Comprehensive treatment for metastatic castration-resistant prostate cancer with neuroendocrine differentiation:a case report

Retrospective analysis of the progression of a case of metastatic castration-resistant prostate cancer with neuroendocrine differentiation:the patient was a 65 year old man with prostate adenocarcinoma on prostate biopsy,Gleason 4+4 score=8,70%,ISUP4 group,localized invasion of nerves.Progressed to metastatic castration-resistant prostate cancer after 8 months of novel endocrine therapy,persistent elevated PSA after endocrine therapy,chemotherapy,and radiation,abdominal metastasis,brain metastasis,gastric metastasis,and staging as neuroendocrine differentiation after second prostate biopsy,which is a highly malignant subtype and has been concerned as a mechanism of resistance to targeted therapies.We discuss how to choose a more optimal treatment plan and outline the patient's diagnostic and therapeutic course.We provide a reflection for the clinical study of metastatic castration-resistant prostate cancer with neuroendocrine type.

Surface-enhanced Raman spectroscopy of serum predicts sensitivity to docetaxel-based chemotherapy in patients with metastatic castration-resistant prostate cancer

Docetaxel-based chemotherapy,as the first-line treatment for metastatic castration-resistant prostate cancer(mCRPC),has succeeded in helping quite a number of patients to improve quality of life and prolong survival time.However,almost half of mCRPC patients are not sensitive to docetaxel chemotherapy initially.This study aimed to establish models to predict sensitivity to docetaxel chemotherapy in patients with mCRPC by using serum surface-enhanced Raman spectroscopy(SERS).A total of 32 mCPRC patients who underwent docetaxel chemo-therapy at our center from July 2016 to March 2018 were included in this study.Patients were dichotomized in prostate-specific antigen(PSA)response group(n=17)versus PSA failure group(n=15)according to the response to docetaxel.In total 64 matched spectra from 32 mCRPC patients were obtained by using SERS of serum at baseline(q0)and after 1 cycle of docetaxel chemotherapy(ql).Comparing Raman peaks of serum samples at baseline(q0)be-tween two groups,significant differences revealed at the peaks of 638,810,890(p<0.05)and 1136cm^(-1)(p<0.01).The prediction models of peak 1363 cm^(-1)and principal component anal-ysis and linear discriminant analysis(PCA-LDA)based on Raman data were established,re-spectively.The sensitivity and specificity of the prediction models were 71%,80%and 69%,78%through the way of leave-one-out cross-validation.According to the results of five-cross-valida-tion,the PCA-LDA model revealed an accuracy of 0.73 and AUC of 0.83.

Comparative analysis of the effectiveness of abiraterone before and after docetaxel in patients with metastatic castration-resistant prostate cancer

AIM: To study the efficacy and safety of abiraterone in patients with and without prior chemotherapy.METHODS: The databases including Pub Med and abstracts presented at the American Society of Clinical Oncology meetings up to April 2014 were systematically searched. Eligible studies included randomized controlled trials(RCTs) in which abiraterone plus prednisone was compared to placebo plus prednisone in metastatic castration-resistant prostate cancer(CRPC) patients. The summary incidence, relative risk, hazard ratio and 95%CI were calculated using random or fixed-effects models. Heterogeneity test was performed to test between-study differences in efficacy and toxicity.RESULTS: A total of two phase III RCTs were included in our analysis, with metastatic CPRC patients before(n = 1088) and after chemotherapy(n = 1195). Prior chemotherapy did not significantly alter the effect of abiraterone on overall survival(P = 0.92) and prostatespecific antigen(PSA) progression-free survival(P = 0.13), but reduced its effect on radiographic-prog-ression-free survival(P = 0.04), objective response rate(P < 0.001), and PSA response rate(P < 0.001). Prior chemotherapy significantly increased the specific risk of fluid retention and edema(P < 0.001) and hypokalemia(P < 0.001), but decreased the risk of all-grade hypertension(P < 0.001) attributable to abiraterone. There was no significant difference of cardiac disorders associated with abiraterone between the two settings(P = 0.58). CONCLUSION: Prior chemotherapy may reduce the effectiveness of abiraterone in patients with metastatic CRPC.

