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Prognostic and predictive value of plasma testosterone levels in patients receiving first-line chemotherapy for metastatic castrate-resistant prostate cancer.

ABSTRACT: Biomarkers for metastatic castration-resistant prostatic cancer (mCRPC) are an unmet medical need.The prognostic and predictive value for survival and response to salvage hormonal therapy (SHT) of baseline testosterone level (TL) was analysed in a cohort of 101 mCRPC patients participating in 9 non-hormonal first-line chemotherapy phase II-III trials. Inclusion criteria in all trials required a TL of <50?ng?dl(-1).Median age: 70 years; visceral metastases: 19.8%; median prostate-specific antigen (PSA): 50.7?ng?ml(-1); median TL: 11.5?ng?dl(-1). Median overall survival (OS; 24.5 months) was significantly longer if baseline TL was above (High TL; n=52) than under (Low TL; n=49) the TL median value (32.7 vs 22.4 months, respectively; P=0.0162, hazard ratio (HR)=0.6). The presence of anaemia was an unfavourable prognostic factor (median OS: 20.6 vs 28.4 months; P=0.0025, HR=1.88 (CI95%: 1.01-3.48)). Patients presenting both anaemia and low testosterone had a worse outcome compared to those with one or none of them (median OS: 17.9 vs 22.4 vs 38.1 months; P=0.0024). High vs Low TL was associated with PSA response rate (55.6% vs 21.7%) in 41 patients receiving SHT.Testosterone level under castration range was a prognostic factor for survival mCRPC patients. The PSA response to SHT differed depending on TLs. Testosterone levels might help in treatment decision.

SUBMITTER: de Liano AG

PROVIDER: S-EPMC4007243 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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Prognostic and predictive value of plasma testosterone levels in patients receiving first-line chemotherapy for metastatic castrate-resistant prostate cancer.

de Liaño A G AG Reig O O Mellado B B Martin C C Rull E U EU Maroto J P JP

British journal of cancer 20140410 9

<h4>Background</h4>Biomarkers for metastatic castration-resistant prostatic cancer (mCRPC) are an unmet medical need.<h4>Methods</h4>The prognostic and predictive value for survival and response to salvage hormonal therapy (SHT) of baseline testosterone level (TL) was analysed in a cohort of 101 mCRPC patients participating in 9 non-hormonal first-line chemotherapy phase II-III trials. Inclusion criteria in all trials required a TL of <50 ng dl(-1).<h4>Results</h4>Median age: 70 years; visceral ...[more]

PMID: 24722180

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Project description:A range of new treatment options has recently become available for patients with advanced metastatic castration-resistant prostate cancer (mCRPC). Androgen deprivation therapy (ADT) with luteinizing hormone-releasing hormone is continued when performing chemotherapy or androgen deprivation with new second-generation therapeutic agents such as enzalutamide or abiraterone acetate. Despite the fact that free testosterone (FT) is the biologically active form, it is common practice that androgen suppression is monitored via total testosterone levels only. The aim of the present study was to evaluate the role of FT as a prognostic biomarker for cancer-specific survival (CSS) and its feasibility as an ADT monitoring biomarker in patients with mCRPC for the first time. The requirement for continued ADT in mCRPC patients is discussed within the basis of the current literature. A total of 34 patients with continuous measurements of FT levels and mCRPC status underwent therapy with docetaxel, abiraterone acetate, enzalutamide, cabozantinib, carboplatin or cabazitaxel. Data were obtained from the Departments of Urology and Urological Oncology, Hannover Medical School (Hannover, Germany) between March 2009 and April 2014. A cutoff point of 0.5 pg/ml was used to discriminate between patients according to FT levels. Statistical evaluation of CSS was performed by applying Kaplan Meier survival estimates, multivariate Cox regression analyses and log-rank tests. The median age of all 34 patients was 72 years (range, 51-86 years). The mean follow-up interval was 16.1 months (range, 0.7-55.6 months). Despite the fact that all patients were undergoing androgen deprivation, the mean serum FT levels for each patient varied; the mean FT concentration in the cohort was 0.328 pg/ml, ranging from 0.01-9.1 pg/ml. A notable difference with regard to CSS was observed for patients with regard to serum FT concentration; CSS was significantly longer for patients with a serum FT level below the cutoff level (43.6 vs. 17.3 months, respectively, P=0.0063). Upon multivariate Cox regression analysis, the mean FT concentration during treatment remained a significant prognostic factor for CSS (hazard ratio, 1.22; 95% confidence interval, 1.03-1.43; P=0.0182). In conclusion, in patients with mCRPC, the serum FT level is a strong predictor of CSS in patients under therapy with second-line anti-hormonal therapeutic medication and chemotherapy. It may be concluded that FT levels should be included into the routine control of androgen suppression while under treatment with ADT and second-generation hormonal therapy.

Dataset Information

Prognostic and predictive value of plasma testosterone levels in patients receiving first-line chemotherapy for metastatic castrate-resistant prostate cancer.

Publications

Prognostic and predictive value of plasma testosterone levels in patients receiving first-line chemotherapy for metastatic castrate-resistant prostate cancer.

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