Serum testosterone level is a useful biomarker for determining the optimal treatment for castration-resistant prostate cancer

Hashimoto, Kimio; Tabata, Hiroki; Shindo, Tetsuya; Tanaka, Toshiaki; Hashimoto, Jiro; Inoue, Ryuta; Mizutani, Takashi; Hara, Hiroshi; Yanase, Masahiro; Kunishima, Yasuharu; Takahashi, Atsushi; Masumori, Naoya

doi:10.1016/j.urolonc.2019.04.026

Cited by 20 publications

(19 citation statements)

References 27 publications

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“…Furthermore, a high serum TST predicted poor post‐docetaxel survival in patients who received subsequent therapy, including ARAT and/or cabazitaxel [ 44 ]. A serum testosterone level of 5 to < 50 ng/dl was a significant predictor for determining the efficacy of AR-targeted therapy [ 45 ]. PFS and OS when serum testosterone level was > 0.05 ng/ml in patients treated with ADT was significantly superior than with testosterone level below 0.05 ng/ml [ 46 ].…”

Section: Resultsmentioning

confidence: 99%

“…Testosterone as prognostic factor demonstrated that lower TST levels were associated with significant longer time to survival to treatment with docetaxel, ARAT and ADT. The mechanism of TST exhibiting benefits at lower levels may be related to acquired resistance than primary resistance, however this role is still unclear [45]. However, one study reported that high levels (> 0.05 ng/ml) was significant predictor of OS on treatment with ARAT, thus though TST is a significant prognostic factor, the role of TST in ARAT is unclear [46].…”

Section: Discussionmentioning

confidence: 99%

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Clinical implication of prognostic and predictive biomarkers for castration-resistant prostate cancer: a systematic review

et al. 2020

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Background: Diagnosis of metastatic castrate resistant prostate cancer (mCRPC) with current biomarkers is difficult and often results in unnecessary invasive procedures as well as over-diagnosis and over-treatment. There are a number of prognostic biomarkers for CRPC, but there are no validated predictive biomarkers to guide in clinical decision-making. Specific biomarkers are needed that enable to understand the natural history and complex biology of this heterogeneous malignancy, identify early response to treatment outcomes and to identify the population of men most likely to benefit from the treatment. In this systematic review, we discuss the existing literature for the role of biomarkers in CRPC and how they aid in the prognosis, treatment selection and survival outcomes. Methods: We performed a literature search on PubMed and EMBASE databases from January 2015 through February 2020 in accordance to Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. Articles were assessed to identify relevant observational studies and randomized controlled trials regarding biomarkers which aid in identifying progression to mCRPC as well as predictive biomarkers which help in treatment selection. Results: We identified 3640 number of hits of which 58 articles were found to be relevant. Here we addressed biomarkers in the context of prognosis, prediction and patient selection of therapy. These biomarkers were found to be effective as prognostic or predictive factors under variety of conditions. The higher levels for all these biomarkers were associated with shorter median OS and sometimes PFS. Lower amounts of biomarkers in serum or urine were associated with prolonged survival outcomes, longer time to CRPC development or CRPC progression and longer median follow-up irrespective of any therapy. Conclusion: We observed that the biomarkers included in our study predicted clinically relevant survival outcomes and treatment exposure. Though the current biomarkers are prognostic when measured prior to initiating treatment, not all are validated as predictive markers in post treatment setting. A greater understanding of biomarkers in CRPC is need of the hour for development of more personalized approach to maximize benefit and minimize harm in men with CRPC.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Clinical implication of prognostic and predictive biomarkers for castration-resistant prostate cancer: a systematic review

et al. 2020

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“…A full-text review was performed for 178 potentially relevant articles. After evaluating the selection criteria, we identified 11 articles with 4206 patients for systematic review and ten articles with 4136 patients for meta-analysis [8][9][10][23][24][25][26][27][28][29][30]. Figure 1 depicts the selection process and list.…”

