The Changing Landscape of Management of Metastatic Renal Cell Carcinoma: Current Treatment Options and Future Directions

Salgia, Nicholas; Dara, Yash; Bergerot, Paulo Gustavo; Salgia, Meghan; Pal, Sumanta K.

doi:10.1007/s11864-019-0638-1

Cited by 27 publications

(16 citation statements)

References 18 publications

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“…Systemic immunotherapies, mainly with IFN and IL-2, have long been the only available treatment for mRCC, with modest improvement of oncological results, frequent severe toxicity, and persistent CR in less than 5-10% of patients receiving high-dose IL-2[ 3 , 4 , 6 , 7 ]. However, a better understanding of the pathogenesis of the ccRCC has determined a substantial evolution in the systemic treatment of mRCC, based on the use of therapeutic agents that affect specific targets of molecular pathways of RCC[ 3 , 4 , 8 ], and led to improved overall oncology outcomes, but with CR in less than 10% of patients[ 8 ]. As a consequence, potentially curative MSX is increasingly considered, whenever possible, in the context of multimodal treatments of mRCC, even though only a minority of patients, about 25% of those with metachronous metastases and probably less than 10% of those with synchronous metastases, seem to be eligible to local treatments, including surgical resection[ 9 , 10 ].…”

Section: Discussionmentioning

confidence: 99%

“…In patients with recurrence after nephrectomy, systemic immunotherapies, mainly with interferon (IFN) and interleukin-2 (IL-2), have been for long the only available treatment approaches, with modest improvement of oncological results, frequent severe toxicity, and with persistent complete responses (CR) in less than 5%-10%[ 3 , 4 , 6 , 8 ]. A better understanding of the pathogenesis of the RCC over the past decades has however determined a substantial evolution in the systemic treatment of mRCC, based on the use of therapeutic agents that affect specific targets of molecular pathways of RCC; these include multikinase inhibitors (sorafenib, sunitinib, pazopanib, axitinib, cabozantinib and lenvatinib); mammalian target of rapamycin (mTOR) inhibitors (everolimus and temsirolimus); bevacizumab, a monoclonal antibody against the vascular endothelial growth factor; and immunomodulatory agents, including inhibitors of immune checkpoint pathways (nivolumab, ipilimumab, atezolizumab, avelumab, pembrolizumab)[ 3 , 4 , 8 ]. Most of these agents, alone or in combination, have been shown to prolong survival and improve overall oncological results, although CR is achieved in less than 10% of patients with mRCC[ 8 ].…”

Section: Introductionmentioning

confidence: 99%

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Twenty-year survival after iterative surgery for metastatic renal cell carcinoma: A case report and review of literature

Raffele¹,

Mirarchi²,

Casadei³

et al. 2020

WJCC

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BACKGROUND The therapeutic approach of metastatic renal cell carcinoma (RCC) represents a real challenge for clinicians, because of the variable clinical course; the recent availability of numerous targeted therapies that have significantly improved overall oncological results, but still with a low percentage of complete responses; and the increasing role of metastasectomy (MSX) as an effective strategy to achieve a durable cure, or at least defer initiation of systemic therapies, in selected patients and in the context of multimodality treatment strategies. CASE SUMMARY We report here the case of a 40-year-old man who was referred to our unit in November 2004 with lung and mediastinal lymph nodes metastases identified during periodic surveillance 6 years after a radical nephrectomy for RCC; he underwent MSX of multiple lung nodules and mediastinal lymphadenectomy, with subsequent systemic therapy with Fluorouracil, Interferon-alpha and Interleukin 2. The subsequent clinical course was characterized by multiple sequential abdominal and thoracic recurrences, successfully treated with multiple systemic treatments, repeated local treatments, including two pancreatic resections, conservative resection and ablation of multiple bilobar liver metastases, resection and stereotactic body radiotherapy of multiple lung metastases. He is alive without evidence of recurrence 20 years after initial nephrectomy and sequential treatment of recurrences in multiple sites, including resection of more than 38 metastases, and 5 years after his last MSX. CONCLUSION This case highlights that effective multimodality therapeutic strategies, including multiple systemic treatments and iterative aggressive surgical resection, can be safely performed with long-term survival in selected patients with multiple metachronous sequential metastases from RCC.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Twenty-year survival after iterative surgery for metastatic renal cell carcinoma: A case report and review of literature

Raffele¹,

Mirarchi²,

Casadei³

et al. 2020

WJCC

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“…Moreover, clinical trials have shown that the combination of VEGFR tyrosine-kinase inhibitors (TKIs) and antibodies targeting PD-1 and PD-L1 present stronger activity when compared to TKI monotherapy [15].…”

Section: Introductionmentioning

confidence: 99%

Angiogenesis and Immunity in Renal Carcinoma: Can We Turn an Unhappy Relationship into a Happy Marriage?

