دورية أكاديمية
Validation of the Decipher genomic classifier in patients receiving salvage radiotherapy without hormone therapy after radical prostatectomy - an ancillary study of the SAKK 09/10 randomized clinical trial.
| العنوان: | Validation of the Decipher genomic classifier in patients receiving salvage radiotherapy without hormone therapy after radical prostatectomy - an ancillary study of the SAKK 09/10 randomized clinical trial. |
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| المؤلفون: | Dal Pra A; Department of Radiation Oncology, University of Miami Miller School of Medicine, Miami, USA; Department of Radiation Oncology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. Electronic address: alan.dalpra@med.miami.edu., Ghadjar P; Charité - Universitätsmedizin Berlin, Berlin, Germany; Department of Radiation Oncology, Kantonsspital Winterthur, Winterthur, Switzerland., Hayoz S; SAKK Coordinating Center, Bern, Switzerland., Liu VYT; Decipher Biosciences (a subsidiary of Veracyte Inc.), San Diego, USA., Spratt DE; Department of Radiation Oncology, University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, USA., Thompson DJS; Emmes Canada, Vancouver, Canada., Davicioni E; Decipher Biosciences (a subsidiary of Veracyte Inc.), San Diego, USA., Huang HC; Decipher Biosciences (a subsidiary of Veracyte Inc.), San Diego, USA., Zhao X; Decipher Biosciences (a subsidiary of Veracyte Inc.), San Diego, USA., Liu Y; Decipher Biosciences (a subsidiary of Veracyte Inc.), San Diego, USA., Schär C; SAKK Coordinating Center, Bern, Switzerland., Gut P; Kantonsspital Luzern, Luzern, Switzerland., Plasswilm L; Department of Radiation Oncology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland; Kantonsspital St. Gallen, St. Gallen, Switzerland., Hölscher T; Department of Radiotherapy and Radiation Oncology, Faculty of Medicine, Technische Universität Dresden, Dresden, Germany., Polat B; Department of Radiation Oncology, University of Wuerzburg, Wuerzburg, Germany., Hildebrandt G; University Hospital Rostock, Rostock, Germany., Müller AC; University Hospital Tübingen, Tübingen, Germany., Pollack A; Department of Radiation Oncology, University of Miami Miller School of Medicine, Miami, USA., Thalmann GN; Department of Urology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland., Zwahlen D; Department of Radiation Oncology, Kantonsspital Winterthur, Winterthur, Switzerland., Aebersold DM; Department of Radiation Oncology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. |
| المصدر: | Annals of oncology : official journal of the European Society for Medical Oncology [Ann Oncol] 2022 Sep; Vol. 33 (9), pp. 950-958. Date of Electronic Publication: 2022 May 28. |
| نوع المنشور: | Clinical Trial, Phase III; Journal Article; Randomized Controlled Trial |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: England NLM ID: 9007735 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1569-8041 (Electronic) Linking ISSN: 09237534 NLM ISO Abbreviation: Ann Oncol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2020- : London : Elsevier Original Publication: Dordrecht ; Boston : Kluwer Academic Publishers, c1990- |
| مواضيع طبية MeSH: | Prostate-Specific Antigen* , Prostatic Neoplasms*/genetics , Prostatic Neoplasms*/radiotherapy , Prostatic Neoplasms*/surgery , Salvage Therapy*/methods, Genomics ; Hormones ; Humans ; Male ; Neoplasm Recurrence, Local/radiotherapy ; Prostatectomy ; Retrospective Studies |
| مستخلص: | Background: The Decipher genomic classifier (GC) has shown to independently prognosticate outcomes in prostate cancer. The objective of this study was to validate the GC in a randomized phase III trial of dose-escalated salvage radiotherapy (SRT) after radical prostatectomy. Patients and Methods: A clinical-grade whole-transcriptome assay was carried out on radical prostatectomy samples obtained from patients enrolled in Swiss Group for Clinical Cancer Research (SAKK) 09/10, a phase III trial of 350 men with biochemical recurrence after radical prostatectomy randomized to 64 Gy versus 70 Gy without concurrent hormonal therapy or pelvic nodal RT. A prespecified statistical plan was developed to assess the impact of the GC on clinical outcomes. The primary endpoint was biochemical progression; secondary endpoints were clinical progression and time to hormone therapy. Multivariable analyses adjusted for age, T-category, Gleason score, postradical prostatectomy persistent prostate-specific antigen (PSA), PSA at randomization, and randomization arm were conducted, accounting for competing risks. Results: The analytic cohort of 226 patients was representative of the overall trial, with a median follow-up of 6.3 years (interquartile range 6.1-7.2 years). The GC (high versus low-intermediate) was independently associated with biochemical progression [subdistribution hazard ratio (sHR) 2.26, 95% confidence interval (CI) 1.42-3.60; P < 0.001], clinical progression (HR 2.29, 95% CI 1.32-3.98; P = 0.003), and use of hormone therapy (sHR 2.99, 95% CI 1.55-5.76; P = 0.001). GC high patients had a 5-year freedom from biochemical progression of 45% versus 71% for GC low-intermediate. Dose escalation did not benefit the overall cohort, nor patients with lower versus higher GC scores. Conclusions: This study represents the first contemporary randomized controlled trial in patients treated with early SRT without concurrent hormone therapy or pelvic nodal RT that has validated the prognostic utility of the GC. Independent of standard clinicopathologic variables and RT dose, high-GC patients were more than twice as likely than lower-GC patients to experience biochemical and clinical progression and receive of salvage hormone therapy. These data confirm the clinical value of Decipher GC to personalize the use of concurrent systemic therapy in the postoperative salvage setting. Competing Interests: Disclosure DES reports funding from Janssen; personal fees from Janssen, Blue Earth, AstraZeneca, and Boston Scientific. LP reports receiving an educational grant from AstraZeneca. DZ reports funding from Astellas, AstraZeneca, and Boston Scientific. VYTL, ED, HCH, YL, and XZ are employees of Decipher Biosciences (Veracyte Inc.). DJST is a contractor to Decipher Biosciences. All other authors have declared no conflicts of interest. (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.) |
| التعليقات: | Comment in: J Urol. 2022 Oct;208(4):931-934. (PMID: 35973210) |
| فهرسة مساهمة: | Keywords: Decipher; biomarkers; postoperative radiotherapy; prognosis; prostate cancer; salvage radiotherapy |
| المشرفين على المادة: | 0 (Hormones) EC 3.4.21.77 (Prostate-Specific Antigen) |
| تواريخ الأحداث: | Date Created: 20220531 Date Completed: 20220913 Latest Revision: 20220921 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1016/j.annonc.2022.05.007 |
| PMID: | 35636621 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1569-8041 |
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| DOI: | 10.1016/j.annonc.2022.05.007 |