scholarly journals Prognostic Value of Novel Liquid Biomarkers in Patients with Metastatic Castration-Resistant Prostate Cancer Treated with Enzalutamide: A Prospective Observational Study

2020 ◽  
Vol 66 (6) ◽  
pp. 842-851
Author(s):  
Guillemette E Benoist ◽  
Inge M van Oort ◽  
Emmy Boerrigter ◽  
Gerald W Verhaegh ◽  
Onno van Hooij ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Regression Analysis ◽  
Observational Study ◽  
Prognostic Value ◽  
Cox Regression ◽  
Response To Therapy ◽  
Castration Resistant Prostate Cancer ◽  
Time To Progression ◽  
Cox Regression Analysis ◽  
Castration Resistant

Abstract Background Several treatment options were recently added for metastatic castration-resistant prostate cancer (mCRPC). However, response to therapy is variable, and biomarkers that can guide treatment selection and response evaluation are lacking. Circulating RNAs are a promising source of biomarkers. We explored messenger RNAs (mRNAs), microRNAs (miRNAs), and long noncoding RNAs (lncRNAs) as potential biomarkers in liquid biopsies of patients with mCRPC treated with enzalutamide. Methods Forty patients were included in this prospective multicenter observational study. Whole blood was drawn at baseline and 1, 3, and 6 months after start of therapy. Four mRNAs, 6 miRNAs, and 5 lncRNAs were analyzed by quantitative PCR. RNA levels in 30 healthy individuals were used as controls. RNA expression data were analyzed by Kaplan–Meier and Cox regression analyses, and the primary end point was progression-free survival. Clinical factors were included in the multivariable Cox regression analysis. Results Levels of 2 miRNAs, miR-375 and miR-3687, and 1 lncRNA, N-acetylated alpha-linked acidic dipeptidase like 2 antisense RNA 2 (NAALADL2-AS2), were more than 2-fold higher in patients with mCRPC compared with healthy volunteers. Patients with higher levels of miR-375 or miR-3687 showed a shorter time to progression. Patients with higher levels of NAALADL2-AS2 showed a longer time to progression. In the multivariable Cox regression analysis, higher miR-375, miR-3687 and serum prostate-specific antigen concentrations were shown to be independent predictors for shorter time to progression. Conclusions We identified miR-3687 as a novel prognostic marker for response in patients with CRPC treated with enzalutamide, and we confirmed the prognostic value of miR-375.

YB-1 variant and androgen receptor axis-targeted agents in metastatic castration-resistant prostate cancer patients

2020 ◽  
Vol 21 (13) ◽  
pp. 919-928
Author(s):  
Ana Afonso ◽  
Jani Silva ◽  
Ana Rita Lopes ◽  
Sara Coelho ◽  
Ana Sofia Patrão ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Cancer Patients ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
Allelic Discrimination ◽  
Cox Regression Analysis ◽  
Castration Resistant ◽  
Increased Risk

Aim: To evaluate the influence of YB-1 rs10493112 variant as a genetic marker for response to second-generation androgen receptor axis-target agents. Methods: A hospital-based cohort study of 78 patients with metastatic castration-resistant prostate cancer was conducted. Genotyping was performed by TaqMan® allelic discrimination technology. Main results: In abiraterone-treated and high-risk patients, YB-1 rs10493112 AA genotype carriers showed lower progression-free survival than C allele genotype patients (4 vs 17 months; p = 0.009). For carriers of AA genotype, multivariate Cox regression analysis revealed a fivefold increased risk of progression (p = 0.035). Conclusion: The study findings suggest that, for metastatic and castration-resistant prostate cancer patients, this polymorphism might be a putative marker for the clinical outcome.

