjuvant therapy. Six months after RARC, the patient visited our institution with a complaint of suddenly occurring generalized pain. Because 18F-fluorodeoxyglucose positron emission tomography-CT showed multiple metastases, including bone, para-aortic lymph nodes, and pleura, pembrolizumab was initiated as a second-line treatment. After two courses of pembrolizumab, the patient's symptoms remarkably improved, and the abnormal systemic accumulation on PET-CT almost disappeared. After 26 months of continuous treatment with pembrolizumab, the patient remains disease-free. Several studies have been reported that focused on tumor subtypes and programmed cell death ligand 1 (PD-L1)-positive tumor cells as candidate biomarkers in relation to the efficacy of pembrolizumab. The higher proportion of PD-L1-positive cells in the sarcomatoid subtype may have resulted in favorable oncological outcomes compared with pure UC.

A Rare Case of Bladder Metastasis From Endometrial Cancer Treated With Robot-Assisted Radical Cystectomy.

Malignant tumors metastasizing to the bladder are uncommon, and bladder metastasis from uterine cancer is particularly rare. Several cases of bladder metastasis from malignant melanoma, gastric cancer, breast cancer, and renal cancer have been documented. However, to our knowledge, only four cases of bladder metastasis from endometrial cancer had been reported up until 2024. Here, we present a case of bladder metastasis of endometrial cancer following modified radical hysterectomy, which was successfully treated through multidisciplinary intervention.

Impact of Cytoreductive Nephrectomy in the Management of Metastatic Renal Cell Carcinoma: A Multicenter Retrospective Study.

In this study, we aimed to determine the utility of cytoreductive nephrectomy (CN) in real-world clinical practice and investigate whether CN contributes to improved oncological outcomes in patients with metastatic renal cell carcinoma (mRCC). This retrospective multicenter cohort study enrolled patients with mRCC who received systemic therapy at six institutions between May 2005 and May 2023. The patients were divided into those who did not undergo CN (Group I) and those who underwent CN (Group II). The primary endpoints were oncological outcomes, including cancer-specific survival (CSS) and progression-free survival (PFS). Altogether, 137 patients with mRCC were included in this study. The median CSS was 14 months in Group I and 32 months in Group II (p < 0.001). Additionally, the median PFS in Groups I and II was 5 and 13 months, respectively (p = 0.006). A multivariate analysis showed that CN was an independent prognostic factor for CSS and PFS. Hence, CN is a potential treatment modality that can improve oncological outcomes in patients with mRCC.

Effects of low-intensity extracorporeal shock wave on bladder and urethral dysfunction in spinal cord injured rats.

PURPOSE: To investigate the effects of low-intensity extracorporeal shock wave therapy (LiESWT) on bladder and urethral dysfunction with detrusor overactivity and detrusor sphincter dyssynergia (DSD) resulting from spinal cord injury (SCI). METHODS: At 3 weeks after Th9 spinal cord transection, LiESWT was performed on the bladder and urethra of adult female Sprague Dawley rats with 300 shots of 2 Hz and an energy flux density of 0.12 mJ/mm2, repeated four times every 3 days, totaling 1200 shots. Six weeks postoperatively, a single cystometrogram (CMG) and an external urethral sphincter electromyogram (EUS-EMG) were simultaneously recorded in awake animals, followed by histological evaluation. RESULTS: Voiding efficiency significantly improved in the LiESWT group (71.2%) compared to that in the control group (51.8%). The reduced EUS activity ratio during voiding (duration of reduced EUS activity during voiding/EUS contraction duration with voiding + duration of reduced EUS activity during voiding) was significantly higher in the LiESWT group (66.9%) compared to the control group (46.3%). Immunohistochemical examination revealed that fibrosis in the urethral muscle layer was reduced, and S-100 stained-positive area, a Schwann cell marker, was significantly increased in the urethra of the LiESWT group. CONCLUSION: LiESWT targeting the urethra after SCI can restore the EUS-EMG tonic activity during voiding, thereby partially ameliorating DSD. Therefore, LiESWT is a promising approach for treating bladder and urethral dysfunction following SCI.

Robotic versus open and laparoscopic pelvic exenterations for pelvic cancer: a multicenter propensity-matched analysis in Japan.

