High dose, focused radiotherapy good option for RCC when surgery is not possible

In patients with renal cell carcinoma (RCC) who were not candidates for surgery, stereotactic ablative radiotherapy (SABR) was well tolerated, effective, and had good preservation of renal function, according to results of a pooled analysis published in Cancer.

The study, led by Shankar Siva, PhD, of the Peter MacCallum Cancer Centre at the University of Melbourne in Australia, pooled patient data from nine institutions across Germany, Australia, the United States, Canada, and Japan to evaluate SABR in patients with RCC.

Although surgery is the standard of care for primary RCC, some patients are not good candidates or may refuse surgery. An emerging treatment option for patients with RCC is SABR, a precise delivery of ablative therapeutic radiation delivered in a single or a few outpatient sessions. Currently, SABR is accepted for treating malignancies of the lung, liver, and spine.

Institutions with published data (prospective or retrospective) regarding SABR for the treatment of primary RCC were invited to contribute to the analysis conducted by the International Radiosurgery Oncology Consortium for Kidney (IROCK). The clinical endpoints analyzed were overall survival, progression-free survival (PFS), local control (LC), distant control, and cancer-specific survival (CSS).

A total of 223 patients from nine institutions were included in the meta-analysis; 118 patients received single-fraction SABR and 105 received multi-fraction SABR. The mean age of patients was 72 years, 69.5% were men, and 87.4% had an Eastern Cooperative Oncology Group (ECOG) performance of 0 or 1. The mean follow-up was 2.6 years, the mean time between initial diagnosis and treatment with SABR was 28.1 months, and clear cell RCC was the most common histologic subtype (86.2%).

In general, patients who received single-fraction SABR were younger, had better performance status, and had smaller tumors.

At two years and four years LC was 97.8%. At two years, CSS, overall survival, and PFS were 95.7%, 82.1%, and 77.4%, respectively; they were 91.9%, 70.7%, and 65.4%, respectively, at four years.

Eighteen patients had disease recurrence. Three had a local recurrence, and 16 had a distant recurrence. One patient had both local and distant recurrence as the first sites of failure. All local failures occurred within two years, and there was no difference between single-fraction and multi-fraction SABR.

Therapy was generally well-tolerated; 86 patients had at least grade 1 toxicity, and 83 had grade 1 or 2 toxicity only. The only difference in toxicity profile between the groups was a higher rate of nausea in the single-fraction cohort (17.0% vs 6.8%).

Overall, renal function was preserved after SABR, the mean (± standard deviation) estimated glomerular filtration rate at baseline was 59.9±21.9 mL/min, and it decreased by 5.5±13.3 mL/min. There was no difference in mean change in renal function between cohorts. During the study, six patients (2.7%) underwent dialysis.

It is of interest to note that in this analysis, single-fraction SABR was associated with better PFS and CSS than multi-fraction regimens. The investigators offered some possible explanations, but they feel it should be confirmed with a randomized trial directly comparing single- and multi-fraction approaches.

The researchers noted that the study had some limitations. Merging data from multiple institutions introduced bias because of variations in data collection. In addition, retrospective reporting of adverse events may lead to underreporting, and not all data requested could be collected from all patients.

The authors point out that while prospective, randomized trials and comparative-effectiveness studies are needed to further evaluate this ablative modality in the treatment of RCC, “SABR is well tolerated and locally effective for treating patients who have primary renal cell carcinoma and has an acceptable impact on renal function.”

To read more about this study, click here.