TY - JOUR
T1 - Retrospective analysis of serum testosterone levels by LC-MS/MS in chemically castrated prostate cancer patients: Biological variation and analytical performance specifications
AU - van Winden, Lennart J.
AU - Lanfermeijer, Mirthe
AU - Heijboer, Annemieke C.
AU - van Tellingen, Olaf
AU - Bergman, Andries M.
AU - van der Poel, Henk G.
AU - Jonker, Niels
AU - van Rossum, Huub H.
N1 - Funding Information: We would like to thank Vincent van der Noort for reviewing statistical details and providing essential advice on data analysis. Publisher Copyright: © 2021 Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/10/1
Y1 - 2021/10/1
N2 - Background: A sensitive liquid chromatography tandem-mass spectrometry (LC-MS/MS) method was used to monitor serum testosterone levels in castrated prostate cancer patients. We subsequently performed an observational and retrospective study to estimate the within- and between-subject biological variation of these patients. Methods: In total, 474 samples from 72 prostate cancer patients in the Netherlands receiving either chemical castration (CAS) or castration plus enzalutamide (ENZA) treatment were selected for data analysis. ANOVA was performed to estimate analytical variation (CV A) and within-patient variation (CV I). A nested ANOVA was applied to estimate between-patient variation (CV G). From these data, the reference change value (RCV) and analytical performance specifications (APS) were calculated. Results: Testosterone levels were significantly higher in the ENZA group (0.318 vs. 0.191 nmol/L, p < 0.005) than the CAS group. Overall, variation components were estimated at 6.1%, 24.6% and 60.3% for CV A, CV I and CV G, respectively. Both groups showed high individuality (<0.6). The RCV was 70.3% for all patients. Desirable APS were 12.3% for imprecision, 16.3% for bias and 26.4% for total error. Conclusion: The generated APS are valuable for sensitive testosterone assays and the high individuality indicates that castrated testosterone levels can be studied as a predictive or prognostic biomarker in prostate cancer patients.
AB - Background: A sensitive liquid chromatography tandem-mass spectrometry (LC-MS/MS) method was used to monitor serum testosterone levels in castrated prostate cancer patients. We subsequently performed an observational and retrospective study to estimate the within- and between-subject biological variation of these patients. Methods: In total, 474 samples from 72 prostate cancer patients in the Netherlands receiving either chemical castration (CAS) or castration plus enzalutamide (ENZA) treatment were selected for data analysis. ANOVA was performed to estimate analytical variation (CV A) and within-patient variation (CV I). A nested ANOVA was applied to estimate between-patient variation (CV G). From these data, the reference change value (RCV) and analytical performance specifications (APS) were calculated. Results: Testosterone levels were significantly higher in the ENZA group (0.318 vs. 0.191 nmol/L, p < 0.005) than the CAS group. Overall, variation components were estimated at 6.1%, 24.6% and 60.3% for CV A, CV I and CV G, respectively. Both groups showed high individuality (<0.6). The RCV was 70.3% for all patients. Desirable APS were 12.3% for imprecision, 16.3% for bias and 26.4% for total error. Conclusion: The generated APS are valuable for sensitive testosterone assays and the high individuality indicates that castrated testosterone levels can be studied as a predictive or prognostic biomarker in prostate cancer patients.
KW - Androgen deprivation therapy
KW - Biological variation
KW - LC-MS/MS
KW - Prostate cancer
KW - Steroids
KW - Testosterone
UR - http://www.scopus.com/inward/record.url?scp=85109184760&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.cca.2021.06.030
DO - https://doi.org/10.1016/j.cca.2021.06.030
M3 - Article
C2 - 34217697
SN - 0009-8981
VL - 521
SP - 70
EP - 75
JO - Clinica Chimica Acta
JF - Clinica Chimica Acta
ER -