Dataset Information

Effect of Prior Local Treatment and Prostate-Specific Antigen Kinetics during Androgen-Deprivation Therapy on the Survival of Castration-Resistant Prostate Cancer.

ABSTRACT: Prostate-specific antigen (PSA) kinetics predicts survival in castration-resistant prostate cancer (CRPC); however, the influence of prior treatment on this relationship is unclear. Patients with CRPC were stratified according to time to PSA nadir and time to CRPC progression to investigate their prognostic significance on prostate cancer-specific survival (PCSS) and whether PSA kinetics may serve as prognosticators regardless of prior local treatment. This multicenter retrospective study included 295 patients diagnosed with CRPC between September 2009 and November 2017. PSA kinetics during androgen-deprivation therapy (ADT) including %PSA decline, PSA nadir level, time to PSA nadir, and time to CRPC progression was investigated. Subgroup analysis was performed according to the prior history of local curative treatment. Patients who did not receive prior local treatment with ?6 months to PSA nadir and <12 months to CRPC, showed lower PCSS rates than those with <6 months to PSA nadir (23.3% vs. 45.3%; p?=?0.031) and ?12 months to CRPC (20.0% vs. 47.8%; p?=?0.001). In patients who had received local treatment, PSA kinetic parameters did not influence PCSS. Our results indicate that time to PSA nadir and time to CRPC progression are prognosticators of PCSS in patients with CRPC who did not previously receive curative local treatment.

SUBMITTER: Hah YS

PROVIDER: S-EPMC6695395 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Effect of Prior Local Treatment and Prostate-Specific Antigen Kinetics during Androgen-Deprivation Therapy on the Survival of Castration-Resistant Prostate Cancer.

Hah Yoon Soo YS Lee Jong Soo JS Rha Koon Ho KH Hong Sung Joon SJ Chung Byung Ha BH Koo Kyo Chul KC

Scientific reports 20190815 1

Prostate-specific antigen (PSA) kinetics predicts survival in castration-resistant prostate cancer (CRPC); however, the influence of prior treatment on this relationship is unclear. Patients with CRPC were stratified according to time to PSA nadir and time to CRPC progression to investigate their prognostic significance on prostate cancer-specific survival (PCSS) and whether PSA kinetics may serve as prognosticators regardless of prior local treatment. This multicenter retrospective study includ ...[more]

PMID: 31417160

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Project description:BACKGROUND:Multiple androgens drive prostate cancer progression and higher pre-treatment levels of androgens, even within the castrate range, have been previously shown to be associated with an improved overall survival (OS) in mCRPC. Docetaxel impairs microtubules, has androgen receptor (AR) inhibitory effects and is used in both the castration resistant and sensitive settings, where androgen dynamics may impact outcome. The present analysis evaluates the association of decline in serum androgen levels (Testosterone (T), Androstenedione (A) and DHEA in docetaxel-treated mCRPC patients with OS. METHODS:Data from 1050 men treated on CALGB 90401 with docetaxel, prednisone and either bevacizumab or placebo were evaluated. Eligibility required progressive mCRPC and no prior chemotherapy. Pre-treatment, 6 week and progression serum assays for T, A and DHEA were performed via tandem Liquid Chromatography-Mass Spectrometry (LC-MS/MS). Changes in T, A and DHEA levels from baseline to 6 weeks were calculated as the ratio of 6-week over baseline. The proportional hazards model was used to assess the prognostic significance of changes in T, A, and DHEA from baseline to 6 weeks in predicting OS adjusting for known prognostic factors. RESULTS:Median baseline values for T, A, and, DHEA were 1.0, 13.5, and 8.1?ng/dL respectively while 6 week levels were 0.64, 7.0, and 6.8?ng/dL respectively. Median OS for low testosterone decline is 20.9 months vs 26.3 months for high testosterone decline. In multivariable analysis including known prognostic variables, change in testosterone levels was independently associated with greater OS; the hazard ratio for death with each unit increase in the 6-week/baseline ratio is 1.02 (95% CI?=?1.01-1.03, p?=?0.001). Decline in A and DHEA were not significant predictors of OS. In multivariable analysis change in the serum changes did not predict PFS however the ratio of T at 6-weeks over baseline was prognostic of ?50% decline in PSA with an odds ratio of 0.93 (95% CI?=?0.85-0.98, p-value?=?0.039). CONCLUSIONS:Declines in testosterone during docetaxel treatment is associated with a longer survival, consistent with a favorable prognostic significance of higher serum androgens in the CRPC.

Project description:ObjectivesThe objective of the study is to compare the efficacy and safety of alternative androgen therapy (AAT) with enzalutamide + androgen deprivation therapy (ADT) and flutamide + ADT in the treatment of Japanese men with metastatic or nonmetastatic castration-resistant prostate cancer (CRPC) who progressed despite combined androgen blockade (CAB) with bicalutamide + ADT. AAT treatment sequence was also investigated.Materials and methodsThe open-label, Phase 4 AFTERCAB study (NCT02918968) was conducted from November 2016 to March 2020 in Japanese men aged ≥20 years with asymptomatic or mildly symptomatic CRPC. Patients were initially randomized to enzalutamide (160 mg/day) + ADT (enzalutamide first) or flutamide (375mg/day [125mg three times daily]) + ADT (flutamide first) as first-line therapy. Following prostate-specific antigen (PSA) progression, other disease progression, or discontinuation of first-line therapy due to an adverse event (AE), patients switched to the other treatment as second-line therapy. The primary endpoint was time to PSA progression with first-line therapy (TTPP1). Secondary endpoints included TTPP2 (TTPP1 + time to PSA progression with second-line therapy). AEs were monitored to assess safety.ResultsOverall, 206 men were randomized (enzalutamide first, n = 102; flutamide first, n = 104) and stratified by study site and disease stage; 133 patients transitioned to second-line therapy (enzalutamide first, n = 48; flutamide first, n = 85). TTPP1 was significantly improved with enzalutamide first versus flutamide first (median 21.4 months vs. 5.8 months; hazard ratio [HR] 0.42; 95% confidence interval [CI] [0.29, 0.61]). TTPP2 was numerically improved with enzalutamide first versus flutamide first (median not reached vs. 21.2 months; HR 0.76; 95% CI [0.48, 1.19]). Both treatments were generally well tolerated, with AEs consistent with their known safety profiles.ConclusionFirst-line AAT with enzalutamide + ADT provided a significant improvement in time to PSA progression versus flutamide + ADT. Enzalutamide + ADT may therefore be the preferred first-line AAT option in Japanese men with metastatic or nonmetastatic CRPC who progress despite CAB with bicalutamide + ADT.

Dataset Information

Effect of Prior Local Treatment and Prostate-Specific Antigen Kinetics during Androgen-Deprivation Therapy on the Survival of Castration-Resistant Prostate Cancer.

Publications

Effect of Prior Local Treatment and Prostate-Specific Antigen Kinetics during Androgen-Deprivation Therapy on the Survival of Castration-Resistant Prostate Cancer.

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