Efficacy Of Chemotherapy Combined With Hormonal Therapy For Metastatic Castration-sensitive Prostate Cancer And Prognosis Of The Patients

Objective To explore the effecacy of docetaxel combined with androgen-deprivation therapy(ADT)for Asian patients with metastatic hormone-sensitive prostate cancer(mHSPC)and the value of prostate specific antigen(PSA)kinetics in predicting the risk of disease progression and castrated resistance.Methods A retrospective analysis was performed for 73 mHSPC patients who had confirmed diagnosis and received initial treatment at the urinary surgery department of Zhejiang Cancer Hospital from June 2012 to October 2017.Among them,40 patients received≥ 3 cycles of docetaxel plus ADT(combined treatment group)compared to 33 patients in the control group receiving ADT.The baseline information and follow-up data of these patients were collected,sorted and analyzed.Kaplan-Meier survival analysis was performed to compare the differences between the two groups in terms of disease progression and prognosis,with subgroup analysis based on forest plot.The Cox proportional-hazards model was used to assess the influence of each risk factor on the time to CRPC progression.Results The median follow-up of our study was 32.3 months.Until the last date of follow-up,there were 7(17.5%)and 16(48.5%)patients died in the combined treatment group and endocrine therapy group,respectively.Among them 1(14.3%)and 7(43.8%)patients died of disease progression,respectively,and there was no significant difference in overall survival(OS,42.9 months versus 34.6 months;HR=0.55;95%CI,0.21-1.39;P>0.05).The castration-resistant prostate cancer free survival(CRPC-FS)of the combined treatment group was longer by 9.9 months than that of the ADT group(25.1 months vs.15.2 months;HR=0.48;95%CI,0.265-0.879;P=0.017).This result was significantly different between patients with high-volume disease(HVD)and high-risk disease(HRD)(P<0.05).The CRPC-FS of the HRD patients in the docetaxel-based chemotherapy group was longer than 12.6 months(25.1 months versus 12.5 months,HR=3.33,95%CI,1.587-6.98,P=0.001).Multivariate analysis showed that the adverse prognostic factors for patients receiving ADT alone were Gleason scores≥8(HR＝9.75;95%CI,2.25-42.16;P=0.002),higher nadir PSA(nPSA)(HR=22.64;95%CI,2.91-175.88;P=0.003)and shorter time to PSA nadir(TTN)(HR=0.06;95%CI,0.01-0.42;P=0.004).In the combined treatment group,the higher nPSA(HR=7.11;95%CI,1.20-25.31;P=0.002)and the elevated AKP level(HR=8.05;95%CI,1.91-33.86;P=0.004)were associated with a much higher risk of progression to mCRPC.Conclusion Docetaxel plus ADT could more effectively slow down the progression of CRPC in mHSPC patients compared with ADT alone.Moreover,the prognosis of patients in the combined treatment was correlated significantly with PSA nadir and baseline AKP levels.In the ADR alone group,patients with Gleason score≥8,higher nPSA level and shorter TTN were easily progress to mCRPC.PSA nadir and baseline AKP level were independent predictors of disease progression in patients treated with combination therapy.