Association of neuroendocrine (NE) mRNA expression profiling in hormone-sensitive tumors samples with adverse clinical outcome in castration-resistant prostate cancer (CRPC) patients.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 165-165
Author(s):  
Mayra Orrillo ◽  
Natalia Jimenez ◽  
Oscar Reig ◽  
Giancarlo Castellano ◽  
Albert Font ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Outcome ◽  
Treatment Strategies ◽  
Gene Signature ◽  
Molecular Profile ◽  
Castration Resistant Prostate Cancer ◽  
Adverse Clinical Outcome ◽  
Related Gene ◽  
Primary Tumors ◽  
Hormone Sensitive

165 Background: NE dedifferentiation is associated to clinical aggressiveness and resistance to androgen receptor inhibition in prostate cancer. We investigated impact of a NE expression signature in the clinical outcome of mCRPC patients treated with taxanes. Methods: This is a multicenter retrospective study. A customized panel of 45 NE-related gene signature was tested in total RNA from formalin-fixed paraffin-embedded hormone-sensitive tumor samples, by the nCounter platform (Nanostring Technologies). Patients were grouped according to their molecular profile by unsupervised clustering. Expression levels were correlated with taxanes response and clinical outcome. Independent association with survival was evaluated by multivariate Cox modeling. Results: Eighty seven patients were included in the study, 79 were treated with docetaxel and 8 with cabazitaxel. Median age was 64.8 (44-88.3) years and median follow-up was 20.7 (1.17-74.4) months. High expression of the NE signature was associated with a shorter time of CRPC development (N=60, median 12.8 vs 21.6, HR 2.4, 95%CI 1.3-4.3, P=0.003) and shorter OS from CRPC diagnosis (median 24.1 vs 41.33, HR 2.3, 95%CI 1.4-3.8, P=0.001). Moreover, according to the outcome to taxanes, high NE signature correlated with lower PSA-PFS (median 6.6 vs 10.1 mo P=0.047, HR 1.6, 95%CI 1-2.7, P=0.05) and OS (median 19 vs 22 mo, HR 1.8, 95%CI 1.1-2.8, P=0.014), and it was independently associated to a lower OS (HR 1.9, 95%CI 1.1-3.2, P=0.016). Conclusions: NE-related gene expression in hormone-sensitive tumor samples is associated with adverse clinical outcome and lower taxane benefit in metastatic CRPC patients. Thus, molecular characterization of primary tumors may be useful to guide treatment strategies in metastatic prostate cancer.

Association of androgen receptor signature and RB1, PTEN, TP53 gene expression with clinical outcome in metastatic hormone-sensitive prostate cancer treated with docetaxel and androgen deprivation therapy.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5069-5069
Author(s):  
Laura Ferrer-Mileo ◽  
Natalia Jiménez ◽  
Oscar Reig ◽  
Miguel Ángel Climent ◽  
Sara Cros ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Androgen Receptor ◽  
Clinical Outcome ◽  
Androgen Deprivation Therapy ◽  
Androgen Deprivation ◽  
Castration Resistant Prostate Cancer ◽  
Mesenchymal Transition ◽  
Hormone Sensitive ◽  
Low Expression

