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OBJECTIVE To determine the optimal therapeutic plan for metastatic hormone-sensitive prostate cancer （mHSPC）， and to provide reference for clinical decision-making. METHODS Retrieved from Medline， Embase， BIOSIS preview， the Cochrane Library and ClinicalTrials. gov systematically， randomized controlled trials about mHSPC therapy， with overall survival （OS） and radiographic progression-free survival （rPFS） as efficacy outcomes and the incidence of serious adverse events （SAEs） as safety outcome， were collected during the inception-Mar. 2022. Two researchers independently screened the literature， extracted data， and evaluated the risk of bias for the included study before conducting a Bayesian network meta-analysis. RESULTS Eight studies with 9 437 patients were finally included. The effectiveness and safety of 7 therapy plans were compared [abiraterone acetate， apalutamide， darolutamide+docetaxel， docetaxel， enzalutamide， standard non-steroidal antiandrogen （SNA） in addition to ADT， and ADT alone]. In terms of efficacy index， the most beneficial regimen （except for ADT+SNA） for OS was ADT+darolutamide+docetaxel （HR＝0.54， 95%CI of 0.44-0.66）， followed by ADT+abiraterone acetate （HR＝0.64，95%CI of 0.57- 0.71）， apalutamide （HR＝0.65， 95%CI of 0.53-0.79）， enzalutamide （HR＝0.66， 95%CI of 0.53-0.82）； the least beneficial regimen for OS was ADT+docetaxel （HR＝0.79， 95%CI of 0.71-0.88）. The most beneficial regimen （except for ADT+SNA） for rPFS was ADT+enzalutamide （HR＝0.39， 95%CI of 0.30-0.50）， followed by ADT+apalutamide （HR＝0.48， 95%CI of 0.39- 0.60）， abiraterone acetate （HR＝0.57， 95%CI of 0.51-0.64）， docetaxel （HR＝0.62， 95%CI of 0.56-0.69）. The results of the tumor- loading subgroup analysis were the same. In terms of safety， ADT+darolutamide+docetaxel （OR＝25.86， 95%CI of 14.08-51.33）， and ADT+docetaxel （OR＝23.35， 95%CI of 13.26-44.81） were associated with markedly increased SAEs； the incidence of SAEs caused by ADT+abiraterone acetate （OR＝1.42，95%CI of 1.10-1.82） was slightly increased， and those of other therapy plans had no significant difference. CONCLUSIONS Compared with ADT alone， ADT+ darolutamide+docetaxel may provide the most significant OS benefit， but the incidence of SAEs is increased greatly； compared with ADT+docetaxel， ADT+abiraterone acetate， apalutamide or enzalutamide provide more OS benefits. ADT+enzalutamide provide optimal rPFS benefits with no increased SAEs.
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Background: Androgen deprivation therapy (ADT) is indispensable part of treatment for metastatic prostate cancer (MPC) patients. There is documented association between ADT and adverse cardiovascular (CV) events, with variability between the different modes. However, there is dearth of evidence on the background CV risk factors of these group of patients at diagnosis. Aims and Objectives: We envisaged this retrospective observational study in the department of oncology to document the background CV risk factors of MPC patients at diagnosis, to help us better select the available ADTs based on their CV risks. Materials and Methods: Over a period of 2 years, all patients registered for treatment with a diagnosis of MPC, indicated for ADT, and available detailed history and background cardiological evaluation at presentation, were included in the study. As indirect indicators of CV risks, history of smoking, presence and treatment of dyslipidemia, and type 2 diabetes mellitus (T2DM), were documented. As direct indicators of CV risks, presence and treatment of hypertension, ischemic heart disease (IHD), congestive cardiac failure (CCF), ECG, and echocardiography changes suggesting cardiac morbidity were documented and the data were analyzed using descriptive statistical methods. Results: Indirect indicators: dyslipidemia, habit of smoking, and T2DM were found in 74%, 29.3%, and 13.3% patients, respectively. Direct indicators: Presence of hypertension, IHD, CCF, abnormalities in ECG, and echocardiography were found in 38.7%, 10.6%, 4%, 28%, and 34.6% patients, respectively. ST-T changes on ECG, low EF, and IHD on echocardiography were seen in 28.5%, 23%, and 26.9%, respectively. Conclusions: MPC patients have a substantial pre-existing CV risk at diagnosis. Our findings warrant a meticulous screening of all MPC patients for CV risk factors, to help in judicious selection of their ADT.
