Search

Background: It remains unclear whether kidney function affects outcomes following immune checkpoint inhibitor (ICI)-based combination therapy for advanced renal cell carcinoma (RCC)., Methods: We retrospectively evaluated data of 167 patients with advanced RCC, including 98 who received ICI dual combination therapy (ie, immunotherapy [IO]-IO) and 69 who received ICI combined with tyrosine kinase inhibitor (TKI) (ie, IO-TKI). In each regimen, treatment profiles were assessed according to the grade of chronic kidney disease (CKD) as defined by the KDIGO 2012 criteria., Results: Of the 98 patients who received IO-IO, 31 (32%), 30 (31%), 15 (15%), and 22 (22%) had CKD G1/2, G3a, G3b, and G4/5, respectively. Of the 69 patients who received IO-TKI, 18 (26%), 25 (36%), and 26 (38%) had G1/2, G3a, and G3b/4/5, respectively. Regarding efficacy, progression-free survival, overall survival, or objective response rate was not different according to the CKD grade in both treatment groups (P > .05). Regarding safety, the rate of adverse events, treatment interruption, or corticosteroid administration was not different according to the CKD grade in the IO-IO group (P > .05), whereas in the IO-TKI group, the incidence of grade ≥ 3 adverse events were significantly higher (P = .0292), and the rates of ICI interruption (P = .0353) and corticosteroid administration (P = .0685) increased, according to the CKD grade., Conclusion: There is a differential safety but comparable efficacy profile between the IO-IO and IO-TKI regimens in patients with CKD. Further prospective studies are required to confirm these findings., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: To examine the surgical and functional outcomes of patients who have undergone repeat open partial nephrectomy (reOPN) or robot-assisted laparoscopic partial nephrectomy (reRAPN)., Methods: Until May 2022, 3310 patients with renal tumors underwent nephron-sparing surgery (NSS) at affiliated institutions. Of these, 22 and 17 patients who underwent reOPN and reRAPN, respectively, were included in this study., Results: No significant differences were found between the groups in terms of sex, age, comorbidities, recurrent tumor size at repeat NSS, interval from recurrence to initial NSS, and nephrometry score. ReRAPN had a shorter operative time (median: 138.0 vs. 214.0 min; p = 0.0023) and less estimated blood loss (median: 50.0 vs. 255.0 mL; p = 0.0261) than reOPN. The incidence of complications with Clavien-Dindo grade ≥ 2 was higher in the reOPN group than in the reRAPN group (31.8 vs. 5.9%; p = 0.0467). The mean decrease in the estimated glomerular filtration rate at 3 months postoperatively was not significantly different between the groups. The trifecta achievement rates in the reRAPN (64.7%) and reOPN (27.3%) groups were significantly different (p = 0.0194). On multivariate analysis, age and surgical method were significant predictors of trifecta achievement after partial nephrectomy., Conclusions: There were no differences in postoperative renal functional outcomes between reOPN and reRAPN. ReRAPN is superior to reOPN in terms of surgical burden. Therefore, ReRAPN is an important minimally invasive surgery for recurrent renal cell carcinoma., (© 2023 The Japanese Urological Association.)

Objectives: To investigate predictive factors and oncological outcomes of pathological T3a upstaging in renal cell carcinoma patients who were initially diagnosed as clinical T1 and treated with partial nephrectomy., Methods and Materials: The clinical records and survival data of 1617 patients, who had undergone partial nephrectomy for clinical T1 renal cell carcinoma at Tokyo Women's Medical University, Tokyo, Japan between January 2011 and December 2020, were analyzed retrospectively., Results: Of 1617 clinical T1 renal cell carcinoma patients who underwent partial nephrectomy, 28 (1.73%) had pathological T3a upstaging. In the multivariable analysis for pathological T3a upstaging using logistic regression models, male sex and clinical T1b were significant factors associated with pathological T3a upstaging (male sex: odds ratio = 5.07, 95% confidence interval: 1.18-21.8, clinical T1b: odds ratio = 8.36, 95% confidence interval: 3.56-19.6). The Kaplan-Meier method of the recurrence-free survival showed shorter recurrence-free survival in patients with pathological T3a upstaging than in those with pathological T1 (P < 0.0001). In the multivariable analysis using Cox proportional hazards regression models, pathological T3a upstaging was no longer significantly associated with recurrence-free survival after adjustment for other pathological factors (hazard ratio = 1.59, 95% confidence interval: 0.58-4.36). In a sensitivity analysis that analyzed its components individually instead of whole pathological T3a, neither perinephric fat invasion, sinus fat invasion, nor renal vein invasion was associated with recurrence-free survival., Conclusions: Male sex and clinical T1b were significant predictors for pathological T3a upstaging after partial nephrectomy in clinical T1 renal cell carcinoma patients. Although patients with pathological T3a upstaging had worse recurrence-free survival compared with those without upstaging, multivariable analyses revealed that pathological T3a upstaging was not an independent predictor for poor recurrence-free survival., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: The objective of the study was to analyze the outcomes of patients with renal cell carcinoma (RCC) arising in end-stage renal disease (ESRD) over a 40-year span., Methods: We retrospectively evaluated data of patients with ESRD-RCC diagnosed between 1979 and 2020 at two institutions. We assessed changes in stage, surgical approaches, and cancer-specific survival (CSS) following nephrectomy according to era between ESRD-RCC and sporadic RCC. Furthermore, perioperative outcomes in patients with ESRD-RCC were compared between laparoscopic and open surgery., Results: Patients with ESRD-RCC (n = 549) were diagnosed at an earlier stage (p = 0.0276), and the ratio of laparoscopic nephrectomy was increased (p < 0.0001) according to eras. Since 2000 (i.e., after implementation of laparoscopic nephrectomy), patients with ESRD-RCC (n = 305) had significantly shorter CSS (p = 0.0063) after nephrectomy than sporadic RCC (n = 2732). After adjustment by multivariate analysis and propensity score matching, ESRD status was independently associated with shorter CSS (p = 0.0055 and p = 0.0473, respectively). Improved CSS in sporadic RCC (p < 0.0001), but not ESRD-RCC (p = 0.904), according to era contributed to this difference. Laparoscopic nephrectomy showed favorable outcomes, including shorter surgery time, lower estimated bleeding volumes, transfusion rates, and readmission rates, and shorter postoperative hospitalization than open nephrectomy (p < 0.05)., Conclusions: Advances in diagnostic and treatment modalities potentially enable early diagnosis and minimally invasive surgery for patients with ESRD-RCC. As ESRD-RCC may not present indolently, careful post-operative monitoring is needed., (© 2023 The Japanese Urological Association.)

