Current Approaches to the Treatment of Advanced or Metastatic Renal Cell Carcinoma

Abstract

The optimal management approach to advanced or metastatic renal cell cancer of the clear cell type continues to rapidly evolve. Risk stratification of patients into favorable-, intermediate-, and poor-risk categories is now routinely performed. In selected individuals with low-volume indolent disease, active surveillance may be an appropriate option. Cytoreductive nephrectomy and/or surgical metastasectomy may be also be considered for selected patients after evaluation by a multidisciplinary tumor board. Systemic frontline therapy options now include immune checkpoint inhibitor–based combination (IBC) therapies such as pembrolizumab/axitinib, nivolumab/ipilimumab, and avelumab/axitinib. With unusual exceptions, monotherapy with vascular growth factor receptor tyrosine kinase inhibitors or mTOR inhibitors are no longer appropriate options in the frontline setting. Despite the established efficacy of frontline IBC, most patients will ultimately require additional lines of therapy, and oncologists must think carefully when switching to another therapy, particularly in situations of drug intolerance or apparent disease progression. Systemic therapy options after IBC are generally tyrosine kinase inhibitor–based, and ongoing clinical trials will help optimize the treatment algorithm further. Despite many recent drug approvals for renal cell cancer (RCC), there remains a pressing need to identify new therapeutic targets. Finally, other systemic therapy or supportive care approaches must be considered for special patient populations such as those with poor performance status, end-organ dysfunction, brain metastases, or who have undergone metastasectomy.

Editorial comment from Dr Yuasa to Pathological complete response after nivolumab therapy following angiogenesis inhibitors in a patient with metastatic renal cell carcinoma

“…The indication and the role of metastasectomy for patients with metastatic renal cell cancer (RCC) remains unclear. 1 Various retrospective studies have reported the survival benefit resulting from the aggressive complete surgical removal in selected patients. 2 It is also true, however, that there is always selection bias and the results have to be interpreted with caution.…”

“…1 The European Society for Medical Oncology recommends that patient selection should be discussed within a multidisciplinary team. 1,3 The patients with good performance status, solitary or oligometastases, metachronous disease with disease-free interval >2 years, the absence of progression on systemic therapy, low or intermediate Fuhrman grade, and complete resection may be good candidates and have been associated with favorable outcome after metastasectomy. 1,3 In this issue of IJU Case Reports, Hagimoto et al reported a case of metastatic RCC who achieved a durable response using nivolumab as the fifth-line therapy following the firstline interferon-alpha, the second-line sunitinib, the third-line axitinib, and the fourth-line everolimus.…”

“…Various retrospective studies have reported the survival benefit resulting from the aggressive complete surgical removal in selected patients 2 . It is also true, however, that there is always selection bias and the results have to be interpreted with caution 1 . To date, there have been no randomized controlled trials that have evaluated the clinical benefit of the metastasectomy 1 .…”

“…It is also true, however, that there is always selection bias and the results have to be interpreted with caution 1 . To date, there have been no randomized controlled trials that have evaluated the clinical benefit of the metastasectomy 1 . The European Society for Medical Oncology recommends that patient selection should be discussed within a multidisciplinary team 1,3 .…”

“…To date, there have been no randomized controlled trials that have evaluated the clinical benefit of the metastasectomy 1 . The European Society for Medical Oncology recommends that patient selection should be discussed within a multidisciplinary team 1,3 . The patients with good performance status, solitary or oligometastases, metachronous disease with disease‐free interval >2 years, the absence of progression on systemic therapy, low or intermediate Fuhrman grade, and complete resection may be good candidates and have been associated with favorable outcome after metastasectomy 1,3 …”