Nonmetastatic castration-resistant prostate cancer: Novel agents to treat a lethal disease

Nonmetastatic castration-resistant prostate cancer(nmCRPC)-defined as prostate-specific antigen(PSA)>2 ng/mL,testosterone castration levels<1.7 nm/L,and the absence of metastatic lesions on conventional imaging(computed tomography or bone scan)-has been defined as a lethal disease by the Prostate Cancer Work Group.One-third of patients with prostate cancer who receive androgen deprivation therapy for biochemical recurrence after local treatment will develop CRPC,with death occurring an average of 2.5 years after diagnosis of castration resistance.Most patients diagnosed with nmCRPC are asymptomatic or minimally symptomatic at diagnosis due to local treatment.In patients with short PSA doubling times(<10 mo)and high baseline PSA levels,there is a high risk of bone metastases followed by prostate cancer-related mortality.These patients also present significant morbidity that negatively impacts quality of life(QoL).Recently,the results of three randomized trials(PROSPER,SPARTAN,and ARAMIS)were published.Those trials evaluated the efficacy of three different androgen receptor inhibitors-enzalutamide,apalutamide,and darolutamide-in patients with nmCRPC.In all three trials,the study drugs improved both metastasis-free survival and overall survival compared to placebo,plus on-going androgen deprivation therapy without a negative impact on QoL.In patients with nmCRPC,the most important clinical objective is early detection and treatment to maintain a low tumor burden and to prolong the symptom-free interval.For patients with nmCRPC,these novel drugs offer new hope for better QoL and survival outcomes.

Prognostic factors in Chinese patients with metastatic castration-resistant prostate cancer treated with docetaxel-based chemotherapy

This study aims to evaluate the potential value of patient characteristics in predicting overall survival （OS） in patients with metastatic castration-resistant prostate cancer （mCRPC） treated with docetaxel-based thermotherapy. A total of 115 patients with mCRPC undergoing a docetaxel q3w regimen were enrolled in this study. A survival analysis was performed using the Kaplan-Meier method. Cox proportional hazards models were used to evaluate the prognostic value of all covariates for OS. OS was also analysed after stratifying patients according to the results of multivariate analysis. The median OS for the entire cohort was 17.0 months. The multivariate analysis showed that the prostate-specific antigen doubling time （PSADT）, baseline haemoglobin （Hb） concentration, alkaline phosphatase （ALP） concentration, cycles of chemotherapy and time to castration resistance were independent prognostic factors of OS. According to the presence of PSADT 〈46.3 days and baseline ALP/〉 110 IU 1-1, all patients were divided into three risk groups： low-risk group （no risk factors）, intermediate-risk group （one risk factor） and high-risk group （two risk factors）. Median OSs for patients in low-, intermediate- and high-risk groups were 28.0 months （95% Ch 23.8-32.2）, 21.0 months （95% Ch 18.9-23.1） and 11.0 months （95% Ch 7.6-14.4）, respectively （P〈O.O01）. In conclusion, PSADT, baseline Hb concentration, ALP concentration, cycles of chemotherapy and time to castration resistance were independent prognostic factors of OS in Chinese patients with mCRPC treated with docetaxel. PSADT combined with the baseline ALP concentration could be a useful risk stratification parameter for evaluating survival outcomes.

The effectiveness of the TAX 327 nomogram in predicting overall survival in Chinese patients with metastatic castration-resistant prostate cancer

Based on the results of TAX 327, a nomogram was developed to predict the overall survival of metastatic castration-resistant prostate cancer （mCRPC） after first-line chemotherapy. The nomogram, however, has not been validated in an independent dataset, especially in a series out of clinical trials. Thus, the objective of the current study was to validate the TAX 327 nomogram in a community setting in China. A total of 146 patients with mCRPC who received first-line chemotherapy （docetaxel or mitoxantrone） were identified. Because clinical trials are limited in China's Mainland, those patients did not receive investigational treatment after the failure of first-line chemotherapy. The predicted overall survival rate was calculated from the TAX 327 nomogram. The validity of the model was assessed with discrimination, calibration and decision curve analysis. The median survival of the cohort was 21 months （docetaxel） and 19 months （mitoxantrone） at last follow-up. The predictive c-index of the TAX 327 nomogram was 0.66 （95% CI： 0.54-0.70）. The calibration plot demonstrated that the 2-year survival rate was underestimated by the nomogram. Decision curve analysis showed a net benefit of the nomogram at a threshold probability greater than 30%. In conclusion, the present validation study did not confirm the predictive value of the TAX 327 nomogram in a contemporary community series of men in China, and further studies with a large sample size to develop or validate nomograms for predicting survival and selecting therapies in advanced prostate cancer are necessary.

