ASCO GU 2020: Transcriptome Profiling of NRG Oncology/RTOG 9601: Validation of a Prognostic Genomic Classifier in Salvage Radiotherapy Prostate Cancer from a Prospective Randomized Trial

San Francisco, CA (UroToday.com) RTOG 9601 was a double-blind, placebo-controlled trial conducted from 1998 through 2003 which assessed whether or not the addition of androgen deprivation therapy (with bicalutamide 150 mg daily) would improve overall survival over placebo for patients receiving salvage radiation therapy in men who had undergone radical prostatectomy.1

PhaseIIITrial.png


In this study, 24 months of antiandrogen therapy with daily bicalutamide to salvage radiation therapy improved overall survival at 12 years (76% vs 71%, HR 0.77) and the 12-year incidence cancer-specific death was 5.8% in the bicalutamide group compared with 13% in the placebo group. Bicalutamide also significantly decreased the risk of metastatic prostate cancer at 12 years (14.5% with bicalutamide and 23% with placebo). Of note, not all patients derived equal benefit. Patients with a PSA 1.6-4 had greater benefits as expected, compared with patients with PSA 0.2-1.5 ng/ml.

Notallequalbenefit.png

Decipher is a validated genomic classifier that evaluates the expression of 22 selected RNA markers based on the tumor from a radical prostatectomy specimen.2 Patients receiving Decipher tests receive a score from 0-1, where 0 is the lowest risk and 1 is the highest risk for the development of metastasis and prostate cancer-specific mortality. In prior small retrospective studies, Decipher has been shown to predict the risk of metastasis at 10 years, independent of age, pre-operative PSA, and Gleason score.3 However, Decipher has not been evaluated in a large randomized clinical trial. This study seeks to validate Decipher in the context of a randomized phase III clinical trial.

In this study, tumor tissue from radical prostatectomy was centrally reviewed and RNA was extracted from the highest-grade tumor available per patient. 352 tumor samples were deemed acceptable by quality control and there was a median follow up of 13 years from this cohort of tumors.

The decipher score, as a continuous variable, was independently associated with distant metastases (HR 1.19 [95%CI 1.06-1.35], p=0.003) and overall survival (HR 1.16 [95%CI 1.06-1.28], p=0.002), after adjusting for age, Gleason, T-stage, margin, entry PSA, and race.

DECIPHER.png

In terms of the treatment impact of bicalutamide, 12-year overall survival for patients with a low Decipher score was improved by 2.4%, compared with 8.9% for patients with a high Decipher score.

AbsoluteBenefit.png

Several randomized trials support the use of adjuvant ADT combined with salvage radiation, most showing a benefit to progression-free survival and some showing benefits to overall survival. However, ADT has numerous side effects and the duration of treatment remains controversial depending on the clinical context. Shared decision making is important in this space and the additional data provided by a genomic classifier may be useful in that conversation. This study suggests that patients who have a low decipher risk score may not derive as much benefit with ADT compared with those with a higher decipher risk.

Presented by: Felix Y. Feng, MD, Associate Professor of Radiation Oncology; Urology; and Medicine Vice Chair for Faculty Development and Director of Translational Research, Department of Radiation Oncology, University of San Francisco, San Francisco, CA

Written by: Jason Zhu, MD. Medical Oncologist, Division of Genitourinary Cancers, Levine Cancer Institute, Twitter: @TheRealJasonZhu, at the 2020 Genitourinary Cancers Symposium, ASCO GU #GU20, February 13-15, 2020, San Francisco, California.

References:

  1. Shipley WU, Seiferheld W, Lukka HR, et al. Radiation with or without Antiandrogen Therapy in Recurrent Prostate Cancer. New England Journal of Medicine 2017;376:417-28.
  2. Dalela D, Löppenberg B, Sood A, Sammon J, Abdollah F. Contemporary role of the Decipher® test in prostate cancer management: current practice and future perspectives. Reviews in urology 2016;18:1.
  3. Klein EA, Haddad Z, Yousefi K, et al. Decipher genomic classifier measured on prostate biopsy predicts metastasis risk. Urology 2016;90:148-52.
email news signup