Phase II trial of stereotactic ablative radiation (SAbR) for oligometastatic kidney cancer.

Abstract

311 Background: Stereotactic ablative radiotherapy (SAbR) is a promising treatment option for selected oligometastatic renal cell carcinoma (RCC) patients that can provide longitudinal disease control while preserving quality of life. Retrospective data have shown a local control (LC) rate greater than 90% and longitudinal disease control of over a year without systemic therapy. However, prospective validation of SAbR for oligometastatic RCC is lacking. In this prospective phase II single arm trial, we evaluated the impact of SAbR on freedom from systemic therapy (FFST). Methods: Treatment naïve patients with RCC confirmed by pathology and radiographic evidence of three or fewer extracranial metastases received SAbR with curative intent to all measurable sites of disease. Follow-up included radiographic imaging at three-month intervals to assess disease control. The primary endpoint was FFST defined as time from SAbR to the initiation of systemic therapy. Secondary endpoints included LC, modified progression-free survival (mPFS) (time from first SAbR to progression not amenable to further SAbR), PFS on subsequent systemic therapy, cancer-specific survival (CSS), overall survival (OS), toxicity and health-related quality of life (QOL) indices as measured with EQ-5D-5L and FACT-G. A Wilcoxon signed-rank test was used to evaluate the QOL indices. Results: The trial completed accrual with the enrollment of 23 patients who received SAbR to a total of 38 sites. At a median follow-up of 12 months (interquartile range 1.8-16), 1-year FFST was 87% (95% CI: 56%-96%). The 1-year mPFS was 79% (95% CI:49%-93%), while the median mPFS has not yet been reached. Three patients had disease progression at individual time points of 3.5, 4.0, and 12 months. One of these patients developed brain metastases that were controlled with gamma knife radiosurgery without initiating systemic therapy. The LC, CSS, and OS were 100% (38/38), 100% (23/23), and 95% (22/23), respectively. When compared to baseline, no significant decline in QOL was detected. Three patients experienced treatment-related grade 1 toxicity; no ≥grade 2 toxicities were reported. One patient died of an unrelated cause. Conclusions: SAbR is a safe and effective treatment for oligometastatic RCC that can provide longitudinal disease control and preserve quality of life. These data support further evaluation of SAbR for oligometastatic RCC in a randomized study. Clinical trial information: NCT02956798 .

Beyond the Knife in Renal Cell Carcinoma: A Systematic Review—To Ablate or Not to Ablate?

“…In systemic combination studies, reported grade ≥ 3 toxicity ranged from 0% to 55% (Table 1a,b). [47][48][49][50][51][52][53][54][55][56][57][58][59][60]. (b) Thermal ablation studies in metastatic extracranial RCC-cryotherapy and radiofrequency ablation [46,[61][62][63].…”

“…ROBINS-I tool for assessment of bias in nonrandomised studies. Abstracts were not able to be assessed[48,[50][51][52][53][54][55][56][57][58][59][60][61][62][63][65][66][67][68].…”

The Emerging Role of Radiation Therapy in Renal Cell Carcinoma

“…This approach was described in a retrospective study where 30% of patients received two or more courses of SAbR to additional sites of metastatic disease [42]. The first phase II trial demonstrating the efficacy of sequential SAbR in the control of systemic therapy naïve oligometastatic RCC reported a one-year progression-free interval of 82.6%, and a one-year freedom from systemic therapy of 91.3% with no measured decline in patient-reported quality of life [44,49]. Tang et al published a prospective feasibility phase II study where subsequent sites of progression were allowed to be treated with SAbR and found a median PFS of 22.7 months with acceptable toxicity [43].…”