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This year in the U.S., it is estimated that 79,000 men and women will be diagnosed with kidney cancer. Clear cell renal cell carcinoma (ccRCC) is the most common subtype and is a leading source of morbidity and mortality. It is also commonly used to study new targeted molecular therapies. The resulting influx of phase III trial results has transformed ccRCC care. “We have an array of different treatment options, and the structure in which these treatments would be applied needed to have expert input. It is an exciting time for kidney cancer, and optimizing therapy now has immediate and meaningful impact into patients longevity,” guideline lead author W. Kimryn Rathmell, MD, PhD, said in an interview.
“The key developments are the emergence of targeted therapies in addition to immune therapies as well as combinations. The order of treatments matters and different patients will have different needs,” said Dr. Rathmell, professor of medicine at Vanderbilt University, Nashville, Tenn.
Dr. Rathmell highlighted the section of the guideline that discusses the need for robust tissue-based diagnosis, as well as active surveillance or cytoreductive nephrectomy. She also emphasized sections on differentiating courses of treatment and plans the use of International Metastatic RCC Database Consortium (IMDC) risk model.
Cytoreductive nephrectomy is an option for patients with one risk factor in which a significant majority of the tumor is within the kidney. The patients should also have good Eastern Cooperative Oncology Group (ECOG) performance status, and no brain, bone, or liver metastases.
Some with metastatic ccRCC can be offered active surveillance. Defining characteristics include favorable or immediate risk, few or no symptoms, a favorable histologic profile, a long interval between nephrectomy and onset of metastasis, or low burden of metastatic disease.
The guidelines also discuss the need to stratify patients within risk groups. Patients rated as intermediate or poor risk in the first line setting should be treated with two immune checkpoint inhibitors (ICI) or an ICI combined with a vascular endothelial growth factor tyrosine kinase inhibitor (VEGFR TKI). ICI combined with a VEGFR TKI can be appropriate for patients with favorable risk but requiring systemic therapy. Those with favorable risk or another medical condition can be offered monotherapy with a VEGFR TKI or an ICI. Another first-line option is high-dose interleukin 2, but there are no established criteria for determining which patients are most likely to benefit.
The guideline discusses second- or later-line therapy options, metastasis-directed therapies, and metastatic subsets including bone, brain, and sarcomatoid carcinomas.
The authors pointed out that significant disparity exists among patients with ccRCC, with some patients having much less access to health care because of racial, geographic, or socioeconomic inequities. There are also known biases within ccRCC care: Females and African Americans are less likely than are males to receive systemic therapy and more likely to receive no treatment; African Americans are less likely to receive systemic therapy; and non-Hispanic African Americans and Hispanics less often undergo cytoreductive nephropathy. African Americans with ccRCC have a pattern of worse survival outcomes than do Whites.
The recommendations cannot be applied to renal cell carcinoma with non-clear cell histology.
“It is important to be comfortable with all of the treatment options for ccRCC, because applying them in the best order, and with the most informed ability to determine efficacy, will have a real impact on patient survival. We are near a goal to offer cure to an increasing number of patients, so choosing therapies that offer that option when it may be possible is important, and when cure is not on the table, we can rationally select therapies that allow patients to have more time with their families, with side effects that are manageable,” Dr. Rathmell said.
The IMDC risk stratification methodology needs to be more widely used in routine practice, Dr. Rathmell said.
“The impact was not significant in patient care until we reached a point of having multiple competing options for treatment. The stakes are higher now, so using this resource is important until we get to the next level with biological classifications,” he said.
Similarly, since the stakes are so high, having an accurate diagnosis is important. Even experts in the field are fooled by imaging findings, and over- or undertreatment of patients has a major impact on outcomes. “This is a message that we need to share for establishing best practices,” he said.
“Just because we have agents, the time to use them is as important as the selection of agent. Similarly, for the cytoreductive nephrectomy issue, new data both clarified and caused some confusion. Not every patient has the luxury of a comprehensive and multidisciplinary tumor board, so we felt it was important to provide some guidance that help making those complex decisions,” Dr. Rathmell said.
Dr. Rathmell has no relevant financial disclosures.