5069 Background: Androgen deprivation therapy (ADT) with docetaxel or new antiandrogens has demonstrated a survival benefit in metastatic hormone-sensitive prostate cancer (mHSPC). However, treatment selection for individual patients (pts) remains a challenge. We propose that TMPRSS2-ERG and cell plasticity [neuroendocrine (NE), epithelial to mesenchymal transition (EMT)], immune-related, androgen receptor (AR) and tumor suppressor genes (TSG) ( RB1, PTEN and TP53) expression signatures may predict clinical outcome in mHSPC pts treated with ADT+docetaxel. Methods: This is a multicenter retrospective biomarker study performed in mHSPC pts treated with ADT+docetaxel. A customized panel of 184 genes was designed and tested in total mRNA from FFPE tumor samples by nCounter platform (Nanostring Technologies). Expression levels were correlated with castration resistance-free survival (CRPC-FS) (primary endpoint) and overall survival (OS) by Kaplan Meier and multivariate Cox modeling. A predictive modeling approach was performed with Bujar R package to develop a signature able to predict CRPC-FS. R (v.3.6.3) software was used for statistical analyses. Results: 136 pts were included, and 120 of them were eligible. Median age was 66.9 years (range 46.3-83.6). Gleason score was ≥ 8 in 80.8% of pts; 87.5% and 20.8% of pts had bone and visceral metastases, respectively. Median follow-up was 30.7 months (m) (range 5.5-70.6). 76 pts (63.3%) developed castration-resistant prostate cancer (CRPC). Median time to CRPC was 20 m (range 16.9-23.1) and median OS was not reached. High AR-signature expression independently correlated with longer CRPC-FS (HR 0.4, 95% CI 0.2-0.7, p = 0.003). Considering AR-signature individual gene expression, ARV7 was independently associated with shorter CRPC-FS (HR 1.7, 95% CI 1.2-2.4, p = 0.003). Low expression of all TSG ( PTEN, RB1 and TP53) independently correlated with shorter CRPC-FS (HR 0.3, 95% CI 0.2-0.7, p = 0.003) and OS (HR 0.2, 95% CI 0.1-0.5, p < 0.001). Similarly, low expression of 2 out of the 3 TSG genes or only RB1 plus PTEN were also independently associated with shorter CRPC-FS (HR 0.5, 95% CI 0.3-0.9, p = 0.015; HR 0.4, 95% CI 0.2-0.7, p = 0.003, respectively) and OS (HR 0.4, 95% CI 0.2-0.9, p = 0.027; HR 0.2, 95% CI 0.1-0.6, p = 0.001, respectively). TMPRSS2-ERG expression, NE, EMT and immune-related signatures were not associated with clinical outcome. Bujar analysis defined a 17-gene signature (including ARV7, RB1, PTEN, BRCA2 and ATM) that was able to discriminate pts at different risk of developing early CRPC. Conclusions: High AR-signature expression correlates with a longer CRPC-FS while ARV7 expression is associated with shorter CRPC-FS. Low expression of TSG is associated with an aggressive clinical evolution in mHSPC pts treated with ADT+taxanes.

AR Copy Number and AR Signaling-directed Therapies in Castrationresistant Prostate Cancer

2018 ◽  
Vol 18 (9) ◽  
pp. 869-876
Author(s):  
Samanta Salvi ◽  
Vincenza Conteduca ◽  
Cristian Lolli ◽  
Sara Testoni ◽  
Valentina Casadio ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Copy Number ◽  
Clinical Trial Design ◽  
Complete Information ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Anti Cancer ◽  
Hormone Sensitive ◽  
Predictive And Prognostic Biomarker

Background: Adaptive upregulation of Androgen Receptor (AR) is the most common event involved in the progression from hormone sensitive to Castration-Resistant Prostate Cancer (CRPC). AR signaling remains the main target of new AR signalling-directed therapies such as abiraterone and enzalutamide in CRPC patients. Objective: In this review, we discuss general mechanisms of resistance to AR-targeted therapies, with a focus on the role of AR Copy Number (CN). We reported methods and clinical applications of AR CN evaluation in tissue and liquid biopsy, thus to have a complete information regarding its role as predictive and prognostic biomarker. Conclusion: Outcomes of CRPC patients are reported to be highly variable as the consequence of tumor heterogeneity. AR CN could contribute to patient selection and tumor monitoring in CRPC treated with new anti-cancer treatment as abiraterone and enzalutamide. Further studies to investigate AR CN effect to these agents and its potential combination with other prognostic or predictive clinical factors are necessary in the context of harmonized clinical trial design.

scholarly journals Three-month early change in prostate-specific antigen levels as a predictive marker for overall survival during hormonal therapy for metastatic hormone-sensitive prostate cancer