The prognostic factors of effective ketoconazole treatment for metastatic castration-resistant prostate cancer： who can benefit from ketoconazole therapy？

We investigated the prognostic value of some variables of effective ketoconazole treatment for metastatic castration-resistant prostate cancer （mCRPC）. In total, 163 patients with mCRPC were eligible, receiving ketoconazole 200-400 mg three times daily with replacement doses of prednisone. Progression-free survival （PFS） was calculated from the beginning of the ketoconazole therapy to the onset of disease progression. The prognostic value of different variables for PFS was assessed by Cox regression analysis. The median PFS was 2.6 months （0.5-8.6 months） for these patients. The serum testosterone level changed during therapy, which decreased when the prostate-specific antigen （PSA） declined; the serum testosterone level increased as the levels of PSA relapsed. The median PFS values for patients associated with different factors were the following： 1.4 and 3.5 months for a nadir PSA of ≥ 0.2 and 〈0.2 ng ml- 1, respectively （hazard rate （HR）=4.767, P〈0.001）; 3.1 and 1.6 months for a baseline testosterone of ≥0.1 and 〈0.1 ng m1-1, respectively （HR=2.865, P=0.012）; 2.8 and 1.9 months for a baseline haemoglobin of ≥ 120 and 〈120 g 1-1, respectively （HR= 1.605, P〈0.001）; and 3.0 and 1.9 months for a PSA doubling time （PSADT） of ≥ 2.0 and 〈2.0 months, respectively （HR= 1.454, P=-0.017）. A risk model was constructed according to the four factors that divided patients into three subgroups of low risk （0-1 factors）, moderate risk （2 factors） and high risk （3-4 factors） with PFS values of 3.6, 3.0 and 1.4 months, respectively （HR=1.619, P〈0.001）. A nadir PSA of ≥0.2 ng m1-1, a baseline testosterone of 〈0.1 ng m1-1, a baseline haemoglobin of 〈 120 g I- 1 and a PSADT of 〈2 months were associated with a poor PFS. This risk model could provide evidence to predict the survival benefit of ketoconazole therapy.

End points of clinical trials in metastatic castration-resistant prostate cancer:A systematic review

AIM： To review the defnition and performance of the commonly used end points in trials of systemic thera-pies in metastatic castration-resistant prostate cancer patients. METHODS： A literature search was undertaken on PubMed database to identify studies meeting estab-lished criteria, with the aim of selecting randomized clinical trials and study definition and performance of their end points. The end points were grouped into three categories： overall survival （OS）, time-to-event end points, and response end points. A special analysis was performed for secondary end points of the studies which documented a beneft in OS in the experimental arm. Finally, publishes analyses for surrogacy of the in-cluded end points were also reported. RESULTS： OS, time-to-event and response end points in 31 selected trials were analyzed. OS was the pri-mary end point in 14 trials, and the secondary end point in 17. A time-to-event end point was the primaryend point in 8 studies, and the secondary end point in 22; the most reported time-to-event end points were composite end points, and the events changed among trials. A response end point was the primary end point in 9 studies, in 3 it was prostate-specifc antigen （PSA）-related, in 3 pain-related and in 3 mixed. A response end point was the secondary end point in 19 studies： PSA response and radiologic response were the most frequently used secondary end points in 19 and 11 tri-als, respectively, while pain response was used in 5 studies.CONCLUSION： A homogeneous defnition of progres-sion in future trials is mandatory. Among response end points, pain-response and PSA-response appear to be the most reliable.

