IKCS 2022: Cytoreductive Nephrectomy for Patients with Metastatic Sarcomatoid and/or Rhabdoid Renal Cell Carcinoma Treated with Immune Checkpoint Therapy

(UroToday.com) The 2022 IKCS North American annual meeting featured a presentation by Dr. Andrew Hahn discussing cytoreductive nephrectomy for patients with metastatic sarcomatoid and/or rhabdoid renal cell carcinoma (RCC) treated with immune checkpoint therapy. RCC with sarcomatoid or rhabdoid dedifferentiation are highly aggressive tumors associated with a poor prognosis but often respond to immune checkpoint therapy.

There remains uncertainty regarding the role of cytoreductive nephrectomy for metastatic RCC patients with sarcomatoid or rhabdoid histology who received immune checkpoint therapy. At the 2022 IKCS North American meeting, Dr. Hahn and colleagues reported outcomes with immune checkpoint therapy for patients with metastatic RCC and sarcomatoid or rhabdoid dedifferentiation by cytoreductive nephrectomy status.

This study included a retrospective review of metastatic RCC patients with sarcomatoid, rhabdoid, or sarcomatoid plus rhabdoid dedifferentiation who received an immune checkpoint therapy-based regimen at two tertiary cancer centers. Immune checkpoint therapy treatment duration and overall survival from immune checkpoint therapy initiation were recorded. To address immortal time bias, they generated a time-dependent Cox regression model that included a time-dependent nephrectomy variable and five confounders identified by a directed acyclic graph.

There were 157 patients with metastatic RCC and sarcomatoid or rhabdoid dedifferentiation that received immune checkpoint therapy. Specifically, 85 patients had intermediate-risk and 57 had poor-risk IMDC. One hundred and eighteen patients underwent cytoreductive nephrectomy, and of those, 89 underwent upfront cytoreductive nephrectomy and 29 underwent a delayed cytoreductive nephrectomy. Nivolumab plus ipilimumab (41%) was the most common treatment followed by immune checkpoint therapy monotherapy (28%):

metastatic RCC chart

Cytoreductive nephrectomy was not associated with immune checkpoint therapy treatment duration (HR 1.01, 95% CI 0.67-1.53), nor was cytoreductive nephrectomy associated with overall survival from immune checkpoint therapy initiation (HR 0.79, 95% CI 0.47-1.33). In patients who underwent upfront cytoreductive nephrectomy compared to those who did not undergo cytoreductive nephrectomy, there was no association with immune checkpoint therapy duration nor overall survival (HR 0.61, 95% CI 0.35-1.06). As follows is the adjusted survival curves for overall survival by cytoreductive nephrectomy status:

Cytoreductive nephrectomy color graph

As follows are the adjusted survival curves for treatment duration on immune checkpoint therapy by cytoreductive nephrectomy status:

adjusted survival curves cytoreductive nephrectomy

Dr. Hahn concluded his presentation by discussing cytoreductive nephrectomy for patients with metastatic sarcomatoid and/or rhabdoid RCC treated with immune checkpoint therapy with the following concluding statements:

  • In this multi-institutional cohort of metastatic RCC with sarcomatoid or rhabdoid dedifferentiation treated with immune checkpoint therapy, cytoreductive nephrectomy was not associated with improved immune checkpoint therapy treatment duration or superior overall survival when accounting for immortal time bias
  • Further studies which explore the impact of cytoreductive nephrectomy in this patient population are needed, including improved tools for patient selection in this setting

Presented by: Andrew Hahn, MD Anderson Cancer Center, Houston, TX

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2022 International Kidney Cancer Symposium (IKCS) North America, November 4-5, Austin, Texas, USA.