Evaluating the role of stereotactic body radiation therapy with respect to androgen receptor signaling inhibitors for metastatic prostate cancer.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 121-121
Author(s):  
Victoria Brennan ◽  
Alexander Spektor ◽  
Christopher Sweeney ◽  
Atish Dipankar Choudhury ◽  
Dana E. Rathkopf ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radiation Therapy ◽  
Androgen Receptor ◽  
Metastatic Prostate Cancer ◽  
Stereotactic Body Radiation Therapy ◽  
External Beam Radiation ◽  
Receptor Signaling ◽  
Androgen Receptor Signaling ◽  
Stereotactic Body Radiation ◽  
Signaling Inhibitors

121 Background: Outcomes of stereotactic body radiation therapy (SBRT) with respect to androgen receptor signaling inhibitors (ARSI) have not been characterized for metastatic prostate cancer. Our purpose is to characterize prostate specific antigen (PSA) response and progression free survival (PFS) following SBRT among men who have received ARSI in castration sensitive and resistant settings. Methods: A single institution retrospective analysis was performed for men treated with SBRT and ARSI and categorized into 4 groups: 1) oligometastatic castration-sensitive prostate cancer (omCSPC), 2) ARSI-sensitive (ARSI-s) oligometastatic castration-resistant prostate cancer (omCRPC), 3) ARSI-resistant (ARSI-r) omCRPC, and 4) polymetastatic CRPC (pmCRPC). We calculated the PSA reduction greater than 50% (PSA50) and median PFS (PSA or radiographic progression) as determined by routine care. We also used Cox regression analysis to determine factors influencing PFS for ARSI-r disease. Results: 73 men with 126 lesions were treated with SBRT and followed for a median of 14.4 months. The percentages of men who achieved a PSA50 for omCSPC, ARSI-s omCRPC, ARSI-r omCRPC and pmCRPC were 100%, 90%, 62.9%, and 16.7%, respectively. Respective median PFS values were: not reached, 17.3, 9.0, and 1.6 months. For the 35 men with ARSI-r omCRPC, incomplete ablation (defined as the presence of untreated lesions after SBRT or prior palliative external beam radiation therapy (EBRT)) (HR 3.51 [1.36, 9.06]; p = 0.01) was associated with worse PFS on multivariable analysis. For the subgroup of 22 men with ARSI-r omCRPC without prior palliative EBRT or untreated metastases, the median PFS was 13.1 months. Conclusions: SBRT may augment the efficacy of ARSI, particularly among men with ARSI-r omCRPC, provided that all lesions received ablative radiation doses. Future prospective study of SBRT for men receiving ARSI is warranted.

Assessment of immunohistochemical testing for androgen receptor splice variant 7 as a biomarker to predict resistance to androgen receptor signaling inhibitors in metastatic prostate cancer.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 308-308
Author(s):  
Ojas Harihar Vyas ◽  
Matthew James Butler ◽  
Elizabeth Ann Bowhay-Carnes ◽  
Muhammad Pathan ◽  
Paromita Datta
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Splice Variant ◽  
Receptor Signaling ◽  
Health Administration ◽  
Primary Resistance ◽  
Androgen Receptor Signaling ◽  
Signaling Inhibitors ◽  
Psa Response ◽  
Androgen Receptor Splice Variant

308 Background: Androgen receptor splice variant 7 (AR-V7) has been shown to confer resistance to androgen receptor signaling inhibitors (ARS-I) such as enzalutamide (enza) and abiraterone (abi). Resistance can be observed at the time of initial treatment, or may be acquired later in the disease course. Prior research has primarily focused on AR-V7 expression in circulating tumor cells (CTCs) but the utility of more affordable immunohistochemical (IHC) testing to predict for primary resistance to ARS-I remains unknown, which is of particular relevance as ARS-I gain use as initial therapy. Methods: We identified patients in the South Texas Veterans Health Administration Tumor Registry with metastatic, castrate-resistant prostate cancer who received ARS-I since 2011. IHC for AR-V7 staining was validated on controls and performed on tissue from the most recent tissue specimen (diagnostic biopsy, prostatectomy, or biopsy of a metastatic site) on all identified patients with adequate tissue available. Results: 25 of 42 (60%) patients receiving abi had PSA response with median duration of response (DOR) of 231 days. 14 of 26 (54%) of patients receiving enza experienced PSA response with a median DOR of 165 days. IHC is currently being interpreted on stored tissue specimens to assess predictive efficacy of AR-V7 staining. The de-novo rate of AR-V7 expression and correlation with response to ARS-I in the veteran population will be reported with final results. Conclusions: IHC testing for AR-V7 may provide a cost-effective biomarker to identify patients resistant to ARS-I, thus avoiding thus avoiding time-consuming and costly treatment with ineffective therapy. Further study is warranted to assess cost-effectiveness and reduction in unnecessary toxicity by the use of IHC testing for AR-V7 in the front-line setting to predict primary resistance for patients that would otherwise qualify for ARS-I.