The safety of radium-223 combined with new-generation hormonal agents in bone metastatic castration-resistant prostate cancer: a systematic review and network meta-analysis

Patients with bone metastatic castration-resistant prostate cancer (mCRPC) might benefit from radium-223 (^(223)Ra) combined withnew-generation hormonal agents (NHAs) in terms of survival and quality of life (QoL). However, the safety of combination therapiesremains unclear. Therefore, we aimed to perform a network meta-analysis by reviewing the literature about the combination of^(223)Ra with abiraterone acetate plus prednisone (AAP) or enzalutamide and to evaluate the safety of combination therapy in bonemCRPC patients. Ultimately, ten studies (2835 patients) were selected, including four randomized controlled trials (RCTs), fiveretrospective cohort studies, and one single-arm study. Overall, there was no difference in the incidence of fracture between the^(223)Ra+NHA combination group and the ^(223)Ra monotherapy group (odds ratio [OR]: 1.46, 95% confidence interval [CI]: 0.91–2.34,P = 0.66), but the incidences in both the ^(223)Ra+NHA combination group (OR: 3.22, 95% CI: 2.24–4.63, P < 0.01) and the ^(223)Ramonotherapy group (OR: 2.24, 95% CI: 1.23–4.08, P < 0.01) were higher than that in the NHA monotherapy group. However, inthe meta-analysis involving only RCTs, there was no difference between the ^(223)Ra monotherapy group and the NHA monotherapygroup (OR: 1.14, 95% CI: 0.22–5.95, P = 0.88), while the difference between the ^(223)Ra+NHA combination group and the NHAmonotherapy group remained significant (OR: 3.22, 95% CI: 2.24–4.63, P < 0.01). Symptomatic skeletal events (SSEs), SSE-freesurvival (SSE-FS), all grades of common adverse events (AEs), and ≥grade 3 AEs among all groups did not show any significantdifference. Our results indicate that the combination of ^(223)Ra with NHAs was well tolerated in bone mCRPC patients compared to ^(223)Ra monotherapy, even though the incidence of fracture was higher in patients who received ^(223)Ra than that among those whoreceived NHA monotherapy. More evidence is needed to explore the safety and efficiency of ^(223)Ra combination therapies.

Relationships of body composition and adipocytokines with outcomes in metastatic castration-resistant prostate cancer patients receiving docetaxel chemotherapy

We evaluated the relationships of body composition and serum adipocytokine levels with progression-free survival(PFS)and overall survival(OS)in metastatic castration-resistant prostate cancer(mCRPC)patients receiving docetaxel.The medical records of mCRPC patients who received docetaxel between January 2011 and December 2015 at Fudan University Shanghai Cancer Center(Shanghai,China)were reviewed.The following body composition parameters were calculated using computed tomography:skeletal muscle index(SMI),visceral adipose tissue index(VATI),and subcutaneous adipose tissue index(SATI).Pretreatment serum adipocytokine levels,including interleukin 6,insulin,leptin,monocyte chemoattractant protein-1,adiponectin,and resistin,were measured using the multiplex bead-based immunoassays.Cox regression and Kaplan–Meier methods were used for survival analyses.Of the 453 mCRPC patients initially identified,105 were included in the analysis.High VATI group patients had longer PFS(median,10 months vs 7 months,P=0.008)and OS(median,24 months vs 15 months,P=0.017),compared with low VATI group patients.SMI and SATI were not significantly associated with PFS or OS.Of the six detected adipocytokines,only leptin was associated with mCRPC prognosis.High leptin group patients had shorter PFS(median,7 months vs 12 months,P=0.0018)and OS(median,17 months vs 22 months,P=0.042),compared with low leptin group patients.Multivariate analysis showed that a high VATI was an independent protective factor for PFS and OS,while a high leptin level was an independent risk factor for PFS and OS.Therefore,VATI and serum leptin levels could provide important information concerning mCRPC prognosis.