Aim: Gamma-delta-T cells (γδT) have potential antitumor roles and have recently been applied in adoptive immunotherapy. In the present study, we focused on the proportion of γδT cells in the peripheral blood just before surgery for renal cell cancer (RCC) and investigated whether their proportion affected recurrence-free survival (RFS) and overall survival (OS) retrospectively., Patients and Methods: A total of 137 patients with localized, non-metastatic RCC who received surgery at our institutes were analyzed retrospectively. The patients were divided into 2 groups: normal and low γδT cell groups based on the proportion of peripheral blood γδT cells. Kaplan-Meier curves were constructed to access the association of the proportion of peripheral blood γδT cells to RFS and OS. Cox regression were also constructed to access the risks to prognosis. Uni- and multivariate logistic regressions were performed to access associations between risk factors and, RFS and OS., Results: Among 137 patients, 40 had a proportion of γδT cells in peripheral blood of less than 1%, which was below the normal range. The remaining 97 patients had these cells in peripheral blood at 1% or higher. In the groups with low γδT cells, 13 patients had recurrences, and 9 patients dies during the observation period. In the groups with normal γδT cells, 16 patients had recurrences, and 8 patients died. The normal γδT cell group demonstrated significantly better prognosis in terms of RFS and OS. Multivariate analysis revealed that a low hemoglobin level, a low proportion of γδT cells, and a high pathological T stage (pT) were statistically independent risk factors for RFS. Age, albumin, C-reactive protein (CRP), % γδT cells, and pT were statistically significant factors affecting OS and only pT was an independent risk factor by multivariate analysis., Conclusion: A low proportion of γδT cells was identified as one of the risk factors for RFS. Our findings will provide clues to develop strategies for early intervention in preventing recurrence even after complete resection of RCC and, such as adoptive immunotherapy using autologous γδT cells in patients with a low proportion of γδT cells., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Real-world data of cabozantinib after failure of immune checkpoint inhibitors for advanced renal cell carcinoma in Japanese population are limited. Additionally, prognostic factors of cabozantinib in this setting are still unknown., Methods: We retrospectively evaluated data of 56 patients treated with cabozantinib subsequent to failed immune checkpoint inhibitors at four institutions. Regarding the efficacy profile, progression-free survival, overall survival and objective response rate were assessed. In terms of the safety profile, rate of adverse events, dose reduction and treatment interruption were assessed. Furthermore, risk factors of progression-free survival were analyzed., Results: Twenty-nine patients (52%) were treated with cabozantinib as second-line therapy. Most frequent prior immune checkpoint inhibitor treatment was nivolumab plus ipilimumab combination therapy as first-line therapy (n = 30, 54%). Median progression-free survival and overall survival were 9.76 and 25.5 months, respectively, and objective response rate was 34%. All patients experienced at least one adverse event, and grade ≥ 3 adverse events were observed in 31 patients (55%). Forty-four (79%) and 31 (55%) patients needed dose reduction and treatment interruption, respectively. Multivariate analysis showed that reduced initial dose (i.e. <60 mg) (hazard ratio: 2.50, P = 0.0355) and presence of lymph node metastasis (hazard ratio: 2.50, P = 0.0172) were independent factors of shorter progression-free survival., Conclusion: Cabozantinib in Japanese patients with advanced renal cell carcinoma who failed immune checkpoint inhibitors was efficacious and had a manageable safety profile. These results appear to be similar to those of previous clinical trials., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Prognostic impact of sex in patients with malignancies treated with immune checkpoint inhibitors has been intensively discussed but remains unclear, especially in advanced renal cell carcinoma., Methods: We retrospectively evaluated a total of 184 patients with advanced renal cell carcinoma treated with either nivolumab plus ipilimumab combined treatment as first-line therapy (n = 73) or nivolumab as later-line therapy (n = 111) at our affiliated institutions. Progression-free survival, overall survival and objective response rate as well as adverse event profile were compared between sexes., Results: Of the total 184 patients, 48 (26%) were female. Female patients had a significantly shorter progression-free survival than male patients (median: 3.8 vs. 8.3 months, P = 0.0005), but overall survival (median: 39.2 vs. 45.1 months, P = 0.283) and objective response rate (29% vs. 42%, P = 0.119) were not different between them. Similar findings were observed when analyzing within each treatment; in both patient groups treated with nivolumab plus ipilimumab combined therapy and nivolumab monotherapy, progression-free survival was significantly shorter in female than in male patients (P = 0.007, P = 0.017), but overall survival (P = 0.914, P = 0.117) and objective response rate (P = 0.109, P = 0.465) were comparable between them. Moreover, in a more restricted cohort consisting of patients with clear-cell renal cell carcinoma, a shorter progression-free survival in female patients was also observed (3.8 vs. 11.0 months, P < 0.0001)., Conclusions: This retrospective study showed that immune checkpoint inhibitors-based treatment for renal cell carcinoma exhibited less marked effects in female than in male patients. Thus, sex may be an important factor for decision-making on systemic therapy as renal cell carcinoma treatment, although further studies are required to validate the present findings., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Clinical trials have demonstrated the superior efficacy of immune checkpoint inhibitor (ICI)-based combination therapy over sunitinib, a multi-target tyrosine kinase inhibitor (TKI), in patients with advanced renal cell carcinoma. However, such benefits have not been elucidated in populations outside of clinical trials., Methods: We retrospectively evaluated data from 467 patients with advanced renal cell carcinoma who received ICI-based combination therapy or TKIs, as first-line therapy. Clinical outcome was compared between ICI-based combination therapy and TKIs in each population divided according to trial eligibility., Results: Among 152 patients treated with ICI-based combination therapy and 315 patients treated with TKIs, 76 (50.0%) and 156 (49.5%) were trial ineligible, respectively. Overall survival (p = 0.0072) and objective response rate (p < 0.0001) were significantly higher in ICI-based combination therapy than in TKIs, but progression-free survival was comparable (p = 0.681). In the trial-eligible population, overall survival was longer (p = 0.0906) and the objective response rate was significantly higher (p = 0.0124) in ICI-based combination therapy than in TKIs. In the trial-ineligible population, overall survival (p = 0.0208) and objective response rate (p = 0.0006) were significantly higher with ICI-based combination therapy than with TKIs. A multivariate analysis also showed that ICI-based combination therapy was independently associated with prolonged overall survival (hazard ratio, 0.47; p = 0.0016). Regardless of trial eligibility, progression-free survival did not differ between ICI-based combination therapy and TKIs (trial eligible: p = 0.287; trial ineligible: p = 0.0708)., Conclusions: The present study, using real-world data, provides evidence indicating the therapeutic benefit of ICI-based combination therapy over TKIs for advanced renal cell carcinoma was more statistically significant in the trial-ineligible population than in the trial-eligible population., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Objectives: To clarify the impact of body mass index (BMI) on treatment outcomes including survival, tumor response, and adverse events (AEs) in patients with advanced renal cell carcinoma (RCC) or urothelial carcinoma (UC) treated with immune checkpoint inhibitors (ICIs) in an Asian population., Methods: We retrospectively evaluated 309 patients with advanced RCC or UC who received ICIs between September 2016 and July 2021. The patients were divided into high- (i.e., ≥25 kg/m 2 ) and low-BMI (<25 kg/m 2 ) groups according to the BMI at the time of treatment initiation., Results: Overall, 57 patients (18.4%) were classified into the high-BMI group. In RCC patients treated with ICIs as first-line therapy or UC treated with pembrolizumab, progression-free survival (PFS) (p = 0.309; p = 0.842), overall survival (OS) (p = 0.701; p = 0.983), and objective response rate (ORR) (p = 0.163; p = 0.553) were comparable between the high- and low-BMI groups. In RCC patients treated with nivolumab monotherapy as later-line therapy, OS (p = 0.101) and ORR (p = 0.102) were comparable, but PFS was significantly longer in the high-BMI group (p = 0.0272). Further, multivariate analysis showed that BMI was not an independent factor of PFS or OS in all the treatment groups (any, p>0.05). As for AE profiles, in nivolumab monotherapy, the rate was significantly higher in the high-BMI group (p = 0.0203), whereas in the other two treatments, the rate was comparable., Conclusions: BMI was not associated with survival or response rates of advanced RCC or UC patients treated with ICIs in an Asian population. AEs might frequently develop in high-BMI patients with RCC in nivolumab monotherapy., (Copyright © 2022. Published by Elsevier Inc.)

