scholarly journals Low Abundance of Circulating Tumor DNA in Localized Prostate Cancer

2019 ◽  
Author(s):  
S. Thomas Hennigan ◽  
Shana Y. Trostel ◽  
Nicholas T. Terrigino ◽  
Olga S. Voznesensky ◽  
Rachel J. Schaefer ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Circulating Tumor Dna ◽  
Localized Prostate Cancer ◽  
Plasma Dna ◽  
Aggressive Disease ◽  
Low Pass ◽  
Risk Patients ◽  
Clinically Significant ◽  
Prostate Cancers ◽  
Tumor Dna

ABSTRACTDespite decreased screening-based detection of clinically insignificant tumors, most diagnosed prostate cancers are still indolent, indicating a need for better strategies for detection of clinically significant disease prior to treatment. We hypothesized that patients with detectable circulating tumor DNA (ctDNA) were more likely to harbor aggressive disease. We applied ultra-low pass whole genome sequencing to profile cell-free DNA from 112 patients diagnosed with localized prostate cancer and performed targeted resequencing of plasma DNA for somatic mutations previously identified in matched solid tumor in nine cases. We also performed similar analyses on patients with metastatic prostate cancer. In all cases of localized disease, even in clinically high-risk patients who subsequently recurred, we did not detect ctDNA by either method in plasma acquired before surgery or before recurrence. In contrast, ctDNA was detected from patients with metastatic disease. Our findings demonstrate clear differences between localized and advanced prostate cancer with respect to the dissemination and detectability of ctDNA. Because allele-specific alterations in ctDNA are below the threshold for detection in localized prostate cancer, other approaches to identify cell-free nucleic acids of tumor origin may demonstrate better specificity for aggressive disease.

scholarly journals Low Abundance of Circulating Tumor DNA in Localized Prostate Cancer

2019 ◽  
pp. 1-13 ◽  
Author(s):  
S. Thomas Hennigan ◽  
Shana Y. Trostel ◽  
Nicholas T. Terrigino ◽  
Olga S. Voznesensky ◽  
Rachel J. Schaefer ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Metastatic Prostate Cancer ◽  
Circulating Tumor Dna ◽  
Localized Prostate Cancer ◽  
Whole Genome ◽  
Aggressive Disease ◽  
Low Pass ◽  
Tumor Dna

PURPOSE Despite decreased screening-based detection of clinically insignificant tumors, most diagnosed prostate cancers are still indolent, indicating a need for better strategies for detection of clinically significant disease before treatment. We hypothesized that patients with detectable circulating tumor DNA (ctDNA) were more likely to harbor aggressive disease. METHODS We applied ultra-low-pass whole-genome sequencing to profile cell-free DNA from 112 patients diagnosed with localized prostate cancer and performed targeted resequencing of plasma DNA for somatic mutations previously identified in matched solid tumor in nine cases. We also performed similar analyses of data from patients with metastatic prostate cancer. RESULTS In all cases of localized prostate cancer, even in clinically high-risk patients who subsequently had recurrent disease, ultra-low-pass whole-genome sequencing and targeted resequencing did not detect ctDNA in plasma acquired before surgery or before recurrence. In contrast, using both approaches, ctDNA was detected in patients with metastatic prostate cancer. CONCLUSION Our findings demonstrate clear differences between localized and advanced prostate cancer with respect to the dissemination and detectability of ctDNA. Because allele-specific alterations in ctDNA are below the threshold for detection in localized prostate cancer, other approaches to identify cell-free nucleic acids of tumor origin may demonstrate better specificity for aggressive disease.

Clinical Utility of the Percentage of Positive Prostate Biopsies in Defining Biochemical Outcome After Radical Prostatectomy for Patients With Clinically Localized Prostate Cancer

2000 ◽  
Vol 18 (6) ◽  
pp. 1164-1172 ◽  
Author(s):  
Anthony V. D’Amico ◽  
Richard Whittington ◽  
S. Bruce Malkowicz ◽  
Delray Schultz ◽  
Julia Fondurulia ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radical Prostatectomy ◽  
Clinical Utility ◽  
Localized Prostate Cancer ◽  
Intermediate Risk ◽  
Prostate Biopsies ◽  
Psa Failure ◽  
Surgical Data ◽  
Risk Patients ◽  
Clinically Significant

PURPOSE: To determine the clinical utility of the percentage of positive prostate biopsies in predicting prostate-specific antigen (PSA) outcome after radical prostatectomy (RP) for men with PSA-detected or clinically palpable prostate cancer. METHODS: A Cox regression multivariable analysis was used to determine whether the percentage of positive prostate biopsies provided clinically relevant information about PSA outcome after RP in 960 men while accounting for the previously established risk groups that are defined according to pretreatment PSA level, biopsy Gleason score, and the 1992 American Joint Committee on Cancer (AJCC) clinical T stage. The findings were then tested using an independent surgical database that included data for 823 men. RESULTS: Controlling for the known prognostic factors, the percentage of positive prostate biopsies added clinically significant information (P < .0001) regarding time to PSA failure after RP. Specifically, 80% of the patients in the intermediate-risk group (1992 AJCC T2b, or biopsy Gleason 7 or PSA > 10 ng/mL and ≤ 20 ng/mL) could be classified into either an 11% or 86% 4-year PSA control cohort using the preoperative prostate biopsy data. These findings were validated in the intermediate-risk patients using an independent surgical data set. CONCLUSION: The validated stratification of PSA outcome after RP using the percentage of positive prostate biopsies in intermediate-risk patients is clinically significant. This information can be used to identify men with newly diagnosed and clinically localized prostate cancer who are at high risk for early (≤ 2 years) PSA failure and, therefore, may benefit from the use of adjuvant therapy.

