There are limited data available on the real-world patterns of molecular testing in men with advanced prostate cancer. We thus sought to evaluate next-generation sequencing (NGS) testing in the United States, focused on single versus serial NGS testing, the different disease states of testing (hormone-sensitive v castration-resistant, metastatic vs nonmetastatic), tissue versus plasma circulating tumor DNA (ctDNA) assays, and how often actionable data were found on each NGS test.
The Prostate Cancer Precision Medicine Multi-Institutional Collaborative Effort clinical-genomic database was used for this retrospective analysis, including 1,597 patients across 15 institutions. Actionable NGS data were defined as including somatic alterations in homologous recombination repair genes, mismatch repair deficiency, microsatellite instability (MSI-high), or a high tumor mutational burden ≥10 mut/MB.
Serial NGS testing (two or more NGS tests with specimens collected more than 60 days apart) was performed in 9% (n = 144) of patients with a median of 182 days in between test results. For the second NGS test and beyond, 82.1% (225 of 274) of tests were from ctDNA assays and 76.1% (217 of 285) were collected in the metastatic castration-resistant setting. New actionable data were found on 11.1% (16 of 144) of second NGS tests, with 3.5% (5 of 144) of tests detecting a new BRCA2 alteration or MSI-high. A targeted therapy (poly (ADP-ribose) polymerase inhibitor or immunotherapy) was given after an actionable result on the second NGS test in 31.3% (5 of 16) of patients.
Repeat somatic NGS testing in men with prostate cancer is infrequently performed in practice and can identify new actionable alterations not present with initial testing, suggesting the utility of repeat molecular profiling with tissue or blood of men with metastatic castration-resistant prostate cancer to guide therapy choices.
JCO precision oncology. 2024 Apr [Epub]
Joseph J Park, Alec Chu, Jinju Li, Alicia Ali, Rana R McKay, Clara Hwang, Matthew K Labriola, Albert Jang, Deepak Kilari, George Mo, Deepak Ravindranathan, Laura S Graham, Alexandra Sokolova, Abhishek Tripathi, Amanda Pilling, Tanya Jindal, Aditya Ravindra, Frank C Cackowski, Patrick L Sweeney, Bicky Thapa, Taylor S Amery, Elisabeth I Heath, Rohan Garje, Yousef Zakharia, Vadim S Koshkin, Mehmet A Bilen, Michael T Schweizer, Pedro C Barata, Tanya B Dorff, Marcin Cieslik, Ajjai S Alva, Andrew J Armstrong
Duke Cancer Institute Center for Prostate and Urologic Cancers, Duke University, Durham, NC., Division of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI., Department of Biostatistics, University of Michigan, Ann Arbor, MI., Division of Hematology and Oncology, Department of Medicine, University of Michigan, Ann Arbor, MI., Moores Cancer Center, University of California San Diego, La Jolla, CA., Division of Hematology/Oncology, Department of Internal Medicine, Henry Ford Health System, Detroit, MI., Tulane Cancer Center, Tulane University, New Orleans, LA., Department of Medicine, Froedtert Cancer Center, Medical College of Wisconsin, Milwaukee, WI., University of Washington/Fred Hutchinson Cancer Center, Seattle, WA., Winship Cancer Institute of Emory University, Atlanta, GA., University of Colorado Anschutz Medical Campus, Aurora, CO., Division of Medical Oncology, Oregon Health Science University, Portland, OR., Department of Medical Oncology & Experimental Therapeutics, City of Hope Comprehensive Cancer Center, Duarte, CA., Division of Hematology and Oncology, Department of Medicine, University of California San Francisco, San Francisco, CA., Holden Comprehensive Cancer Center, Iowa City, IA., Karmanos Cancer Institute, Wayne State University, Detroit, MI., Miami Cancer Institute, Miami, FL.