Very late relapse metastatic renal cell carcinoma: Characteristics and outcomes of patients with a disease-free interval of greater than 10 years.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 541-541 ◽  
Author(s):  
John Ross Kucharczyk ◽  
Marc Ryan Matrana

541 Background: Late relapse of renal cell carcinoma (RCC), or presentation with metastatic disease after a disease free interval of >5 years, is a known behavior of RCC. Recent studies have concluded that late relapse RCC is associated with favorable patient and tumor characteristics as well as an improved response to targeted therapy (TT) when compared to early relapse patients. Less studied are patients who relapse very late, with a disease free interval >10 years. We evaluated the clinical characteristics, response to TT and outcomes of this unique population. Methods: We collected data on consecutive patients with metastatic RCC who had disease recurrence >10 years after nephrectomy. Outcomes were tabulated using basic statistical techniques; adverse events were graded using CTCAE v4.0 and treatment response graded using RECIST 1.1. Results: Among 720 RCC patients treated with nephrectomy, we identified 8 who developed recurrent metastatic disease after a >10 year disease free interval (median: 16.7 years; range: 11.7-29.0). All patients presented with clear cell histology; 88% favorable IMDC and MSKCC risk subgroups. All patients presented with multiple metastases, with the most common sites being lung and bone, while unusual sites such as soft tissue, pancreas and adrenal were also detected. Median time on first-line TT was 20.1 months; 4, 3 and 1 patient received pazopanib (best response: PR), sunitinib (best response: SD) and cytokine (best response: PD) as first-line therapy, respectively. The median number of sequential TT received was 2 (range: 1-4). Four patients died, median OS was 46.6 months (range: 9.8-129), 3 year OS rate was 63%. Common adverse events to TT were fatigue (88%), anorexia (38%) and diarrhea (50%), 94% grade 1/2. Conclusions: Patients are at life-long risk of recurrence after resection of localized RCC as it is possible for metastases to present >10 years after resection. Patients in our study had relatively large metastatic burden and a wide distribution of metastatic sites, insights that may be useful clinically during surveillance. Our cohort demonstrated favorable prognostic features and outcomes when compared to historical controls.

2009 ◽  
Vol 125 (2) ◽  
pp. 474-482 ◽  
Author(s):  
Daniela Wuttig ◽  
Barbara Baier ◽  
Susanne Fuessel ◽  
Matthias Meinhardt ◽  
Alexander Herr ◽  
...  

Neurosurgery ◽  
1983 ◽  
Vol 13 (4) ◽  
pp. 430-434 ◽  
Author(s):  
K. Killebrew ◽  
M. Krigman ◽  
M. S. Mahaley ◽  
J. H. Scatliff

Abstract We report a patient with renal cell carcinoma metastatic to the left trigone, which mimicked an intraventricular meningioma. The metastasis was recognized 13 years after removal of the primary tumor, a longer disease-free interval than any previously reported cases with brain metastases of renal cell carcinoma. The patient is now free of disease 4 years after resection and 17 years after the discovery of the primary tumor. Metastatic disease should be considered in all patients with prior resection of renal cell carcinoma who experience the onset of neurological disease, even after a prolonged disease-free interval. Long term survival is observed after the resection of solitary metastases, particularly if these appear after a prolonged disease-free interval.


2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A205-A206
Author(s):  
Vasilii Bushunow ◽  
Leonard Appleman ◽  
Roby Thomas