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Objective:To investigate the efficacy and adverse reactions of moderately hypofractionated intensity modulated radiation therapy (IMRT) combined with androgen deprivation therapy (ADT) for locally advanced prostate cancer (LAPC).Methods:This study retrospectively analyzed the medical records of 40 LAPC patients who were admitted in The Second Hospital of Dalian Medical University during 2014-2020. The planning gross target volume (PGTV) dose for prostate gland and seminal vesicle gland was 64.8-70.0 Gy/25-28 f, 2.4-2.8 Gy/f and the dose of PGTVnd in 20 cases with positive pelvic lymph nodes was 60.0-64.4 Gy/25-28 f, 2.3-2.4 Gy/f. The dose of planning target volume (PTV) for the drainage area of pelvic lymph nodes was 45.0-50.4 Gy/25-28 f. The enrolled patients were treated with long-term ADT, including neoadjuvant, simultaneous, and adjuvant therapies. The efficacy and adverse reactions were evaluated. The prognostic factors affecting the biochemical failure-free survival (BFFS) were analyzed.Results:The median follow-up time was 31 months. The 2- and 3-year overall survival (OS) rates were 100% and 96.9%, respectively. The 1-, 2-, and 3-year BFFS rates were 90%, 76.8% and 72%, respectively. The 1-, 2-, and 3-year distant metastasis-free survival (DMFS) rates were 92.2%, 82.8% and 75.1%, respectively. Gleason (GS) score ( χ2=10.00, P < 0.05) and adjacent tissue invasion ( χ2=8.85, P<0.05) were prognostic factors related to BFFS for LAPC. Adjacent tissue invasion and GS 9-10 were independent poor prognostic factors. The incidence of acute urinary adverse reaction and rectal injury (grade≥2) was 7.5% and 20%, respectively. The incidence of late urinary adverse reaction and rectal injury (grade≥2) was 12.5% and 17.5%, respectively. Adverse reactions at grade 3-4 did not occur. Conclusions:The moderately hypofractionated IMRT combined with ADT is feasible for LAPC treatment, achieving satisfactory survival effects. 70 Gy/25-28 f, 2.5-2.8 Gy/f is a safe and effective moderate hypofraction scheme. Adjacent tissue invasion and GS score are prognostic factors related to BFFS for LAPC.
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Studies have investigated the effects of androgen deprivation therapy (ADT) use on the incidence and clinical outcomes of coronavirus disease 2019 (COVID-19); however, the results have been inconsistent. We searched the PubMed, Medline, Cochrane, Scopus, and Web of Science databases from inception to March 2022; 13 studies covering 84 003 prostate cancer (PCa) patients with or without ADT met the eligibility criteria and were included in the meta-analysis. We calculated the pooled risk ratios (RRs) with 95% confidence intervals (CIs) to explore the association between ADT use and the infection risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and severity of COVID-19. After synthesizing the evidence, the pooled RR in the SARS-CoV-2 positive group was equal to 1.17, and the SARS-CoV-2 positive risk in PCa patients using ADT was not significantly different from that in those not using ADT (P = 0.544). Moreover, no significant results concerning the beneficial effect of ADT on the rate of intensive care unit admission (RR = 1.04, P = 0.872) or death risk (RR = 1.23, P = 0.53) were found. However, PCa patients with a history of ADT use had a markedly higher COVID-19 hospitalization rate (RR = 1.31, P = 0.015) than those with no history of ADT use. These findings indicate that ADT use by PCa patients is associated with a high risk of hospitalization during infection with SARS-CoV-2. A large number of high quality studies are needed to confirm these results.