BACKGROUND: Pelvic exenteration (PE) is the last resort for achieving a complete cure for pelvic cancer; however, it is burdensome for patients. Minimally invasive surgeries, including robot-assisted surgery, have been widely used to treat malignant tumors and have also recently been used in PE. This study aimed to evaluate the safety and efficacy of robot-assisted PE (RPE) by comparing the outcomes of open PE (OPE) with those of conventional laparoscopic PE (LPE) for treating pelvic tumors. METHODS: Following the ethics committee approval, a multicenter retrospective analysis of patients who underwent pelvic exenteration between January 2012 and October 2022 was conducted. Data on patient demographics, tumor characteristics, and perioperative outcomes were collected. A 1:1 propensity score-matched analysis was performed to minimize group selection bias. RESULTS: In total, 261 patients met the study criteria, of whom 61 underwent RPE, 90 underwent OPE, and 110 underwent LPE. After propensity score matching, 50 pairs were created for RPE and OPE and 59 for RPE and LPE. RPE was associated with significantly less blood loss (RPE vs. OPE: 408 mL vs. 2385 ml, p < 0.001), lower transfusion rate (RPE vs. OPE: 32% vs. 82%, p < 0.001), and lower rate of complications over Clavien-Dindo grade II (RPE vs. OPE: 48% vs. 74%, p = 0.013; RPE vs. LPE: 48% vs. 76%, p = 0.002). CONCLUSION: This multicenter study suggests that RPE reduces blood loss and transfusion compared with OPE and has a lower rate of complications compared with OPE and LPE in patients with locally advanced and recurrent pelvic tumors.

Prognostic outcomes in Japanese patients with metastatic castration-sensitive prostate cancer: Comparative assessments between conventional androgen deprivation therapy (ADT) and ADT with novel androgen receptor signal inhibitor.

OBJECTIVE: The objective of this study was to compare the prognostic outcomes between metastatic castration-sensitive prostate cancer (mCSPC) patients receiving conventional androgen deprivation therapy (ADT) and those receiving ADT plus a novel androgen-receptor signaling inhibitor (ARSI) in routine clinical practice in Japan. METHODS: This was conducted as a retrospective multicenter study including 581 mCSPC patients, consisting of 305 receiving ADT alone or in combination with bicalutamide (group 1) and 276 receiving ADT plus one of the following ARSIs: abiraterone acetate, apalutamide, or enzalutamide (group 2). Prognostic outcomes between these 2 groups were comprehensively compared. RESULTS: In the entire cohort, prostate-specific antigen-progression-free survival (PSA-PFS) in group 2 was significantly longer than that in group 1, while no significant difference was noted in overall survival (OS) between the two groups. In patients corresponding to the LATITUDE high-risk group, however, both PSA-PFS and OS in group 2 were significantly longer than those in group 1. Of several factors examined, the following were identified as independent predictors of poor PSA-PFS in the entire cohort as well as the LATITUDE high-risk group: high C-reactive protein, high lactate dehydrogenase, high alkaline phosphatase, high Gleason score, and group 1. Furthermore, it was possible to precisely classify both the entire cohort and LATITUDE high-risk group into 3 risk groups regarding PSA-PFS according to the positive numbers of independent factors: positive for ≤1 factor, favorable; 2 factors, intermediate; and ≥3 factors, poor. CONCLUSION: Combined use of ARSIs with ADT could improve the prognostic outcomes of mCSPC patients, particularly those in the LATITUDE high-risk group, in real-world clinical practice in Japan.

Discrepancy in the Location of Prostate Cancer Indicated on Biparametric Magnetic Resonance Imaging and Pathologically Diagnosed Using Surgical Specimens.

Accurate diagnosis of the localization of prostate cancer (PCa) on magnetic resonance imaging (MRI) remains a challenge. We aimed to assess discrepancy between the location of PCa pathologically diagnosed using surgical specimens and lesions indicated as possible PCa by the Prostate Imaging Reporting and Data System on MRI. The primary endpoint was the concordance rate between the site of probable clinically significant PCa (csPCa) identified using biparametric MRI (bpMRI) and location of PCa in the surgical specimen obtained using robot-assisted total prostatectomy. Among 85 lesions identified in 30 patients; 42 (49.4%) were identified as possible PCa on MRI. The 85 PCa lesions were divided into positive and negative groups based on the bpMRI results. None of the patients had missed csPCa. Although the diagnostic accuracy of bpMRI was relatively high for PCas located in the middle of the prostate (p = 0.029), it was relatively low for PCa located at the base of the prostate, all of which were csPCas. Although current modalities can accurately diagnose PCa, the possibility that PCa is present with multiple lesions in the prostate should be considered, even if MRI does not detect PCa.

