Active surveillance (AS) may be used in the management of metastatic renal cell carcinoma (mRCC), but consensus regarding its application is lacking. We report an exploratory analysis of prospectively collected specimens prespecified in the only modern clinical trial evaluating AS in mRCC. Whole-exome and RNA sequencing were performed for patients providing consent to identify putative biomarkers associated with time on AS (TAS), the primary endpoint. Log-rank tests and multivariable Cox proportional-hazards models were used for analyses. Patients with mutations in either TP53 or SMARCA4 tumor suppressor genes had shorter TAS (7.5 vs 14.2 mo; log-rank p = 0.004). While these patients exhibited features of aggressive disease clinically, the two-gene model was independently predictive in multivariable analyses (hazard ratio 3.30, 95% confidence interval 1.07-10.18; p = 0.038). In conclusion, insight into the underlying RCC biology improves patient selection for AS. If validated, this two-gene model could help in stratifying patients with mRCC and identifying those who are poor candidates for AS. PATIENT SUMMARY: In this study, we analyzed tumors from patients with metastatic kidney cancer enrolled in a clinical trial of imaging surveillance. We found that tumors with mutations in either the TP53 or SMARCA4 gene progressed faster than tumors without these mutations. Thus, patients harboring mutations in these genes may not be good candidates for AS.
European urology. 2021 Dec 31 [Epub ahead of print]
Oscar Reig Torras, Akhilesh Mishra, Alana Christie, Tiffani McKenzie, Oreoluwa Onabolu, Nirmish Singla, Elizabeth R Plimack, Cristina Suárez, Moshe C Ornstein, R Katherine Alpaugh, Roy Elias, I Alex Bowman, Renee M McKay, Christopher Przybycin, Payal Kapur, James Brugarolas, Brian Rini
Kidney Cancer Program, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX, USA; Translational Genomic and Targeted Therapeutics in Solid Tumors, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain; Department of Medical Oncology, Hospital Clínic of Barcelona, Barcelona, Spain., Kidney Cancer Program, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX, USA., Kidney Cancer Program, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX, USA; Division of Biostatistics, Department of Clinical Sciences, The University of Texas Southwestern Medical Center, Dallas, TX, USA., Kidney Cancer Program, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Pathology, The University of Texas Southwestern Medical Center, Dallas, TX, USA., Kidney Cancer Program, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Urology, The University of Texas Southwestern Medical Center, Dallas, TX, USA., Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA., Vall d'Hebron University Hospital and Institute of Oncology, Universitat Autònoma de Barcelona, Barcelona, Spain., Department of Hematology and Medical Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, USA., Protocol Support Laboratory, Fox Chase Cancer Center, Philadelphia, PA, USA., Kidney Cancer Program, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX, USA., Robert J. Tomsich Institute of Pathology and Laboratory Medicine, Department of Pathology, Cleveland Clinic, Cleveland, OH, USA., Kidney Cancer Program, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX, USA. Electronic address: ., Department of Hematology and Medical Oncology, Vanderbilt University Medical Center, Nashville, TN, USA. Electronic address: .