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Male , Humans , Prostatic Neoplasms/chemically induced , Androgen Antagonists/adverse effects , COVID-19 , Androgens/therapeutic use , SARS-CoV-2ABSTRACT
We aimed to study radiomics approach based on biparametric magnetic resonance imaging (MRI) for determining significant residual cancer after androgen deprivation therapy (ADT). Ninety-two post-ADT prostate cancer patients underwent MRI before prostatectomy (62 with significant residual disease and 30 with complete response or minimum residual disease [CR/MRD]). Totally, 100 significant residual, 52 CR/MRD lesions, and 70 benign tissues were selected according to pathology. First, 381 radiomics features were extracted from T2-weighted imaging, diffusion-weighted imaging, and apparent diffusion coefficient (ADC) maps. Optimal features were selected using a support vector machine with a recursive feature elimination algorithm (SVM-RFE). Then, ADC values of significant residual, CR/MRD lesions, and benign tissues were compared by one-way analysis of variance. Logistic regression was used to construct models with SVM features to differentiate between each pair of tissues. Third, the efficiencies of ADC value and radiomics models for differentiating the three tissues were assessed by area under receiver operating characteristic curve (AUC). The ADC value (mean ± standard deviation [s.d.]) of significant residual lesions ([1.10 ± 0.02] × 10-3 mm2 s-1) was significantly lower than that of CR/MRD ([1.17 ± 0.02] × 10-3 mm2 s-1), which was significantly lower than that of benign tissues ([1.30 ± 0.02] × 10-3 mm2 s-1; both P < 0.05). The SVM feature models were comparable to ADC value in distinguishing CR/MRD from benign tissue (AUC: 0.766 vs 0.792) and distinguishing residual from benign tissue (AUC: 0.825 vs 0.835) (both P > 0.05), but superior to ADC value in differentiating significant residual from CR/MRD (AUC: 0.748 vs 0.558; P = 0.041). Radiomics approach with biparametric MRI could promote the detection of significant residual prostate cancer after ADT.
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Male , Humans , Prostatic Neoplasms/drug therapy , Androgen Antagonists/therapeutic use , Androgens , Neoplasm, Residual , Retrospective Studies , Magnetic Resonance Imaging/methods , Diffusion Magnetic Resonance Imaging/methodsABSTRACT
Androgen deprivation therapy (ADT) using gonadotropin?releasing hormone agonist (s) (GnRH?A) remains the backbone of advanced prostate cancer treatment. In this review, we assessed the efficacy, safety, and convenience of administration of various GnRH?A. All GnRH?A (goserelin, triptorelin, buserelin, histrelin, and leuprorelin) have comparable potential to suppress testosterone (T) levels (?50 ng/dL in a month and ?20 ng/dL in 3 months). However, goserelin has shown better efficacy in maintaining T levels ?50 ng/dL compared with leuprolide. The incidences of T escape are lower with goserelin and leuprolide than buserelin. Goserelin also has maximum benefit in prostate?specific antigen suppression. In neoadjuvant setting, when only goserelin was used, the 10?year overall survival (OS) rate was 42.6% to 86%. When either goserelin or leuprolide was used, the 10?year OS rate was 62%. As an adjuvant to radical prostatectomy, goserelin had a 10?year survival rate of 87%, and triptorelin had an 8?year survival rate of 84.6%. Goserelin further showed an absolute survival rate of 49% when used as an adjuvant to radiotherapy. The survival rates further improved when GnRH?A are used as combined androgen blockade compared with monotherapy. The frequency and severity of adverse events (hot flushes, fatigue, sexual dysfunction) are comparable among the GnRH?A. Goserelin appears to be the most convenient of all the GnRH?A for administration. Lack of conclusive comparative evidence makes it imperative to have a holistic approach of considering the patient profile and the disease characteristics to select the appropriate GnRH?A for ADT in prostate cancer.