Impact of Robotic-Assisted Partial Nephrectomy with Single Layer versus Double Layer Renorrhaphy on Postoperative Renal Function.

We aimed to investigate the differences in renal function between patients who underwent single inner-layer renorrhaphy (SILR) or double-layer renorrhaphy (DLR) among those with renal tumors who underwent robot-assisted partial nephrectomy (RAPN). This retrospective multicenter cohort study was conducted between November 2018 and October 2023 at two institutions and included patients who underwent RAPN. In total, 93 eligible patients who underwent RAPN were analyzed. Preoperative renal function and prevalence of chronic kidney disease were not significantly different between the two groups. Although urinary leakage was observed in three patients (5.9%) in the SILR group, there was no significant difference between the two groups regarding surgical outcomes (p = 0.249). Serum creatinine levels after RAPN were significantly lower in the SILR group than in the DLR group on postoperative days 1 and 365 following RAPN (p = 0.04). The estimated glomerular filtration rate (eGFR) was significantly lower in the DLR group than in the SILR group only on postoperative day 1; however, there was no significant difference between the two groups thereafter. Multivariate analysis showed that the method of renorrhaphy was not a predictor for maintaining renal function after RAPN even though it was associated with eGFR on postoperative day 1.

Recombinant antithrombin attenuates acute kidney injury associated with rhabdomyolysis: an in vivo animal study.

BACKGROUND: Rhabdomyolysis is characterized by the destruction and necrosis of skeletal muscle tissue, resulting in acute kidney injury (AKI). Recombinant antithrombin (rAT) has DNA repair and vascular endothelial-protection properties. Herein, we investigated whether rAT therapy has beneficial effects against rhabdomyolysis-induced AKI. Ten-week-old male B6 mice were injected with 5 mL/kg of 50% glycerol intramuscularly in the left thigh after 24 h of fasting to create a rhabdomyolysis mouse model. Further, 750 IU/kg rAT was injected intraperitoneally at 24 and 72 h after the rhabdomyolysis model was established. The mice were euthanized after 96 h for histological analysis. Saline was administered to mice in the control group. RESULTS: Blood tests show elevated serum creatinine, urea nitrogen, and neutrophil gelatinase-associated lipocalin levels in rhabdomyolysis. Loss of tubular epithelial cell nuclei and destruction of the tubular luminal surface structure was observed in the untreated group, which improved with rAT treatment. Immunostaining for Ki-67 showed increased Ki-67-positive nuclei in the tubular epithelial cells in the rAT group, suggesting that rAT may promote tubular epithelial cell regeneration. The microvilli of the brush border of the renal tubules were shed during rhabdomyolysis, and rAT treatment reduced this injury. The vascular endothelial glycocalyx, which is usually impaired by rhabdomyolysis, became functional following rAT treatment. CONCLUSIONS: Treatment with rAT suppressed rhabdomyolysis-induced AKI, suggesting that rAT therapy may be a novel therapeutic approach.

Comparison of perioperative outcomes and complications between intracorporeal, extracorporeal, and hybrid ileal conduit urinary diversion during robot-assisted radical cystectomy: a comparative propensity score-matched analysis from nationwide multi-institutional study in Japan.

BACKGROUND: To investigate the impact of different urinary diversion (UD) techniques on the peri- and postoperative complications of robot-assisted radical cystectomy (RARC) with ileal conduit. METHODS: We retrospectively analyzed 373 patients undergoing RARC with ileal conduit at 11 institutions in Japan between April 2018 and December 2021. Propensity score weighting was performed to adjust for confounding factors such as age, sex, body mass index, performance status, American Society of Anesthesiologists score, previous abdominal surgery, neoadjuvant chemotherapy, and preoperative high T stage (≥ cT3) and high N stage (≥ cN1). Perioperative complications were then compared among three groups: extracorporeal, intracorporeal, and hybrid urinary diversion (ECUD, ICUD, and HUD, respectively). RESULTS: A total of 150, 68, and 155 patients received ECUD, HUD, and ICUD, respectively. Bowel reconstruction time and UD time were significantly shorter in the ECUD group (p < 0.001), and console time was significantly longer and blood loss was significantly higher in the ICUD group (p < 0.001). For postoperative complications (Clavien-Dindo Classification grade ≥ 3), surgical site infection (p = 0.004), pelvic abscess (p = 0.013), anastomotic urine leak (p = 0.007), and pelvic organ prolapse (p = 0.011) significantly occurred in the ECUD group. For all grades, ileus was more common in the HUD group, whereas anastomotic stricture was more common in the ECUD group compared with the other groups (p < 0.05). CONCLUSIONS: Severe complications did not increase after HUD and ICUD compared with ECUD; however, console time tended to be longer and blood loss was slightly higher during RARC.

