Abstract
To date, only few data concerning the biologically active, free form of testosterone (FT) are available in metastatic prostate cancer (mPC) and the impact of FT on disease, therapy and outcome is largely unknown. We retrospectively studied the effect of docetaxel on FT and total testosterone (TT) serum levels in 67 mPC patients monitored between April 2008 and November 2020. FT and TT levels were measured before and weekly during therapy. The primary endpoint was overall survival (OS). Secondary endpoints were prostate-specific antigen response and radiographic response (PSAR, RR), progression-free survival (PFS), FT/TT levels and safety. Median FT and TT serum levels were completely suppressed to below the detection limit during docetaxel treatment (FT: from 0.32 to < 0.18 pg/mL and TT: from 0.12 to < 0.05 ng/mL, respectively). Multivariate Cox regression analyses identified requirement of non-narcotics, PSAR, complete FT suppression and FT nadir values < 0.18 pg/mL as independent parameters for PFS. Prior androgen-receptor targeted therapy (ART), soft tissue metastasis and complete FT suppression were independent prognostic factors for OS. FT was not predictive for treatment outcome in mPC patients with a history of ART.
Highlights
To date, only few data concerning the biologically active, free form of testosterone (FT) are available in metastatic prostate cancer and the impact of FT on disease, therapy and outcome is largely unknown
Seven patients were castration-naïve, 26 patients were castration-resistant after androgen deprivation therapy (ADT) and 34 patients were castration resistant after ADT plus androgen-receptor targeted therapy (ART)
We demonstrate that TT and FT serum levels are reduced during docetaxel chemotherapy and that FT suppression under the detection limit (100%) resulted in better progression-free survival (PFS) and overall survival (OS) in mCNPC and mCRPC patients, but not in mCRPC patients with a history of ART
Summary
Only few data concerning the biologically active, free form of testosterone (FT) are available in metastatic prostate cancer (mPC) and the impact of FT on disease, therapy and outcome is largely unknown. We retrospectively studied the effect of docetaxel on FT and total testosterone (TT) serum levels in 67 mPC patients monitored between April 2008 and November 2020. Secondary endpoints were prostate-specific antigen response and radiographic response (PSAR, RR), progression-free survival (PFS), FT/TT levels and safety. Prior androgen-receptor targeted therapy (ART), soft tissue metastasis and complete FT suppression were independent prognostic factors for OS. A testosterone suppression target of less than 20 ng/dL improves patient survival and delays tumor p rogression. Androgen receptor (AR) targeted therapy (ART) in combination with ADT led to testosterone suppression to near zero and further improved patient survival. Ryan et al found that docetaxel therapy significantly reduced androgen levels, including total testosterone (TT), with increased OS (26.3 vs 20.9 months), with better outcome in patients with high versus low reduction of androgen levels, r espectively. The goal of this study was to investigate the effect of docetaxel on FT and TT at different stages of metastatic PC (e.g. castrationnaïve (mCNPC, group 1), castration-resistant (mCRPC, group 2) and castration-resistant patients with prior ART (mCRPC-ART, group 3))
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