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Owing to incurable castration-resistant prostate cancer (CRPC) ultimately developing after treating with androgen deprivation therapy (ADT), it is vital to devise new therapeutic strategies to treat CRPC. Treatments that target programmed cell death protein 1 (PD-1) and programmed death ligand-1 (PD-L1) have been approved for human cancers with clinical benefit. However, many patients, especially prostate cancer, fail to respond to anti-PD-1/PD-L1 treatment, so it is an urgent need to seek a support strategy for improving the traditional PD-1/PD-L1 targeting immunotherapy. In the present study, analyzing the data from our prostate cancer tissue microarray, we found that PD-L1 expression was positively correlated with the expression of heterogeneous nuclear ribonucleoprotein L (HnRNP L). Hence, we further investigated the potential role of HnRNP L on the PD-L1 expression, the sensitivity of cancer cells to T-cell killing and the synergistic effect with anti-PD-1 therapy in CRPC. Indeed, HnRNP L knockdown effectively decreased PD-L1 expression and recovered the sensitivity of cancer cells to T-cell killing in vitro and in vivo, on the contrary, HnRNP L overexpression led to the opposite effect in CRPC cells. In addition, consistent with the previous study, we revealed that ferroptosis played a critical role in T-cell-induced cancer cell death, and HnRNP L promoted the cancer immune escape partly through targeting YY1/PD-L1 axis and inhibiting ferroptosis in CRPC cells. Furthermore, HnRNP L knockdown enhanced antitumor immunity by recruiting infiltrating CD8+ T cells and synergized with anti-PD-1 therapy in CRPC tumors. This study provided biological evidence that HnRNP L knockdown might be a novel therapeutic agent in PD-L1/PD-1 blockade strategy that enhanced anti-tumor immune response in CRPC.
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Androgen deprivation therapy is one of the main treatments for prostate cancer patients. In recent years, many studies have revealed that androgen deprivation therapy increases the risk of cardiovascular disease, which leads to the cause of death alongside tumor-related deaths. The mechanism may be related to the elevation of testosterone levels, follicle-stimulating hormone levels and unstable atherosclerotic plaque. Standardized cardiovascular disease management in this population is a key issue to improve survival and prognosis. This paper summarizes a management plan covering 5 areas, including history collecting and data examination, assessment, referral, health education, and regimen selection.
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Androgen deprivation therapy (ADT) is currently the mainstay of treatment for advanced prostate cancer. The peptide formulations of gonadotropin-releasing hormone (GnRH) antagonists need to be given subcutaneously every month. This led to the development of an oral, nonpeptide GnRH antagonist formulation relugolix which promptly lowers the levels of testosterone, luteinizing hormone, and follicular-stimulating hormone. On December 18, 2020, the US Food and Drug Administration approved relugolix for the treatment of adult advanced prostate cancer. The recommended loading dose of 360 mg on the 1st day of treatment, followed by 120 mg once daily orally, approximately the same time each day. The maximum plasma concentration (Tmax) is obtained within 2.25 h and is metabolized to a major extent by CYP3A mediated mechanism. Hot flushes, musculoskeletal pain, and fatigue are some of its common adverse effects. High rates of testosterone suppression with a limited adverse event profile make it an ideal therapy for the treatment of advanced prostate cancer.
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Objective:To explore the predictive effect of alternative splicing events and splicing factors on the prognosis of prostate cancer patients with androgen deprivation therapy (ADT).Methods:The relevant clinical and transcriptome information of 60 prostate cancer patients with ADT were downloaded from TCGA database, and the alternative splicing events information was obtained. LASSO and Cox regression models were used to screen the relevant alternative splicing events and splice factors through R language package. The related model was established, and the independent prognostic analysis and related regulatory network analysis were performed.Results:A total of 44 070 associated alternate splicing events were identified in prostate cancer patients, including 3 525 alternate acceptor sites (AA), 3 101 alternate donor sites (AD), 9 035 alternate promoters (AP), 8 663 alternate terminators (AT), 16 772 exon skipping (ES), 228 exon mutual exclusion (ME), and 2 747 retained intron (RI). Through univariate Cox proportional hazard regression model, 1 349 alternate splicing events were identified as disease-free survival-related splicing events (DFS-SE) related to ADT, including 145 AA events, 102 AD events, 243 AP events, 189 AT events, 557 ES events, 6 ME events, and 107 RI events. Multivariate Cox regression analysis show that after adding clinical related information, ME events (ANK3|11852|ME, TCF7L2|151705|ME, UBR2|127390|ME and SLC39A14|140283|ME) may be independent prognostic factors for predicting ADT resistance ( HR = 1.398, 95% CI 1.156-1.689, P<0.01). Conclusion:The combination of ME-type alternate splicing events and related clinical data has certain significances in predicting the effectiveness of ADT in prostate cancer patients, and plays an important role in the research on the resistance of prostate cancer patients to ADT.
