In a single-center phase II study reported in The Lancet Oncology, Tang et al found that definitive radiotherapy in place of systemic therapy was feasible and effective for the treatment of oligometastatic renal cell carcinoma.
As stated by the investigators, “The role of radiotherapy in metastatic renal cell carcinoma is controversial. We prospectively tested the feasibility and efficacy of radiotherapy to defer systemic therapy for patients with oligometastatic renal cell carcinoma.”
Study Details
The study included 30 eligible patients who had undergone nephrectomy, had five or fewer metastatic lesions, and had received no more than one prior systemic therapy enrolled at The University of Texas MD Anderson Cancer Center between July 2018 and September 2020. All patients had clear cell histology.
Patients received stereotactic body radiotherapy (SBRT), defined as five or fewer fractions with ≥ 7 Gy per fraction, to all lesions without receiving systemic therapy; among those with disease location precluding SBRT, treatment consisted of hypofractionated regimens of 60 to 70 Gy in 10 fractions or 52.5 to 67.5 Gy in 15 fractions. Additional rounds of radiotherapy were allowed to treat subsequent sites of disease progression.
The co-primary endpoints were feasibility (defined as all planned radiotherapy completed with less than 7 days of unplanned breaks) and progression-free survival in the intention-to-treat population.
Feasibility and Efficacy Measures
All 30 patients completed at least one round of radiotherapy with less than 7 days of unplanned breaks, thus demonstrating feasibility of the radiotherapy approach. During the first round of radiotherapy, the longest unplanned delay was 3 days. Among 13 patients receiving a second round, the longest delay was 6 days (due to a winter storm).
At a median follow-up of 17.5 months (interquartile range [IQR] = 13.2–24.6 months), median progression-free survival was 22.7 months (95% confidence interval [CI] = 10.4 months–not reached), with a 1-year rate of 64% (95% CI = 48%–85%).
KEY POINTS
- Feasibility of the approach was demonstrated, with no patients having an unplanned delay in radiotherapy of more than 7 days.
- Median progression free survival was 22.7 months; median systemic therapy–free survival was not reached.
Among 13 patients with disease progression, 1 (8%) had local failure in a para-aortic lymph node treated with 52.5 Gy in 15 fractions and 12 developed new lesions, yielding a local control rate of 97% (95% CI = 90%–100%). The 12-month probability of freedom from new lesions was 67% (95% CI = 51%–87%). All patients were alive at data cutoff (12-month overall survival = 100%, 95% CI = 100%–100%).
A total of seven patients (23%) patients began systemic therapy, yielding a 1-year systemic therapy–free survival probability of 82% (95% CI = 70%–98%); median systemic therapy–free survival was not reached (95% CI = 16.1 months–not reached). A total of six patients (20%) initiated systemic therapy for disease progression judged not salvageable by definitive radiotherapy, including the one patient with local progression and five with a new lesion; one (3%) initiated systemic therapy due to provider choice with no evidence of disease progression.
Toxicity
Adverse events of grade ≥ 2 considered at least possibly related to treatment occurred in six patients (20%). Grade 3 or 4 adverse events considered at least possibly related to treatment occurred in three patients (10%). The two grade 3 events reported were back pain after 35 Gy in five fractions to a paraspinal muscle metastasis and muscle weakness after 24 Gy in one fraction to a vertebral metastasis; the one grade 4 event reported was hyperglycemia after 67.5 Gy in 15 fractions for a pancreatic metastasis. No treatment-related deaths occurred.
The investigators concluded, “Sequential radiotherapy might facilitate deferral of systemic therapy initiation and could allow sustained systemic therapy breaks for select patients with oligometastatic renal cell carcinoma.”
Chad Tang, MD, of the Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by the Anna Fuller Foundation, Cancer Prevention and Research Institute of Texas, and National Cancer Institute. For full disclosures of the study authors, visit thelancet.com.