Survival Rate and Factors Influencing It in Triptorelin-Castrated Metastatic Prostate Cancer Patients

Background: Most newly diagnosed prostate cancers in Benin are metastatic diseases and patients are reluctant to undergo orchiectomy. Still, chemical androgen deprivation therapy is not always available and not every patient can afford it. Thus, it will be interesting to evaluate the results of that therapy in the country. Objective: To analyze the survival rate and factors influencing it in metastatic prostate cancer patients who underwent triptorelin-based androgen deprivation therapy at the former Military Teaching Hospital of Cotonou from January 1, 2012, to December 31, 2022. Patients and Method: Metastatic prostate cancer patients received intragluteal injections of triptorelin 11.25 mg every 3 months. We retrospectively collected follow-up data from the patients’ medical records. By means of the software StataTM version 15, we performed a descriptive analysis of qualitative data. We used Kaplan-Meir method to estimate the overall survival rate in the whole cohort and in specific subgroups of patients. We compared survival rates by using the log-rank test. Results: 68 metastatic prostate cancer patients aged 47-86 years (mean = 69.9) with initial PSA ranging from 24.25 to 6334 ng/mL (mean = 666.1) started triptorelin-based castration. The tumor grade in 21 (33.3%), 14 (22.2%), 15 (23.8), 8 (12.7%), and 5 (7.9%) patients was respectively ISUP grade groups 5, 4, 3, 2, and 1. 15 (22.1%), 4 (5.9%), 2 (2.9%), 1 (1.5%), 11 (16.2%), and 7 (10.3%) patients respectively had hypertension, diabetes mellitus, peptic ulcer, asthma, unilateral or bilateral hydronephrosis, and paralysis. The mean nadir PSA level was 22.5 ng/mL (range: 0.01-220.25). The mean time to nadir PSA level was 8.9 months (range: 3-57). The overall survival rate was 42.6%. There was no significant survival difference between age groups (p = 0.475), relating to the presence of diabetes or hypertension (p = 0.757) or to the presence of paralysis or hydronephrosis (p = 0.090). The initial PSA level exerted no significant impact on patients’ survival (p = 0.461). Neither did the time to PSA nadir (p = 0.263). The PSA nadir less than 4 ng/mL (p = 0.005) and the PSA nadir less than 4 ng/mL achieved in 12 months or less (p = 0.002) were predictive of longer survival rate. The difference in survival rate through the ISUP grade groups was not significant (p = 0.061). Conclusion: The overall survival rate was 42.6% at 5 years. Achieving PSA nadir of less than 4 ng/mL in less than 12 months of castration was predictive of longer survival rate in triptorelin-castrated metastatic prostate cancer patients.

Indirect comparison between abiraterone acetate and enzalutamide for the treatment of metastatic castration-resistant prostate cancer： a systematic review

This study was designed to evaluate the efficacy, tolerability, and sequential administration of abiraterone acetate （AA） and enzalutamide （Enz） for metastatic castration-resistant prostate cancer （mCRPC）. A literature search was performed with PubMed, Embase, and Web of Science databases to identify relevant studies. Reviewed literature included published phase III trials of AA or Enz in mCRPC and studies regarding their sequential administration. Given the difference in control arms in AA （active comparator） and Enz （true placebo） randomized phase III studies, indirect comparisons between AA and Enz in mCRPC showed no statistically significant difference in overall survival in prechemotherapy and postchemotherapy settings （HR. 0.90, 95% CI, 0.73-1.11; HR： 0.85, 95% CI, 0.68-1.07）. Compared with AA, Enz may better outperform control arms in treating mCRPC both before and after chemotherapy regarding secondary endpoints based on indirect comparisons： time to prostate-specific antigen （PSA） progression （HR. 0.34, 95% CI, 0.28-0.42; HR： 0.40, 95% CI, 0.30-0.53）, radiographic progression-free survival （HR： 0.37, 95% CI, 0.28-0.48; HR： 0.61, 95% CI, 0.50-0.74）, and PSA response rate （OR： 18.29, 95% CI, 11.20-29.88; OR： 10.69, 95% CI, 3.92-29.20）. With regard to the effectiveness of Enz following AA or AA following Enz, recent retrospective case series reported overall survival and secondary endpoints for patients with mCRPC progression after chemotherapy. However, confirmatory head-to-head trials are necessary to determine the optimal sequencing of these agents.