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Androgen deprivation therapy (ADT) combined with abiraterone and prednisone.for metastatic hormone sensitive prostate cancer (mHSPC) is proved effective in many researches, but it is not verified in china. We present the case of a 62-year-old man who was referred to our hospital for high-risk mHSPC with the main symptoms of dysuria and weak stream. the level of prostate-specific antigen (PSA) was elevated, and the results of biopsy, magnetic resonance and PET-CT showed prostate cancer with multiple lymph node metastases to the right scapula and right pubic bone (T 3bN 1M 1b). The patients were treated with the combination of ADT plus abiraterone and prednisone. After treatment, the level of PSA and testosterone returned to normal and were well-controlled.
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Conclusion:Patients with OlimHSPC who are not sensitive to traditional CAB treatment, ADT combined with abiraterone acetate neoadjuvant therapy and postoperative adjuvant therapy can be attempted.
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Many clinical trials have shown that androgen deprivation therapy (ADT) combined with novel hormonal therapy or chemotherapy can improve the overall outcome of metastatic hormone-sensitive prostate cancer (mHSPC) patients. In this article, we report a patient with mHSPC diagnosed as stage T 3bN 0M 1b, who had a significant PSA decrease after receiving ADT combined with abiraterone acetate and underwent corticosteroid switch due to adverse events. This case suggest that ADT combined with abiraterone acetate could improve the overall survival of mHSPC patients, but clinicians should make individualized treatment plan based on patients special condition.
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Metastatic castration-resistant prostate cancer (mCRPC) is the inevitable form of most prostate cancers after endocrine therapy, and conventional drugs are not effective at this time.In this case, an elderly mCRPC patient with cardiopulmonary diseases admitted to the First Hospital of Shanxi Medical University in August 2020 was selected. After the failure of traditional endocrine therapy, enzalumide+ ADT regimen was adopted, and the patient's blood PSA was significantly reduced without cardiopulmonary adverse events.
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This case was a 75-year-old prostate cancer patient with multiple cardiovascular diseases. The clinical stage was T 3bN 1M 0.After regular follow-up with androgen deprivation therapy (ADT)(Goserelin+ bicalutamide), the PSA increased slowly at the 13th month, and at the 17th month, the trend of progression to castrated resistant prostate cancer (CRPC) was considered, combined with patients with a variety of cardiovascular diseases, we choose the first-line application of Enzaluamine treatment, the disease has been effectively controlled. Through the diagnosis and treatment of this case, we should consider not only the effectiveness and safety of the treatment, but also the influence and risk of the treatment to the cardiovascular disease.
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Androgen deprivation therapy is one of the main therapies for metastatic hormone sensitive prostate cancer. A case of metastatic hormone sensitive prostate cancer was reported, a 55 year old patient was admitted to the hospital due to increased PSA in physical examination. PET-CT examination showed multiple clinical metastases in the left neck, abdominal cavity, retroperitoneal cavity and pelvic cavity. Bone metastases occurred in the right fourth rib and the left sixth and seventh ribs; after 8 months of endocrine therapy and the second generation of anti androgen therapy, the reexamination of imaging examination showed that the prostate lesions, seminal vesicle invasion, bone metastases were all subsided.
