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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.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/mOverall, 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, p0.05). 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.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.

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 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 efficacy of combined immunotherapy for papillary renal cell carcinoma (pRCC) based on prolonged progression-free survival (PFS) and overall survival in several clinical trials remains unknown. We aimed to compare the efficacy of cabozantinib in patients with pRCC and those with clear-cell renal cell carcinoma (ccRCC).This retrospective study included 27 patients with metastatic RCC who received cabozantinib as second-line or later therapy between June 2020 and October 2021. Objective response, PFS, and toxicity were compared between the ccRCC and pRCC groups.Out of 27 patients, seven and 20 were diagnosed with pRCC and ccRCC, respectively. Out of the seven patients with pRCC, cabozantinib was used as second-line treatment in four patients and as third-line treatment in three patients, and all seven patients had had prior immunotherapy. One and two patients achieved complete and partial responses, respectively; four patients had stable disease, and none had progressive disease. The rates of objective response (43% vs. 30%, p=0.65) and disease control (100% vs. 85%, p=0.54) were similarly high in patients with pRCC and ccRCC. Changes in the target lesions were -19% and -10% (p=0.11), respectively. With a median follow-up of 7.1 months, the median PFS tended to be longer in patients with pRCC than in those with ccRCC (not reached vs. 10.7 months, p=0.12). Discontinuation due to toxicity was observed in four (57%) patients with pRCC and 10 (50%) patients with ccRCC.Cabozantinib is effective for pRCC, similar to ccRCC. This information may help physicians to select treatment options for pRCC.

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 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.

Serum C-reactive protein (CRP) is reportedly associated with metastatic renal cell carcinoma (mRCC) activity. However, in the era of immune checkpoint inhibitors, the predictive value of CRP is unclear. In this study, we investigated the predictive impact of pretreatment CRP levels and early changes in CRP levels for the treatment of mRCC with nivolumab plus ipilimumab (NIVO-IPI) therapy.Forty-eight patients with mRCC treated with NIVO-IPI as a first-line therapy were retrospectively analyzed. First, patients were divided into 2 groups: initial CRP ≥ 1.0 mg/dL and1.0 mg/dL. Progression-free survival (PFS) was compared between the 2 groups. Second, based on the CRP change within the first 3 months of NIVO-IPI, patients were placed in the normal group (CRP remains1.0 mg/dL), normalized group (CRP decreased1.0 mg/dL), and non-normalized group (CRP remained or increased to ≥ 1.0 mg/dL). The predictive association between CRP change and PFS was evaluated.PFS was significantly lower in the high initial CRP group (n = 24, 50%) compared to the normal CRP group (n = 24, 50%) (median: 4.3 vs. 28.1 months, P = .03). As for the early CRP change, the normal (2.7 vs. 28.1, P = .0002) and normalized (2.7 vs. 11.0, P = .0094) groups showed significantly higher PFS, compared to the non-normalized group. Meanwhile, there was no significant difference between normal, and normalized groups (P = .51). The objective response rate was higher in the normal (57.1% vs. 18.7%, P = .015) and normalized (81.8 vs. 18.7%, P = .0008) groups, compared to the non-normalized group. Multivariate Cox regression analysis showed that normal [Hazard ratio (HR) = 0.15, 95% Confidence interval (CI) = 0.02-0.70, P = .026] and normalized (HR 0.21, 95% CI = 0.05-0.73, P = .015) CRP showed significant association with PFS.In the NIVO-IPI therapy for mRCC, early changes in CRP could predict PFS. This data may be useful for the early detection of ineffective NIVO-IPI therapy and conversion to subsequent therapies.