Mennitto

Huber

Ratta

et al. 2020

JCM

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The frontline treatment options for patients with metastatic renal cell carcinoma (mRCC) are evolving rapidly since the approval of combination immunotherapies by the U.S. Food and Drug Administration (USFDA) and the European Medicines Agency (EMA). In particular, in combination with vascular endothelial growth factor receptor (VEGFR) tyrosine-kinase inhibitors (TKIs), immune checkpoint inhibitors (ICIs) have significantly improved the outcome of patients with mRCC compared to TKI monotherapy. Here, we review the preclinical data supporting the combination of ICIs with VEGFR TKIs. The VEGF-signaling inhibition could ideally sustain immunotherapy through a positive modulation of the tumor microenvironment (TME). Antiangiogenetics, in fact, with their inhibitory activity on myelopoiesis that indirectly reduces myeloid-derived suppressor cells (MDSCs) and regulatory T cells’ (Tregs) frequency and function, could have a role in determining an effective anti-tumor immune response. These findings are relevant for the challenges posed to clinicians concerning the clinical impact on treatment strategies for mRCC.

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“…Of note, collection of complete clinical and histopathological data of patients undergoing hepatic metastasectomy, especially in the early observation period, was partially not possible since patients, relatives, and even physicians in charge were deceased at the time of analysis. We believe, however, that it is essential to report on patient series with a comparatively rare surgical indication and that our findings could contribute to facilitating optimal patient selection and subsequent outcome in the future of a rapidly evolving therapeutic landscape [31].…”

Section: Discussionmentioning

confidence: 92%

Extended hepatic metastasectomy for renal cell carcinoma—new aspects in times of targeted therapy: a single-center experience over three decades

Beetz

Söffker

Cammann

et al. 2020

Langenbecks Arch Surg

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Purpose Despite the introduction of novel targeted therapies on patients with renal cell carcinoma, syn-and metachronous metastases (including hepatic lesions) are observed frequently and significantly influence patient survival. With introduction of targeted therapies as an effective alternative to surgery, therapeutical strategies in stage IV disease must be reevaluated. Methods This is a retrospective analysis of 40 patients undergoing hepatic resection of histologically confirmed RCC metastases at our institution between April 1993 and April 2017. Results The interval between nephrectomy for renal cell carcinoma and hepatic metastasectomy was 44.0 months (3.3-278.5). Liver resections of different extents were performed, including multivisceral resections. The median follow-up was 37.8 months (0.5-286.5). Tumor recurrence after resection of hepatic metastases occurred in 19 patients resulting in a median disease-free survival of 16.2 months (0.7-265.1) and a median overall survival of 37.8 months (0.5-286.5). Multivariable analysis identified multivisceral resection as an independent risk factor for disease-free and overall survival (p = 0.043 and p = 0.001, respectively). A longer interval between nephrectomy and hepatic metastasectomy was identified as an independent significant protective factor for overall survival (p < 0.001). Patients undergoing metastasectomy after introduction of sunitinib in Europe in 2006 (n = 15) showed a significantly longer overall survival (45.2 (9.1-111.0) versus 27.5 (0.5-286.52) months in the preceding era; p = 0.038). Conclusion Hepatic metastasectomy, including major and extended resections, on patients with metastasized renal cell carcinoma can be performed safely and may facilitate long-term survival. Due to significant morbidity and increased mortality, multivisceral resections must be weighed against other options, such as targeted therapy.

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The Changing Landscape of Management of Metastatic Renal Cell Carcinoma: Current Treatment Options and Future Directions

Cited by 27 publications

References 18 publications

Twenty-year survival after iterative surgery for metastatic renal cell carcinoma: A case report and review of literature

Twenty-year survival after iterative surgery for metastatic renal cell carcinoma: A case report and review of literature

Angiogenesis and Immunity in Renal Carcinoma: Can We Turn an Unhappy Relationship into a Happy Marriage?

Extended hepatic metastasectomy for renal cell carcinoma—new aspects in times of targeted therapy: a single-center experience over three decades

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