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Objective@#To investigte the efficacy of docetaxel combined with androgen deprivation therapy for the treatment of metastatic hormone-sensitive prostate cancer based on Chinese population.@*Methods@#A total of 497 patients were enrolled from January 2004 to July 2018 in the Changhai Hospital. 459 patients received androgen deprivation therapy alone and 38 patients received androgen deprivation therapy combined with docetaxel. The mean age was (72.1±8.7)years. The median PSA level was 100.0 ng/ml, ranging 42.3-999.0 ng/ml. Patients of clinical T2, T3, T4 stage were 213(42.9%), 160(32.2%), 124(24.9%), respectively. Patients of clinical N0, N1, Nx stage were 319(64.2%), 144(29.0%), 34(6.8%), respectively. Patients of clinical M0, M1a, M1b, M1c, Mx stage were 100(20.1%), 51(10.3%), 332(66.8%), 9(1.8%), 5(1.0%), respectively. Gleason scores of biopsy showed that 146(29.4%) patients was ≤7, 103(20.7%) was 8 and 248(49.9%)was ≥9. Propensity score matching was used to match the baseline between groups. Caliper value was set at 0.02. SPSS 22 software was used to achieve a 1∶1 match between the two groups. There were no statistical difference in the age(P=0.102), PSA(P=0.713), T stage(P=0.113), N stage(P=0.226), M stage(P=0.514), Gleason score(P=0.612), tumor loading(P=0.812)between the two groups. The castration resistance-free rate and cancer specific survival rate of the two groups were compared by log-rank and breslow-wilcoxon test. Furthermore, forest plots were used to display the analysis results of different subgroups such as age, PSA, clinical stage, Gleason score, tumor load, whether patients had received palliative resection, and the differences in castration resistance-free rate were compared between the subgroups with high tumor load.@*Results@#The median follow-up time was 22.6 months in the androgen deprivation therapy group and 13.7 months in the combined therapy group. The number of patients with castration resistance in the two groups was 23 and 17, respectively. There were 3 and 6 deaths, respectively. There was no statistically significant difference in the overall progression time to castration resistance between the two groups (10.3 m vs. 16.5 m, P>0.05), and no statistically significant difference in the prostate cancer specific survival rate (21.9 m vs.14.8 m, P>0.05). When subgroup analysis was performed, it was found that patients in the high-metastasis-volume subgroup who received the combination therapy had a significantly longer castration resistance free lifetime (10.6 m vs. 7.2 m, P=0.044), but there was no significant difference in the low- metastasis-volume subgroup(10.5 m vs.12.6 m, P>0.05).@*Conclusion@#Docetaxel combined with androgen deprivation therapy can improve the castration resistance free rate in patients with high metastasis volume, but not in low metastasis volume group.
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Objective To evaluate the effect of neoadjuvant androgen deprivation therapy (ADT) for prostate cancer on diffusion weighted imaging base on the pathological results after radical prostatectomy.Methods Medical records of 33 patients diagnosed with prostate cancer and treated with neoadjuvant androgen deprivation therapy and radical prostatectomy between January 2016 and September 2019 at Peking University First Hospital were retrospectively reviewed.Average age of patients was 67.7 (49-81) years old.All of the patients underwent prostate MRI examination before and after neoadjuvant ADT.Results Mean prostate volume after neoadjuvant ADT is 28.5 (6.25-113.76) em3,which decreased significantly by therapy (Z =-4.458,P ＜ 0.05).Apparent diffusion coefficient (ADC) values increased significantly in tumor (1.070 ± 0.325) vs.(0.828 ± 0.291) × 10-3 mm2/s (P ＜ 0.001) and decreased in benign prostatic tissue (P ＜ 0.05).Relative changes in ADC differed significantly between low-median level ISUP group and high level ISUP group (0.315 ± 0.173) vs.(0.164 ± 0.224) × 10-3 mm2/s (P ＜ 0.05),as well as obvious reaction group and focal reaction group(0.278 ± 0.21) vs.(0.094 ± 0.119) × 10-3 mm2/s (P ＜ 0.05).Conclusions There were significant,quantitative measurable changes of ADC value in prostate cancer after neoadjuvant ADT.DWI can be used to assess the efficacy of neoadjuvant ADT for prostate cancer as well as predicting pathological features.
