Journal article
Impact of postprogression therapies on overall survival: Recommendations from the 2023 kidney cancer association think tank meeting
Urologic oncology, Vol.43(3), pp.135-146
03/2025
DOI: 10.1016/j.urolonc.2024.10.022
PMID: 39500687
Abstract
•Accounting for postprogression therapies improves overall survival (OS) estimation.•Multistage treatment strategies (MTS) guide treatment sequence decisions to optimize OS.•Sequentially Multiple Assignment Randomized Trials (SMART) offer unbiased comparisons of MTS.•SMART designs are underutilized in oncology.•Modernizing trial design and data collection can facilitate MTS estimation.
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.
Details
- Title: Subtitle
- Impact of postprogression therapies on overall survival: Recommendations from the 2023 kidney cancer association think tank meeting
- Creators
- Stephanie A. Berg - Dana-Farber Cancer InstituteSalvatore La Rosa - Kidney Cancer AssociationTian Zhang - The University of Texas Southwestern Medical CenterPhillip M. Pierorazio - University of PennsylvaniaLaurence Albiges - Institut Gustave RoussyKathryn E. Beckermann - Vanderbilt University Medical CenterMatthew T. Campbell - The University of Texas MD Anderson Cancer CenterMaria I. Carlo - Memorial Sloan Kettering Cancer CenterKatie Coleman - Chromophobe and Oncocytic Tumor Alliance, Austin TX, USADaniel J. George - Duke UniversityDaniel M. Geynisman - Fox Chase Cancer CenterRitchie Johnson - Johnson FoundationEric Jonasch - The University of Texas MD Anderson Cancer CenterJodi K. Maranchie - University of PittsburghBradley A. McGregor - Dana-Farber Cancer InstituteDaniel D. Shapiro - University of Wisconsin–MadisonEric A. Singer - The Ohio State UniversityBrian M. Shuch - University of California, Los AngelesWalter M. Stadler - University of ChicagoNizar M. Tannir - The University of Texas MD Anderson Cancer CenterYousef Zakharia - University of IowaUlka N. Vaishampayan - University of Michigan–Ann ArborPeter F. Thall - The University of Texas MD Anderson Cancer CenterPavlos Msaouel - The University of Texas MD Anderson Cancer Center
- Resource Type
- Journal article
- Publication Details
- Urologic oncology, Vol.43(3), pp.135-146
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.urolonc.2024.10.022
- PMID
- 39500687
- ISSN
- 1078-1439
- eISSN
- 1873-2496
- Grant note
- National Cancer InstituteAndrew Sabin Family Foundation FellowshipGateway for Cancer ResearchUnited States Department of Defense: KC200096P1 Kidney Cancer AssociationV FoundationMD Anderson Physician-Scientist AwardFinneran Family EndowmentNIH/NCI: 1R01CA261978 Cancer Center Support Grant: 5 P30 CA016672 Family of Mike and Mary Allen
The authors thank Jose Perez Torrealba and Tasha Hall for participating and Exelixis for providing support for the IKCSNA23 think tank. Pavlos Msaouel was supported by the National Cancer Institute R37CA288448, the Andrew Sabin Family Foundation Fellowship, Gateway for Cancer Research, a Translational Research Partnership Award (KC200096P1) by the United States Department of Defense, an Advanced Discovery Award by the Kidney Cancer Association, a Translational Research Award by the V Foundation, the MD Anderson Physician-Scientist Award, donations from the Renal Medullary Carcinoma Research Foundation in honor of Ryse Williams, the Finneran Family Endowment, as well as philanthropic donations by the Chris "CJ" Johnson Foundation, and by the family of Mike and Mary Allen. Peter Thall was supported by the NIH/NCI R01 grant 1R01CA261978, and Cancer Center Support Grant 5 P30 CA016672.
- Language
- English
- Electronic publication date
- 11/04/2024
- Date published
- 03/2025
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984745459002771
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