Predictors of efficacy of corticosteroid switching from abiraterone plus prednisone to dexamethasone in patients with metastatic castration-resistant prostate cancer

Corticosteroid switching can reverse abiraterone resistance in some patients with metastatic castration-resistant prostate cancer(mCRPC).Here,we investigated the potential biomarkers for predicting the efficacy of corticosteroid switching during treatment with abiraterone acetate(AA).We retrospectively analyzed 101 mCRPC patients receiving corticosteroid switching from West China Hospital and Sun Yat-Sen University Cancer Center between January 2016 and December 2018.All cases received AA plus prednisone as first-line therapy during mCRPC.Primary end points were biochemical progression-free survival(bPFS)and overall survival(OS).The risk groups were defined based on multivariate analysis.A total of 42(41.6%)and 25(24.8%)patients achieved 30%and 50%decline in prostate-specific antigen(PSA),respectively,after corticosteroid switching.The median bPFS and median OS on AA plus dexamethasone were 4.9(95%confidence interval[CI]:3.7–6.0)months and 18.8(95%CI:16.2–30.2)months,respectively.Aldo-keto reductase family 1 member C3(AKR1C3)expression(hazard ratio[HR]:2.15,95%Cl:1.22–3.80,P=0.008)and baseline serum alkaline phosphatase(ALP;HR:4.95,95%Cl:2.40–10.19,P<0.001)were independent predictors of efficacy before corticosteroid switching in the multivariate analysis of bPFS.Only baseline serum ALP>160 IU l−1(HR:3.41,95%Cl:1.57–7.38,P=0.002)together with PSA level at switch≥50 ng ml−1(HR:2.59,95%Cl:1.22–5.47,P=0.013)independently predicted poorer OS.Based on the predictive factors in multivariate analysis,we developed two risk stratification tools to select candidates for corticosteroid switching.Detection of serum ALP level,PSA level,and tissue AKR1C3 expression in mCRPC patients could help make clinical decisions for corticosteroid switching.

Development of AR-V7 as a putative treatment selection marker for metastatic castration-resistant prostate cancer

Prostate cancer cells demonstrate a remarkable ＂addiction＂ to androgen receptor （AR） signaling in all stages of disease progression. As such, suppression of AR signaling remains the therapeutic goal in systemic treatment of prostate cancer. A number of molecular alterations arise in patients treated with AR-directed therapies. These molecular alterations may indicate the emergence of treatment resistance and may be targeted for the development of novel agents for prostate cancer. The presence of functional androgen receptor splice variants may represent a potential explanation for resistance to abiraterone and enzalutamide, newer AR-directed agents developed to treat metastatic castration-resistant prostate cancer （mCRPC）. In the last 8 years, many androgen receptor splice variants have been identified and characterized. Among these, androgen receptor splice variant-7 （AR-V7） has been investigated extensively. In AR-V7, the entire COOH-terminal ligand-binding domain of the canonical AR is truncated and replaced with a variant-specific peptide of 16 amino acids. Functionally, AR-V7 is capable of mediating constitutive nuclear localization and androgen receptor signaling in the absence of androgens, or in the presence of enzalutamide. In this review, we will focus on clinical translational studies involving detection/measurement of AR-V7. Methods have been developed to detect AR-V7 in clinical mCRPC specimens. AR-V7 can be reliably measured in both tissue and circulating tumor cells derived from mCRPC patients, making it possible to conduct both cross-sectional and longitudinal clinical correlative studies. Current evidence derived from studies focusing on detection of AR-V7 in mCRPC support its potential clinical utility as a treatment selection marker.

Understanding prostate-specific antigen dynamics in monitoring metastatic castration-resistant prostate cancer： implications for clinical practice

Availability of novel hormonal therapies as well as docetaxel and cabazitaxel treatment for metastatic castration-resistant prostate cancer （CRPC） has changed the outlook for this group of patients with improvements in progression-free survival and overall survival. Physicians often diagnose the progression of prostate cancer using serum prostate-specific antigen （PSA）. However, serum PSA is not always correlated with the clinical status in CRPC. To evaluate the PSA dynamics with greater precision, understanding of the control of PSA and of the mechanisms of development of CRPC is needed. Moreover, it is necessary to use new hormonal therapies with an appropriate timing to optimally improve the prognosis and the QOL of the patients. In the present review, we ascertain the PSA dynamics and the mechanisms of the development of CRPC to assist in optimal utilization of the new treatments for mCRPC.