2021 ◽  
Author(s):  
Shotaro Nakanishi ◽  
Masato Goya ◽  
Mitsuyoshi Tamaki ◽  
Takuma Oshiro ◽  
Seiichi Saito
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Prostate Specific Antigen ◽  
Characteristic Curve ◽  
Specific Antigen ◽  
Predictive Marker ◽  
Castration Resistant Prostate Cancer ◽  
Pretreatment Level ◽  
Castration Resistant ◽  
Hormone Sensitive

Abstract Objective: To date, there are no useful markers for predicting the prognosis of metastatic hormone-sensitive prostate cancer (mHSPC). We evaluated the effect of early changes in prostate-specific antigen (PSA) levels after androgen deprivation therapy (ADT) on castration-resistant prostate cancer (CRPC) progression and overall survival (OS) in mHSPC patients. Results: In 71 primary mHSPC patients treated with ADT, the median times to CRPC and OS were 15 months and 92 months, respectively. In multivariate analysis, a Gleason score of ≥8 (p = 0.004), an extent of disease value (EOD) of ≥2 (p = 0.004), and a 3-month PSA level >1% of the pretreatment level (p = 0.017) were independent predictors of shorter time to CRPC. The area under the receiver operating characteristic curve was feasible at 0.822. For OS, a 3-month PSA level >1% of the pretreatment level was an independent predictor of time to CRPC (p = 0.004).Three factors were independent predictors of shorter time to CRPC. A 3-month PSA level >1% of the pretreatment level correlated with poor a prognosis.

Interrogation ofERGgene rearrangements in prostate cancer identifies a prognostic 10-gene signature with relevant implication to patients' clinical outcome

2013 ◽  
Vol 113 (2) ◽  
pp. 309-319 ◽  
Author(s):  
Tarek A. Bismar ◽  
Mohammed Alshalalfa ◽  
Lars F. Petersen ◽  
Liang Hong Teng ◽  
Travis Gerke ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Outcome ◽  
Gene Signature ◽  
Relevant Implication

scholarly journals Serum Pre-Albumin Predicts the Clinical Outcome in Metastatic Castration-Resistant Prostate Cancer Patients Treated With Abiraterone

2017 ◽  
Vol 8 (17) ◽  
pp. 3448-3455 ◽  
Author(s):  
Liancheng Fan ◽  
Chenfei Chi ◽  
Sanwei Guo ◽  
Yanqing Wang ◽  
Wen Cai ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Outcome ◽  
Cancer Patients ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant

scholarly journals BRCA Mutations in Prostate Cancer: Prognostic and Predictive Implications

2020 ◽  
Vol 2020 ◽  
pp. 1-7 ◽  
Author(s):  
Carlo Messina ◽  
Carlo Cattrini ◽  
Davide Soldato ◽  
Giacomo Vallome ◽  
Orazio Caffo ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Parp Inhibitors ◽  
Castration Resistant Prostate Cancer ◽  
Brca Mutations ◽  
Primary Tumors ◽  
Receptor Signalling ◽  
Castration Resistant ◽  
Damage Repair ◽  
Poor Outcomes

Despite chemotherapy and novel androgen-receptor signalling inhibitors (ARSi) have been approved during the last decades, metastatic castration-resistant prostate cancer (mCRPC) remains a lethal disease with poor clinical outcomes. Several studies found that germline or acquired DNA damage repair (DDR) defects affect a high percentage of mCRPC patients. Among DDR defects, BRCA mutations show relevant clinical implications. BRCA mutations are associated with adverse clinical features in primary tumors and with poor outcomes in patients with mCRPC. In addition, BRCA mutations predict good response to poly-ADP ribose polymerase (PARP) inhibitors, such as olaparib, rucaparib, and niraparib. However, concerns still remain on the role of extensive mutational testing in prostate cancer patients, given the implications for patients and for their progeny. The present comprehensive review attempts to provide an overview of BRCA mutations in prostate cancer, focusing on their prognostic and predictive roles.

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