The Geriatric Nutritional Risk Index Predicts Prognosis in Japanese Patients with LATITUDE High-Risk Metastatic Hormone-Sensitive Prostate Cancer: A Multi-Center Study.

Malnutrition is associated with prognosis in cancer. The geriatric nutritional risk index (GNRI), based on the ratio of actual to ideal body weight and also serum albumin level, is a simple screening tool for assessing nutrition. We investigated the GNRI as a prognostic factor for oncological outcomes in patients with high-risk metastatic hormone-sensitive prostate cancer (mHSPC) using a Japanese multicenter cohort. This study included a total of 175 patients with LATITUDE high-risk mHSPC, of whom 102 had received androgen deprivation therapy (ADT) plus upfront abiraterone acetate, and 73 had received ADT plus bicalutamide (Bica), from 14 institutions associated with the Tokai Urologic Oncology Research Seminar. Patients were classified into GNRI-low (<98) or GNRI-high (≥98) groups. The GNRI was based on the body mass index and serum albumin level. Kaplan-Meier analysis revealed that the median overall survival (OS) of a GNRI-low group (median 33.7 months; 95% confidence interval [CI]: 26.2-not reached [NR]) was significantly worse than that of a GNRI-high group (median: NR; 95% CI: NR-NR; p < 0.001). Multivariate analysis identified Bica and low GNRI (<98) as independent prognostic factors for reduced times to both castration-resistant prostate cancer and OS, and, therefore, a poor prognosis. Our findings indicate the GNRI may be a practical prognostic indicator in the evaluation of survival outcomes in patients with LATITUDE high-risk mHSPC.

Temporary Tumor Shrinkage Following Enfortumab Vedotin Therapy for Metastatic Urothelial Carcinoma After Radical Cystectomy With Neoadjuvant Chemotherapy: A Case Report.

A 39-year-old Japanese male patient presented with a chief complaint of gross hematuria persistent for two months. However, no relevant findings in the patient's medical and family history were observed. He was diagnosed with muscle-invasive bladder cancer, clinical stage T2bN0M0. After four courses of neoadjuvant chemotherapy with gemcitabine and cisplatin, the tumor size reduced by approximately 30%. The patient underwent robot-assisted radical cystectomy with standard lymph node dissection followed by intracorporeal ileal conduit reconstruction. Histologically, the tumor was diagnosed as a high-grade urothelial carcinoma invading the fatty tissue surrounding the bladder and metastasizing to the lymph nodes, with a pathological stage of ypT3aypN2M0. Four months after surgery, multiple metastases were detected, and treatment with pembrolizumab was initiated immediately. However, the patient did not respond to pembrolizumab. Therefore, a third-line treatment with enfortumab vedotin (EV) was initiated. Thereafter, the metastatic lesion shrank quickly, and the metastatic lesions almost disappeared after two courses of EV administration. Although new metastases were observed at other sites, there has been no regrowth to date. EV-related adverse events were not observed during follow-up. Eighteen months after the surgery, the patient remains alive with multiple metastases. Therefore, the sequence of treatment should be considered to maximize the therapeutic effect of EV, and, consequently, administering EV as early as possible may be important.

Prognostic Factors for Resolution Delay of Lower Urinary Tract Symptoms in Patients with Prostate Cancer after Low-Dose-Rate Brachytherapy.

