Modern advances in systemic and localized therapies for patients with renal cell carcinoma (RCC) have significantly improved patients' outcomes. If disease progression occurs after initial treatment, clinicians often have multiple options for a first salvage therapy. Because salvage and initial treatments both may affect overall survival time, and they may interact in unanticipated ways, there is a growing need to determine sequences of initial therapy and first salvage therapy that maximize overall survival while maintaining quality of life. The complexity of this problem grows if a second salvage therapy must be chosen for patients with treatment-resistant disease or a second progression occurs following first salvage. On November 9, 2023, a think tank was convened during the International Kidney Cancer Symposium (IKCS) North America to discuss challenges in accounting for postprogression therapies when estimating overall survival (OS) time based on randomized controlled trial (RCT) data. The present manuscript summarizes the topics discussed, with the aim to encourage adoption of statistical methods that account for salvage therapy effects to obtain scientifically valid OS estimation. We highlight limitations of traditional methods for estimating OS that account for initial treatments while ignoring salvage therapy effects and discuss advantages of applying more sophisticated statistical methods for estimation and trial design. These include identifying multistage treatment strategies, correcting for confounding due to salvage therapy effects, and conducting Sequentially Multiple Assignment Randomized Trials (SMARTs) to obtain unbiased comparisons between multistage strategies. We emphasize the critical role of patient input in trial design, and the potential for information technology (IT) advances to support complex trial designs and real-time data analyses. By addressing these challenges, future RCTs can better inform clinical decision-making and improve patient outcomes in RCC.
Urologic oncology. 2024 Nov 04 [Epub ahead of print]
Stephanie A Berg, Salvatore La Rosa, Tian Zhang, Phillip M Pierorazio, Laurence Albiges, Kathryn E Beckermann, Matthew T Campbell, Maria I Carlo, Katie Coleman, Daniel J George, Daniel M Geynisman, Ritchie Johnson, Eric Jonasch, Jodi K Maranchie, Bradley A McGregor, Daniel D Shapiro, Eric A Singer, Brian M Shuch, Walter M Stadler, Nizar M Tannir, Yousef Zakharia, Ulka N Vaishampayan, Peter F Thall, Pavlos Msaouel
Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. Electronic address: ., Kidney Cancer Association, Houston, TX, USA., Division of Hematology and Oncology, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA., Division of Urology, Department of Surgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA., Institut Gustave Roussy, Paris, France., Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA., Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Chromophobe and Oncocytic Tumor Alliance, Austin TX, USA., Duke Cancer Institute Center for Prostate and Urologic Cancers, Duke University, Durham, NC, USA., Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA., Chris "CJ" Johnson Foundation, Sugar Land, TX, USA., Department of Urology, University of Pittsburgh, Pittsburgh, PA, USA., Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA., Department of Urology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA., Division of Urologic Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio, USA., Department of Urology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA., Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, IL, USA., Division of Hematology Oncology, University of Iowa Hospitals and Clinics, Iowa City, IA, USA., Department of Medicine/Oncology, University of Michigan, Ann Arbor, MI, USA., Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; David H. Koch Center for Applied Research of Genitourinary Cancers, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA. Electronic address: .