Background: The prognostic impact of immune-related adverse events during immune checkpoint inhibitor-based combination therapy for advanced renal cell carcinoma remains unclear, especially in terms of differences between regimens., Objective: We aimed to clarify the prognostic impact of immune-related adverse events in patients with advanced renal cell carcinoma receiving immune checkpoint inhibitor dual combination therapy (IO-IO) or immune checkpoint inhibitor plus tyrosine kinase inhibitor combination therapy (IO-TKI)., Methods: We retrospectively evaluated the data of 148 patients who received immune checkpoint inhibitor-based combination therapy as first-line therapy. Patients were divided into two groups based on regimens, namely IO-IO and IO-TKI. The associations between immune-related adverse event development and outcomes, such as progression-free survival, overall survival, and objective response rate, were compared between the two groups., Results: In the IO-IO and IO-TKI groups, 67 of 91 (74%) and 31 of 57 (54%) patients, respectively, experienced at least one immune-related adverse event and the rate was significantly higher in the IO-IO group (p = 0.0204), where immune-related adverse events development was significantly associated with longer progression-free survival (p < 0.0001) and overall survival (p = 0.0102), and a higher objective response rate (p = 0.0028). A multivariate analysis revealed immune-related adverse event development as an independent factor for longer progression-free survival (hazard ratio, 0.25; p < 0.0001) and overall survival (hazard ratio, 0.42; p = 0.0287). There were no significant associations between immune-related adverse events and progression-free survival, overall survival, or objective response rate in the IO-TKI group., Conclusions: The development of immune-related adverse events was positively associated with the outcome of patients with advanced renal cell carcinoma treated with IO-IO combination therapy; no such correlation was observed for IO-TKI combination therapy., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Objectives: To explore the therapeutic role of deferred cytoreductive nephrectomy in patients with metastatic renal cell carcinoma treated with nivolumab plus ipilimumab., Patients and Methods: Forty-one patients with synchronous metastatic renal cell carcinoma who received nivolumab plus ipilimumab as first-line systemic therapy at our affiliated institutions were retrospectively evaluated. We focused on the prognosis, including tumor responses in primary kidney and metastatic lesions in patients treated with deferred cytoreductive nephrectomy. In addition, the overall survival according to nephrectomy status (i.e. deferred cytoreductive nephrectomy vs. upfront cytoreductive nephrectomy vs. without cytoreductive nephrectomy) was compared., Results: During a median follow-up period of 12.0 months, seven (30%) patients received deferred cytoreductive nephrectomy at a median time of 10.4 months after nivolumab plus ipilimumab initiation. All the patients showed tumor shrinkage in their primary kidney lesions, including six (86%) patients with ≥30% of shrinkage. Metastatic lesions were also shrunk by ≥30% in six (86%) patients, including two (29%) obtaining complete response. At the last time of follow-up, three (43%) patients were disease-free. The overall survival rate after nivolumab plus ipilimumab initiation tended to be higher in patients with deferred cytoreductive nephrectomy compared with those with upfront cytoreductive nephrectomy (1-year survival rate: 100% vs. 72.4%, P = 0.0587) and those without cytoreductive nephrectomy (vs. 58.2%, P = 0.0613)., Conclusions: The present retrospective data showed that deferred cytoreductive nephrectomy had the potential to exert a therapeutic effect in a subset of patients who obtained favorable tumor responses to nivolumab plus ipilimumab for a certain period. Prospective randomized clinical trials are needed to confirm the prognostic impact of deferred cytoreductive nephrectomy after frontline immunotherapy in synchronous metastatic renal cell carcinoma., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Cancer development in adolescents and young adults (AYAs) has elicited recent interest. We investigated the surgical and functional outcomes of robot-assisted laparoscopic partial nephrectomy (RAPN) for renal cell carcinoma (RCC) in AYAs., Methods: We retrospectively reviewed the medical records of 1023 patients with clinical stage I RCC who underwent RAPN before January 2021. Patients were divided into two groups: AYAs (aged 18-39 years) and non-AYAs (aged 40-89 years). The trifecta criteria, defined as a negative surgical margin, no perioperative complications (Clavien-Dindo grade > 2), and preserved postoperative renal function (1-year postoperative estimated glomerular filtration rate > 90% of baseline), were used to compare outcomes. We performed 1:1 propensity-score matching on the patient cohort., Results: There were initially 125 and 898 patients in the AYAs and non-AYAs groups, respectively, and 108 patients were included in each group after propensity score matching. There were no significant differences in surgical factors (operation time, clamping ischemia time, estimated blood loss, length of hospital stay, surgical complication rate) or renal function in the early postoperative period. The mean postoperative renal function was better (p = 0.0200) and the decrease in estimated glomerular filtration rate was lower (p = 0.0026) in AYAs than in non-AYAs 12 months postoperatively. The trifecta achievement rates in the AYAs and non-AYAs groups were significantly different (67.6% and 53.7%, respectively, p = 0.0220)., Conclusion: Although there was no difference in surgical burden between the groups, the estimated glomerular filtration rate was better preserved in AYAs than in non-AYAs at 6 and 12 months post-RAPN., (© 2022. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Objectives: To investigate the long-term follow-up outcomes of nivolumab monotherapy for previously treated metastatic renal cell carcinoma, using real-world data., Methods: A total of 121 patients were treated with nivolumab monotherapy as subsequent therapy after the failure of prior tyrosine kinase inhibitor therapy between January 2013 and December 2021 at four affiliated institutions. To evaluate the outcome after 2 years or more, we selected patients in whom nivolumab therapy was started in December 2019 or earlier because data collection was performed until the end of December 2021., Results: Seventy-four patients were evaluated. During the median follow-up period of 25.8 months, 62 (84%) and 40 (54%) patients had disease progression and died, respectively. Nivolumab was administered as second-line therapy in 43 patients (58%). The median progression-free survival and overall survival were 5.52 and 31.1 months, respectively, and objective response rate was 36%. There was no difference in progression-free survival or overall survival based on the treatment line of nivolumab (P = 0.915, P = 0.559). The magnitude of tumor response and development of immune-related adverse events were significantly associated with progression-free survival (P < 0.0001, P < 0.0001, respectively) and overall survival (P < 0.0001, P = 0.0002, respectively). Treatment-related adverse events developed in 38 patients (51%), including 33 (45%) who had immune-related adverse events. Steroid administration was needed in nine patients (12%)., Conclusions: The present real-world multi-institution study with long-term follow-up data demonstrates that nivolumab monotherapy is effective for previously treated metastatic renal cell carcinoma, prolonging survival, improving tumor response and has a manageable safety profile., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Background: Data regarding the efficacy and safety profiles of immune checkpoint inhibitors (ICIs) for metastatic renal cell carcinoma (mRCC) trial-ineligible patients in the real world remain unclear., Objectives: The aim of this study was to clarify the impact of trial eligibility on ICI-based combination therapy for mRCC., Patients and Methods: We collected clinical data of mRCC patients receiving ICIs since 2016, and 222 patients were registered. Among these patients, we evaluated 93 patients treated with ICI-based combination therapy, including nivolumab plus ipilimumab, pembrolizumab plus axitinib, or avelumab plus axitinib, as first-line therapy. Patients were classified into the trial-ineligible group when they had at least one of the following factors at the time of treatment initiation: Karnofsky performance status (KPS) < 70%, hemoglobin level < 9.0 g/dL, estimated glomerular filtration rate (eGFR) < 40 mL/min/1.73 m 2 , platelet count < 100,000/µL, neutrophil count < 1500/µL, non-clear cell histology, or brain metastasis. The remaining patients were classified into the trial-eligible group., Results: Forty-eight patients (52%) were classified into the trial-ineligible group. The frequency of patients with trial-ineligible factors was highest for low eGFR (n = 20, 45%), followed by non-clear cell histology (n = 17, 36%) and low KPS score (n = 12, 25%). There was no significant difference in progression-free survival (median: 24.0 vs. 11.0 months, p = 0.416), overall survival (1-year rate: 87.0% vs. 85.3%, p = 0.634), or objective response rate (52% vs. 42%, p = 0.308) between the trial-eligible and -ineligible patients. The incidence rate of adverse events was higher in the trial-eligible patients than in the trial-ineligible patients (91% vs. 75%, p = 0.0397); however, the rate of grade 3 or higher adverse events was comparable between the two groups (42% vs. 40%, p = 0.796)., Conclusions: There are many trial-ineligible patients in the real world. Nevertheless, the efficacy and safety of ICI-based combination therapy in trial-ineligible patients were non-inferior compared with those of trial-eligible patients., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Knowledge of changes in the outcome in patients with metastatic renal cell carcinoma from the molecular-targeted therapy era to the immune checkpoint inhibitor (ICI) era remains limited in the real-world setting., Objectives: We aimed to clarify outcome changes from the previous molecular-targeted therapy era to the current ICI era in patients with metastatic renal cell carcinoma using multi-institution real-world data., Methods: We retrospectively evaluated 415 patients with metastatic renal cell carcinoma who received first-line systemic therapy at five Japanese institutions between January 2008 and August 2021. We divided the patients into two groups based on the treatment era: molecular-targeted therapy era (January 2008-August 2018) and ICI era (September 2018-August 2021). According to the era, progression-free survival, overall survival, and objective response rate from first-line systemic therapy were compared., Results: Overall, 304 (73.3%) and 111 (26.7%) patients were categorized into the molecular-targeted therapy and ICI eras, respectively. The proportion of patients without prior nephrectomy (p = 0.0030) or those with low Karnofsky Performance Status scores [≤ 70] (p = 0.0258) were significantly higher in the ICI era group. The patients in the ICI era group had significantly longer overall survival (median: not reached vs 23.2 months, p = 0.0001) and a higher objective response rate (47.8% vs 24.7%, p < 0.0001) than those in the molecular-targeted therapy era group, and progression-free survival tended to be longer in the ICI era group (median: 13.3 vs 8.75 months, p = 0.0579). Multivariate analysis further showed that the treatment era (ICI vs molecular-targeted therapy) was an independent factor for overall survival and objective response (both, p < 0.0001)., Conclusions: The present multi-institution real-world data showed the improved outcome of previously untreated patients with metastatic renal cell carcinoma in the ICI era group compared with that in the molecular-targeted therapy era group. These findings strongly encourage the use of ICI-based treatment for patients with metastatic renal cell carcinoma in the real-world setting. Further studies with extended follow-up periods are needed to confirm our findings., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Objective: The aim of the study was to evaluate the prognostic impact of trial-eligibility criteria on outcome in real-world metastatic renal cell carcinoma (mRCC) patients treated with tyrosine kinase inhibitors (TKIs)., Patients and Methods: mRCC patients treated with TKIs as first-line systemic therapy were retrospectively evaluated. The patients were determined as trial-ineligible when they met at least 1 following trial-ineligible criteria; Karnofsky performance status score <70, hemoglobin <9.0 g/dL, creatinine >2.4 mg/dL (male) or >2.0 mg/dL (female), calcium >12.0 mg/dL, platelet <100,000 /μL, neutrophil <1,500 /μL, nonclear-cell histology, and brain metastasis., Results: Of 238 patients, 101 patients (42%) were determined as trial-ineligible. Progression-free survival (PFS) and overall survival (OS) after the TKI initiation were significantly shorter in the trial-ineligible patients than in the trial-eligible patients (median PFS: 5.53 vs. 15.8 months, p < 0.0001; OS: 13.8 vs. 43.4 months, p < 0.0001). Objective response rate was also significantly lower in the trial-ineligible patients (15% vs. 37%, p = 0.0003). Multivariate analysis further showed that the trial-eligibility was an independent factor for PFS (hazard ratio [HR]: 2.46, p < 0.0001) and OS (HR: 2.39, p < 0.0001). In addition, the number of trial-ineligible factors were negatively correlated with PFS and OS., Conclusions: In real-word, the substantial number of mRCC patients did not meet the trial-eligibility criteria, and their outcome was worse than that in the trial-eligible patients. Further studies focusing on the outcome in real-world trial-ineligible patients in the immune checkpoint inhibitor era are warranted., (© 2021 S. Karger AG, Basel.)

