BackgroundLuteinizing hormone-releasing hormone (LH-RH) agonists are the standard for androgen deprivation therapy (ADT) in prostate cancer (PCa) patients. Current guidelines recommend serum testosterone measurement to assess the efficacy of ADT and to define castration resistance. However, serum testosterone does not reflect the exclusive effect of castration due to its extratesticular production. The aim of this study is to analyze if serum LH reflects better than serum testosterone the activity of LH-RH agonists.MethodsSerum LH and serum testosterone were measured with chemiluminescent immunoassay (CLIA) in a cohort study of 1091 participants: 488 PCa patients “on LH-RH agonists”, 303 “off LH-RH agonist” in whom LH-RH agonists were withdrawn, and 350 men with PCa suspicion “no LH-RH agonist” who never received LH-RH agonists. In a validation cohort of 147 PCa patients, 124 on “LH-RH agonists” and 19 “off LH-RH agonists”, serum testosterone was also measured with liquid chromatography and tandem mass spectrometry (LC MSMS).ResultsThe area under the curve (AUC) to distinguish patients “on versus off LH-RH agonists” was 0.997 for serum LH and 0.740 for serum testosterone, P < 0.001. The 97.5 percentile of serum LH in patients “on LH-RH agonists” was 0.97 U/L, been the most efficient threshold 1.1 U/L. The AUCs for serum LH, testosterone measured with CLIA and with LC MSMS, in the validation cohort, were respectively 1.000, 0.646 and 0.814, P < 0.001. The efficacy to distinguish patients “on versus off LH-RH agonists” was 98.6%, 78.3%, and 89.5% respectively, using 1.1 U/L as threshold for serum LH and 50 ng/dL for serum testosterone regardless the method.ConclusionsSerum LH is more accurate than serum testosterone regardless the method, to distinguish patients “on versus off LH-RH agonists”. The castrate level of serum LH is 1.1 U/l. These findings suggest that assessment of LH-RH agonist efficacy and castration resistance definition should be reviewed.
INTRODUCTION AND OBJECTIVES: Serum testosterone (ST) measurement is recommended in prostate cancer (PCa) patients undergoing androgen deprivation therapy (ADT) to assess its efficacy and to diagnose castration resistance (CR). ST up to 50 ng/dL is a strong criteria to define CR. Although liquid chromatography and tandem mass espectrometry (LC-MSMS) is the appropriate method, chemiluminiscent immunoassays (CLIAs) are widely used in spite of their lack of accuracy and reproducibility, given that they are automatable, fast, sensitive and inexpensive. Our objective here is to release that the information provided by the measurement of ST with CLIAs is misleading and can lead to wrong decisions.METHODS: ST was measured in 143 PCa patients undergoing luteinizing hormone-releasing hormone (LH-RH) agonist with LC-MSMS (Agilent Inc), Advia-Centaur CLIA (Siemens Inc) and Cobas 8000 CLIA (Roche Inc). Behaviour of ST according to the method is analysed, especially the rate of levels behind 50 ng/dL. RESULTS: Median ST (range) was 15.0 ng/dL (2-102) with LC-MSMS, 32.3 ng/dL (10-91.6) with AC-CLIA, p <0.001, and 10.3 ng/dL (2.5-54.6) with Cobas-CLIA, p <0.001. ST with LC-MSMS was below 20 ng/dL in 87 patients (60.8%), between 20 and 50 ng/dL in 48 (33.6%) and behind 50 ng/dL in 8 (5.6%). The rate of patients having ST behind 50 ng/dL with the AC-CLIA was in 18.2%, while it was 1.4% with the Cobas-CLIA, p <0.001.CONCLUSIONS: CLIAs are not accurate to measure ST in PCa patients undergoing LH-RH agonist. They can overestimate and underestimate the true levels of ST measured with LC-MSMS. Because ST up to 50 ng/dl is a strong criteria to define CR, wrong clinical decisions can be made based on the measurement of ST with inappropriate methods.
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