Urinary storage symptoms after low-dose-rate brachytherapy (LDR-BT) with iodine-125 have been noted to be less likely to improve to baseline compared to voiding symptoms. This study aimed to evaluate the chronological changes in the overactive bladder symptom score (OABSS) and the time-to-resolution of OABSS in patients undergoing LDR-BT. Patients with prostate cancer who underwent LDR-BT at Gifu University Hospital were enrolled. The OABSS was evaluated before and after LDR-BT. Patients were divided into the OABSS resolution and resolution delay groups, and the association between OABSS resolution delay and clinicopathological covariates was evaluated. In total, 237 patients were enrolled in this study, with a median follow-up of 88.3 months. The OABSS in both groups worsened at 3 months following operation and gradually recovered at 9 months; however, the OABSS in the resolution delay group tended to worsen again after that. In the multivariate analysis, preoperative OABSS and the change from baseline to maximal OABSS were associated with OABSS resolution. To our knowledge, this is the first study to evaluate the delayed resolution of OABSS after LDR-BT in patients with prostate cancer. A low baseline OABSS and significant changes in the OABSS from baseline were independent predictors of delayed OABSS resolution.

Utility and safety of robot-assisted radical cystectomy in older patients with bladder cancer.

Introduction: This study aimed to investigate the efficacy and safety of robot-assisted radical cystectomy (RARC) in older patients with bladder cancer (BCa).Material and methods: We reviewed the clinical and pathological records of 110 patients with BCa who underwent RARC at Gifu University Hospital between February 2019 and January 2023. Older patients were defined as those with BCa aged ≥ 75 years. The enrolled patients were divided into two groups: those aged < 75 years (Group I) and those aged ≥ 75 years (Group II). Oncological outcomes, including overall survival (OS) and recurrence-free survival (RFS), were the primary endpoints of the study; the secondary endpoints were the surgical and pathological outcomes.Results: A shorter console time, less blood loss, and reduced time to postoperative fluid and food intake in Group II may be attributed to the fact that more patients opted for ureterocutaneostomy in Group II than in Group I. In all patients, the three-year OS and RFS rates were 84.7% and 88.5%, respectively. There were no significant differences in OS or RFS between the two groups. (p = .403, p = .963, respectively).Conclusions: RARC appears to be a safe and useful treatment option for older patients with BCa.

Perilesional Targeted Biopsy Combined with MRI-TRUS Image Fusion-Guided Targeted Prostate Biopsy: An Analysis According to PI-RADS Scores.

A prostate-targeted biopsy (TB) core is usually collected from a site where magnetic resonance imaging (MRI) indicates possible cancer. However, the extent of the lesion is difficult to accurately predict using MRI or TB alone. Therefore, we performed several biopsies around the TB site (perilesional [p] TB) and analyzed the association between the positive cores obtained using TB and pTB and the Prostate Imaging Reporting and Data System (PI-RADS) scores. This retrospective study included patients who underwent prostate biopsies. The extent of pTB was defined as the area within 10 mm of a TB site. A total of 162 eligible patients were enrolled. Prostate cancer (PCa) was diagnosed in 75.2% of patients undergoing TB, with a positivity rate of 50.7% for a PI-RADS score of 3, 95.8% for a PI-RADS score of 4, and 100% for a PI-RADS score of 5. Patients diagnosed with PCa according to both TB and pTB had significantly higher positivity rates for PI-RADS scores of 4 and 5 than for a PI-RADS score of 3 (p < 0.0001 and p = 0.0009, respectively). Additional pTB may be performed in patients with PI-RADS ≥ 4 regions of interest for assessing PCa malignancy.

Biochemical recurrence after chemohormonal therapy followed by robot-assisted radical prostatectomy in very-high-risk prostate cancer patients.

Robot-assisted radical prostatectomy (RARP) has become one of the standard radical treatments for prostate cancer (PCa). A retrospective single-center cohort study was conducted on patients with PCa who underwent RARP at Gifu University Hospital between September 2017 and September 2022. In this study, patients were classified into three groups based on the National Comprehensive Cancer Network risk classification: low/intermediate-risk, high-risk, and very-high-risk groups. Patients with high- and very-high-risk PCa who were registered in the study received neoadjuvant chemohormonal therapy prior to RARP. Biochemical recurrence-free survival (BRFS) after RARP in patients with PCa was the primary endpoint of this study. The secondary endpoint was the relationship between biochemical recurrence (BCR) and clinical covariates. We enrolled 230 patients with PCa in our study, with a median follow-up of 17.0 months. When the time of follow-up was over, 19 patients (8.3%) had BCR, and the 2 years BRFS rate for the enrolled patients was 90.9%. Although there was no significant difference in BRFS between the low- and intermediate-risk group and the high/very-high-risk group, the 2 years BRFS rate was 100% in the high-risk group and 68.3% in the very-high-risk group (P = 0.0029). Multivariate analysis showed that positive surgical margins were a significant predictor of BCR in patients with PCa treated with RARP. Multimodal therapies may be necessary to improve the BCR in patients with very-high-risk PCa.