Purpose: To clarify the efficacy and safety profile of immune checkpoint inhibitors (ICIs) for elderly patients with metastatic renal cell carcinoma (mRCC)., Methods: We retrospectively evaluated 149 mRCC patients treated with nivolumab monotherapy as subsequent therapy (n = 89) and nivolumab plus ipilimumab as first-line therapy (n = 60) at 5 affiliated institutions. The patients were divided according to age: > 70 (elderly) vs. ≤ 70 years (young). Efficacy was analyzed by comparing progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and disease control rate (DCR) between elderly and young patients. Safety was assessed by comparing the incidence rates of immune-related adverse events (irAEs)., Results: In the nivolumab monotherapy group, 34/89 patients (38%) were classified as elderly. There was no significant difference in PFS (p = 0.607), OS (p = 0.383), ORR (p = 0.0699), or DCR (p = 0.881) between elderly and young patients. In the nivolumab plus ipilimumab group, 20/60 patients (33%) were classified as elderly. There was no significant difference in PFS (p = 0.995), OS (p = 0.714), ORR (p = 0.763), or DCR (p = 1.000) between the two groups. The incidence rate of irAEs was not significantly different in the nivolumab (any grade: p = 0.121; grade ≥ 3: p = 0.542) or in the nivolumab plus ipilimumab (any grade: p = 0.666; grade ≥ 3: p = 0.576) group; a higher rate of gastrointestinal irAEs was observed in elderly than in young patients (any grade 15% vs. 3%)., Conclusions: The efficacy and safety of nivolumab monotherapy and nivolumab plus ipilimumab were comparable between elderly and young patients. Thus, chronological age alone should not be a contraindication in the use of ICIs for mRCC., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Objectives: To investigate the prognostic impact of tumor burden in patients receiving nivolumab plus ipilimumab as first-line therapy for previously untreated metastatic renal cell carcinoma (mRCC)., Methods: We retrospectively evaluated 62 patients with IMDC intermediate- or poor-risk mRCC, treated with nivolumab plus ipilimumab as first-line therapy at five affiliated institutions. Tumor burden was defined as the sum of diameters of baseline targeted lesions according to the RECIST version.1.1. We categorized the patients into two groups based on the median value of tumor burden (i.e., high vs. low). The association of tumor burden with progression-free survival (PFS), overall survival (OS) and objective response rate (ORR) with nivolumab plus ipilimumab treatment was analyzed., Results: The median tumor burden was 63.0 cm (interquartile range: 34.2-125.8). PFS was significantly shorter in patients with high tumor burden (n = 31) than in those with low tumor burden (n = 31) (median: 6.08 [95% CI: 2.73-9.70] vs. 12.5 [4.77-24.0] months, P = 0.0134). In addition, OS tended to be shorter in patients with high tumor burden; however, there was no statistically significant difference (1-year rate: 77.3 vs. 96.7%, P = 0.166). ORR was not significantly different between patients with high and low tumor burden (35 vs. 55%, P = 0.202). Multivariate analysis of PFS further showed that tumor burden was an independent factor (HR: 2.22 [95% CI: 1.11-4.45], P = 0.0242)., Conclusions: Tumor burden might be a useful factor for outcome prediction, at least for PFS prediction, in patients receiving nivolumab plus ipilimumab for mRCC. Further prospective studies are warranted to confirm our findings., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Objective: We investigated the incidence of hypopituitarism in Japanese patients with metastatic renal cell carcinoma (mRCC) who received ipilimumab and nivolumab (I-P) therapy and compared patient characteristics and survival rates between patients with hypopituitarism and those without., Methods: Twenty-two patients with mRCC who received I-P therapy as first-line treatment were the subjects of this retrospective study. The diagnosis of hypopituitarism was based on the hormone loading test., Results: Hypopituitarism occurred in 41% (9/22) patients who received I-P therapy. Median time of diagnosis was 12 weeks (IQR: 9.5-20). Clinical symptoms, such as fatigue, weakness or fever, were observed in 7 patients, while 2 patients had no clinical presentation. The following deficiency patterns were observed: isolated ACTH in 4 patients, ACTH and GH in 2 patients, ACTH and TSH in 2 patients and triple deficiency (ACTH, GH and TSH) in 1 patient. All patients with hypopituitarism were in the IMDC intermediate group, while 46% of those without hypopituitarism were in the IMDC intermediate group. Other patient characteristics were not different between the two groups. Object response rate was 33% (3/9) in patients with hypopituitarism and 23% (3/13) in those without (P = 0.5954). Progression free survival (PFS) was significantly longer in those with hypopituitarism than those without (median: 24.7 vs. 4.5 months, P = 0.0008), while overall survival did not differ (P = 0.136)., Conclusions: Compared with the clinical trial, the incidence of hypopituitarism was higher than expected. Patients with hypopituitarism tended to have longer PFS, which may suggest that optimal management of hypopituitarism results in better prognosis., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Acquired cystic disease (ACD) associated renal cell carcinoma (RCC) is designated as a new subtype unique to patients with end-stage renal disease (ESRD) according to the 2016 World Health Organization (WHO) classification. However, the oncological outcomes of the prognostic factors for patients with this subtype are not fully understood. In the present study, we compared the survival of ACD associated RCC patients who underwent nephrectomy with that of patients with other histological subtypes who developed ESRD. Over 378 patients who underwent nephrectomy at three Japanese institutes between 1987 and 2016 were included in this study. A central pathologist reviewed the sections from all patients according to the 2016 WHO classification. The central pathological review showed a clear cell subtype in 165 patients (43.6%), ACD associated RCC in 112 (29.6%), papillary in 61 (16.1%), and others in 40 (10.7%). The proportion of patients with pathological stage 1 was extremely high in both clear cell and ACD associated RCC cohorts (86.6%, 85.7%). The cancer specific survival (CSS) and recurrence free survival rates of patients with ACD associated RCC were comparable with those with clear cell carcinoma and significantly better than those with the papillary subtype. The factors predictive of unfavourable outcomes were long dialysis duration, tumour size, pathological stage, grade 4 tumour, and the presence of lymphovascular invasion or a sarcomatoid component. Patients with a pre-operative dialysis duration of 20 years or longer showed a significantly worse CSS than other patients, probably owing to sarcomatoid differentiation and stage migration during the advanced stages. In conclusion, this study included the largest number of patients with ACD associated RCC, showing a survival similar to that of clear cell histology patients with ESRD, except for the rarity of late recurrence. ACD associated RCC was not as indolent as initially recognised when patients were on long term dialysis., (Copyright © 2021 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.)

Background/aim: The relationship between albumin-to-alkaline phosphatase ratio (AAPR) and the outcome of patients with metastatic renal cell carcinoma (mRCC) treated with immune checkpoint inhibitors remains unresolved. We aimed to clarify the prognostic role of AAPR in nivolumab monotherapy for previously treated mRCC., Patients and Methods: We retrospectively evaluated 60 patients with mRCC treated with nivolumab after failure of at least one molecular targeted therapy. The patients were stratified into two groups based on the baseline AAPR. The threshold of AAPR was determined using receiver-operating characteristics and Youden index analyses. Overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) of nivolumab therapy were compared between the high and low AAPR groups., Results: The threshold of AAPR was set at 0.3, and 20 patients (33%) were assigned to the low AAPR group. The median OS and PFS were significantly lower in the low AAPR group than those in the high group (OS: 8.3 months vs. not reached, p<0.0001; PFS: 2.9 vs. 10.4 months, p=0.0006). Moreover, ORR was significantly lower in the low AAPR group than in the high group (16% vs. 45%, p=0.0397). Multivariate analyses further showed that AAPR was an independent factor for OS [HR=0.27 (95% CI=0.09-0.77), p=0.0151] but not for PFS (p=0.174)., Conclusion: Baseline AAPR was significantly associated with outcome in patients with mRCC receiving nivolumab monotherapy and may, therefore, constitute an effective prognostic factor for nivolumab treatment., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: It remains unclear how early treatment interruption of nivolumab plus ipilimumab due to immune-related adverse events affects the outcome of previously untreated metastatic renal cell carcinoma (mRCC)., Objective: To investigate the prognostic impact of the early interruption of nivolumab plus ipilimumab, used as first-line therapy for mRCC., Patients and Methods: We retrospectively evaluated 59 intermediate- or poor-risk mRCC patients who received nivolumab plus ipilimumab as first-line therapy. Based on whether early treatment interruption was implemented within the initial four treatment cycles (i.e., 3 months) or not, progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) were compared. The prognostic association was further compared with that of 186 patients treated with tyrosine kinase inhibitors (TKIs) as first-line therapy., Results: Twenty-three of the 59 patients (39%) experienced interruption of nivolumab plus ipilimumab therapy. The patients with interruption had longer PFS (p = 0.0055), similar OS (p = 0.366), and likely higher ORR (p = 0.0660) than those without interruption. Of the patients treated with TKIs, 60 of 186 (32%) experienced interruption, with shorter PFS (p = 0.0121), similar OS (p = 0.378), and similar ORR (p = 0.738) than those without interruption. In the 23 patients with nivolumab plus ipilimumab interruption, high-dose corticosteroids were administered in seven patients (30%). PFS (p = 0.638), OS (p = 0.968), or ORR (p = 0.760) did not differ based on corticosteroid administration., Conclusions: Early treatment interruption, which exerted a negative effect for TKIs, was a preferable event for nivolumab plus ipilimumab when considering PFS. Furthermore, early administration of high-dose corticosteroids did not diminish the anti-tumor effect of nivolumab plus ipilimumab.

Background: The data regarding oncological outcome in advanced renal cell carcinoma (RCC) arising in end-stage renal disease (ESRD) are limited., Methods: Patients diagnosed with advanced RCC on maintenance dialysis therapy (ESRD-RCC) and treated with tyrosine kinase inhibitors (TKIs) were retrospectively evaluated. Progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) after initiation of first-line TKI therapy in ESRD-RCC patients were compared to those in RCC arising in the general population (sporadic RCC)., Results: A total of 36 and 240 patients were diagnosed with advanced ESRD-RCC and sporadic RCC, respectively. PFS and OS were significantly shorter in patients with ESRD-RCC than in those with sporadic RCC (p = 0.0004 and p = 0.0045). After adjusting for histopathological type, MSKCC risk and liver metastasis status, ESRD status (ESRD-RCC vs. sporadic RCC) was not an independent risk factor for PFS or OS (both, p > 0.05). The ORR tended to be lower in patients with ESRD-RCC than in those with sporadic RCC (11% vs. 28%, p = 0.0833). In 34 patients with ESRD-RCC treated with sorafenib, longer duration of dialysis was an independent prognostic factor for shorter OS (hazard ratio 3.21, p = 0.0370)., Conclusions: Outcome of advanced ESRD-RCC was poorer than that of sporadic RCC, but this finding was affected by other prognostic factors. Nevertheless, the study suggested that advanced ESRD-RCC was not an indolent disease. Additionally, patients with a longer duration of dialysis therapy might require careful monitoring.

