BACKGROUND: Several systemic therapeutic options exist for metastatic castrate-sensitive prostate cancer (mCSPC). Circulating tumor DNA (ctDNA) can molecularly profile metastatic castration-resistant prostate cancer and can influence decision-making, but remains untested in mCSPC. OBJECTIVE: To determine ctDNA abundance at de novo mCSPC diagnosis and whether ctDNA provides complementary clinically relevant information to a prostate biopsy. DESIGN, SETTING, AND PARTICIPANTS: We collected plasma cell-free DNA (cfDNA) from 53 patients newly diagnosed with mCSPC and, where possible, during treatment. Targeted sequencing was performed on cfDNA and DNA from diagnostic prostate tissue. RESULTS AND LIMITATIONS: The median ctDNA fraction was 11% (range 0-84%) among untreated patients but was lower (1.0%, range 0-51%) among patients after short-term (median 22d) androgen deprivation therapy (ADT). TP53 mutations and DNA repair defects were identified in 47% and 21% of the cohort, respectively. The concordance for mutation detection in matched samples was 80%. Combined ctDNA and tissue analysis identified potential driver alterations in 94% of patients, whereas ctDNA or prostate biopsy alone was insufficient in 19 cases (36%). Limitations include the use of a narrow gene panel and undersampling of primary disease by prostate biopsy. CONCLUSIONS: ctDNA provides additional information to a prostate biopsy in men with de novo mCSPC, but ADT rapidly reduces ctDNA availability. Primary tissue and ctDNA share relevant somatic alterations, suggesting that either is suitable for molecular subtyping in de novo mCSPC. The optimal approach for biomarker development should utilize both a tissue and liquid biopsy at diagnosis, as neither captures clinically relevant somatic alterations in all patients. PATIENT SUMMARY: In men with advanced prostate cancer, tumor DNA shed into the bloodstream can be measured via a blood test. The information from this test provides complementary information to a prostate needle biopsy and could be used to guide management strategies. Sequencing data were deposited in the European Genome-phenome Archive (EGA) under study identifier EGAS00001003351.
BACKGROUND: Several systemic therapeutic options exist for metastatic castrate-sensitive prostate cancer (mCSPC). Circulating tumor DNA (ctDNA) can molecularly profile metastatic castration-resistant prostate cancer and can influence decision-making, but remains untested in mCSPC. OBJECTIVE: To determine ctDNA abundance at de novo mCSPC diagnosis and whether ctDNA provides complementary clinically relevant information to a prostate biopsy. DESIGN, SETTING, AND PARTICIPANTS: We collected plasma cell-free DNA (cfDNA) from 53 patients newly diagnosed with mCSPC and, where possible, during treatment. Targeted sequencing was performed on cfDNA and DNA from diagnostic prostate tissue. RESULTS AND LIMITATIONS: The median ctDNA fraction was 11% (range 0-84%) among untreated patients but was lower (1.0%, range 0-51%) among patients after short-term (median 22d) androgen deprivation therapy (ADT). TP53 mutations and DNA repair defects were identified in 47% and 21% of the cohort, respectively. The concordance for mutation detection in matched samples was 80%. Combined ctDNA and tissue analysis identified potential driver alterations in 94% of patients, whereas ctDNA or prostate biopsy alone was insufficient in 19 cases (36%). Limitations include the use of a narrow gene panel and undersampling of primary disease by prostate biopsy. CONCLUSIONS: ctDNA provides additional information to a prostate biopsy in men with de novo mCSPC, but ADT rapidly reduces ctDNA availability. Primary tissue and ctDNA share relevant somatic alterations, suggesting that either is suitable for molecular subtyping in de novo mCSPC. The optimal approach for biomarker development should utilize both a tissue and liquid biopsy at diagnosis, as neither captures clinically relevant somatic alterations in all patients. PATIENT SUMMARY: In men with advanced prostate cancer, tumor DNA shed into the bloodstream can be measured via a blood test. The information from this test provides complementary information to a prostate needle biopsy and could be used to guide management strategies. Sequencing data were deposited in the European Genome-phenome Archive (EGA) under study identifier EGAS00001003351.
Authors: Melissa A Reimers; Steven M Yip; Li Zhang; Marcin Cieslik; Mallika Dhawan; Bruce Montgomery; Alexander W Wyatt; Kim N Chi; Eric J Small; Arul M Chinnaiyan; Ajjai S Alva; Felix Y Feng; Jonathan Chou Journal: Eur Urol Date: 2019-10-20 Impact factor: 20.096
Authors: Gareth J Morrison; Alexander T Cunha; Nita Jojo; Yucheng Xu; Yili Xu; Eric Kwok; Peggy Robinson; Tanya Dorff; David Quinn; John Carpten; Zarko Manojlovic; Amir Goldkorn Journal: Int J Cancer Date: 2020-02-27 Impact factor: 7.396
Authors: Ha X Dang; Pradeep S Chauhan; Haley Ellis; Wenjia Feng; Peter K Harris; Grace Smith; Mark Qiao; Katherine Dienstbach; Rachel Beck; Andrew Atkocius; Faridi Qaium; Jingqin Luo; Jeff M Michalski; Joel Picus; Russell K Pachynski; Christopher A Maher; Aadel A Chaudhuri Journal: JCO Precis Oncol Date: 2020-06-18
Authors: David Gonzalez; Joaquin Mateo; Albrecht Stenzinger; Federico Rojo; Michelle Shiller; Alexander W Wyatt; Frédérique Penault-Llorca; Leonard G Gomella; Ros Eeles; Anders Bjartell Journal: J Pathol Clin Res Date: 2021-02-25
Authors: Bernard Pereira; Christopher T Chen; Lipika Goyal; Charlotte Walmsley; Christopher J Pinto; Islam Baiev; Read Allen; Laura Henderson; Supriya Saha; Stephanie Reyes; Martin S Taylor; Donna M Fitzgerald; Maida Williams Broudo; Avinash Sahu; Xin Gao; Wendy Winckler; A Rose Brannon; Jeffrey A Engelman; Rebecca Leary; James R Stone; Catarina D Campbell; Dejan Juric Journal: Nat Commun Date: 2021-05-27 Impact factor: 14.919