To enhance risk stratification in metastatic castrate-resistant prostate cancer (mCRPC), we developed clinical and integrated clinico-genomic prognostic nomograms combining clinical prognostic factors with copy number alteration-based risk scores (RSs) in circulating tumor DNA (ctDNA) and metastatic tissue to predict 1-, 2-, and 3-year overall survival (OS) probabilities.
A clinical prognostic nomogram was developed from publicly accessed Yale University Open Data Access (YODA) data-sciences project (N = 1088 patients). A second publicly available independent dataset (N = 82) with an 11-gene prognostic RS developed concurrently obtained ctDNA and matched metastatic tissue specimens (gains: AR, MYC, COL22A1, PIK3CA, PIK3CB, NOTCH1; losses: TMPRSS2, NCOR1, ZBTB18, TP53, NKX3-1) was used to develop an integrated clinico-genomic survival nomogram. Independent predictors for survival were identified in each dataset using univariate and multivariate Cox proportional hazard. Multivariate regression coefficients with statistical significance (P < .05) were used to develop prognostic nomograms to estimate 1-, 2- and 3-year OS probabilities. Nomogram performances were assessed using time-dependent area under curves (t-AUCs). All analyses were conducted in RStudio (v4.1.2).
The YODA dataset t-AUCs for the prognostic nomogram for estimating OS at 1, 2, and 3 years were 0.74, 0.70, and 0.74. In the independent second dataset, the integrated clinico-genomic prognostic nomogram was observed to have higher t-AUCs for predicting 3-year mCRPC survival at 0.807 compared with 0.714 using clinical factors alone.
An integrated clinico-genomic nomogram with ctDNA RSs achieved the highest t-AUC for 3-year survival in mCRPC and may enable precision in identification of poor-prognosis subgroups based on somatic alterations.
JNCI cancer spectrum. 2026 May 09 [Epub]
Manish Kohli, Anushka Shankar, Jennifer Lloyd, Liang Wang, Xingyue Huo, Muhammad Zaki Fadlullah, Aik Choon Tan, Joseph Finkelstein
Division of Oncology, Department of Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, United States., College of Nursing, University of Utah, Salt Lake City, UT, United States., Department of Tumor Biology, H. Lee Moffitt Cancer Center, Tampa, FL, United States., Arizona Center for Telemedicine and Digital Health, Department of Medicine, Division of General Internal Medicine, Geriatrics and Palliative Medicine, College of Medicine - Tucson, University of Arizona, Tucson, AZ, United States., Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, United States.