Objective: Sarcopenia is associated with oncological outcomes in various types of cancer. However, the impact of sarcopenia in renal cell carcinoma with inferior vena cava thrombus remains unclear. We herein evaluated the prognostic significance of sarcopenia for renal cell carcinoma with inferior vena cava thrombus following nephrectomy and thrombectomy., Methods: Patients who underwent nephrectomy and thrombectomy for renal cell carcinoma with inferior vena cava thrombus at our department between 2004 and 2019 were retrospectively evaluated. Their sarcopenic status, determined by sex, body mass index and skeletal muscle index, was calculated using pre-surgical radiographic imaging. We compared the post-operative cancer-specific survival and overall survival, surgical data and duration of post-operative hospitalization of sarcopenic and non-sarcopenic patients., Results: Out of 83 patients, 54 (65%) were sarcopenic. Sarcopenic patients had significantly shorter cancer-specific survival (median: 33.3 months vs. not reached, P = 0.0323) and overall survival (32.0 months vs. not reached, P = 0.0173) than non-sarcopenic patients. Furthermore, multivariate analyses showed that sarcopenia was an independent factor for cancer-specific survival (hazard ratio: 2.76, P = 0.0212) and overall survival (hazard ratio: 2.93, P = 0.014). The incidence rate of surgical complications (any grade: 35.2% vs. 27.6%, P = 0.482; grades ≥ 3: 7.4% vs. 10.3%, P = 0.648) or duration of post-operative hospitalization (median: 11 vs. 10 days, P = 0.148) was not significantly different between sarcopenic and non-sarcopenic patients., Conclusions: In conclusion, this study showed that sarcopenia was an independent prognostic factor for renal cell carcinoma with inferior vena cava thrombus after nephrectomy and tumor thrombectomy. Thus, sarcopenia evaluation can be utilized as an effective prognosticator of post-operative survival., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Studies assessing outcome improvements over a long period according to systemic therapy strategies for metastatic renal cell carcinoma using real-world data, including the results of the recent era of immune checkpoint inhibitors, are limited. Herein, we retrospectively evaluated patients who were diagnosed with metastatic renal cell carcinoma over a 40-year span., Methods: Patients were classified into four groups based on when their metastases were diagnosed as follows: (i) the pre-cytokine era (1980-1986), (ii) the cytokine era (1987-2007), (iii) the molecular-targeted therapy (mTT) era (2008 to August 2016) and (iv) the immune checkpoint inhibitor era (September 2016 to 2018). The immune checkpoint inhibitor era consisted of second- or later-line nivolumab. Overall survival from the diagnoses of metastases was evaluated., Results: In total, 576 patients were evaluated, including 22 (3.82%), 231 (40.1%), 253 (43.9%) and 70 (12.2%) patients from the pre-cytokine, cytokine, molecular-targeted therapy and immune checkpoint inhibitor eras, respectively. The overall survival significantly improved with each successive era (median: 13.1 vs. 24.5 vs. 44.4 months vs. not reached in pre-cytokine vs. cytokine vs. molecular-targeted therapy vs. immune checkpoint inhibitor eras, P < 0.0001). The implementation of molecular-targeted therapy improved overall survival compared with that of cytokine (cytokine vs. molecular-targeted therapy eras, P < 0.0001). Multivariate analysis demonstrated that the era was an independent factor for overall survival (P < 0.0001), together with histopathological type; metastasis status (i.e. synchronous or metachronous); systemic therapy status (i.e. absence or presence) and bone, liver or lymph node metastasis status (all, P < 0.05)., Conclusion: This retrospective study of real-world data indicated that metastatic renal cell carcinoma outcomes improved with successive systemic therapy paradigms., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Purpose: Combined immunotherapy of nivolumab plus ipilimumab for intermediate- and poor-risk metastatic clear cell renal cell carcinoma showed prolonged progression-free survival and high objective response rate in a randomized phase III clinical trial. However, the efficacy of this treatment for papillary renal cell carcinoma remains unclear. In the present study, we analysed the efficacy of nivolumab plus ipilimumab therapy for papillary renal cell carcinoma compared with that for clear cell renal cell carcinoma., Materials and Methods: This is a retrospective study of 30 patients with metastatic renal cell carcinoma who received nivolumab and ipilimumab as first-line therapy between December 2015 and May 2020. The objective response rate, progression-free survival and toxicity were compared between the two groups (clear cell renal cell carcinoma and papillary renal cell carcinoma)., Results: Out of 30 patients, 7 and 23 were diagnosed with papillary renal cell carcinoma and clear cell renal cell carcinoma, respectively. With a median follow-up of 7.2 months, the median progression-free survival was significantly shorter in papillary renal cell carcinoma than in clear cell renal cell carcinoma (2.4 vs. 28.1 months, P = 0.014). Of the seven patients with papillary renal cell carcinoma, one had partial response, one had stable disease and five had progressive disease, resulting in an objective response rate of 14.2%, which was lower compared to that of clear cell renal cell carcinoma (14.2 vs. 52.1%, P = 0.06). Discontinuation due to toxicity was not observed with papillary renal cell carcinoma, meanwhile 60.8% of patient with clear cell renal cell carcinoma discontinued treatment due to toxicity., Conclusion: Nivolumab plus ipilimumab had modest efficacy for papillary renal cell carcinoma compared with that for clear cell renal cell carcinoma. Nivolumab plus ipilimumab remains an option for a limited number of patients with intermediate- or poor-risk papillary renal cell carcinoma., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Objective: Limited data are available regarding the effect of systemic therapy change in the post-cytokine era on survival of metastatic renal cell carcinoma (mRCC) patients undergoing cytoreductive nephrectomy (CN)., Methods: Overall, 161 patients with synchronously mRCC were retrospectively evaluated. The patients were classified into three groups based on the time of diagnosis: (i) early molecular-targeted therapy (mTT) (2008-2011), (ii) late mTT (2012-8/2016) and (iii) immune checkpoint inhibitor (ICI) eras (9/2016-2018). Overall survival (OS) after the diagnosis was compared among the eras., Results: Of the 161 patients, 52 (32%), 75 (46%), and 34 patients (21%) were classified into the early mTT, late mTT and ICI eras, respectively. OS was significantly longer in the ICI and late mTT eras than that in the early mTT era (P = 0.0065 and P = 0.0010, respectively) but did not significantly differ between the ICI and late mTT eras (P = 0.389). In 112 patients undergoing CN and systemic therapy, OS was significantly longer in the ICI and late mTT eras than that in the early mTT era (P = 0.0432 and P = 0.0498, respectively) but did not significantly differ between the ICI and late mTT eras (P = 0.320). Multivariate analysis of OS in the 161 synchronous mRCC patients revealed that the era was an independent factor (P < 0.0001), together with the histopathological type (P = 0.0130), CN status (P = 0.0010), International Metastatic Renal Cell Carcinoma Database Consortium risk (P = 0.0002) and liver metastasis status (P = 0.0124)., Conclusion: This retrospective analysis showed that systemic therapy change in the post-cytokine era improved OS of mRCC patients undergoing CN., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Objective: To compare the surgical outcomes between the transperitoneal (TP) and retroperitoneal (RP) approaches in robot-assisted laparoscopic partial nephrectomy (RAPN) for lateral tumors., Methods: This study included patients who underwent RAPN for lateral renal tumors between 2013 and 2019. Lateral tumors were defined as X of A factors in the RENAL nephrometry score. In total, 290 and 48 patients with TP and RP, respectively, were included in the analysis. To minimize the effects of selection bias, the following variables were adjusted using 1:1 propensity score matching: age, sex, body mass index, American Society of Anesthesiologists score, preoperative estimated glomerular filtration rate, tumor size, and RENAL nephrometry score., Results: After matching, 48 patients were allocated to each group. The mean age was 55 years, and the mean preoperative estimated glomerular filtration rate (eGFR) was 68-69 mL/min/1.73 m 2 . The mean tumor size was 30-31 mm. The RP group had a shorter operative time (124 vs. 151 min, p = 0.0002), shorter console time (74 vs. 110 min, p < 0.0001), shorter warm ischemic time (14 vs. 17 min, p = 0.0343), lower estimated blood loss (EBL) (33 vs. 52 ml, p = 0.0002), and shorter postoperative length of hospital stay (PLOS) (3.3 vs. 4.0 days, p < 0.0001) than the TP group. The change in eGFR, incidence rate of perioperative complication, and positive surgical margin rate did not significantly differ between the two groups., Conclusion: RP had better surgical outcomes, including shorter operative time, lower EBL, and shorter PLOS for lateral renal tumors, which may suggest that RP is the optimal approach for selected lateral renal tumors.

Objectives: To compare the efficacy of nivolumab with that of molecular-targeted therapy as a second-line therapy for metastatic renal cell carcinoma using real-world data., Methods: We retrospectively evaluated patients who received nivolumab or molecular-targeted therapy after the failure of first-line molecular-targeted therapy between January 2008 and December 2019 at two Japanese institutions. Progression-free survival and overall survival after the initiation of second-line therapy were calculated using the Kaplan-Meier method and compared using the log-rank test. Objective response rate was assessed based on the Response Evaluation Criteria in Solid Tumors version 1.1., Results: Among 159 patients, 43 (27%) and 116 (73%) patients received nivolumab and molecular-targeted therapy as second-line therapy, respectively. During follow up (median 11.1 months), 129 (81%) and 98 (62%) patients had disease progression and died, respectively. Progression-free survival was comparable between the two treatments (median 5.06 vs 5.95 months, P = 0.881), whereas overall survival was significantly longer with nivolumab than with molecular-targeted therapy (not reached vs 13.0 months, P = 0.0008). Multivariate analysis further showed that nivolumab therapy was an independent favorable factor for overall survival (hazard ratio 0.33, P = 0.0007). In 151 patients with eligible radiographic data, the objective response rate was significantly higher in nivolumab than in molecular-targeted therapy (n = 14/41 [34%] vs n = 20/110 [18%], P = 0.0485)., Conclusions: Real-world data analysis suggests superior efficacy of nivolumab over molecular-targeted therapy as second-line therapy for metastatic renal cell carcinoma., (© 2020 The Japanese Urological Association.)

