Assistant Professor MD Anderson Cancer Center Houston, TX, United States
Background: RCC with S/R dedifferentiation are highly aggressive tumors associated with a poor prognosis but often respond to ICT. There remains uncertainly regarding the role of CN for mRCC patients with S/R who received ICT. Here, we report outcomes with ICT for patients with mRCC and S/R dedifferentiation by CN status.
Methods: We performed a retrospective review of mRCC patients with sarcomatoid, rhabdoid, or sarcomatoid plus rhabdoid dedifferentiation who received an ICT-based regimen at two tertiary cancer centers. ICT treatment duration (TD) and overall survival (OS) from ICT initiation were recorded. To address immortal time bias, we generated a time-dependent Cox regression model that included a time-dependent nephrectomy variable and five confounders identified by a directed acyclic graph.
Results: 157 patients with mRCC and S/R dedifferentiation received ICT. 85 patients had intermediate-risk and 57 had poor-risk IMDC. 118 patients underwent CN, and of those, 89 underwent upfront CN and 29 underwent a delayed CN. Nivolumab plus ipilimumab (41%) was the most common treatment followed by ICT monotherapy (28%). CN was not associated with ICT TD (HR 1.01, 95% CI 0.67-1.53), nor was CN associated with OS from ICT initiation (HR 0.79, 95% CI 0.47-1.33, p=0.37). In patients who underwent upfront CN compared to those who did not undergo CN, there was no association with ICT duration nor OS (HR 0.61, 95% CI 0.35-1.06, p=0.08).
Conclusions: In this multi-institutional cohort of mRCC with S/R dedifferentiation treated with ICT, CN was not associated with improved ICT treatment duration or superior OS when accounting for immortal time bias. Further studies which explore the impact of CN in this patient population are needed, including improved tools for patient selection in this setting.
