Mary E Hall1, Bimal Bhindi2,3, Amy N Luckenbaugh1, Aaron A Laviana1, Kelvin A Moses1, Raj Satkunasivam4,5, Brian Rini6, Zachary Klaassen7,8, Christopher J D Wallis9. 1. Department of Urology, Vanderbilt University Medical Center, A1302 Medical Center North, Nashville, TN, 37232-2765, USA. 2. Section of Urology, Department of Surgery, University of Calgary, Calgary, AB, Canada. 3. Southern Alberta Institute of Urology, Calgary, AB, Canada. 4. Department of Urology, Houston Methodist Hospital, Houston, TX, USA. 5. Center for Outcomes Research, Houston Methodist Hospital, Houston, TX, USA. 6. Department of Medical Oncology, Vanderbilt University Medical Center, Nashville, TN, USA. 7. Division of Urology, Medical College of Georgia At Augusta University, Augusta, GA, USA. 8. Georgia Cancer Center, Augusta, GA, USA. 9. Department of Urology, Vanderbilt University Medical Center, A1302 Medical Center North, Nashville, TN, 37232-2765, USA. wallis.cjd@gmail.com.
Abstract
PURPOSE: Cytoreductive nephrectomy (CN) has played a role in treatment of metastatic renal cell carcinoma (mRCC) since trials demonstrated a survival benefit in patients receiving CN with interferon. With the publication of CARMENA, it became clear that the value of CN may depend on the co-therapy administered. We sought to assess the benefit of CN in the era of modern immunotherapy (IO). METHODS: We performed a systematic review to identify studies assessing CN in patients receiving TT or IO. We extracted multivariable-adjusted hazard ratios for the association between CN and overall survival (OS) and performed random effects meta-analysis. We tested for effect modification by systemic therapy approach on the association between CN and OS by pooling the difference in logHR associated with CN for patients treated with TT versus IO. RESULTS: We identified three comparisons assessing CN in patients receiving TT or IO. Pooled analysis indicated improved survival with CN in both the TT (2 cohorts, pooled HR: 0.52, 95% CI 0.46-0.59; I2 = 80%) and IO era (2 cohorts; pooled HR: 0.28, 95% CI 0.16-0.49; I2 = 21%), with a stronger association in the IO era (p = 0.01; I2 = 0%). CONCLUSION: In observational datasets, we observed a larger survival benefit to CN in patients treated with IO-based regimens versus those treated with TT-based regimens. While the role of CN for patients receiving TT has recently been questioned, this suggests that the results of CARMENA do not necessarily preclude a benefit to CN when combined with IO-based regimens.
PURPOSE: Cytoreductive nephrectomy (CN) has played a role in treatment of metastatic renal cell carcinoma (mRCC) since trials demonstrated a survival benefit in patients receiving CN with interferon. With the publication of CARMENA, it became clear that the value of CN may depend on the co-therapy administered. We sought to assess the benefit of CN in the era of modern immunotherapy (IO). METHODS: We performed a systematic review to identify studies assessing CN in patients receiving TT or IO. We extracted multivariable-adjusted hazard ratios for the association between CN and overall survival (OS) and performed random effects meta-analysis. We tested for effect modification by systemic therapy approach on the association between CN and OS by pooling the difference in logHR associated with CN for patients treated with TT versus IO. RESULTS: We identified three comparisons assessing CN in patients receiving TT or IO. Pooled analysis indicated improved survival with CN in both the TT (2 cohorts, pooled HR: 0.52, 95% CI 0.46-0.59; I2 = 80%) and IO era (2 cohorts; pooled HR: 0.28, 95% CI 0.16-0.49; I2 = 21%), with a stronger association in the IO era (p = 0.01; I2 = 0%). CONCLUSION: In observational datasets, we observed a larger survival benefit to CN in patients treated with IO-based regimens versus those treated with TT-based regimens. While the role of CN for patients receiving TT has recently been questioned, this suggests that the results of CARMENA do not necessarily preclude a benefit to CN when combined with IO-based regimens.
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