ASCO 2021: Validation of the Decipher Genomic Classifier in SAKK 09/10: A phase III Randomized Trial Of Dose-Escalated Salvage Radiotherapy After Radical Prostatectomy

(UroToday.com) The disease natural history of patients with biochemical recurrence following radical prostatectomy is varied – while some men will have an indolent course without treatment, others progress quickly in spite of aggressive therapy. Further, treatments are not without consequence in terms of cost, inconvenience, and morbidity. Thus, better understanding disease aggressivity to target treatment intensification would be valuable. The Decipher® Genomic Classifier (GC) has been shown to independently prognosticate outcomes in prostate cancer. In the Prostate, Testicular, Penile Poster Discussion session at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, Dr. Dal Pra presented an analysis validating the Decipher genomic classifier within the SAKK 09/10 trial.

This study reports a pre-planned secondary analysis of the SAKK 09/10 trial (NCT01272050) which randomized 350 patients with biochemical recurrence after radical prostatectomy to salvage radiotherapy with 64Gy vs 70Gy. Androgen deprivation therapy (ADT) and pelvic nodal radiotherapy were not utilized within this study.

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To derive the GC scores, radical prostatectomy samples were centrally reviewed to identify the highest-grade tumor and those passing quality control (QC) were run on a clinical-grade whole-transcriptome assay to derive the GC score. The GC score was operationalized as low (<0.45), intermediate (0.45-0.6) or high (> 0.6). The primary objective was to validate the GC as a predictor of freedom from biochemical progression (FFBP) using Cox multivariable analysis (MVA) adjusting for known prognosticators including age, T-category, Gleason score, persistent PSA after radical prostatectomy, PSA at randomization, and randomization arm. Secondarily, the authors evaluated the association of GC with clinical progression-free survival (CPFS) and use of salvage ADT with further exploratory endpoints including rapid (18 months or shorter) biochemical progression, distant metastases, and metastasis-free survival.

Among the 350 patients included within the SAKK 09/10 trial, 233 patients had tissue available, and 226 passed QC and were included for analysis. In spite of a significant decrease in sample size, the final GC cohort was a representative sample of the overall cohort.

Over a median follow-up of 6.3 years (IQR 6.0-7.2), GC score (operationalized continuously per 0.1 unit, score 0-1) was independently associated with FFBP (HR 1.14 [95% CI 1.03-1.25], p = 0.009). Additionally, assessing secondary outcomes, higher GC scores were independently associated with CPFS, use of salvage ADT, and rapid biochemical failure (< 18 months after SRT).

When operationalized in a binary fashion, high- vs. low/intermediate-GC showed a HR of 2.22 ([95% CI 1.37-3.58], p = 0.001) for FFBP.

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Patients with high-GC had 5-year FFBP of 45% [95% CI 32-59] compared with 71% [95% CI 64-78] among those with low-intermediate GC. The prognostic value of GC was seen in both the 64Gy and 70Gy arms of the trial (GC high: 5-year FFBP of 51% [95% CI 32-70] vs 39% [95% CI 20-59]; GC low-intermediate 75% [95% CI 65-84] vs 69% [95% CI 59-78]).

Assessing the secondary and exploratory endpoints, when operationalized in a binary fashion, high- vs. low/intermediate-GC showed a HR of 2.29 ([95% CI 1.32-3.98], p = 0.003) for CPFS, and 2.99 ([95% CI 1.50-5.95], p = 0.002) for use of salvage ADT.

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The authors conclude that this is the first contemporary randomized controlled trial validating the prognostic utility of the Genomic Classifier in patients with recurrent prostate cancer treated with early SRT without ADT. Thus, they conclude that Decipher GC has value for tailoring treatment in the postoperative salvage setting.

Presented by: Alan Dal Pra, MD, Assistant Professor and Associate Director of Clinical Research in the Department of Radiation Oncology at the University of Miami Miller School of Medicine. He also serves as Medical Director of Radiation Oncology at Sylvester at Coral Gables, The Lennar Foundation Medical Center.

Written by: Christopher J.D. Wallis, Urologic Oncology Fellow, Vanderbilt University Medical Center, Contact: @WallisCJD on Twitter at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, Virtual Annual Meeting #ASCO21, June, 4-8, 2021

Relateed Content: ASCO GU 2021: Dose-Intensified Versus Conventional Dose-Salvage Radiotherapy for Biochemically Recurrent Prostate Cancer After Prostatectomy: Six-Year Outcomes of the SAKK 09/10 Randomized Phase III Trial

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