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Cytoreductive nephrectomy for metastatic renal cell carcinoma
Abstract
The incidence of renal cell carcinoma is increasing, with up to one-third of patients presenting with metastatic disease. Combination therapy is used to prolong survival in patients with metastatic renal cell carcinoma, which carries a poor prognosis. Although two pivotal phase 3 trials have demonstrated the efficacy of immunotherapy after cytoreductive nephrectomy for metastatic disease, for now, targeted therapy has replaced immunotherapy as the preferred systemic treatment in these patients. Two ongoing phase 3 trials are evaluating the role of cytoreductive nephrectomy prior to targeted therapy. Proper patient selection is paramount in achieving successful outcomes. © 2016, Millennium Medical Publishing, Inc. All rights reserved.
... Therefore, the clinical benefit of presurgical axitinib therapy might be limited to patients with low volume, manageable metastatic lesions. Two ongoing prospective, randomized, phase III trials (CARMENA and SURTIME) evaluating the role of cytoreductive nephrectomy prior to targeted therapy in metastatic RCC [21] will hopefully provide insight for difficult cases such as these. ...
Background:
Clinical benefits of presurgical axitinib therapy for renal cell carcinoma (RCC) extending into the inferior vena cava (IVC) remain unclear. We aimed to investigate surgical benefits and pathological antitumor effects of presurgical axitinib therapy for RCC with IVC thrombus.
Methods:
Of 56 consecutive RCC patients with IVC thrombus between January 1994 and December 2016, 41 patients who underwent radical nephrectomy (RN) were categorized as upfront RN (Upfront group) or presurgical axitinib followed by RN (Presurgical group). We retrospectively evaluated safety, radiologic tumor responses, and Ki-67 proliferation index before and after axitinib administration in the Presurgical group. Surgical outcomes, postoperative complications, and fibrosis within the IVC thrombus were compared between the Upfront and Presurgical groups.
Results:
The number of patients in the Upfront and Presurgical groups was 31 and 10, respectively. Major presurgical axitinib-related adverse events were grade 2 or 3 hypertension (50%). The median radiological tumor response in the renal tumor, IVC thrombus length, and IVC thrombus volume were -19%, -21 mm, and -54%, respectively. The fibrosis within the IVC thrombus was significantly higher in the Presurgical group (10%) than in the Upfront group (3.4%). The Ki-67 proliferation index was significantly decreased in RN specimens (7.3%) versus needle biopsy specimens (23%) in the Presurgical group. Blood loss and operative duration were significantly lower and shorter, respectively, in the Presurgical group than in the Upfront group.
Conclusions:
Presurgical axitinib therapy enhanced tumor reduction accompanied by fibrosis and may contribute to surgical risk reduction for selected patients.
The role for cytoreductive nephrectomy (CN) in the treatment of metastatic renal cell carcinoma (mRCC) has evolved with advancements in systemic therapy. During the cytokine-based immunotherapy era, CN provided a clear survival benefit and was considered standard of care in management of mRCC. The development of targeted systemic therapy directed at the vascular endothelial growth factor pathway altered the treatment paradigm and accentuated the importance of risk stratification in treatment selection. This article reviews the literature evaluating the benefit of CN during the evolution of systemic therapy and provides clinical recommendations for current utilization of CN in patients with mRCC.
Introduction
The objective of this study was to determine the reproducibility in a murine model of renal tumors of various histological strains that could be useful for investigating the response to target drugs.
Material and methods
Development and analysis of the “in vivo” model: tumor xenograft of renal cell carcinomas with Balb/c nude athymic mice. Nontumourous human renal tissue was implanted in the interscapular region of 5 mice, chromophobe renal cell carcinoma was implanted in 5 mice (which, after checking its growth, was prepared for implantation in another 10 mice) and Fuhrman grade 2 clear cell renal cell carcinoma (CCRCC) was implanted in 5 mice (which was also subsequently implanted in 10 mice).
We monitored the tumor size, onset of metastases and increase in size and number of tumors. When the size had reached a point greater than or equal to locally advanced or metastatic carcinoma, the animals were euthanised for a pathological and immunohistochemical study and a second phase of implantation.
Results
The subcutaneous xenograft of the healthy tissue did not grow. The animals were euthanised at 6 months and no renal tissue was found. The chromophobe renal cell carcinoma cells grew in the initial phase (100%); however, in the second phase, we observed a chronic lymphomonocyte inflammatory reaction and a foreign body reaction. The CCRCC grew at 5–8 months both in the first and second phase (100%), maintaining the tumor type and grade.
Conclusions
The model with athymic Balb/c nude mice is useful for reproducing CCRCC, with the same histological characteristics and aggressiveness as native human tumors, promoting the development of the second experimental phase.
Purpose:
The role of cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (mRCC) has become unclear since the introduction of targeted therapies (TT). We sought to evaluate contemporary utilization rates of CN and to examine the survival benefit of CN compared with non-CN patients treated with TT.
Methods:
We used the National Cancer Data Base to identify patients with clinical mRCC treated with TT between 2006 and 2013. The intervention of interest was CN. Multivariable logistic regression predicting receipt of CN was performed. Overall survival (OS) was examined using Cox regression models and incremental survival analyses were performed. Sensitivity analyses using propensity scores were conducted.
Results:
Of 15,390 patients treated with TT, 5,374 (35%) underwent CN between 2006 and 2013. Patients who were younger, privately insured, treated at an academic center, and had lower tumor stage and cN0 disease were more likely to undergo CN. The median OS of CN versus non-CN patients was 17.1 (95% CI, 16.3 to 18.0 months) versus 7.7 months (95% CI, 7.4 to 7.9 months; P < .001). In sensitivity analyses using propensity scores adjustment in addition to other available covariates, CN patients had a lower risk of any death (hazard ratio, 0.45; 95% CI, 0.40 to 0.50; P < .001). The survival benefit of CN was +0.7 and +3.6 months in patients who survived ≤ 6 and ≤ 24 months, respectively, versus no CN.
Conclusion:
CN is performed in three of 10 patients with mRCC who are receiving TT. Several patient and sociodemographic characteristics were associated with receipt of CN. When feasible, CN may offer an OS benefit when combined with TT.
The role of interleukin-2 based immunotherapy in advanced renal cell carcinoma is gradually expanding. Among patients who achieve significant responses to these regimens the subsequent development of isolated recurrences raises difficult management questions. We report 2 unusual cases of isolated recurrence in the remaining kidney following a sustained, complete response to interleukin-2 based adoptive immunotherapy. Both patients were treated with interleukin-2 based therapy following surgical resection of the primary renal tumor. The disease course of each patient is described and the literature is reviewed. Both patients were free of disease after relatively short-term followup. Surgery for patients with limited recurrence of renal cell carcinoma following an objective response to immunotherapy may, in select cases, be a reasonable treatment alternative.