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Objective To determine the influence of abiraterone acetate (AA) on neuroendocrine differentiation (NED) in metastatic castration-resistant prostate cancer (mCRPC) and the prognostic predicting value of the serum NED markers in mCRPC patients treated with AA.Methods We conducted an analysis in 115 chemotherapy-naive mCRPC patients who were treated with chemotherapy in Renji hospital from 2013 to 2017.The median age was 70,ranged from 65 to 76 years old.The median CgA,NSE and PSA levels were 101.1 ng/ml (78.5-150.0 ng/ml),13.4 ng/ml (10.5-17.6 ng/ml) and 38.8 ng/ml (11.2-123.2 ng/ml),respectively.Among them,48 cases were classified as the group without AA treatment.The other 67 cases were classified as group after AA failure.In group without AA treatment,the median CgA,NSE and PSA levels were 109.1 ng/ml(80-151.5 ng/ml);13.8 ng/ml(10.8-18.2 ng/ml) and 39.2 ng/ml (8.6-200 ng/ml),respectively.In group after AA failure,the median CgA,NSE and PSA levels were 105.4 ng/ml(78.8-175.5 ng/ml),13.8 ng/ml(10.8-17.6 ng/ml) and 39.0 ng/ml(8.4-219.8 ng/ml),respectively.In the group with serial evaluation of NED markers during AA treatment,the median serum CgA,NSE levels at baseline were 115.9 ng/ml(90.1-201.5 ng/ml),13.3 ng/ml (10.4-18.1 ng/ml),respectively.The endpoints were PSA PFS(progression-free survival) and radiographic PFS (rPFS).Results In 34 patients with serial evaluation,serum NED markers level in 19 patients increased after the failure of AA treatment.Median serum CgA and NSE levels were 115.9 ng/ml(90.1-201.5 ng/ml)and 13.25 ng/ml (10.37-18.14 ng/ml) at baseline.Median serum CgA and NSE levels were 129.6ng/ml (75.5-230.5 ng/ml) and 14.7 ng/ml (11.8-19.1 ng/ml) after 6 months treatment,respectively.The median serum CgA and NSE levels were 130.4 ng/ml (95.7-205.7 ng/ml) and 15.2 ng/ml(12.4-18.7 ng/ml) at the time of failure of AA treatment,respectively.There was no significant difference of NED markers between baseline and failure of AA treatment (P =0.243).In logistic univariate analysis,AA treatment and its duration were not independent factors influencing NED(P =0.30;P =0.52).Compared with the NED markers elevation group in the first 6 months of AA treatment and baseline supranormal NED markers group,the NED markers decline group(PSA PFS(17.1 vs.10.4 months,P ＜ 0.001) and rPFS (17.0 vs.10.4 months,P =0.003)) and baseline normal NED markers group(PSA PFS(14.1 vs.9.5 months,P =0.001) and rPFS(16.4 vs.10.5 months,P ＜ 0.001)) has a longer median PSA PFS and rPFS respectively.In multivariate Cox analysis,baseline NED markers level and NED markers variation during the first 6 months of AA treatment remained significant predictors of rPFS(P ＜ 0.05),and PSA-PFS (P ＜ 0.05).Conclusions We found there was heterogeneity in changes of NED markers in different mCRPC patients during AA treatment,and AA might not significantly lead to progression of NED of mCRPC in general.Serial CgA and NSE evaluation might help clinicians guide clinical treatment of mCRPC patients.Serum NED markers elevation during the first 6 months of AA treatment and elevated baseline NED markers levels indicated poor prognosis in mCRPC treated with AA.
