Cytoreductive Nephrectomy for Patients with Metastatic Sarcomatoid and/or Rhabdoid Renal Cell Carcinoma Treated with Immune Checkpoint Therapy Journal Article


Authors: Hahn, A. W.; Kotecha, R. R.; Viscuse, P. V.; Pieretti, A. C.; Wiele, A. J.; Jonasch, E.; Lee, C. H.; Gao, J.; Zurita, A. J.; Shah, A. Y.; Campbell, M. T.; Sharma, P.; Motzer, R. J.; Russo, P.; Wood, C. G.; Tannir, N. M.; Voss, M. H.; Karam, J. A.; Hakimi, A. A.; Msaouel, P.
Article Title: Cytoreductive Nephrectomy for Patients with Metastatic Sarcomatoid and/or Rhabdoid Renal Cell Carcinoma Treated with Immune Checkpoint Therapy
Abstract: Background: Renal cell carcinoma (RCC) with sarcomatoid and/or rhabdoid (S/R) dedifferentiation is a highly aggressive tumor with a poor prognosis. Immune checkpoint therapy (ICT) has shown significant treatment efficacy in this subtype. There remains uncertainly regarding the role of cytoreductive nephrectomy (CN) for patients with metastatic RCC (mRCC) with S/R who received ICT. Objective: Here, we report the outcomes with ICT for patients with mRCC and S/R dedifferentiation by CN status. Design, setting, and participants: A retrospective review was conducted of 157 patients with sarcomatoid, rhabdoid, or sarcomatoid plus rhabdoid dedifferentiation who received an ICT-based regimen at two cancer centers. Intervention: CN performed at any time point; nephrectomy with curative intent was excluded. Outcome measurements and statistical analysis: ICT treatment duration (TD) and overall survival (OS) from ICT initiation were recorded. To address the immortal time bias, a time-dependent Cox regression model was generated that accounted for confounders identified by a directed acyclic graph as well as a time-dependent nephrectomy variable. Results and limitations: A total of 118 patients underwent CN, and of them, 89 underwent upfront CN. The results did not contradict the supposition that CN does not improve ICT TD (hazard ratio [HR] 0.98, 95% confidence interval [CI] 0.65–1.47, p = 0.94) or OS from ICT initiation (HR 0.79, 95% CI 0.47–1.33, p = 0.37). In patients who underwent upfront CN compared with those who did not undergo CN, there was no association with ICT duration or OS (HR 0.61, 95% CI 0.35–1.06, p = 0.08). A detailed clinical summary of 49 patients with mRCC and rhabdoid dedifferentiation is provided. Conclusions: In this multi-institutional cohort of mRCC with S/R dedifferentiation treated with ICT, CN was not significantly associated with improved TD or superior OS when accounting for the lead time bias. There appears to be a subset of patients who derive meaningful benefit from CN, so improved tools for stratification prior to CN are needed to optimize outcomes. Patient summary: Immunotherapy has improved outcomes for patients with metastatic renal cell carcinoma (mRCC) who have sarcomatoid and/or rhabdoid (S/R) dedifferentiation, which is an aggressive and uncommon feature; yet, the utility of a nephrectomy in this setting is unclear. We found that nephrectomy did not significantly improve survival or time on immunotherapy for these patients with mRCC and S/R dedifferentiation; yet, there may be a subset of patients who benefit from this surgical approach. © 2023 European Association of Urology
Keywords: adult; cancer survival; controlled study; treatment outcome; aged; major clinical study; overall survival; cancer combination chemotherapy; monotherapy; treatment duration; follow up; cytoreductive surgery; phenotype; ipilimumab; cohort analysis; retrospective study; renal cell carcinoma; kidney neoplasms; nephrectomy; confidence interval; proportional hazards model; kidney tumor; carcinoma, renal cell; multicenter study; hazard ratio; neoplasms, second primary; sarcomatoid; rhabdoid tumor; metastatic renal cell carcinoma; clinical outcome; cytoreductive nephrectomy; procedures; rhabdoid; nivolumab; very elderly; humans; human; male; female; article; cytoreduction surgical procedures; second primary neoplasm; checkpoint inhibitor therapy; carmena; confounding bias
Journal Title: European Urology Focus
Volume: 9
Issue: 5
ISSN: 2405-4569
Publisher: Elsevier B.V.  
Date Published: 2023-09-01
Start Page: 734
End Page: 741
Language: English
DOI: 10.1016/j.euf.2023.02.008
PUBMED: 36863962
PROVIDER: scopus
PMCID: PMC10460829
DOI/URL:
Notes: Source: Scopus
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MSK Authors
  1. Carol Lee
    25 Lee
  2. Padmanee Sharma
    9 Sharma
  3. Jianjiong Gao
    132 Gao
  4. Abraham Ari Hakimi
    323 Hakimi