BackgroundImmune checkpoint inhibitors (ICI) are first-line therapy for tumors including metastatic renal cell carcinoma (mRCC). Use of ICI is complicated by diverse immune-related adverse events (irAEs), which can add significant morbidity but are also associated with improved efficacy of therapy.1 2 Risk factors for development of irAE are still poorly understood. We hypothesized that patients with mRCC treated with ICI as first-line therapy have higher rates of developing irAE’s than patients previously treated with other therapies.MethodsWe conducted a single-institution, retrospective medical record review of patients with mRCC treated with immune-checkpoint inhibitors from March 2011 through April 15, 2020. We identified therapy duration, and presence, severity, and treatment of adverse events. We defined overall survival as time elapsed from date of diagnosis until death or until completion of study. We classified severity of adverse events according to CTCAE guidelines. Statistical methods included univariate Cox proportional hazards and logistic regression models, and Kaplan-Meier curves were plotted for subgroups.ResultsA total of 64 unique charts were reviewed. 18 patients (28%) of patients were treated with ICI as first-line therapy. 28 patients (44%) experienced immune-related adverse events with a total of 40 irAE’s identified. Most irAE were grade I-II (78%), with 7 (17%) grade III and 1 (2.4%) grade IV irAE’s. Most common sites were skin (29%), thyroid (20%) and gastrointestinal (15%). Patients with irAE had increased survival compared to those who did not have irAE (median survival not reached, vs 139 weeks, p=0.0004) (figure 1). This finding remained after excluding patients who had only experienced dermatologic irAE (median survival not reached in non-derm irAE subgroup, vs 144 weeks for dermatologic or no irAE, p=0.01) (figure 2). Patients treated with ICI as first line therapy had greater rates of developing irAE (72%) than those who had prior therapies (32%) (OR 5.4; p = 0.006). There was no association between histology type and rate of irAE.Abstract 191 Figure 1Kaplan-Meier survival plot of OS between patients with any irAE and those without any irAEAbstract 191 Figure 2Kaplan-Meier survival plot of OS between patients with non-dermatologic irAE and those without any irAE or only dermatologic irAEConclusionsThe development of irAE’s in patients with mRCC treated with ICI is associated with longer survival. This study joins the growing body of evidence showing that presence of irAE’s is associated with increased treatment efficacy. Use of ICI as first-line therapy is associated with higher risk of irAE. Given growing use of ICI as first-line therapy, further study to predict onset and severity of irAE’s is required.AcknowledgementsHong Wang, PhD, for statistical support.Ethics ApprovalThis study was approved by the University of Pittsburgh Institutional Review Board. Approval number STUDY19100386.ReferencesElias R, Yan N, Singla N, Levonyack N, Formella J, Christie A, et al. Immune-related adverse events are associated with improved outcomes in ICI-treated renal cell carcinoma patients. J Clin Oncol 2019;37(7):S645.Verzoni E, Cartenì G, Cortesi E, et al. Real-world efficacy and safety of nivolumab in previously-treated metastatic renal cell carcinoma, and association between immune-related adverse events and survival: the Italian expanded access program. J Immunother Cancer 2019;7(1):99.


2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 666-666
Author(s):  
Ilya Tsimafeyeu ◽  
Pavel Borisov ◽  
Ahmed Abdelgafur ◽  
Roman Leonenkov ◽  
Olga Novikova ◽  
...  

666 Background: Targeted therapy with axitinib resulted in a greater objective response rate and prolonged progression-free survival (PFS) compared to sorafenib in patients with previously treated metastatic renal cell carcinoma (mRCC) in AXIS study. 75% of patients had intermediate and poor IMDC prognosis. In this phase 2 study, we assessed the activity of axitinib in mRCC patients with favourable risk and a history of prior VEGFR-directed therapy. Methods: Patients were required to have clear cell mRCC, favourable risk according to IMDC criteria, and to have received first-line treatment with sunitinib or pazopanib. Prior treatment with other agents was not permitted. The primary endpoint of the study was PFS. Additional endpoints included response rate, safety, and overall survival (OS). Results: A total of 21 patients were enrolled, 62% of whom were male. Median age was 59 years. 11 (52%) patients had 2 and more metastatic sites. 67% and 33% of patients received first-line sunitinib or pazopanib with a median PFS of 17 months (95% CI 14-20). After a median follow-up of 16 months, the median PFS and OS was not yet reached. The current study did achieve its primary endpoint based on the 10-month PFS of 71.4%. 3 (14.3%) patients had confirmed partial responses and 14 (66.7%) had stable disease. No grade 3/4 treatment-related adverse events were observed; the most frequent grade 1/2 treatment-related adverse events were hypertension (57.1%), fatigue (57.1%), GI (33%) and skin (19%) toxicity. 7 patients had dose-escalation of axitinib and 1 patient had dose reduction. Conclusions: The encouraging PFS and favorable safety profile observed in FavorAx study support the administration of axitinib in mRCC patients with favourable IMDC risk and a history of prior sunitinib or pazopanib. Clinical trial information: NCT02700568.