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Objective To investigate the efficacy and safety of docetaxel chemotherapy combined with androgen-deprivation therapy (ADT) for patients with metastatic hormone-sensitive prostate cancer.Methods One hundred and ninety-two cases of metastatic hormone-sensitive prostate cancer in Renji Hospital between January 2015 and July 2016 were analyzed retrospectively.Patients' age was 39 to 90,the median age was 71 years.The median prostate-specific antigen (PSA) at diagnosis was 90.6ng/ml (4.1-2 556.0 ng/ml).One hundred and eighty were with bone metastasis and 12 were with distant lymphatic metastasis.Sixty-one of them received docetaxel chemotherapy plus ADT for 3 weeks,131 received hormonal treatment alone.The median age of combination therapy group was 67 years (39-80 years),that of single treatment group was 75 years (50-93 years) (P ＜ 0.001).The median PSA baseline of the two groups were 91.6 ng/ml (35.5-157.5ng/ml) and 89.1 ng/ml (59.6-191.0 ng/ml) (P =0.324).Gleason score of combination therapy group showed that 3 cases (4.9％) was 6,23 cases (37.7％) 7,35 cases (57.4％) ≥8.That of single treatment group showed that 17 cases (13.0％) 6,51 cases (38.9％) 7,63 cases (48.1％) ≥8.There was no statistic difference between the two groups (P =0.122).But there was statistic difference in the rate of T3 or T4 clinical stage in primary lesion,that of combination therapy group was 50.7％ (37/61) and 34.4％ (21/61),and that of single treatment group was 60.3％ (79/131) and 21.4％ (28/131) (P =0.011).Imaging showed local lymph node metastasis in the two groups (80.3％ vs.67.9％,P =0.005).As to physical condition,the combination therapy group showed a lower ECOG score than the single treatment group (P ＜ 0.001).All the patients' survival condition,PSA response rate and adverse events were analyzed.Results One hundred and ninety-two patients were regularly followedup.The median follow-up time was 23.3 (14.4-33.4) months.Median progression free survival time of combination therapy group and single treatment group were respectively 24.4 (7.5-31.3) months vs.17.5(3.0-30.7) months (P ＜ 0.001).There were 1 and 16 cases died in the two groups due to disease progression.During the treatment,the rate of PSA level less than 0.2 ng/ml was 29.5％ (18/61) vs.13.7％ (18/131) in combination therapy group and single treatment group.Regarding the tolerance of combination therapy group,the incidence rate of grade 3-4 neutropenia was 27.9％ (17/61).Skin and mucous membrane damaged in 24.6％ (15/61) patients,transaminase rised in 13.1％ (8/61) patients,and peripheral nerve toxicity occurred in 9.8％ (6/61) patients.There was no significant difference between the 2 groups in relevant events caused by ADT,gynecomastia (14.8％ vs.16.3％) and erectile dysfunction (100％ vs.100％).Most of them could be relieved by symptomatic treatment.Conclusions For metastatic hormone-sensitive prostate cancer,docetaxel combined with hormonal treatment showed longer progression free survival than ADT alone with adverse reactions acceptable.
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Objective· To assess the efficacy of abiraterone acetate (AA) plus prednisone treating metastatic castration-resistant prostate cancer (mCRPC) patients and analyze the prognostic factors for this treatment. Methods · The medical history of 112 patients with mCRPC treated in Renji Hospital affiliated to Shanghai Jiao Tong University School of Medicine, including 70 patients in the chemotherapy-na?ve setting and 42 in the post-chemotherapy setting, were retrospectively reviewed. Coprimary end points were prostate specific antigen progression-free survival (PSA PFS), radiographic PFS (rPFS) and overall survival (OS). Univariable and multivariable Cox analyses were performed to determine prognostic factors that were associated with PSA PFS, rPFS and OS. Results · At a median follow-up of 20.2 months, 59 (52.7%) patients had died. The median PSA PFS, rPFS and OS were 8.9 (7.8~10.0) months, 9.7 (9.0~10.4) months, and 22.2 (20.3~24.1) months, respectively. In multivariate analysis, previous chemotherapy, neutrophil lymphocyte ratio(≥3 vs<3),serum lactate dehydrogenase level(≥196 U/L vs<196 U/L)and ECOG PS(≤?1 vs 2)were independent predictors for PSA PFS and rPFS,and previous chemotherapy,ECOG PS(≤?1 vs 2)remained significant predictors for OS. Conclusion·These results further support the favourable profile of AA plus prednisone in patients with mCRPC in China.Previous chemotherapy,ECOG PS(≤?1 vs 2)remained significant predictors for OS.