Kaori Yamashita,1,2 Yudai Ishiyama,1 Maki Yoshino,1 Hidekazu Tachibana,1 Daisuke Toki,1 Ryuichiro Konda,2 Tunenori Kondo1 1Department of Urology, Tokyo Women’s Medical University Medical Center East, Tokyo, Japan; 2Tomioka Clinic, Tokiwa Foundation, Fukushima, JapanCorrespondence: Kaori Yamashita,Department of Urology, Tokyo Women’s Medical University Medical Center East, 2-1-10, Nishi-ogu, Arakawa-ku, Tokyo, 116-8567, Japan, Tel +81 338101111, Fax +81 338940282, Email kmurology@yahoo.co.jpIntroduction: The aim of this study was to analyze urinalysis findings and urinary bacterial culture in hemodialysis-dependent end-stage renal disease patients. The research goal was to understand the proportion, risk factors, and the causative organisms of urinary tract infection in hemodialysis-dependent end-stage renal disease patients.Materials and Methods: Between May 2020 and June 2021, this study included 100 hemodialysis-dependent end-stage renal disease patients (50 male patients and 50 female patients). The urine underwent microscopic examination, pyuria was defined as ≥ 5 white blood cells per high-power field, and urinary bacterial cultures were conducted for patients with pyuria. Bacteriuria was defined as ≥ 104 colony-forming units/mL in men and ≥ 105 colony-forming units/mL in women. Daily urine output was investigated by oral listening. Postvoiding residual urine volume was measured.Results: Fifty-six percent of male patients and 30% of female patients had normosthenuria, 24% of male patients and 38% of female patients had pyuria, and 20% of male patients and 32% of female patients had a urinary tract infection. A comparison of normosthenuria and urinary tract infection revealed no statistically significant difference in age, time on dialysis, daily urine output, and postvoiding residual urine volume. The proportion of female patients among those with normosthenuria was 34.8%, whereas the proportion of female patients among those with UTI was 61.5%. Urinary bacterial cultures showed that the major causative organisms were Escherichia coli (45%; 18/40 cultures) and extended spectrum beta-lactamase-producing Escherichia coli (17.5%; 7/40 cultures).Conclusion: The incidence of urinary tract infection was higher in female patients than in male patients. The proportion of resistant bacteria as the causative organisms was high in hemodialysis-dependent end-stage renal disease patients. Urinary bacterial culture should be checked while patients are able to void urine.Keywords: bacteriuria, pyuria, renal dialysis, urinary tract infection, urine

Background/Aim: Whether anesthesia can affect oncological outcomes in urothelial carcinoma of the upper urinary tract undergoing radical nephroureterectomy (RNU) is not clear. Patients and Methods: One-hundred an ninety-seven patients who underwent RNU were retrospectively recruited and divided into total intravenous (TIVA, n=90) and volatile inhalation anesthesia (VIA, n=107) groups. A 1:1 propensity score-matching method was employed to minimize selection bias (n=70 each). Cancer-specific (CSS), overall (OS) and metastasis-free (MFS) survival were compared between groups before and after matching. Results: For all survival endpoints, no significant differences were observed between the two study groups, both before (hazard ratio for TIVA: CSS: 0.70, OS: 0.75, MFS: 0.78) and after (hazard ratios for TIV: CSS: 1.21, OS: 0.82, MFS: 0.84) matching. Conclusion: With no survival difference observed according to anesthetic technique for RNU, the choice should be based on factors such as accessibility, prevention of side-effects, or costs.

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.

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.

OBJECTIVES To evaluate the association between extended (≥30 min) warm ischemic time and renal function in patients undergoing robot-assisted partial nephrectomy. METHODS This multi-institutional study retrospectively recruited 1131 patients who underwent robot-assisted partial nephrectomy. Patients were classified into shorter (

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.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).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.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 (p0.0001) 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; p0.0001) 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.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.

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). To investigate the prognostic impact of the early interruption of nivolumab plus ipilimumab, used as first-line therapy for mRCC. 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. 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. 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/Aim: To clarify the perioperative and oncological outcomes of robot-assisted radical cystectomy (RARC) in advanced bladder cancer (BC) patients treated with maintenance hemodialysis (HD) therapy. Patients and Methods: We retrospectively evaluated patients receiving HD therapy who had undergone RARC or open radical cystectomy (ORC) for BC between April 1988 and December 2021 at two affiliated institutions. We compared the surgical outcomes and survival after radical cystectomy between patients treated with RARC and those treated with ORC. Results: Thirty-six patients were evaluated, and eight (22%) and 28 (78%) received RARC and ORC, respectively. RARC was more frequently conducted than ORC in elderly patients (median: 75.5 vs. 68.2 years, p

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.