Objectives: To explore the real-world data regarding survival following metastasectomy (MS) for renal cell carcinoma (RCC) in the postcytokine therapy era., Patients and Methods: Patients diagnosed with metastatic renal cell carcinoma (mRCC) between January 2008 and December 2018 at our institutions were retrospectively evaluated. The patients were classified into three groups according to their MS status: (1) complete MS (cMS), (2) incomplete MS (icMS), and (3) without MS (nonMS). Factors for overall survival (OS) after diagnosis were analyzed., Results: Overall, 314 patients were evaluated. During the follow-up period (median: 25.3 months), a total of 98 patients (31.2%) underwent at least one MS. The cMS group (n = 45, 14.3%) had a significantly longer OS (median: not reached [N.R.]) than the icMS (n = 53, 16.9%) (81.5 months, P= 0.0042) and nonMS groups (28.1 months, P< 0.0001). The icMS group had a significantly longer OS than the nonMS group did (P= 0.0010). Multivariate analysis showed that the MS status was an independent factor for OS (cMS vs. nonMS: P= 0.0004; icMS vs. nonMS: P= 0.0176), together with histopathological type, International Metastatic Renal Cell Carcinoma Database Consortium risk, liver metastasis status, and prior nephrectomy status (all, P< 0.05). In addition, the OS was comparable throughout the eras of systemic therapy (early molecular-targeted therapy, late molecular-targeted therapy, and immune checkpoint inhibitor eras) in the MS group (median: 121.9 vs. N.R. vs. N.R. months, P= 0.948)., Conclusions: MS, especially cMS improved survival in selected patients with mRCC in the postcytokine therapy era. In addition, MS still plays a significant role in the current systemic therapy., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: When local recurrence of renal cell carcinoma (RCC) occurs after nephron-sparing surgery (NSS) on the ipsilateral side, some surgeons hesitate to perform reoperative surgery because of possible difficulties. We aimed to evaluate the clinical outcomes of repeat partial nephrectomy (RePN) compared with those of initial partial nephrectomy (iPN) for RCC of a solitary kidney., Methods: Until September 2017, 1671 patients with renal tumors underwent NSS. Of these, 79 patients who underwent NSS for sporadic RCC of a solitary kidney were included. Parameters were compared using the Mann-Whitney U, Pearson Chi-square, and Fisher exact tests., Results: Eleven patients underwent RePN and 68 underwent iPN. The RePN group had a relatively smaller tumor size (p = 0.0432), longer operative time (p = 0.0432), and higher estimated blood loss (p = 0.0002) than the iPN group. No significant differences in the other clinical factors were found between the groups. The rates of perioperative complications greater than Clavien-Dindo grade II were 18.2% and 17.6% in the RePN group and iPN group, respectively. The mean decreasing rate of estimated glomerular filtration rate was not different between the groups at 3 and 6 months postoperatively. No significant differences were found in hemodialysis-free survival (p = 0.7392) and intrarenal recurrence-free survival (p = 0.4924) between the groups., Conclusions: The clinical outcomes of RePN were not significantly different compared with those of iPN for patients with sporadic RCC of a solitary kidney. RePN is technically feasible with acceptable complication and local recurrence rates with better postoperative kidney function.

Background: The aspartate transaminase (AST)/alanine transaminase (ALT) ratio (ie, the De Ritis ratio) is associated with prognosis in some types of cancers including renal cell carcinoma (RCC). Meanwhile, an effective prognosticator for end-stage renal disease (ESRD)-associated RCC remains unknown. Thus, we investigated the prognostic impact of the AST/ALT ratio in patients with ESRD-associated RCC., Patients and Methods: We retrospectively evaluated 243 patients receiving radical nephrectomy for nonmetastatic ESRD-associated RCC. The patients were divided according to the cutoff value of preoperative AST/ALT ratio. Prognostic factors associated with cancer-specific survival (CSS) after radical nephrectomy were analyzed., Results: The maximum Youden index showed that the cutoff value of the AST/ALT ratio was 1.42. The high AST/ALT ratio group (≥ 1.42; n = 88) had a significantly shorter 10-year CSS than the low AST/ALT ratio group (64.3% vs. 87.2%; P = .0027). Multivariate analysis revealed that the AST/ALT ratio was an independent prognostic factor of CSS (hazard ratio [HR], 3.03; P = .0020), together with serum C-reactive protein level (HR, 4.84; P < .0001), pathologic stage (HR, 2.79; P = .0030), and tumor grade (HR, 7.08; P = .0087). Based on these independent factors, the patients were further classified into 3 groups: low (0-1 factor), intermediate (2 factors), and high risk (3-4 factors). The 10-year CSS in the high-risk group was significantly shorter than that of the other groups (68.9% vs. 70.9% vs. 94.4%; P < .0001)., Conclusion: The AST/ALT ratio can aid in the risk classification of patients with ESRD-associated RCC., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: Identifying the predictive factors for tumor recurrence after partial nephrectomy (PN) is useful to determine patients who require careful observation after surgery. Therefore, we investigated recurrence after partial nephrectomy (PN) in patients with clinical T1 renal cell carcinoma (RCC) and analyzed predictive factors for recurrence-free survival (RFS)., Methods: This study included 1227 patients who underwent PN for clinical T1 RCC and retrospectively investigated patients' characteristics and tumor factors that are associated with tumor recurrence., Results: The median patient age was 59 years, and the median tumor size was 30 mm. Although 970 (74%) and 319 (26%) patients had clinical T1a and T1b RCCs, respectively, 20 patients (1.6%) were upstaged to pathological T3a. A positive surgical margin was found in 19 (1.5%) patients. The distribution of surgical approaches was open surgery in 428 (35%) patients and minimally invasive surgery in 799 (65%) patients. With a median follow-up of 35 months (Interquartile range 19-55 months), 39 (3.2%) patients, including ten with local recurrence, five with recurrence in the ipsilateral kidney, and 28 with other organs or lymph-nude, developed recurrence. The 3-year RFS was 99%, and the median recurrence time from PN was 19 months (interquartile range: 11-37 months). Multivariate analysis identified high grade tumor and upstaging to pT3a as significant predictors for worse RFS., Conclusion: Patients with high grade tumors and tumors upstaged to pT3 had a high risk of worse RFS, which suggested that careful monitoring is required for such patients after PN, even if a good prognosis is achieved in patients with clinical T1 RCC.

Objectives: Complete metastasectomy is expected to improve the survival of patients with metastatic renal cell carcinoma (mRCC). However, many patients develop re-recurrence, despite achieving complete remission with surgery. We examined recurrence-free survival (RFS) and analyzed predictive factors for recurrence after complete metastasectomy., Methods: Fifty-one patients with mRCC who underwent complete metastasectomy between 2008 and 2018 were included in this study. Multivariate Cox regression analyses were performed to identify the prognostic factors for RFS., Results: Of 51 patients, 6 (12%) had multiple metastatic sites and 45 (88%) had solitary metastasis. The pathological subtype was clear cell in 42 (82%), papillary in 8 (17%), and other subtype in 1 (2%) patient. Sarcomatoid features were found in 2 (4%) patients. The Memorial Sloan Kettering Cancer Center risk category was favorable in 43%, intermediate in 53%, and poor in 4% of patients. The median duration from nephrectomy to metastasectomy was 32 months. Of the total cohort, 39 patients (74%) developed recurrence after complete metastasectomy. The median RFS was 22 months, and the 2- and 5-year RFS rates were 45% and 25%, respectively. Multivariate Cox regression revealed that ≥2 metastatic sites (vs. 1 site; HR = 4.52; P = 0.024) and sarcomatoid features (HR = 11.5; P = 0.0171) were independent predictive factors for recurrence. The 2- and 5-year cancer-specific survival rates were 98% and 82%, respectively., Conclusion: The number of metastatic sites and sarcomatoid features were associated with recurrence after complete metastasectomy, which suggests that careful observation is required for such patients, even after achieving complete remission with metastasectomy., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The aim of this study was to compare the efficacy and safety of nivolumab as second-line and later-line (third-line or thereafter) therapy in metastatic renal cell carcinoma (mRCC)., Methods: Sixty-seven patients who received nivolumab after the failure of at least one molecular-targeted therapy were evaluated. The patients were divided into two groups based on the line of nivolumab: second-line and later-line groups. Efficacy was assessed using progression-free survival and overall survival (OS) after nivolumab initiation, and objective response rate. Safety was assessed using the incidence of immune-related adverse events. These outcomes were compared between the second-line and later-line groups., Results: Forty-two patients (62.7%) received nivolumab as second-line therapy. There was no significant difference in the progression-free survival (median: 5.06 vs. 6.28 months, p = 0.691) or objective response rate (35.7% vs. 32.0%, p = 0.757) between the second-line and later-line groups. The OS tended to be longer in the second-line group (not reached vs. 26.0 months, p = 0.118), and the rate of patients who received subsequent therapy after nivolumab failure was significantly higher in the second-line group (90.9% vs. 55.0%, p = 0.0025). There was no difference in the incidences of immune-related adverse events between the second-line and later-line groups (any grade: 54.8% vs. 48.0%, p = 0.592; grade ≥ 3: 19.1% vs. 20.0%, p = 0.924)., Conclusions: The efficacy of nivolumab did not deteriorate and the tolerability was also maintained even in later-line therapy. However, a tendency of longer OS and a higher chance of subsequent therapy after nivolumab failure were observed with nivolumab as second-line therapy.

A histological grading system of chromophobe renal cell carcinoma (chRCC) is highly desirable to identify approximately 5-10% of tumors at risk for progression. Validation studies failed to demonstrate a correlation between the four-tiered WHO/ISUP grade and outcome. Previous proposals with three-tiered chromophobe grading systems could not be validated. In this study, the presence of sarcomatoid differentiation, necrosis, and mitosis was analyzed in a Swiss cohort (n = 42), an Italian cohort (n = 103), a German cohort (n = 54), a Japanese cohort (n = 119), and The Cancer Genome Atlas cohort (n = 64). All 3 histological parameters were significantly associated with shorter time to tumor progression and overall survival in univariate analysis. Interobserver variability for identification of these parameters was measured by Krippendorff's alpha coefficient and showed high concordance for the identification of sarcomatoid differentiation and tumor necrosis, but only low to medium concordance for the identification of mitosis. Therefore, we tested a two-tiered tumor grading system (low versus high grade) based only on the presence of sarcomatoid differentiation and/or necrosis finding in the combined cohorts (n = 382). pT stage, patient's age (> 65 vs ≤ 65), lymph node and/or distant metastasis, and the two-tiered grading system (low versus high grade) were significantly associated with overall survival and were independent prognostic parameters in multivariate analysis (Cox proportional hazard). This multi-institutional evaluation of prognostic parameters suggests tumor necrosis and sarcomatoid differentiation as reproducible components of a two-tiered chromophobe tumor grading system.

