Dataset Information

Impact of Time to Castration Resistance on Cytoreductive Radiotherapy in Metastatic Castration-Resistant Prostate Cancer.

ABSTRACT:

Background

The role of local radiotherapy in metastatic castration-resistant prostate cancer (mCRPC) remains undefined. This study aimed to identify the value of local radiotherapy and potential candidates for mCRPC.

Methods

A total of 215 patients with mCRPC treated with or without cytoreductive radiotherapy (CRT) between June 2011 and February 2019 were analyzed. Overall survival (OS) was calculated from the onset of mCRPC. The receiver-operating characteristic (ROC) curve was used to find the cutoff point for time to castration resistance (TCR).

Results

One-hundred and fifty-five (72.1%) patients received abiraterone after mCRPC, and 54 (25.1%) patients received CRT. The median TCR was 14.9 months. After a median follow-up of 31.7 months, the median OS was 33.3 months. The Eastern Cooperative Oncology Group (ECOG) performance scores 0-1, oligometastases, abiraterone after mCRPC, CRT, and TCR ?9 months were independent prognostic factors for better OS. Stratified analyses showed improved survival when CRT was applied to patients treated with abiraterone (HR 0.44; 95% CI 0.23-0.83; P = 0.012) and TCR ?9 months (HR 0.39; 95% CI 0.21-0.74; P = 0.004). The percentage of PSA response after radiotherapy was higher in patients with TCR ?9 months compared to those with TCR <9 months. No grade 3 or worse adverse events after radiotherapy were reported.

Conclusions

ECOG performance score, oligometastases, abiraterone application, TCR and CRT were independent prognostic factors for OS in patients with mCRPC. Patients with a short duration of response to primary androgen deprivation therapy were less likely to benefit from CRT.

SUBMITTER: Mai L

PROVIDER: S-EPMC7746838 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

Impact of Time to Castration Resistance on Cytoreductive Radiotherapy in Metastatic Castration-Resistant Prostate Cancer.

Mai Lixin L Zhang Zitong Z Li Yonghong Y Liu Ruiqi R Li Jibin J Huang Sijuan S Lin Maosheng M Liu Boji B Cao Wufei W Wu Jianhua J Liu Mengzhong M Zhou Fangjian F Liu Yang Y He Liru L

Frontiers in oncology 20201204

<h4>Background</h4>The role of local radiotherapy in metastatic castration-resistant prostate cancer (mCRPC) remains undefined. This study aimed to identify the value of local radiotherapy and potential candidates for mCRPC.<h4>Methods</h4>A total of 215 patients with mCRPC treated with or without cytoreductive radiotherapy (CRT) between June 2011 and February 2019 were analyzed. Overall survival (OS) was calculated from the onset of mCRPC. The receiver-operating characteristic (ROC) curve was u ...[more]

PMID: 33344256

Similar Datasets

Project description:BackgroundMetastatic castration-resistant prostate cancer (mCRPC) is the lethal form of the disease. Several recent studies have identified genomic alterations in mCRPC, but the clinical implications of these genomic alterations have not been fully elucidated.ObjectiveTo use whole-genome sequencing (WGS) to assess the association between key driver gene alterations and overall survival (OS), and to use whole-transcriptome RNA sequencing to identify genomic drivers of enzalutamide resistance.Design, setting, and participantsWe performed survival analyses and gene set enrichment analysis (GSEA) on WGS and RNA sequencing results for a cohort of 101 mCRPC patients.Outcome measurements and statistical analysisOS was the clinical endpoint for all univariate and multivariable survival analyses. Candidate drivers of enzalutamide resistance were identified in an unbiased manner, and mutations of the top candidate were further assessed for enrichment among enzalutamide-resistant patients using Fisher's exact test.Results and limitationsHarboring two DNA alterations in RB1 was independently predictive of poor OS (median 14.1 vs 42.0mo; p=0.007) for men with mCRPC. GSEA identified the Wnt/β-catenin pathway as the top differentially modulated pathway among enzalutamide-resistant patients. Furthermore, β-catenin mutations were exclusive to enzalutamide-resistant patients (p=0.01) and independently predictive of poor OS (median 13.6 vs 41.7mo; p=0.025).ConclusionsThe presence of two RB1 DNA alterations identified in our WGS analysis was independently associated with poor OS among men with mCRPC. The Wnt/β-catenin pathway plays an important role in enzalutamide resistance, with differential pathway expression and enrichment of β-catenin mutations in enzalutamide-resistant patients. Moreover, β-catenin mutations were predictive of poor OS in our cohort.Patient summaryWe observed a correlation between genomic findings for biopsy samples from metastases from men with metastatic castration-resistant prostate cancer (mCRPC) and clinical outcomes. This work sheds new light on clinically relevant genomic alterations in mCRPC and provides a roadmap for the development of new personalized treatment regimens in mCRPC.

Dataset Information

Impact of Time to Castration Resistance on Cytoreductive Radiotherapy in Metastatic Castration-Resistant Prostate Cancer.

Background

Methods

Results

Conclusions

Publications

Impact of Time to Castration Resistance on Cytoreductive Radiotherapy in Metastatic Castration-Resistant Prostate Cancer.

Similar Datasets

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