ASCO GU 2018: Creation of a Tissue Expression Biomarker-augmented Prognostic Model for Patients with Metastatic Renal Cell Carcinoma
For this study, 602 patients with metastatic ccRCC who underwent nephrectomy between 1990-2004 were identified using the Mayo Clinic Nephrectomy Registry. Sections from paraffin-embedded primary tumor tissue blocks were used for immunohistochemistry staining for PD-1, B7-H1 (PD-L1), B7-H3, Bim (downstream pro-apoptotic signaling molecule in PD-1 pathway), CA-IX, IMP3, Ki67, and survivin. CSS was the primary outcome. Biomarkers that were significantly associated with CSS after adjusting for the metastases score were used to develop a biomarker-specific multivariable model using a bootstrap resampling approach and forward selection. Predictive ability was summarized using a bootstrap-corrected c-index.
Among these 602 patients, 192 (32%) had metastases at diagnosis and 410 (68%) developed metastases after nephrectomy. Median follow-up among survivors was 9.6 years (IQR 4.2, 12.8) and 504 (84%) patients died of RCC. Bim, IMP3, Ki67, and survivin expression were significantly associated with CSS after adjusting for the metastases score and were used to develop a biomarker-specific model. High Bim (HR 1.44, 95%CI 1.16-1.78), high survivin (HR 1.35, 95%CI 1.08-1.68), and the metastases score (HR 1.13 per one point, 95%CI 1.10-1.16) were retained as independent predictors in the final multivariable model (c-index 0.69).
The authors concluded that a prognostic model combining the clinical metastases score and two primary tissue expression biomarkers, Bim and survivin, for patients with metastatic RCC who underwent nephrectomy predicted CSS. Dr. Bhindi notes that external validation will be required prior to clinical use.
Presented by: Bimal Bhindi, MD Mayo Clinic, Rochester, MN
Co-Authors: Christine M. Lohse, John C. Cheville, Ross Mason, Matthew K. Tollefson, Susan Harrington, Haidong Dong, Alexander S. Parker, Stephen A. Boorjian, Robert Houston Thompson, Bradley C. Leibovich, Mayo Clinic, Jacksonville, FL
Written by: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, @zklaassen_md at the 2018 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, February 8-10, 2018 - San Francisco, CA