Prior switching to a second-line nonsteroidal antiandrogen does not impact the therapeutic efficacy of abiraterone acetate in patients with metastatic castration-resistant prostate cancer： a real-world retrospective study

Even in the era of novel targeted agents, switching to a second-line nonsteroidal antiandrogen （NSAA） is still widely used in treating metastatic castration-resistant prostate cancer （mCRPC）, especially in undeveloped countries. However, whether prior treatment with a second-line NSAA would impact the efficacy of abiraterone acetate （Abi） remains uncertain, in the current study, 87 mCRPC patients treated with Abi were analyzed. Among them, 21 were treated with a second-line NSAA （from bicalutamide to flutamide） before receiving abiraterone, while the remaining 66 received Abi directly. Therapeutic efficacy of Abi was compared between those with and without prior second-line NSAA using Kaplan-Meier curves, log-rank test, and Cox regression models. The therapeutic efficacy of Abi was similar between those with or without the prior switching treatment of flutamide, in terms of either prostate-specific antigen progression-free survival （PSA-PFS, 5.5 vs 5.6 months, P = 0.967）, radiographic progression-free survival （rPFS, 12.8 vs 13.4 months, P = 0.508）, overall survival （OS, not reached vs 30.6 months, P = 0.606）, or PSA-response rate （71.4% [15121] vs 60.6% [40166], P = 0.370）. This is the first time that the impact of prior switching of treatment to a second-line NSAA on the efficacy of Abi in mCRPC patients has been addressed. Our data support that, use of prior sequential bicalutamide and flutamide does not seem to preclude response to abiraterone, although larger cohort studies and, ideally, a randomized controlled trial are needed. These findings will facilitate doctors＇ decision-making in the treatment of mCRPC patients, especially for those with previous experience of switching NSAA second-line treatments in the clinic.

Clinical activity of abiraterone plus prednisone in docetaxel-naive and docetaxel-resistant Chinese patients with metastatic castration-resistant prostate cancer

This study investigated the clinical activity of abiraterone plus prednisone in docetaxel-naive and docetaxel-resistant Chinese patients with metastatic castratio n-resista nt prostate can cer(mCRPC).A total of 146 patie nts with docetaxel-naive group(103 cases)and docetaxel-resista nt group(43 cases)were en rolled from the Sha nghai Cancer Center(Sha nghai,Chin a)in this retrospective cohort study.The efficacy endpoints were prostate-specific antigen response rate,prostate-specific antigen progress!on-free survival,clinical/radiographic progression-free survival,and overall survival in response to abiraterone plus prednisone.Significantly higher prostate-specific antigen response rate was found in docetaxel-naive group(54.4%,56/103)compared to docetaxel-resistant group(34.9%,15/43)(P=0.047).In addition,significantly higher median prostate-specific antigen progress!on-free survival(14.0 vs 7.7 months,P=0.005),clinical or radiographic progression-free survival(17.0 vs 12.5 months,P=0.003),and overall survival(27.0 vs 18.0 mon ths,P=0.016)were found in docetaxel-naTve group compared to docetaxel-resistant group,respectively.The univariate and multivariate analyses indicated that lower albumin and visceral metastases were independent significant predictors for shorter overall survival.To sum up,our data suggested that abiraterone plus prednisone was efficient in both docetaxel-naTve and docetaxel-resistant Chinese patients.Moreover,higher PSA response rate and longer overall survival were observed in the docetaxel-naTve group,which suggested that abiraterone was more effective for docetaxel-naive patients than for docetaxel failures.