Chronological Changes of Lower Urinary Tract Symptoms in Elderly Patients with Prostate Cancer after Low-Dose-Rate Prostate Brachytherapy.

BACKGROUND: To compare chronological changes in lower urinary tract symptoms (LUTS) after low-dose-rate prostate extended-release therapy (LDR-BT) using the overactive bladder symptom score (OABSS) in patients aged ≥ 75 years (elderly group) versus those aged < 75 years (control group). MATERIALS AND METHODS: Patients with prostate cancer who underwent LDR-BT at Gifu University Hospital were included in this study. The International Prostate Symptom Score (IPSS), OABSS, and quality of life-based on urinary symptoms (IPSS-QOL) were evaluated before and after LDR-BT. We compared chronological changes in IPSS, OABSS, and IPSS-QOL in the elderly group with those in the control group and assessed the association between the resolution of OABSS and clinicopathological covariates. RESULTS: A total of 484 patients were enrolled in this study. In the elderly group, the total IPSS, OABSS, and frequency scores increased at 1 month postoperatively, whereas the control group showed an increase at 3 months postoperatively. Multivariate analysis identified changes from baseline to the maximum OABSS and pre-treatment OABSS as significant predictors of delayed resolution of OABSS after LDR-BT. CONCLUSIONS: Changes in pre-treatment OABSS and pre- and post-LDR-BT OABSS values were independent predictors of delayed resolution of OABSS; however, no correlation was found with age.

Case of extragonadal germ cell tumor mimicking left adrenal tumor.

A 30-year-old man presented to his previous physician with left abdominal pain. Computed tomography revealed a left retroperitoneal mass with calcification, measuring 15 × 9 × 6 cm, and the patient was referred to our hospital for further examination. Based on the endocrinologic examination and magnetic resonance imaging results, the patient was diagnosed with a nonfunctional left adrenal tumor, and laparoscopic left adrenalectomy was performed. Histopathology revealed well-defined boundaries between the tumor and the left adrenal gland, and the tumor was diagnosed as a non-seminoma consisting mainly of an immature teratoma with germ cell neoplasm in situ.

Efficacy and Safety of First-Line Cytokines versus Sunitinib and Second-Line Axitinib for Patients with Metastatic Renal Cell Carcinoma (ESCAPE Study): A Phase III, Randomized, Sequential Open-Label Study.

BACKGROUND: The sequence of first-line cytokine and second-line molecular targeted therapies may be suitable for some patients with metastatic renal cell carcinoma (mRCC) because of the expectation of complete remission and durable response achieved with cytokine therapy. METHODS: This was a phase III randomized controlled trial investigating the outcomes of low-dose interleukin-2 (IL-2) plus interferon alfa (IFNα) versus sunitinib as the first line and axitinib as the second line in patients with low- and intermediate-risk mRCC. RESULTS: Thirty-five patients were randomly assigned. The total progression-free survival (PFS) to the end of the second line was 29.0 months (95% CI, 11.7-46.3) in the IL-2 + IFNα group and 16.3 months (95% CI, 6.3-26.4) in the sunitinib group. The PFS hazard ratio for the IL-2 + IFNα group relative to the sunitinib group was 0.401 (95% CI, 0.121-1.328; p = 0.135). The hazard ratio for overall survival (OS) was 1.675 (95% CI, 0.418-6.705; p = 0.466), which was better in the sunitinib group than in the IL-2 + IFNα group but not statistically significant. The types of adverse events (AEs) differed significantly, although there was no significant difference in the incidence of AEs. CONCLUSIONS: There was a trend toward better total PFS for IL-2 + IFNα, but it was not significant. There was also no advantage of IL-2 + IFNα in terms of OS. The study was underpowered to draw any definitive conclusions. The results showed no clear advantage of IL-2 + IFNα over sunitinib in the first-line setting; however, it may be an option in some relatively low-risk mRCC cases due to the difference in the AE profile. This trial was registered with the University Hospital Medical Information Network (UMIN), center identifier UMIN 000012522.