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.
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.
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.
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.
Annals of oncology : official journal of the European Society for Medical Oncology. 2022 May 28 [Epub]
A Dal Pra, P Ghadjar, S Hayoz, V Y T Liu, D E Spratt, D J S Thompson, E Davicioni, H-C Huang, X Zhao, Y Liu, C Schär, P Gut, L Plasswilm, T Hölscher, B Polat, G Hildebrandt, A-C Müller, A Pollack, G N Thalmann, D Zwahlen, D M Aebersold
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: ., Charité - Universitätsmedizin Berlin, Berlin, Germany; Department of Radiation Oncology, Kantonsspital Winterthur, Winterthur, Switzerland., SAKK Coordinating Center, Bern, Switzerland., Decipher Biosciences (a subsidiary of Veracyte Inc.), San Diego, USA., Department of Radiation Oncology, University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, USA., Emmes Canada, Vancouver, Canada., Kantonsspital Luzern, Luzern, Switzerland., Department of Radiation Oncology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland; Kantonsspital St. Gallen, St. Gallen, Switzerland., Department of Radiotherapy and Radiation Oncology, Faculty of Medicine, Technische Universität Dresden, Dresden, Germany., Department of Radiation Oncology, University of Wuerzburg, Wuerzburg, Germany., University Hospital Rostock, Rostock, Germany., University Hospital Tübingen, Tübingen, Germany., Department of Radiation Oncology, University of Miami Miller School of Medicine, Miami, USA., Department of Urology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland., Department of Radiation Oncology, Kantonsspital Winterthur, Winterthur, Switzerland., Department of Radiation Oncology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.