Olaparib Efficacy in Patients with Metastatic Castration-resistant Prostate Cancer and BRCA1, BRCA2, or ATM Alterations Identified by Testing Circulating Tumor DNA

Article Oncology

Olaparib in patients with mCRPC with homologous recombination repair gene alterations: PROfound Asian subset analysis

Nobuaki Matsubara et al.

Summary: The exploratory analysis of the PROfound trial suggests that olaparib improves outcomes for Asian patients, with similar safety and tolerability compared to the global population.

JAPANESE JOURNAL OF CLINICAL ONCOLOGY (2022)

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Article Urology & Nephrology

Advanced Prostate Cancer: AUA/ASTRO/SUO Guideline PART II

William T. Lowrance et al.

Summary: This guideline aims to assist clinicians in managing patients with advanced prostate cancer, providing evidence- and consensus-based guidance statements. Continued research and publication of high-quality evidence from future trials are crucial to enhance the level of care for these patients.

JOURNAL OF UROLOGY (2021)

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Article Oncology

BRCA2, ATM, and CDK12 Defects Differentially Shape Prostate Tumor Driver Genomics and Clinical Aggression

Evan Warner et al.

Summary: The study identifies BRCA2, ATM, and CDK12 as the most frequently disrupted DDR genes in ctDNA of metastatic prostate cancer patients, collectively mutated in 15% of cases. ATM defects and TP53 mutations were rare, with most patients showing biallelic gene disruption. Loss of BRCA2 and CDK12, but not ATM, was associated with poor clinical outcomes.

CLINICAL CANCER RESEARCH (2021)

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Article Oncology

Genotype-Specific Differences in Circulating Tumor DNA Levels in Advanced NSCLC

Vincent K. Lam et al.

Summary: The study found a moderate but significant correlation between ctDNA variant allele frequency and imaging measures of tumor burden, with varying strengths based on tumor genotypes. Factors such as TP53 and EGFR mutations, visceral metastasis, and tumor burden were independent predictors of increased ctDNA shedding, suggesting that ctDNA levels are affected by both tumor burden and genotype.

JOURNAL OF THORACIC ONCOLOGY (2021)

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Article Oncology

Association of Clonal Hematopoiesis in DNA Repair Genes With Prostate Cancer Plasma Cell-free DNA Testing Interference

Kendal Jensen et al.

Summary: This case series study found that approximately 10% of men with advanced prostate cancer had CHIP interference in plasma cfDNA in genes used for PARPi therapy eligibility, with the most common variant being in ATM. The study highlights the need for using a whole-blood control sample to distinguish CHIP variants from prostate cancer in cfDNA testing.

JAMA ONCOLOGY (2021)

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Article Oncology

Genomic Analysis of Circulating Tumor DNA in 3,334 Patients with Advanced Prostate Cancer Identifies Targetable BRCA Alterations and AR Resistance Mechanisms

Hanna Tukachinsky et al.

Summary: Comprehensive genomic profiling (CGP) of cell-free circulating tumor DNA (ctDNA) is a promising approach for patients with metastatic castration-resistant prostate cancer (mCRPC), providing a minimally invasive alternative for detecting targetable genomic alterations. Analysis of ctDNA revealed a high concordance with tissue-based CGP, particularly in detecting BRCA1/2 mutations, while also identifying additional acquired resistance alterations. This highlights the potential of ctDNA as a clinical complement to tissue CGP, with reflex to tissue CGP in case of negative actionable variants.

CLINICAL CANCER RESEARCH (2021)

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Meeting Abstract Oncology

PI3K/AKT pathway biomarkers analysis from the phase III IPATential150 trial of ipatasertib plus abiraterone in metastatic castration-resistant prostate cancer.

Johann S. De Bono et al.

JOURNAL OF CLINICAL ONCOLOGY (2021)

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Meeting Abstract Oncology

Concordance of BRCA1, BRCA2 (BRCA), and ATM mutations identified in matched tumor tissue and circulating tumor DNA (ctDNA) in men with metastatic castration-resistant prostate cancer (mCRPC) screened in the PROfound study.

Kim N. Chi et al.

JOURNAL OF CLINICAL ONCOLOGY (2021)

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Article Oncology

Prostate Cancer, Version 1.2021 Featured Updates to the NCCN Guidelines

Edward Schaeffer et al.

Summary: The NCCN Guidelines for Prostate Cancer provide recommendations for staging and risk assessment post-diagnosis, with management options for localized, regional, and metastatic disease. The guidelines also cover disease monitoring and treatment of recurrent disease. The NCCN Prostate Cancer Panel meets annually to update recommendations based on new clinical data, aiming to provide the most effective care for patients.

JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK (2021)

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Review Pathology

Practical considerations for optimising homologous recombination repair mutation testing in patients with metastatic prostate cancer

David Gonzalez et al.

Summary: Analysis of the genomic landscape of prostate cancer has identified different molecular subgroups, highlighting the need for molecular diagnostics to identify patients who can benefit from targeted therapies. Recommendations for specimen handling and testing pathways are crucial for maximizing the success rates of clinical genomic analysis in prostate cancer. Early involvement of a multidisciplinary team is key to optimal workflow and specimen preservation, with an urgent need to incorporate high-quality genomic testing in the routine clinical pathway of patients with mCRPC.

JOURNAL OF PATHOLOGY CLINICAL RESEARCH (2021)

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Article Urology & Nephrology

Elucidating Prostate Cancer Behaviour During Treatment via Low-pass Whole-genome Sequencing of Circulating Tumour DNA

Semini Sumanasuriya et al.

Summary: This study analyzed cell-free DNA in blood samples from patients with prostate cancer and found that levels of DNA in blood were indicative of disease prognosis, with changes after treatment detectable. The study also observed a genetic scar associated with certain previous treatments, showing the potential of this test to complement existing tests, offer insights into drug response, and detect clinically relevant genetic changes.

EUROPEAN UROLOGY (2021)

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Article Oncology

Biomarkers Associating with PARP Inhibitor Benefit in Prostate Cancer in the TOPARP-B Trial

Suzanne Carreira et al.

Summary: PARP inhibitors show varied effects in treating APCs with DNA repair defects. The greatest benefit is seen in patients with BRCA2 homozygous deletion, biallelic loss of PALB2, and loss of ATM protein expression. Loss of RAD51 foci, evaluating homologous recombination repair function, is predominantly found in tumors with biallelic BRCA1/2 and PALB2 alterations.

CANCER DISCOVERY (2021)

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Article Oncology

Concordance of DNA Repair Gene Mutations in Paired Primary Prostate Cancer Samples and Metastatic Tissue or Cell-Free DNA

Michael T. Schweizer et al.

Summary: DDR gene mutations are key actionable alterations for precision medicine strategies in advanced prostate cancer. Primary prostate tissue accurately reflects the mutational status of DDR genes in metastatic tissue, with potential mechanisms of resistance detected in ctDNA profiling.

JAMA ONCOLOGY (2021)

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Article Oncology