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- Title
Plasma Glutamine as a Prognostic Biomarker in Localized Prostate Cancer: Comparison of Conventional Variables in Risk Stratification.
- Authors
Smith, Bethany; Sungjin Kim; Tighiouart, Mourad; Posadas, Edwin; Chung, Leland; Figlin, Robert; Bhowmick, Neil; Jun Gong
- Abstract
BACKGROUND: Glutamine uptake has been shown to contribute to local prostate cancer growth and therapeutic resistance. We investigated the biomarker potential of glutamine among known prognostic variables in localized prostate cancer. METHODS: Plasma glutamine was measured by bioluminescence assay (Promega) in clinically annotated, pre--radical prostatectomy (RP) samples granted by the Prostate Cancer Biorepository Network. Univariate and multivariable Cox regressions of biochemical recurrence-free survival (bRFS) were performed. The performance of multivariable models was assessed with Harrell's c-statistics with internal validation by estimating and correcting possible optimism in c-statistics using the bootstrap method with 1000 replicates. RESULTS: Plasma glutamine levels were measured in a total of 125 patients with localized prostate cancer prior to RP. The majority were Gleason score 7 (70%), pathologic T2c (59%), and N0 (95%). The median plasma glutamine level was 442 µmol/L (interquartile range [IQR], 387-533) and median pre-RP prostate-specific antigen (PSA) was 5.36 (IQR, 4.4-7.5). The median bRFS was 6.19 years (95% CI, 3.96-6.82) with a 5-year bRFS rate of 55% (95% CI, 46%-63%). On univariate analysis, glutamine level was not significantly associated with known prognostic variables or bRFS (HR, 0.98; 95% CI, 0.83-1.15; P = .80), although higher pre-RP PSA and Gleason score, perforated capsule, positive margins, N1 disease, higher pathologic T stage, and higher D'Amico and Cambridge Prognostic Group (CPG) risk scores were significantly associated with bRFS (all P <.05). In the absence of correlation between glutamine and bRFS, we assessed the performance of 10 multivariable models incorporating various pre-RP and post-RP clinicopathologic variables to predict for bRFS in our cohort. A model with Gleason score, pre-RP PSA, and clinical T stage carried the highest predictive accuracy (c-statistic, 0.73; 95% CI, 0.65-0.80), although the D'Amico risk score (c-index, 0.64) had a lower predictive accuracy than the CPG risk score (c-index, 0.69). CONCLUSIONS: Pre-RP glutamine levels are not predictive of prognosis in localized prostate cancer. Risk scores such as D'Amico or CPG remain the top predictors of bRFS in our cohort. Further development of novel prognostic biomarkers--eg, genomic classifiers--is needed to better risk stratify indolent from biologically aggressive prostate cancer.
- Subjects
STATISTICS; SURVIVAL; CONFIDENCE intervals; PREOPERATIVE period; RADICAL prostatectomy; MULTIVARIATE analysis; COMPARATIVE studies; RISK assessment; DESCRIPTIVE statistics; GLUTAMINE; TUMOR markers; RISK management in business; PROSTATE-specific antigen; STATISTICAL correlation; PROSTATE tumors; LUMINESCENCE spectroscopy; PROPORTIONAL hazards models; TUMOR grading
- Publication
Oncology (08909091), 2021, Vol 35, Issue 9, p528
- ISSN
0890-9091
- Publication type
Article
- DOI
10.46883/onc.2021.3509.0528