Journal article
Creation of a primary tumor tissue expression biomarker-augmented prognostic model for patients with metastatic renal cell carcinoma
Urologic oncology, Vol.39(2), pp.135.e1-135.e8
02/2021
DOI: 10.1016/j.urolonc.2020.08.028
PMID: 33309297
Abstract
Clinical and pathological factors alone have limited prognostic ability in patients with metastatic clear cell renal cell carcinoma (ccRCC). Bim, a downstream pro-apoptotic molecule in the PD-1 signaling pathway, has recently been associated with survival in other malignancies. We sought to determine if tissue biomarkers including Bim, added to a previously reported clinical metastases score, improved prediction of cancer-specific survival (CSS) for patients with metastatic ccRCC.
Patients with metastatic ccRCC who underwent nephrectomy between 1990 and 2004 were identified using our institutional registry. Sections from paraffin-embedded primary tumor tissue blocks were used for immunohistochemistry staining for Bim, PD-1, B7-H1 (PD-L1), B7-H3, CA-IX, IMP3, Ki67, and survivin. 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.
The cohort included 602 patients: 192 (32%) with metastases at diagnosis and 410 (68%) who developed metastases after nephrectomy. Median follow-up was 9.6 years (IQR 4.2–12.8), during which 504 patients died of RCC. Bim, IMP3, Ki67, and survivin expression were significantly associated with CSS after adjusting for the metastases score, and were eligible for biomarker-specific model inclusion. After variable selection, high Bim (hazard ratio [HR] = 1.44; 95% confidence interval [CI] 1.16–1.78; P <0.001), high survivin (HR = 1.35; 95% CI 1.08–1.68; P = 0.008), and the metastases score (HR = 1.13 per 1 point; 95% CI 1.10–1.16; P <0.001) were retained in the final multivariable model (c-index = 0.69).
We created a prognostic model combining the clinical metastases score and 2 primary tumor tissue expression biomarkers, Bim and survivin, for patients with metastatic renal cell carcinoma who underwent nephrectomy.
Details
- Title: Subtitle
- Creation of a primary tumor tissue expression biomarker-augmented prognostic model for patients with metastatic renal cell carcinoma
- Creators
- Elizabeth N. Bearrick - Mayo ClinicVignesh Packiam - Mayo ClinicBimal Bhindi - University of CalgaryChristine M. Lohse - Mayo ClinicJohn C. Cheville - Mayo ClinicRoss J. Mason - Dalhousie UniversityMatthew Tollefson - Department of Urology Mayo Clinic Rochester MNSusan Harrington - Department of Urology Mayo Clinic Rochester MNHaidong Dong - Department of Urology Mayo Clinic Rochester MNAlexander S. Parker - Department of Epidemiology, University of Florida, Jacksonville, FL.Stephen A. Boorjian - Department of Urology Mayo Clinic Rochester MNR. Houston Thompson - Department of Urology Mayo Clinic Rochester MNBradley C. Leibovich - Department of Urology Mayo Clinic Rochester MN
- Resource Type
- Journal article
- Publication Details
- Urologic oncology, Vol.39(2), pp.135.e1-135.e8
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.urolonc.2020.08.028
- PMID
- 33309297
- ISSN
- 1078-1439
- eISSN
- 1873-2496
- Language
- English
- Date published
- 02/2021
- Academic Unit
- Urology
- Record Identifier
- 9984319992502771
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