2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Xiaoteng Yu ◽  
Bing Wang ◽  
Xuesong Li ◽  
Gang Lin ◽  
Cuijian Zhang ◽  
...  

Objective. To investigate the efficacy of surgery in the treatment of metastatic renal cell carcinoma (mRCC) and to identify prognostic factors. Methods. A single center retrospective study of 96 patients with mRCC from December 2004 to August 2013. Results. The median follow-up time was 45 months. Thirty-one (32.3%) of the patients received complete resection of metastatic sites, 11 (11.5%) of the patients underwent incomplete resection of metastatic sites, and 54 (56.3%) of the patients received no surgery. In the univariate Kaplan-Meier analysis, the median overall survival times of the three groups were 52 months, 16 months, and 22 months, respectively (p<0.001). The difference in the overall survival time was statistically significant between complete resection and no surgery groups (HR = 0.43, p=0.009), while there was no significant difference between the incomplete metastasectomy and no surgery groups (HR = 1.80, p=0.102). According to the multivariate Cox regression analysis, complete metastasectomy (HR = 0.49, p=0.033), T stage > 3 (HR = 1.88, p=0.015), disease free interval <12 months (HR = 2.34, p=0.003), and multiorgan involvement (HR = 2.00, p=0.011) were significant prognostic factors. Conclusion. In the era of targeted therapy, complete metastasectomy can improve overall survival. Complete metastasectomy, T stage > 3, disease free interval <12 months, and multiorgan involvement are independent prognostic factors.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16576-e16576
Author(s):  
Amit Rauthan ◽  
Poonam Patil ◽  
Nitin Yashas Murthy ◽  
SP Somashekhar ◽  
Shabber Zaveri ◽  
...  

e16576 Background: Immuno-oncology (IO) agents in combination with oral tyrosine kinase inhibitors (TKIs) has become a standard first line therapy in metastatic renal cell carcinoma (mRCC) patients. Various combinations such as pembrolizumab + axitinib, avelumab + axitinib, nivolumab + cabozantinib and pembrolizumab + lenvatinib have all shown better results than sunitinib. There is very limited data about this from India. Methods: This is a single center, retrospective study of mRCC patients, who received first line treatment was nivolumab or pembrolizumab with axitinib or lenvatinib. The endpoints were objective response rate (ORR), progression free survival (PFS), overall survival (OS) and adverse events (AE). Results: Between Jan 2019 to Jan 2021, 22 patients were treated with IO + TKI combination. 12 patients received axitinib, and 10 lenvatinib. Age range was 35 to 78 years with 18 males and 4 females. IMDC risk stratification showed 3 favorable (13.6%), 13 intermediate (59%) and 6 poor risk (27.2%) patients. 2 patients (9%) achieved complete response(CR), 13 (59%) partial response (PR), 4 (18.2%) had stable disease and 3 (13.6%) progressed. The ORR was 68%. Median PFS was 22 months (1 month- 24 months). OS at 1 year was 92%, and median OS was not reached. Grade 3/4 immune related adverse events (AEs) were seen in 3 (14.2%) patients (1 colitis,1 pneumonitis,1 encephalitis), for whom the IO was discontinued. TKI related grade 3/4 AEs were seen in 8 patients (38%), and were managed with dose reductions. Conclusions: Combination IO + TKI is a very effective first line therapy in mRCC. An ORR of 68%, median PFS of 22 months and 1 year OS of 92% is the best we have seen in our patients. The efficacy of this combination is seen in all IMDC subgroups. The combination is well tolerated, and the TKI AEs are comfortably managed with dose reduction. IO combinations should be preferred over single agent TKIs (sunitinib or pazopanib) as first line therapy.


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