Renal cell carcinoma (RCC) is associated with various genetic alterations. Although whole-genome/exome sequencing analysis has revealed that nuclear genome alterations are associated with clinical outcomes, the association between nucleotide alterations in the mitochondrial genome and RCC clinical outcomes remains unclear. In this study, we analyzed somatic mutations in the mitochondrial D-loop region, using RCC samples from 61 consecutive patients with localized RCC. Moreover, we analyzed the relationship between D-loop mutations and NADH dehydrogenase subunit 1 ( MT-ND1 ) mutations, which we previously found to be associated with clinical outcomes in localized RCC. Among the 61 localized RCCs, 34 patients (55.7%) had at least one mitochondrial D-loop mutation. The number of D-loop mutations was associated with larger tumor diameter (> 32 mm) and higher nuclear grade (≥ ISUP grade 3). Moreover, patients with D-loop mutations showed no differences in cancer-specific survival when compared with patients without D-loop mutations. However, the co-occurrence of D-loop and MT-ND1 mutations improved the predictive accuracy of cancer-related deaths among our cohort, increasing the concordance index (C-index) from 0.757 to 0.810. Thus, we found that D-loop mutations are associated with adverse pathological features in localized RCC and may improve predictive accuracy for cancer-specific deaths when combined with MT-ND1 mutations., Competing Interests: The authors declare no conflict of interest.

Background: Treatment modification due to adverse events reduces the dose intensity in cancer treatment. The prognostic impact of sunitinib treatment interruption within the initial period of therapy for metastatic renal cell carcinoma (mRCC) remains unknown., Patients and Methods: We retrospectively evaluated 97 patients with mRCC treated with first-line sunitinib treatment. The patients were classified into two groups according to the presence of treatment interruption (TI) within the initial two cycles. The prognostic impact of TI was analyzed using the Kaplan-Meier method and log-rank test, and multivariate analyses using the Cox proportional hazard model., Results: Thirty-eight patients (39.2%) experienced an immediate TI. The median progression-free (PFS) and overall (OS) survival were significantly shorter in patients with a TI than in those without (PFS= 6.54 vs. 11.3 months, p=0.0246; OS=16.9 vs. 30.0 months, p=0.0420). Multivariate analyses for PFS and OS showed that TI was an independent factor predicting poorer PFS (hazard ratio(HR)=1.93, p=0.0141) and OS (HR=2.09, p=0.0102). In addition, the relative dose intensity within the initial two cycles was significantly lower in patients with a TI than in those without (52.7% vs. 75.0%, p<0.0001)., Conclusion: This study showed the significantly negative effect of immediate TI on survival of patients under sunitinib treatment for mRCC. Therefore, the careful monitoring of patient tolerability is required in order to maintain therapeutic efficacy in the early phase of sunitinib treatment., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background and Objective: We assessed the aggressiveness of localized renal cell carcinoma (N0M0 RCC) with rhabdoid differentiation (RD) after partial or radical nephrectomy., Methods: A total of 604 patients with N0M0 RCC who had undergone partial or radical nephrectomy at a single institution were included in this study. Clinicopathological and outcome data on recurrence-free survival (RFS), cancer-specific survival (CSS), and time to recurrence (TTR) were analyzed using Kaplan-Meier methods, log-rank test, univariate and multivariable Cox proportional hazard models, and concordance index. We also evaluated the RFS and CSS in a propensity score-matched cohort to reduce inherent differences. Among the 604 patients, RD was identified in RCC specimens from 24 patients., Results: At the median postoperative follow-up period of 53 months, 58 patients (12 with RD) showed recurrence and 26 patients (7 with RD) had died from RCC. Multivariate analyses showed that RD was an independent risk factor of RFS (hazard ratio 2.81; P = 0.0266) and CSS (hazard ratio 5.18; P = 0.00182). By RD adding to standard risk factors, the concordance indices for RFS and CSS increased 0.77 to 0.79, and 0.76 to 0.79, respectively. Subgroup analysis showed that the presence of RD in RCC specimens was more important for predicting poor RFS and CSS in the early pathological tumor category (≤pT2) subgroup compared to in the advanced tumor category (≥pT3) subgroup. Patients with RD showed a significantly shorter TTR than patients with RCC without RD (7.5 vs. 18 months: P = 0.0150). The propensity score-matched cohort included 24 patients with RD and 24 without RD, of which patients RD showed significantly shorter RFS than those without RD (P = 0.0026)., Conclusions: In summary, the aggressiveness of N0M0 RCC with RD increased the risk of postoperative recurrence, particularly in the early pathological stage. The short TTR also demonstrated the aggressiveness of RCC with RD., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Predictive factors that can be routinely used in clinical practice are critically needed for immune checkpoint inhibitor therapy in metastatic renal cell carcinoma (mRCC)., Objective: To comprehensively analyze the predictive impact of peripheral blood markers and C-reactive protein (CRP) in nivolumab therapy for mRCC., Methods: Fifty-eight patients were retrospectively evaluated. We evaluated neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), absolute eosinophil count (AEC), and absolute monocyte count (AMC) as peripheral blood markers as well as serum CRP levels. The primary endpoints were progression-free survival (PFS) and overall survival (OS) after nivolumab initiation., Results: Median PFS was significantly shorter in patients with high NLR (≥ 3) versus low NLR (p = 0.0356), high MLR (≥ 0.3) versus low MLR (p = 0.0013), or high PLR (≥ 160) versus low PLR (p = 0.0073), and median OS was significantly shorter in patients with high NLR versus low NLR (p = 0.0025), high MLR versus low MLR (p = 0.0025), high PLR versus low PLR (p = 0.0256), or high CRP (≥ 1.0 mg/dl) versus low CRP (p = 0.0006). Multivariate analyses showed that MLR (HR 2.65, p = 0.0068) was an independent factor for PFS and that NLR (HR 3.34, p = 0.0218), MLR (HR 3.42, p = 0.0381), and CRP (HR 4.98, p = 0.0108) were independent factors for OS., Conclusions: The systemic inflammatory factors NLR, MLR, and CRP were predictive factors in nivolumab therapy for mRCC. These easily monitored factors can contribute to effective treatment and follow-up.

Objective: To evaluate the change in the operated parenchymal volume during robot-assisted partial nephrectomy limited to the enucleation technique, and to analyze the predictors of decrease in operated parenchymal volume, including the tumor contact surface area., Methods: The study included 135 patients who underwent robot-assisted partial nephrectomy for T1 renal tumors using the enucleation technique. Measurements of the parenchymal volume, tumor volume and contact surface area were obtained in the venous phase on enhanced computed tomography. All measurements, including volumetric and renal function analysis, were carried out <2 months before and 6 months after surgery., Results: The mean age of included participants was 56 years, and the mean tumor size was 33 mm. The mean tumor volume was 26 cc, and the mean contact surface area was 22 cm 2 . In the complete cohort, the mean preoperative and postoperative normal parenchymal volumes of the operated kidney were 158 and 141 cc, respectively. The mean change in parenchymal volume of the operated kidney was -10%. In contrast, the mean change in global estimated glomerular filtration was just -4.0%. Univariate analysis showed that the RENAL nephrometry score, contact surface area, tumor volume and warm ischemia time were associated with the change in the operated kidney parenchymal volume. However, in the multivariate analysis, a large contact surface area was the only independent predictor of decreased operated parenchymal volume <10 cm 3 ., Conclusion: Contact surface area is a strong predictor of the decrease in the parenchymal volume in the operated kidney during robot-assisted partial nephrectomy carried out using the enucleation technique for T1 renal tumors., (© 2019 The Japanese Urological Association.)

Objectives: Immune-related adverse events (irAEs) develop in a subset of patients with metastatic renal cell carcinoma (mRCC) treated with immune checkpoint inhibitors. The relationship between presence of irAEs and prognosis in these patients remains unknown. Thus, we evaluated the prognostic impact of irAEs caused by nivolumab therapy in mRCC patients who had received prior molecular-targeted therapies., Methods: We retrospectively evaluated 47 patients with mRCC who were treated with nivolumab after receiving at least 1 molecular-targeted therapy. The irAEs assessed in this study included cutaneous, gastrointestinal, endocrine, pulmonary, hepatobiliary, renal, and other (rheumatic disease and pancreatitis) manifestations. The grade of irAEs was defined based on the Common Terminology Criteria for Adverse Events version 4.0., Results: In total, 23/47 patients (48.9%) experienced 29 irAEs. The most frequent irAE was rash/pruritus (12/23, 52.2%). The median progression-free survival (PFS) and overall survival after the initiation of nivolumab therapy were significantly longer in patients with irAEs than in those without irAEs (PFS: 13.1 vs. 4.87 months, P < 0.0001; overall survival: 26.0 vs. not reached, P = 0.0072). The multivariate analysis of PFS showed that irAE development was an independent prognostic factor (hazard ratio: 0.25, P = 0.0009). Additionally, the 2-cycle landmark analysis showed that PFS was significantly longer in patients with irAEs than in those without irAEs (median: not reached vs. 6.28 months, P = 0.0279)., Conclusions: This retrospective study revealed a significant association between nivolumab-associated irAEs and prognosis in previously treated mRCC. Further prospective studies are necessary to confirm our findings., (Copyright © 2019 Elsevier Inc. All rights reserved.)