Evaluating the effect of therapy duration on survival in patients with metastatic castration-resistant prostate cancer receiving radium-223.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. e593-e593
Author(s):  
Noelle L. Williams ◽  
Kamila Nowak-Choi ◽  
Jenna Skowronski ◽  
Tu Dan ◽  
Harriet Belding Eldredge ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Second Generation ◽  
Cox Regression ◽  
Rank Test ◽  
Maximal Effect ◽  
Castration Resistant Prostate Cancer ◽  
Cox Regression Analysis ◽  
Castration Resistant ◽  
Full Treatment ◽  
Radium 223

e593 Background: The use of radium-223 in patients with metastatic castration-resistant prostate cancer (mCRPC) improves overall survival (OS) and quality of life. Combination of radium-223 with second-generation anti-androgens has further improved OS; however, the optimal length of radium-223 treatment for maximal effect remains unknown. Methods: We reviewed 35 consecutive patients with mCRPC who received radium-223 from December 2012 to August 2015 at Thomas Jefferson University. Patients were divided into two groups: those who received full treatment of 6 injections (n = 18) versus those who received less than 6 injections (n = 17). Kaplan-Meier analysis of OS were tested for difference by treatment group using Log Rank test. Univariable association with survival outcomes was calculated with univariable Cox regression and Log Rank tests. Results: Mean age was 73 ± 10 years and Karnofsky performance status (KPS) ranged from 50-90 (median, 80). Median follow-up was 13.9 months. Eighteen patients were receiving concurrent second generation anti-androgens at the start of treatment. Median OS was 12 months for patients who received 6 injections and 6.48 months for patients who received less than 6 injections (p = 0.0045). The results of univariate Cox regression analysis revealed full treatment was associated with increased OS (p = 0.0013). On multivariate analysis accounting for KPS, full treatment was significantly associated with improved OS (p = 0.0028). Conclusions: In this retrospective, single-institution analysis, we demonstrated that full course completion of radium-223 was associated with improved OS in patients with mCRPC. These patients should be optimally supported during treatment to allow for therapy completion.

scholarly journals Treatment-Emergent Co-Morbidities and Survival in Patients With Metastatic Castration-Resistant Prostate Cancer Receiving Abiraterone or Enzalutamide

2021 ◽  
Vol 12 ◽  
Author(s):  
Yi-Ting Lin ◽  
Yen-Chun Huang ◽  
Chih-Kuan Liu ◽  
Tian-Shyug Lee ◽  
Mingchih Chen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Hormone Therapy ◽  
Cox Regression ◽  
Castration Resistant Prostate Cancer ◽  
Drug Induced ◽  
Cox Regression Analysis ◽  
Castration Resistant ◽  
Significant Difference ◽  
Taiwan National Health Insurance

Secondary hormone therapy, abiraterone and enzalutamide, has improved outcomes for metastatic castration-resistant prostate cancer (mCRPC) and prolonged patients’ lives significantly. Various studies have compared the cancer-related outcomes, adverse effects, and drug-induced comorbidities in patients with mCRPC who are treated with abiraterone or enzalutamide. However, few studies have explored associations between survival and comorbidities or comprehensive analyzed newly developed comorbidities during and after secondary hormone therapy. We attempted to clarify whether the Charlson comorbidity index (CCI) overall or itemized is predictive for overall survival, and we compared newly developed comorbidities between abiraterone and enzalutamide groups. We extracted data about expenses and comorbidities for patients who have mCRPC, received abiraterone and enzalutamide and met pre-examination operation criteria between September 2016 and December 2017 from the Taiwan National Health Insurance database. A total of 1153 patients with mCRPC who received abiraterone (n = 782) or enzalutamide (n = 371) with or without previous chemotherapy were included. We used the propensity score to match confounding factors, including age, pre-existing comorbidities, and precipitating factors for comorbidity (e.g., hypertension, hyperlipidemia), to eliminate selection bias in the comparison of newly developed comorbidities. Cox regression analysis was used for overall survival. We found that enzalutamide is superior to abiraterone with regard to overall survival. Our study revealed that there is no statistically significant difference in development of new comorbidities between abiraterone and enzalutamide group. Moreover, the CCI score, rather than any single item of the CCI, was a statistically significant predictor for overall survival.

Treatment outcome and identification of factors influencing overall survival after Lu-177-PSMA-617 radioligand therapy in metastatic prostate cancer

2021 ◽  
Author(s):  
Charlotte A. Schneider ◽  
Philipp Täger ◽  
Jochen Hammes ◽  
Thomas Fischer ◽  
Alexander Drzezga ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Alkaline Phosphatase ◽  
Regression Analysis ◽  
Cox Regression ◽  
Specific Antigen ◽  
Castration Resistant Prostate Cancer ◽  
Radioligand Therapy ◽  
Cox Regression Analysis ◽  
Cumulative Activity