Genomic analysis of circulating tumor DNA in 3,334 patients with advanced prostate cancer to identify targetable BRCA alterations and AR resistance mechanisms.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 25-25
Author(s):  
Hanna Tukachinsky ◽  
Russell Madison ◽  
Jon Chung ◽  
Lucas Dennis ◽  
Bernard Fendler ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Advanced Prostate Cancer ◽  
Acquired Resistance ◽  
Genomic Analysis ◽  
Circulating Tumor Dna ◽  
Resistance Mechanisms ◽  
Cancer Tissue ◽  
Castration Resistant Prostate Cancer ◽  
High Level ◽  
Tumor Dna

25 Background: Comprehensive genomic profiling (CGP) by next-generation sequencing (NGS) of circulating tumor DNA (ctDNA) from plasma provides a minimally invasive method to identify targetable genomic alterations (GAs) and resistance mechanisms in patients with metastatic castration-resistant prostate cancer (mCRPC). The circulating tumor fraction in patients with mCRPC and the clinical validity of GAs detected in plasma remain unknown. We evaluated the landscape of GAs using ctDNA-based CGP and assessed concordance with tissue-based CGP. Methods: Plasma from 3,334 patients with advanced prostate cancer (including 1,674 mCRPC screening samples from the TRITON2/3 trials and 1,660 samples from routine clinical CGP) was analyzed using hybrid-capture-based gene panel NGS assays. Results were compared with CGP of 2,006 metastatic prostate cancer tissue biopsies. Concordance was evaluated in 837 patients with both tissue (archival or contemporaneous) and plasma NGS results. Results: 3,127 patients [94%] had detectable ctDNA. BRCA1/2 were mutated in 295 patients [8.8%]. In concordance analysis, 72/837 [8.6%] patients had BRCA1/2 mutations detected in tissue, 67 [93%] of whom were also identified by ctDNA, and 20 patients were identified using ctDNA but not tissue [23% of all patients identified using ctDNA]. ctDNA detected subclonal BRCA1/2 reversions in 10 of 1,660 [0.6%] routine clinical CGP samples. AR alterations, including amplifications and hotspot mutations, which were detected in 940/2,213 patients [42%]. Rare AR compound mutations, rearrangements, and novel in-frame deletions were identified. Altered pathways included PI3K/AKT/mTOR [14%], WNT/β-catenin [17%], and RAS/RAF/MEK [5%]. Microsatellite instability was detected in 31/2,213 patients [1.4%]. Conclusions: In the largest study of mCRPC plasma samples conducted to date, CGP of ctDNA recapitulated the genomic landscape detected in tissue biopsies, with a high level of agreement in detection of BRCA1/2 alterations. It also identified patients who may have gained somatic BRCA1/2 alterations since archival tissue was collected. ctDNA detected more acquired resistance GAs than tissue, including novel AR-activating variants. The large percentage of patients with rich genomic signal from ctDNA, and the sensitive, specific detection of BRCA1/2 alterations position liquid biopsy as a compelling clinical complement to tissue CGP for patients with mCRPC.

Treatment and relapse in breast cancer show significant correlations to noninvasive testing using urinary and plasma DNA

2020 ◽  
Vol 16 (13) ◽  
pp. 849-858
Author(s):  
Jinling Zhang ◽  
Xueli Zhang ◽  
Shuwei Shen
Keyword(s):  
Breast Cancer ◽  
Circulating Tumor Dna ◽  
Noninvasive Testing ◽  
Plasma Dna ◽  
Operating Characteristics ◽  
Risk Profiling ◽  
Routine Monitoring ◽  
Plasma And Urine Samples ◽  
Serial Time Point ◽  
Tumor Dna

Aim: Circulating tumor DNA is promising for routine monitoring of breast cancer. Noninvasive testing allows regular probing using plasma and urine samples. Methods: Peripheral blood and simultaneous urine collection from patients were quantified. Concordance between methods were made. Serial time-point measurements were correlated to disease outcome. Results: Index measurements demonstrate over 90% concordance with biopsy. Receiver operating characteristics curves showed over 0.95 for both plasma and urine results comparing with controls. Patients with lower risk of relapse experienced greater declines in detected DNA levels. Maximal declines were registered at 4.0- and 6.8-fold for plasma and urine results, respectively. Conclusion: Measuring and monitoring DNA levels complement existing testing regimes and provides better risk profiling of patients for possible relapse.

scholarly journals Clinical Impact of Circulating Tumor Cells in Patients with Localized Prostate Cancer

Cells ◽  
2019 ◽  
Vol 8 (7) ◽  
pp. 676 ◽  
Author(s):  
Broncy ◽  
Paterlini-Bréchot
Keyword(s):  
Prostate Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Early Stage ◽  
Clinical Impact ◽  
Localized Prostate Cancer ◽  
Aggressive Cancer ◽  
Highly Sensitive ◽  
Prostate Cancers ◽  
Suitable Marker

The main issue concerning localized prostate cancers is the lack of a suitable marker which could help patients’ stratification at diagnosis and distinguish those with a benign disease from patients with a more aggressive cancer. Circulating Tumor Cells (CTC) are spread in the blood by invasive tumors and could be the ideal marker in this setting. Therefore, we have compiled data from the literature in order to obtain clues about the clinical impact of CTC in patients with localized prostate cancer. Forty-three publications have been found reporting analyses of CTC in patients with non-metastatic prostate cancer. Of these, we have made a further selection of 11 studies targeting patients with clinical or pathological stages T1 and T2 and reporting the clinical impact of CTC. The results of this search show encouraging data toward the use of CTC in patients with early-stage cancer. However, they also highlight the lack of standardized methods providing a highly sensitive and specific approach for the detection of prostate-derived CTC.

Sign in / Sign up

Export Citation Format

Share Document