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.The aim of this study was to clarify the impact of trial eligibility on ICI-based combination therapy for mRCC.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 mForty-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).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.

BACKGROUND/AIM We investigated the prognostic nutritional index (PNI), comprised of lymphocytes and albumin, as a potential prognosticator of metastatic urothelial carcinoma (mUC) patients receiving pembrolizumab. PATIENTS AND METHODS Sixty-five patients were retrospectively enrolled and classified as low (

The data regarding oncological outcome in advanced renal cell carcinoma (RCC) arising in end-stage renal disease (ESRD) are limited. 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). 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). 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.

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

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.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.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.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).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.

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.

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.

To investigate the predictive impact of a change in serum C-reactive protein (CRP) levels during the early phase of nivolumab therapy for metastatic renal cell carcinoma (mRCC).Seventy mRCC patients treated with nivolumab after molecular-targeted therapy failure were retrospectively evaluated. Based on the CRP change, patients were classified as (1) normal: if pretreatment levels were1 mg/dl; (2) normalized: if pretreatment levels were ≥1.0 mg/dl and nadir levels within the initial three months of nivolumab therapy declined to1.0 mg/dl; and (3) non-normalized: if pretreatment levels were ≥1 mg/dl and nadir levels remained ≥1.0 mg/dl. The predictive association between the CRP change and progression-free survival (PFS) and overall survival (OS) after nivolumab initiation was evaluated.The PFS was significantly lower in the non-normalized group (n = 25, 35.7%) than in the normal (n = 29, 41.4%) (median: 2.33 vs. 6.28 months, P = 0.0009) and normalized (n = 16, 22.9%) (2.33 vs. 8.38 months, P = 0.0006) groups, while no differences were observed between normal and normalized groups (P = 0.610). The OS was significantly lower in the non-normalized group than in the normal (8.02 months vs. not reached, P0.0001) and normalized groups (8.02 vs. 26.0 months, P = 0.0047); further, the OS of the normalized group was lower than that of the normal group (P = 0.0454). Multivariate analyses showed that the CRP change was an independent factor for PFS (P = 0.0025) and OS (P = 0.0009).The CRP change during the early phase of nivolumab therapy was significantly associated with mRCC patient survival and may thus be used for outcome prediction.

Background/Aim: Whether molecular-targeted therapy, particularly axitinib, is effective after failure of immune checkpoint inhibitors in metastatic renal cell carcinoma (mRCC) remains unclear. Here, we evaluated the therapeutic effect of axitinib as a third-line therapy following second-line nivolumab monotherapy for mRCC. Patients and Methods: Data from patients treated with axitinib as a third-line therapy after failure of first-line tyrosine kinase inhibitor (TKI) and second-line nivolumab monotherapy were reviewed. The progression-free survival (PFS), overall survival (OS), and objective response rate during axitinib therapy were retrospectively evaluated. Tumor responses were assessed according to the Response Evaluation Criteria in Solid Tumors version 1.1. Results: Seventeen patients were treated with third-line axitinib after failure of prior TKI and nivolumab. During a median follow-up of 8.15 months, eight (47.1%) and three (17.6%) patients showed disease progression and died, respectively. The median PFS was 12.8 months [95% confidence interval=(CI)4.08-21.7], the 1-year PFS rate was 51.3%, and the 1-year OS rate was 71.6%. The median magnitude of maximum changes of targeted lesions from baseline was –11.9% (95%CI=–36.1-0.44%). The objective response rate and disease control rates were 29.4% (n=5) and 94.1% (n=16), respectively. Univariate analysis for PFS showed a shorter PFS in patients with non-clear cell histopathological types or those with liver metastases (p-Value