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Objective To investigte the efficacy of docetaxel combined with androgen deprivation therapy for the treatment of metastatic hormone-sensitive prostate cancer based on Chinese population.Methods A total of 497 patients were enrolled from January 2004 to July 2018 in the Changhai Hospital.459 patients received androgen deprivation therapy alone and 38 patients received androgen deprivation therapy combined with docetaxel.The mean age was (72.1 ± 8.7)years.The median PSA level was 100.0 ng/ml,ranging 42.3-999.0 ng/ml.Patients of clinical T2,T3,T4 stage were 213 (42.9％),160 (32.2％),124(24.9％),respectively.Patients of clinical N0,N1,Nx stage were 319 (64.2％),144 (29.0％),34 (6.8％),respectively.Patients of clinical M0,M1a,M1b,M1c,Mx stage were 100(20.1％),51 (10.3％),332 (66.8％),9 (1.8％),5 (1.0％),respectively.Gleason scores of biopsy showed that 146 (29.4％) patients was ≤7,103(20.7％) was 8 and 248(49.9％)was ≥9.Propensity score matching was used to match the baseline between groups.Caliper value was set at 0.02.SPSS 22 software was used to achieve a 1:1 match between the two groups.There were no statistical difference in the age(P =0.102),PSA (P =0.713),T stage (P =0.113),N stage (P =0.226),M stage (P =0.514),Gleason score (P =0.612),tumor loading(P =0.812) between the two groups.The castration resistance-free rate and cancer specific survival rate of the two groups were compared by log-rank and breslow-wilcoxon test.Furthermore,forest plots were used to display the analysis results of different subgroups such as age,PSA,clinical stage,Gleason score,tumor load,whether patients had received palliative resection,and the differences in castration resistance-free rate were compared between the subgroups with high tumor load.Results The median follow-up time was 22.6 months in the androgen deprivation therapy group and 13.7 months in the combined therapy group.The number of patients with castration resistance in the two groups was 23 and 17,respectively.There were 3 and 6 deaths,respectively.There was no statistically significant difference in the overall progression time to castration resistance between the two groups (10.3 m vs.16.5 m,P ＞ 0.05),and no statistically significant difference in the prostate cancer specific survival rate (21.9 m vs.14.8 m,P ＞ 0.05).When subgroup analysis was performed,it was found that patients in the high-metastasis-volume subgroup who received the combination therapy had a significantly longer castration resistance free lifetime (10.6 m vs.7.2 m,P =0.044),but there was no significant difference in the low-metastasis-volume subgroup (10.5 m vs.12.6 m,P ＞ 0.05).Conclusion Docetaxel combined with androgen deprivation therapy can improve the castration resistance free rate in patients with high metastasis volume,but not in low metastasis volume group.
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PURPOSE: The purpose of this study was to evaluate the association of androgen deprivation therapy (ADT) with cognitive dysfunction. MATERIALS AND METHODS: Using the National Health Insurance Service database of the entire Korean adult prostate cancer population (n=236,391), data on ADT and cognitive dysfunction between 2008 and 2015 were analyzed. We excluded patients previously diagnosed with cognitive dysfunction, dementia, or a cerebral event history. We tested the effect of ADT on the risk of cognitive dysfunction using propensity score–matched Cox proportional hazards regression models and Kaplan-Meier survival analysis. Our final cohort comprised of 35,401 individuals with prostate cancer, including 24,567 men (70.6%) who underwent ADT. RESULTS: During a mean follow-up period of 4.1 years, 4,741 patients were newly diagnosed with cognitive dysfunction. A statistically significant association was found between ADT and the risk of cognitive dysfunction (hazard ratio, 1.169; p=0.002). Meanwhile, age (≥ 70 years), diabetes, hypertension, cardiovascular history, and peripheral vascular disease were identified as factors that contribute to the increased risk of cognitive dysfunction. In contrast, the use of statins and aspirin was associated with a lower risk of cognitive dysfunction. Kaplan-Meier analysis demonstrated that patients aged 70 years or older who underwent ADT had the lowest cumulative probability of remaining cognitive dysfunction-free (log-rank p < 0.001). CONCLUSION: Our results revealed an association between the use of ADT for the treatment of prostate cancer and an increased risk of cognitive dysfunction in a nationwide population-based study. This finding should be further evaluated in prospective studies.