Section: Literature Searchmentioning

confidence: 99%

Prognostic value of testosterone for the castration-resistant prostate cancer patients: a systematic review and meta-analysis

et al. 2020

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Introduction This systematic review and meta-analysis aimed to assess the prognostic value of testosterone in patients with castration-resistant prostate cancer (CRPC). Materials and methods PubMed, Web of Science, and Scopus databases were systematically searched until December 2019, according to the Preferred Reporting Items for Systemic Review and Meta-analysis statement. The endpoints were progression-free survival (PFS) and overall survival (OS). Results We identified 11 articles with 4206 patients for systematic review and nine articles with 4136 patients for meta-analysis. Higher testosterone levels were significantly associated with better OS (pooled HR 0.74, 95% CI 0.58–0.95) and better PFS (pooled HR 0.51, 95% CI 0.30–0.87). Subgroup analyses based on the treatment type revealed that higher testosterone levels were significantly associated with better OS in CRPC patients treated with androgen receptor-targeted agents (ARTAs) (pooled HR 0.64, 95% CI 0.55–0.75), but not in those treated with chemotherapy (pooled HR 0.78, 95% CI 0.53–1.14). Conclusion This meta-analysis demonstrated that the PFS and OS were significantly greater in patients with CRPC in those with higher testosterone levels than that of those with lower testosterone levels. In the subgroup analyses, lower testosterone levels were a consistently poor prognostic factor for OS in patients treated with ARTAs, but not in those treated with chemotherapy. Therefore, higher testosterone levels could be a useful biomarker to identify patient subgroups in which ARTAs should be preferentially recommended in the CRPC setting.

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“…However, since the primary goal of ADT is T reduction to castration levels, efficacy should be validated by T measurement. 21 This is increasingly important with the advent of new therapies of castration resistant disease which require a correct diagnosis before initiation. LHRH agonist package inserts recommend periodic T assessment to monitor suppression (table 1).…”

Section: Discussionmentioning

confidence: 99%

The Impact of Late Luteinizing Hormone-Releasing Hormone Agonist Dosing on Testosterone Suppression in Patients with Prostate Cancer: An Analysis of United States Clinical Data

et al. 2020

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Purpose: We evaluated the timeliness of androgen deprivation therapy dosing, the impact of dosing nonadherence on testosterone, and the frequency of testosterone and prostate specific antigen testing in patients with prostate cancer. Materials and Methods: We retrospectively analyzed the records of 22,860 patients with prostate cancer treated with luteinizing hormone-releasing hormone agonists. Analyses were done using 2 definitions of month, including a 28-day month (late dosing after day 28, 84, 112 or 168) and an extended month (late after day 32, 97, 128 or 194) for 1, 3, 4 and 6-month formulations, respectively. The prevalence of late dosing, associated testosterone values, and the frequency of testosterone and prostate specific antigen testing were assessed. Statistical significance was assessed with the unpaired t-test. Results: Of the injections 84% and 27% were late for the 28-day and extended month analyses, respectively. For the 28-day month 60% and 29% of injections were late by more than 1 and more than 2 weeks, respectively. Of testosterone values 4% were greater than 50 ng/dl for early/on time injections using both definitions, and 15% and 27% were greater than 50 ng/dl when late, and for the 28-day month and the extended month, respectively. For early/on time vs late injections 22% vs 31% of testosterone values were greater than 20 ng/dl for the 28-day month and 21% vs 43% for the extended month. Mean testosterone was higher when late (49 ng/dl for 28-day month, 79 ng/dl for extended month) vs early/ on time (both 21 ng/dl). Of the injections prostate specific antigen measurements were performed in 83% and testosterone assessment was done in only 13%.

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Serum testosterone level is a useful biomarker for determining the optimal treatment for castration-resistant prostate cancer

Cited by 20 publications

References 27 publications

Clinical implication of prognostic and predictive biomarkers for castration-resistant prostate cancer: a systematic review

Clinical implication of prognostic and predictive biomarkers for castration-resistant prostate cancer: a systematic review

Prognostic value of testosterone for the castration-resistant prostate cancer patients: a systematic review and meta-analysis

The Impact of Late Luteinizing Hormone-Releasing Hormone Agonist Dosing on Testosterone Suppression in Patients with Prostate Cancer: An Analysis of United States Clinical Data

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