Enzalutamide:a new indication for nonmetastatic castration-resistant prostate cancer

PROSPER is an international Phase III trial demonstrating the beneficial role of enzalutamide,an androgen receptor antagonist,in prolonging metastasisfree survival in men with nonmetastatic castration-resistant prostate cancer.The trial showed that the median metastasis-free survival was 21.9 months longer for those treated with enzalutamide(36.6 months)compared to those treated with placebo(14.7 months).Enzalutamide also showed prolonged time to PSA progression,PSA response,and time to initiating additional antineoplastic therapy although overall survival is not yet reached.Enzalutamide is the second antiandrogen(next to apalutamide)that has gained the United States Food and Drug Administration(US FDA)label indication for use in the setting of nonmetastatic castration-resistant prostate cancer.

Prostate Cancer, Castration-Resistant Prostate Cancer (CRPC), Radium-223 Dichloride Injection for Bone Metastasized Prostate Cancer

Purpose: The purpose of this paper is to discuss the most important facts about prostate cancer, its treatments and efficacy, the type of prostate cancer that does not improve with hormonal therapy (Castration-Resistant Prostate Cancer-CRPC), and the recently approved Radium-223 dichloride targeted therapy for CRPC that has metastasized to bones. Prostate cancer is the third most common malignancy diagnosed worldwide and the most common malignant disease in men. Also, the incidence of prostate cancer varies between regions. So it’s important to have a proper understanding of all above points to prevent the further development and spread of cancer and improve the cure rate. Design: The paper begins by discussing what prostate cancer is, the risk factors, clinical manifestations, and the treatments for prostate cancer. It covers the clinical manifestations, pathology, screening (cancer biomarker Prostate Specific Antigen, Digital Rectal Examination—DRE, prostate biopsy, and imaging) and treatments for prostate cancer. The paper then delves into the main treatment methods for prostate cancer, including how Castration-Resistant Prostate Cancer (CRPC) differs from normal prostate cancer after hormone suppression therapy. Additionally, it discusses the effectiveness of the recently introduced Radium-223 dichloride injection as a radiation-targeted therapy for treating CRPC that has metastasized to bones. This section covers the properties of radium-223 dichloride injection, its pharmacokinetics, pharmacodynamics, absorption and volume of distribution, half-life, metabolism, route of elimination, clearance, toxicity, adverse effects, and mechanism of action at the tumor site. It also discusses preclinical studies related to radium-223 dichloride injection and its effectiveness in treating CRPC patients with bone metastasis. Conclusion: Prostate cancer is a common cancer that can be treated with surgery or hormonal therapy. However, if the cancer progresses despite hormonal therapy, Radium-223 dichloride injection can be used as a radiation target therapy to treat patients with CRPC and symptomatic bone metastases. This treatment kills tumor cells in bones and reduces associated pain with minimal damage to surrounding normal tissue. However, the metastatic disease cannot be cured and can only offer palliation for the patient. Suggestions: Based on the facts, Radium-223 target therapy is effective in treating and providing palliation for cancers. It is suggested to further develop the usage of radiation target therapy and to test the safety and efficacy of more than 6 injections of Radium-223 dichloride and its combination with currently used chemotherapy drugs for bone metastasized CRPC. This paper aims to contribute to future research designs related to cancer therapies using radiation and to design new studies and practical implementations, especially regarding the usage of radium-223 dichloride.

Radium-223 in metastatic castration resistant prostate cancer

In 2004, docetaxel was approved for the treatment of metastatic castration-resistant prostate cancer （mCRPC）. For the next several years, there was a lull in drug approvals. However, from 2010 onwards, 5 additional therapies have been approved on the basis of showing a survival benefit in phase III studies. These agents include sipuleuceI-T, cabazitaxel, abiraterone, enzalutamide and （most recently） radium-223. Amongst radiopharmaceuticals currently used for advanced prostate cancer （e.g. samarium-153 and strontium-89）, radium-223 possesses several unique properties. As an alpha-emitting compound, the agent produces a high-energy output over a short range, facilitating selective destruction of tissue within the bone in the region of osteoblastic lesions while sparing surrounding normal tissue. The current review will outline biological rationale for radium-223 and also provide an overview of preclinical and clinical development of the agent. Rational sequencing of radium-223 and combinations, in the increasingly complex landscape of mCRPC will be discussed, along with factors influencing clinical implementation.