Purpose The study aim was to externally validate a new predictive model for new baseline glomerular filtration rate post-nephrectomy among Japanese patients. Materials and methods Patients with renal tumors who underwent radical nephrectomy or robot-assisted partial nephrectomy at a single Japanese institution in 2000-2020 were retrospectively analyzed. New baseline glomerular filtration rate is defined as the final estimated glomerular filtration rate within postoperative 3-12 months. The correlation/bias/accuracy/precision of the equation was examined by comparing the calculated new baseline glomerular filtration rate with the observed rate. Results The study included 485 cases of radical nephrectomy, and 1030 cases of robot-assisted partial nephrectomy. The correlation/bias/accuracy/precision of the new equation predicting new baseline glomerular filtration rate were 0.86/-0.92/95.9/-5.65-3.62 in robot-assisted partial nephrectomy and 0.79/-1.02/87.8/-6.26-3.91 in radical nephrectomy, respectively. The fractional polynomial regression line approximated zero and its pointwise 95% confidence interval was considerably tight for the majority of both cohorts. The 95% confidence interval to discriminate new baseline glomerular filtration rates of ≥45 ml/min/1.73 m2 from receiver operating curves was 0.96 (0.95-0.97) and 0.89 (0.87-0.92) in robot-assisted partial nephrectomy and radical nephrectomy, respectively. Various preoperative factors including age, tumor size, complexity, body mass index, hypertension, and diabetes did not affect the predictive ability (correlation > 0.7) from the subgroup analysis. Conclusion The novel simple equation can accurately predict new baseline glomerular filtration rates after radical and robot-assisted partial nephrectomies in Japanese patients. This model will help physicians choose surgical treatments for renal tumors in daily clinical practice.

INTRODUCTION AND OBJECTIVE:Tumor enucleation technique in robot-assisted partial nephrectomy (RAPN) reportedly contributes to renal function preservation. Which tumors to and which part to utilize ...

INTRODUCTION AND OBJECTIVE:The use of antibiotics alters gut microbiota and has been reported to impact outcomes in immune checkpoint inhibitor (ICI) treatment in various types of cancer. We invest...

Sunitinib is listed as first-line therapy for non clear-cell renal cell carcinoma (RCC) in several guidelines. However, in the era of immunotherapy, there is an urgent need for updated evidence for the treatment of metastatic non clear-cell RCC. Herein, we present three cases of patients with type 2 papillary RCC who were effectively treated with cabozantinib. The first case was a 48-year-old woman who underwent radical nephrectomy (pT3aN0M0). The tumor relapsed in the retroperitoneum 3 months postoperatively and was unresponsive to first-line nivolumab plus ipilimumab (NI). After the use of cabozantinib, the tumors drastically shrunk in 2 weeks, and complete response was achieved 3 months later. The second case was a 55-year-old man who underwent radical nephrectomy (pT3aN2M1). Metastatic lesions continued to grow with first-line NI, and cabozantinib was used as the second-line therapy. All metastatic lesions had shrunk by 50% after 4 months. The third case was a 36-year-old man with multiple tumors in the left solitary kidney and iliopsoas muscle metastasis. First-line therapy with NI was ineffective; subsequently, second-line axitinib was used for 5 months, and the disease was identified as progressive. Cabozantinib was started as third-line therapy. Multiple tumors shrunk in 2 weeks. There is little evidence concerning the treatment of papillary RCC. We experienced low efficacy of NI for first-line treatment of papillary RCC for three patients who were subsequently effectively treated with cabozantinib. Cabozantinib inhibits multiple tyrosine kinase receptors, which may suppress aggressive tumor progression of type 2 papillary RCC. Cabozantinib or combination with immuno-oncological drugs may be a promising treatment option for papillary RCC.

Background: Tumor enucleation technique in robot-assisted partial nephrectomy (RAPN) reportedly contributes to renal function preservation. Which tumors and which part to utilize this technique hav...

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 2.4 mg/dL (male) or >2.0 mg/dL (female), calcium >12.0 mg/dL, platelet 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.