Young age to predict for transient elevation in PSA after definitive stereotactic body radiation therapy for prostate cancer.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 118-118
Author(s):  
Seth Blacksburg ◽  
Aaron Katz ◽  
Matthew R. Witten ◽  
Owen Clancey ◽  
Jonathan A. Haas
Keyword(s):  
Prostate Cancer ◽  
Radiation Therapy ◽  
Stereotactic Body Radiation Therapy ◽  
External Beam Radiation ◽  
Rare Occurrence ◽  
Stereotactic Body Radiation ◽  
Temporary Rise ◽  
Transient Elevation ◽  
Chi Square Analysis ◽  
Baseline Psa

118 Background: Stereotactic Body Radiation Therapy (SBRT) is a standard therapeutic option for men with prostate adenocarcinoma. There is a small body of literature characterizing a PSA bump after treatment with SBRT. Despite this, there is a paucity of data addressing rates of transient PSA increase immediately after SBRT treatment and what factors portend for this rare occurrence. This study reports outcomes on initial PSA after SBRT therapy for men who have received definitive SBRT for prostate cancer. Methods: Between May 2006 and February 2014, 921 patients with prostate cancer were treated with SBRT delivered via Cyberknife therapy. The mean age was 67 years old. 68.5% of patients were Caucasian, 17.4% African American, and 14.1% were another ethnicity. Patients were divided into prognostic risk groups with 44.7%, 43.5%, and 11.1% of patients falling in the low, intermediate, and high risk stratifications. Gleason scores were < 6 in 44.4%, 7 in 41.3%, and 8-10 in 14.2%. 37 patients also received supplemental external beam radiation (median dose 4500cGy) and 8.9% of patients received Androgen Deprivation Therapy (ADT) as part of their treatment regimen. Pre-treatment PSA was 0.8 – 205 ng/ml (median 6.1). Results: At 3 months’ follow-up, 2.8% of patients had a PSA elevated above their baseline value. 27.8% of patients age ≤50 (p<.0001) and 8.4% of patients age ≤60 (p=.001) experienced an increased in baseline PSA. African Americans were more likely to experience a transient increase in PSA over Caucasians (7.8% vs. 3.0%, p=.06). Patients treated with fewer beams were also more likely have a temporary rise in PSA (p=.056). Gleason Score, Risk grouping, prostate volume, ADT, and EBRT did not predict for rise on Pearson Chi-Square analysis. On multivariate analysis, only age ≤50 (p<.0001) portended for increased PSA at 3 months’ time. Conclusions: This represents the largest series evaluating elevation of PSA after definitive SBRT for prostate cancer. Temporary rise in baseline PSA after SBRT is rare. Despite that, a significant cohort of younger patients can experience transient elevation. Patient age ≤50 was found to be the only predictor of this otherwise rare occurrence.

A circulating tumor cell RNA assay for dynamic assessment of androgen receptor signaling inhibitors sensitivity in metastatic castration-resistant prostate cancer.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 157-157
Author(s):  
Yu Jen Jan ◽  
Junhee Yoon ◽  
Jie-Fu Chen ◽  
Pin-Jung Chen ◽  
Pai-Chi Teng ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Androgen Receptor ◽  
Dynamic Assessment ◽  
Receptor Signaling ◽  
Z Score ◽  
Androgen Receptor Signaling ◽  
Clinical Behavior ◽  
Gene Signatures ◽  
Signaling Inhibitors

157 Background: Tissue-based gene signatures can predict clinical behavior in prostate cancer (PC). Our objective was to extend their application to circulating tumor cells (CTCs) and to show that changes in the signature were associated with changes in clinical behavior. Methods: Our approach combined the Thermoresponsive(TR)-NanoVelcro CTC purification system with the Nanostring nCounter system for cellular purification and transcriptomic analysis. The Prostate Cancer Classification System (PCS) panel was modified for use in CTCs. We selected 31 blood samples from 23 PC patients receiving androgen receptor signaling inhibitors (ARSI) and measured the PCS1 Z score (probability). These findings were compared with clinical outcome data (responsiveness/resistance). Results: A modified, 16-gene PCS1 signature was established and validated through a rigorous bioinformatics process. We performed analytical validation of our combined CTC-RNA system to ensure reproducibility and specificity. In patient bloods, ARSI-resistant samples (ARSI-R, n = 14) had significantly higher PCS1 Z scores as compared with ARSI-sensitive samples (ARSI-S, n = 17) (Rank-sum test, P = 0.003). The analyzed bloods contained samples from 8 patients who developed resistance to an ARSI allowing for dynamic measurement of gene expression. Our analysis found that the PCS1 Z score increased at the time that ARSI-resistance emerged (Pairwise T-test, P = 0.016). Conclusions: Using this new methodology, contemporary, clinically-relevant gene signatures such as PCS could be measured non-invasively in CTCs. These findings can be used to relate gene expression to clinical drug response. This approach also allowed for measurement of dynamic variations of gene expression in individual patients over time that correlated to ARSI sensitivity.

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