PURPOSE: To provide recommendations for the management of patients with metastatic clear cell renal cell carcinoma (ccRCC).METHODS: An Expert Panel conducted a systematic literature review to obtain evidence to guide treatment recommendations.RESULTS: The panel considered peer-reviewed reports published in English.RECOMMENDATIONS: The diagnosis of metastatic ccRCC should be made using tissue biopsy of the primary tumor or a metastatic site with the inclusion of markers and/or stains to support the diagnosis. The International Metastatic RCC Database Consortium risk criteria should be used to inform treatment. Cytoreductive nephrectomy may be offered to select patients with kidney-in-place and favorable- or intermediate-risk disease. For those who have already had a nephrectomy, an initial period of active surveillance may be offered if they are asymptomatic with a low burden of disease. Patients with favorable-risk disease who need systemic therapy may be offered an immune checkpoint inhibitor (ICI) in combination with a vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI); patients with intermediate or poor risk should be offered a doublet regimen (no recommendation was provided between ICIs or an ICI in combination with a VEGFR TKI). For select patients, monotherapy with either an ICI or a VEGFR TKI may be offered on the basis of comorbidities. Interleukin-2 remains an option, although selection criteria could not be identified. Recommendations are also provided for second- and subsequent-line therapy as well as the treatment of bone metastases, brain metastases, or the presence of sarcomatoid features. Participation in clinical trials is highly encouraged for patients with metastatic ccRCC. Additional information is available at www.asco.org/genitourinary-cancer-guidelines

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co‐primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. The initial STOMP and ORIOLE trial reports suggested that metastasis-directed therapy (MDT) in oligometastatic castration-sensitive prostate cancer (omCSPC) was associated with improved treatment outcomes. Here, we present long-term outcomes of MDT in omCSPC by pooling STOMP and ORIOLE and assess the ability of a high-risk mutational signature to risk stratify outcomes after MDT. The primary end point was progression-free survival (PFS) calculated using the Kaplan-Meier method. High-risk mutations were defined as pathogenic somatic mutations within ATM, BRCA1/ 2, Rb1, or TP53. The median follow-up for the whole group was 52.5 months. Median PFS was prolonged with MDT compared with observation (pooled hazard ratio [HR], 0.44; 95% CI, 0.29 to 0.66; P value < .001), with the largest benefit of MDT in patients with a high-risk mutation (HR high-risk, 0.05; HR no high-risk, 0.42; P value for interaction: .12). Within the MDT cohort, the PFS was 13.4 months in those without a high-risk mutation, compared with 7.5 months in those with a high-risk mutation (HR, 0.53; 95% CI, 0.25 to 1.11; P = .09). Long-term outcomes from the only two randomized trials in omCSPC suggest a sustained clinical benefit to MDT over observation. A high-risk mutational signature may help risk stratify treatment outcomes after MDT.

Hypofractionated stereotactic body radiotherapy (SBRT) is an emerging noninvasive technique for the treatment of oligometastatic cancer. The use of small numbers of large doses, should in theory, achieve high rates of local control. The aim of this literature review is to critically assess the use of SBRT for the treatment of pulmonary metastases as judged by its effect on local control, survival, and toxicity. A systematic literature search was performed. Both single fraction stereotactic radiosurgery (SRS) and hypofractionated radiotherapy (SBRT) were considered individually. Thirteen institutions reported results regarding SBRT and seven institutions regarding SRS (a total of 29 publications). Outcomes, techniques, radiobiology, and the scientific rigor of the reported studies were analyzed. A wide range of techniques, doses, and dose fractionation schedules were found. Three hundred thirty-four patients with 564 targets were reported in the SBRT series. The 2-year weighted local control was 77.9%. The corresponding 2-year weighted overall survival was 53.7%, with a 4% rate of grade 3 or higher radiation toxicities. One hundred fifty-four patients with 174 targets were treated in the SRS series. The 2-year weighted local control was 78.6%. The corresponding weighted 2-year overall survival was 50.3%, with 2.6% rate of grade 3 or higher toxicities. There was insufficient evidence to recommend a consensus view for optimal tumor parameters, dose fractionation, and technical delivery of treatment. This indicates the need for further prospective studies. However, high local control rates that could potentially lead to a survival benefit justifies the consideration of stereotactic radiotherapy for patients with limited pulmonary oligometastases.