We reviewed the clinical efficacy of axitinib after nivolumab treatment failure in six patients with metastatic renal cell carcinoma (RCC); the patients had received nivolumab treatment following vascular endothelial growth factor receptor (VEGFR) inhibitors. Most had undergone radical nephrectomy; five had clear-cell carcinoma and acquired cystic disease-associated carcinoma. The patients were finally diagnosed with progressive disease during nivolumab treatment. Immediately after nivolumab treatment failure, one patient receiving pazopanib had an adverse event soon after, and subsequently received axitinib, which the others received. The size of the metastatic tumors treated with axitinib after nivolumab was on average 33.9% smaller. Following treatment, three patients experienced partial response with remarkable tumor shrinkage and three had stable disease (SD), of which most maintained for >5 months. One patient with SD died from gradual tumor progression after axitinib treatment. Axitinib treatment after nivolumab treatment failure can be beneficial for some patients with metastatic RCC., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To investigate peritumoral pseudocapsule status in patients with renal cell carcinoma who underwent robot-assisted laparoscopic partial nephrectomy, and to examine predictive factors associated with the absence of peritumoral pseudocapsule., Methods: A total of 367 patients with clinical T1 renal cell carcinoma who underwent robot-assisted laparoscopic partial nephrectomy were divided into two groups according to peritumoral pseudocapsule status. The groups were compared in terms of patient and tumor characteristics. Multivariate logistic regression analysis was carried out to identify predictive factors for the absence of peritumoral pseudocapsule., Results: Of the 367 tumors, 323 (88%) were surrounded by a peritumoral pseudocapsule. The mean tumor size was 30 mm, and 70% of the patients were male. Tumors with a peritumoral pseudocapsule had a larger diameter than those without (31 vs 26 mm; P = 0.0008). A peritumoral pseudocapsule was observed in 92% of the clear cell, in 89% of the papillary and in 86% of the clear cell papillary renal cell carcinoma cases compared with just 50% in the chromophobe renal cell carcinoma cases (P < 0.0001). Sex, age, Fuhrman grade and tumor complexity did not differ among patients. A multivariate analysis showed that smaller tumor size (≥34 vs <34 mm, odds ratio 3.31; P = 0.0023) and chromophobe renal cell carcinoma (vs other subtypes, odds ratio 12.5; P < 0.0001) predicted an absence of peritumoral pseudocapsule., Conclusions: Small tumor size and chromophobe renal cell carcinoma were significant predictors of a lack of peritumoral pseudocapsule, suggesting that a positive surgical margin must be avoided for these tumors when an enucleation technique is used for robot-assisted laparoscopic partial nephrectomy., (© 2019 The Japanese Urological Association.)

Background: Patients in the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) intermediate-risk group have heterogeneous prognoses and thus may benefit from improved risk stratification., Objective: The aim of this study was to analyze inflammatory parameters such as C-reactive protein (CRP) and neutrophil-to-lymphocyte ratio (NLR) as prognostic markers for IMDC intermediate-risk patients., Methods: Patients with metastatic clear cell renal cell carcinoma (n = 71) with IMDC intermediate risk who received tyrosine kinase inhibitors as first-line therapy were included in this retrospective study. Multivariate Cox regression analyses were performed to identify prognostic factors for overall survival (OS)., Results: As first-line systemic therapy, 46 (65%), 19 (27%), and 6 (8%) patients received sunitinib, sorafenib, and pazopanib, respectively. An IMDC prognostic score of 1 and 2 were observed in 34 (48%) and 37 (52%) patients, respectively. Mean CRP level was 1.06 mg/dL, and mean NLR was 3.0. Multivariate Cox regression revealed several factors significantly associated with poor OS, including NLR ≥ 3 (vs NLR < 3; hazard ratio [HR] 2.57; p = 0.0228), CRP level ≥ 1 mg/dL (vs CRP < 1 mg/dL; HR 2.89; p = 0.0279), and two or more metastatic organs (vs one organ; HR 3.77; p = 0.0008). Using these risk factors, patients were stratified into the following three risk categories: F0 (no prognostic factors; n = 20), in which the median OS (mOS) was not achieved; F1 (1 prognostic factor; n = 31), in which the mOS was 31 months; and F2-3 (2 or 3 prognostic factors; n = 20) in which the mOS was 13 months (log-rank p < 0.0001)., Conclusion: CRP, NLR, and the number of metastatic organs were independent prognostic factors in IMDC intermediate-risk patients.

The correlation between the magnitudes of best tumor response (bTR) and patient survival in immune checkpoint inhibitor therapy for metastatic renal cell carcinoma (mRCC) remains unclear. In this article, we retrospectively investigated the prognostic association of the magnitude of bTR in nivolumab therapy for mRCC. Fifty-five patients treated with nivolumab after failure of at least one molecular-targeted therapy were evaluated. Assessment of the magnitude of bTR was based on the Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1. Endpoints were progression-free survival (PFS) and overall survival (OS) after the initiation of nivolumab therapy. In regard to the magnitude of bTR, complete response, partial response, stable disease, and progressive disease were observed in three (5.46%), 15 (27.3%), 19 (34.5%), and 18 (32.7%) patients, respectively. PFS and OS were significantly correlated with the magnitude of bTR (median PFS: not reached (N.R.) [95% confidence interval (CI) 16.8-N.R.] vs. 13.0 [8.38-56.0] vs. 5.95 [4.27-7.30] vs. 1.92 [0.53-3.91] months, p < 0.0001; OS: N.R. [N.R.-N.R.] vs. N.R. [21.4-N.R.] vs. 23.3 [23.3-N.R.] vs. 7.36 [1.41-N.R.] months, p < 0.0001). In addition, multivariate analyses show that the magnitude of bTR was an independent factor for PFS (p < 0.0001) and OS (p = 0.0010). In conclusion, this retrospective study shows the significant correlation between the magnitude of bTR and patient survival in nivolumab therapy for mRCC. The magnitude of bTR can be an effective surrogate marker for survival.

New pathological subtypes of renal cell carcinoma (RCC) were designated in the 2016 World Health Organization (WHO) classification corresponding to the features commonly seen in patients with end-stage renal disease (ESRD). To determine the clinicopathological findings of new subtypes, we reanalyzed all sections from 315 kidneys in 291 ESRD patients bearing RCC tumors surgically resected in three Japanese institutes by the central pathologist. Clear cell RCC was diagnosed in 144 kidneys (45.7%), acquired cystic disease (ACD)-associated RCC in 100 (31.7%), papillary RCC in 41 (13.0%), and other minor subtypes in 30 (9.52%). Multivariate analysis showed that longer duration of dialysis, young age, and male sex were independent prognostic clinical factors for the occurrence of ACD-associated RCC. ACD-associated RCC included more WHO/International Society of Urologic Pathology (ISUP) grade 3/4 cases compared to other RCCs. In contrast, other unfavorable findings were less frequent in ACD-associated RCC, including the presence of a sarcomatoid component, lymphovascular invasion, and necrosis. In conclusion, ACD-associated RCC is a common histology in Japanese patients with ESRD. In addition, ACD-associated RCC showed more cases with a higher WHO/ISUP grade, but fewer cases with other unfavorable pathological features, suggesting a favorable prognosis of ACD-associated RCC., (© 2018 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.)

Objectives: Mayo adhesive probability (MAP) score quantifies adherent perinephric fat (APF) and is associated with the prolongation of surgery duration or the increase of surgical complication rates., Patients and Methods: In this study, 311 patients who underwent robot-assisted partial nephrectomy (RAPN) at our institute were included. APF was quantified using the MAP score calculated using perinephric fat thickness and stranding seen on a preoperative enhanced CT scans. The surgery duration was classified into the dissection (robotic manipulation to hilar clamping) and resection (hilar clamping to robotic surgery completion) phases., Results: The MAP score was found to be 0, 1, 2, 3, 4, and 5 in 98 (32%), 86 (28%), 21 (7%), 48 (15%), 44 (14%), and 14 (4%) patients, respectively. The dissection and resection phase times increased with an increase in the MAP score. The median dissection phase times for MAP scores of 0, 1, 2, 3, 4, and 5 were 71.7, 79.1, 88.9, 97.0, 99.7, and 118.8 minutes, respectively. The MAP score was more strongly associated with the prolongation of the dissection phase than with the prolongation of the resection phase. In multivariate analysis for dissection phase time of more than 90 minutes, the body mass index [odds ratio (OR) = 1.09, p = 0.0209], early surgical experience (first 100 cases) (OR = 2.32, p = 0.0024), and MAP score ≥3 (OR = 6.20, p < 0.0001) significantly associated with the prolongation of dissection phase in a logistic regression model., Conclusions: The MAP score is a factor significantly associated with the prolongation of the dissection phase during RAPN.

We investigated the efficacy of nivolumab treatment in patients with metastatic renal cell carcinoma who discontinued nivolumab treatment due to reasons other than disease progression. Of the 34 patients, 3 patients discontinued nivolumab therapy due to adverse events and were subsequently observed without additional treatment. The first patient discontinued nivolumab after 14 cycles of treatment due to type 1 diabetes mellitus and has maintained partial remission for 8 months. The second patient discontinued nivolumab after 11 cycles of treatment due to interstitial pneumonitis, and durable response was confirmed for 5 months. However, multiple lung lesions reappeared at 6 months after discontinuing nivolumab. The third patient discontinued nivolumab due to elevated liver enzymes after three cycles of treatment. At the time of discontinuation, a new liver lesion appeared, but the lesion decreased in size at 6 months after discontinuation. In the present study, a relatively durable response was observed in three patients who discontinued nivolumab without additional treatment.

Background: Relative dose intensity is an indicator of therapeutic efficacy in sunitinib treatment for metastatic renal cell carcinoma. However, the number of studies investigating the influence of decreased relative dose intensity during the early phase on oncological outcome is limited., Methods: A total of 105 patients who received first-line sunitinib treatment for metastatic renal cell carcinoma were evaluated. We assessed the relative dose intensity during the initial first cycle (1c-RDI). We found that an optimal threshold of 1c-RDI was associated with progression-free survival and overall survival after the initiation of sunitinib treatment. Additionally, predictive factors for decreased 1c-RDI were analyzed., Results: The 1c-RDI threshold was determined at 60%. Patients with low 1c-RDI (<60%, n = 26, [24.8%]) had significantly shorter median progression-free survival (5.79 vs. 14.0 months, P = 0.0014) and overall survival (13.3 vs. 34.4 months, P = 0.0005) durations than those with high 1c-RDI (≥60%, n = 79 [75.2%]). Multivariate analysis showed that the development of dose-limiting toxicity was an independent factor for low 1c-RDI (odds ratio: 3.09, 95% confidence interval: 1.14-8.37, P = 0.0266) after adjustment with an initial dose of sunitinib., Conclusions: More than 60% of 1c-RDI is needed for effective sunitinib treatment. Patient tolerability should be carefully monitored to avoid the development of dose-limiting toxicity during the early phase of treatment.