Abstract Objective To examine the clinical benefit of Lu-177-PSMA-617 radioligand therapy for patients with metastatic castration-resistant prostate cancer (mCRPC). Patients and Methods Between November 2014 and December 2018, a total of 56 consecutive patients (median age 69.5 years; range 55–84 years) with mCRPC were included in this retrospective analysis. Patients received between 1 and 4 therapy cycles with a mean activity of 6.8 GBq per cycle. Biochemical response was evaluated using Prostate Cancer Working Group Criteria 3 (PCWG 3). Survival was assessed using Kaplan-Meier estimates and Cox proportional hazards regression analysis. This retrospective study was approved by the local ethics committee. Results A total of 139 treatment cycles with Lu-177-PSMA-617 were performed. A decline of 50% or more of prostate-specific antigen (PSA) level occurred in 54% and a PSA decline of any amount in 65% of patients. The estimated median overall survival (OS) was 16 months, in the chemotherapy subgroup 14 months. A longer OS was associated with a PSA-decline ≥50%, more than 2 cycles of therapy, cumulative activity >15 GBq and an initial alkaline phosphatase ≤ 220 [U/l]. These identified predictors remained significant on uni- and multivariate Cox regression analysis. Moreover, 40% of the patients who were non-responders after the first therapy cycle turned into responders after the second one. Conclusion PSA-decline ≥50%, a cumulative activity >15 GBq and an initial alkaline phosphatase ≤ 220 [U/l] were identified as key predictors of prolonged OS in patients with mCRPC. In contrast rapid clinical deterioration mostly due to skeletal carcinomatosis resulted in early treatment failure.

Identification and Validation of a Seven m6A-related lncRNAs Signature Predicting Prognosis of Ovarian Cancer

2021 ◽  
Author(s):  
Yan Li ◽  
Xiaoying Wang ◽  
Yue Han ◽  
Xun Li
Keyword(s):  
Ovarian Cancer ◽  
Regression Analysis ◽  
Correlation Analysis ◽  
Prognostic Value ◽  
Cox Regression ◽  
Risk Group ◽  
Pearson Correlation ◽  
Regression Analyses ◽  
Cox Regression Analysis ◽  
Pearson Correlation Analysis

Abstract Background: Long non-coding RNAs (lncRNAs) play an important role in angiogenesis, immune response, inflammatory response and tumor development and metastasis. m6 A (N6 - methyladenosine) is one of the most common RNA modifications in eukaryotes. The aim of our research was to investigate the potential prognostic value of m6A-related lncRNAs in ovarian cancer (OC).Methods: The data we need for our research was downloaded from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database. Pearson correlation analysis between 21 m6A regulators and lncRNAs was performed to identify m6A-related lncRNAs. Univariate Cox regression analysis was implemented to screen for lncRNAs with prognostic value. A least absolute shrinkage and selection operator (LASSO) Cox regression and multivariate Cox regression analyses was used to further reduct the lncRNAs with prognostic value and construct a m6A-related lncRNAs signature for predicting the prognosis of OC patients. Results: 275 m6A-related lncRNAs were obtained using pearson correlation analysis. 29 m6A-related lncRNAs with prognostic value was selected through univariate Cox regression analysis. Then, a seven m6A-related lncRNAs signature was identified by LASSO Cox regression. Each patient obtained a riskscore through multivariate Cox regression analyses and the patients were classified into high-and low-risk group using the median riskscore as a cutoff. Kaplan-Meier curve revealed that the patients in high-risk group have poor outcome. The receiver operating characteristic curve revealed that the predictive potential of the m6A-related lncRNAs signature for OC was powerful. The predictive potential of the m6A-related lncRNAs signature was successfully validated in the GSE9891, GSE26193 datasets and our clinical specimens. Multivariate analyses suggested that the m6A-related lncRNAs signature was an independent prognostic factor for OC patients. Moreover, a nomogram based on the expression level of the seven m6A-related lncRNAs was established to predict survival rate of patients with OC. Finally, a competing endogenous RNA (ceRNA) network associated with the seven m6A-related lncRNAs was constructed to understand the possible mechanisms of the m6A-related lncRNAs involed in the progression of OC.Conclusions: In conclusion, our research revealed that the m6A-related lncRNAs may affect the prognosis of OC patients and identified a seven m6A-related lncRNAs signature to predict the prognosis of OC patients.

Sign in / Sign up

Export Citation Format

Share Document