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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. [ABSTRACT FROM AUTHOR]

• RAPN is effective in multiple allograft RCCs. • RAPN helps ensure renal function preservation postop. • RAPN has minimal postoperative complications. • RAPN has significant utility in complex allograft cases. • Our findings advance minimally invasive approaches in transplants. Partial nephrectomy (PN) is strongly recommended as nephron-sparing surgery for T1 renal tumors. Although there have been some reports of robot-assisted PN (RAPN) for solitary allograft renal tumors, only a few cases of RAPN for multifocal allograft renal tumors have been reported. Herein, we report a case of a patient who underwent RAPN for multifocal allograft renal cell carcinoma (RCCs). A 77-year-old male was diagnosed with 24- and 15-mm lesions in the middle portion of a right iliac fossa renal allograft. RAPN was performed using a transperitoneal approach 22 years after the kidney transplantation. The allograft renal artery was clamped, and the tumors were resected. Pathological examination revealed clear-cell RCC with negative surgical margins. There were no perioperative complications, and kidney function did not significantly change during surgery. RAPN is a feasible and effective treatment option for multiple allograft RCCs. The successful preservation of renal function coupled with minimal perioperative complications underscores the potential of RAPN. Our observations suggest that RAPN can be safely implemented in similar high-risk cases, offering a nephron-sparing alternative that might extend quality of life and reduce the need for dialysis in transplant recipients. [ABSTRACT FROM AUTHOR]

Objectives: Some "on-target" adverse events, such as hypertension and thrombocytopenia, have been reported to predict the antitumor efficacy of sunitinib as first-line therapy in patients with metastatic renal cell carcinoma (mRCC). However, it is unclear whether the degree of deterioration of renal function resulting from inhibition of the vascular endothelial growth factor signaling pathway can predict the antitumor efficacy of sunitinib. Therefore, the aim of the present study was to investigate whether the degree of deterioration of renal function can predict the antitumor efficacy of sunitinib in patients with mRCC.Materials and Methods: The present study retrospectively reviewed the medical records of patients with histologically confirmed mRCC who were treated with sunitinib for>3 months between March 2008 and September 2014. The degree of deterioration of the estimated glomerular filtration rate (eGFR) and the progression-free survival (PFS) and overall survival (OS) were compared.Results: The study included 62 patients with mRCC. The 62 study patients were divided into the following 2 subgroups according to whether they had a≥10% decrease in the eGFR during sunitinib therapy: Group 1 (≥10% decrease in the eGFR, N = 47 [76%]) and Group 2 (<10% decrease in the eGFR, N = 15 [24%]). PFS was significantly longer in Group 1 than in Group 2 (16mo vs. 6mo, P = 0.001). In multivariate analysis, the Memorial Sloan-Kettering Cancer Center risk group (favorable vs. intermediate, hazard ratio [HR] = 3.7; favorable vs. poor, HR = 14.7, P = 0.05), number of sunitinib courses (HR = 0.64, P<0.0001), baseline eGFR (HR = 0.96, P = 0.0057), and a≥10% decrease in the eGFR (HR = 3.2, P = 0.017) were identified as independent predictors of PFS. In addition, the OS was significantly longer in Group 1 than in Group 2 (not reached vs. 13mo, P = 0.034). In multivariate analysis, a≥10% decrease in the eGFR (HR = 0.98, P = 0.97) was not identified as an independent predictor of OS.Conclusions: The degree of deterioration of renal function might predict the antitumor efficacy of sunitinib in patients with mRCC. [ABSTRACT FROM AUTHOR]

• Sarcopenia, defined by a loss of skeletal muscles, was not associated with immune checkpoint inhibitor combination therapy for renal cell carcinoma. • Patients with increased subcutaneous fat tissues had favorable outcomes of combination therapy of immune checkpoint inhibitors and tyrosine kinase inhibitors. • Assessment of subcutaneous fat tissues can be used for patient selection and outcome prediction of first-line immune checkpoint inhibitor combination therapy for renal cell carcinoma. Data on the association between body composition and outcomes in patients with advanced renal cell carcinoma (RCC) treated with immune checkpoint inhibitor (ICI) combination therapy are limited. We retrospectively evaluated the clinical and radiographic data of 159 patients with advanced RCC, including 84 receiving ICI dual combination therapy (immunotherapy [IO]-IO group) and 75 receiving combinations of ICIs with tyrosine kinase inhibitors (TKIs) (IO-TKI group). Pretreatment computed tomography images were used to calculate body composition, including skeletal muscle mass and fat tissue area. Sarcopenia was defined based on skeletal muscle and psoas muscle indexes. The total fat index, subcutaneous fat index (SFI), and visceral fat index were also calculated. In the IO-IO treatment group, there was no significant association between body composition and survival or tumor response (P > 0.05). In the IO-TKI treatment group, the high SFI was associated with longer progression-free survival (hazard ratio, 2.70; P = 0.0091) and overall survival (hazard ratio, 26.0; P = 0.0246) than the low SFI, which remained significant after adjusting for covariates. Furthermore, in the high-SFI population, patients treated with IO-TKI therapy had longer progression-free survival (P = 0.0019) and overall survival (P = 0.0287) than those treated with IO-IO therapy, while there was no significant survival difference between the 2 treatment groups in the low-SFI population (P > 0.05). The SFI can be potentially utilized as an effective predictive and prognostic biomarker for first-line ICI combination therapy for advanced RCC. [ABSTRACT FROM AUTHOR]

Objective: 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).Patients and Methods: 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 were <1 mg/dl; (2) normalized: if pretreatment levels were ≥1.0 mg/dl and nadir levels within the initial three months of nivolumab therapy declined to <1.0 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.Results: 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, P < 0.0001) 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).Conclusions: 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. [ABSTRACT FROM AUTHOR]

Objectives: Evidence regarding the prognostic impact of immune-related adverse events (irAEs) remains limited in patients with metastatic renal cell carcinoma (mRCC) treated with nivolumab plus ipilimumab as a first-line systemic therapy. Thus, we investigated the association between irAE development and oncological outcomes during nivolumab plus ipilimumab therapy.Methods: We retrospectively evaluated 46 patients with mRCC who were treated with nivolumab plus ipilimumab at our hospital and its affiliated institutions. The associations between irAE development and progression-free survival (PFS), overall survival (OS), and objective response rates (ORRs) were assessed after treatment initiation.Results: A total of 60 irAEs occurred in 33 patients (72%), with 24 grade ≥ 3 irAEs developed in 20 patients (43%). PFS was significantly longer in patients with irAEs than that in patients without irAEs (P < 0.0001); however, OS was not different (P = 0.571). Multivariable analysis further revealed that the development of irAEs was an independent predictor of a longer PFS (hazard ratio: 0.18, P = 0.0005). A landmark analysis for the initial four cycles of nivolumab plus ipilimumab administration also showed that PFS was significantly longer in patients with irAEs than that in patients without irAEs (P = 0.0386). The ORRs were also higher in patients with irAEs (P = 0.0064). Furthermore, in 22 patients (48%) who discontinued nivolumab plus ipilimumab treatment, the 6-month PFS rate was 87%.Conclusion: This multi-institutional study showed that irAE development was significantly associated with PFS but not with OS in patients treated with nivolumab plus ipilimumab as a first-line therapy. The development of irAEs may be used as a surrogate prognostic marker for PFS in this treatment regimen. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]