Efficacy And Toxicity Of Radiotherapy For Oligoprogression Of Metastatic Renal Cell carcinoma (mRCC)

Abstract

Recent studies highlight the utility of radiotherapy (RT) as an adjunct to systemic therapy in mRCC (Hammers et al ASCO GU 2020). In the setting of oligoprogression, there is scant data related to the effectiveness of RT, although it is routinely used in clinical practice. We sought to determine the safety and efficacy of RT for oligoprogression in patients (pts) receiving contemporary systemic regimens. From an institutional database, pts with mRCC receiving systemic therapy with FDA approved regimens were identified. Pts who received RT for 1-5 sites of progressive disease concurrently with systemic therapy were identified. Clinicopathologic characteristics were collected along with duration of therapy (DOT). DOT was further analyzed relative to the time of onset of systemic therapy with the a priori hypothesis that DOT prior to radiation (DOT[P]) would be shorter than the DOT subsequent to radiation (DOT[S]) – i.e., DOT[S]/DOT[P]>1.0. Of 399 pts with mRCC, 329 pts received VEGF-TKIs, 41 pts received checkpoint inhibitors (CPIs), and 29 pts received a combination of both. Of 89 pts who received RT, oligoprogression-directed RT was applied across 15 events in 11 pts. During these 15 events, 7 occurred while pts were receiving VEGF-TKIs and 8 when pts were receiving CPIs. The most frequently applied sites of RT sites included lung (7), bone (6), and lymph nodes (1), with a median of 1 site treated per patient (range, 1-2). The median dosing of RT was 30 Gy (range, 20-50 Gy) and median dose per fraction was 6 Gy (range, 3-12 Gy). The most common toxicity was fatigue, experienced in 20% of RT events. Median DOT[P] was 7.2 mos (range, 0.4-38.8 mos) and median DOT[S] was 9.5 mos (range, 0.2-21.4 mos), with a median DOT[S]/DOT[P] ratio of 0.55 (range, 0.01-23.8). At current, 7 patients remain on therapy following RT (5 of whom exhibit a DOT[S]/DOT[P]<0.2), necessitating prolonged follow-up which will be reported at the time of the meeting. RT to oligoprogressive mRCC lesions represents a viable approach, with encouraging data observed in this institutional cohort. Long-term follow up of patients still on therapy is necessary to better characterize duration of response following oligoprogression-directed RT. Further validation of this approach in randomized studies would be ideal.