359 - Hallmark Interferon-Alpha Response Analysis in Localized Prostate Cancer: Analysis of the NRG Oncology/RTOG 9202, 9413, 9902, 0126, and 0521 Clinical Trials

10:50am - 11:00am PT

Room 154

Presenter(s)

Adam Olson, MD, MS - UPMC Hillman Cancer Center, Pittsburgh, PA

A. C. Olson^1,2, H. Wang³, W. A. Hall⁴, P. T. Tran⁵, P. F. Nguyen-Tan⁶, J. M. Michalski⁷, H. M. Sandler⁸, M. Roach III⁹, S. A. Rosenthal¹⁰, D. Yee¹¹, E. Winquist¹², A. B. Shah¹³, A. D. Currey¹⁴, N. S. Kapadia¹⁵, M. Duclos¹⁶, H. Lukka¹⁷, O. E. Streeter Jr¹⁸, J. A. Efstathiou¹⁹, S. Pugh^20,21, and P. L. Nguyen²²; ¹UPMC-Shadyside Hospital, Pittsburgh, PA, ²Department of Radiation Oncology, UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, ³University of Pittsburgh School of Medicine, Pittsburgh, PA, ⁴Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI, ⁵University of Maryland School of Medicine, Baltimore, MD, ⁶CHUM - Centre Hospitalier de l'Universite de Montreal, Montreal, QC, Canada, ⁷Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO, ⁸Cedars-Sinai Medical Center, Los Angeles, CA, ⁹University of California San Francisco, Department of Radiation Oncology, San Francisco, CA, ¹⁰Sutter Medical Group and Cancer Center, Sacramento, CA, ¹¹Cross Cancer Institute, Edmonton, AB, Canada, ¹²Department of Medical Oncology, Western University, London Health Sciences Centre, London, ON, Canada, ¹³York Cancer Center, York, PA, United States, ¹⁴The Milwaukee VA Medical Center, Milwaukee, WI, ¹⁵Dartmouth Institute for Health Policy and Clinical Practice, Geisel School of Medicine, Dartmouth College, Hanover, NH, ¹⁶Cedars Cancer Center, Montreal, QC, Canada, ¹⁷Juravinski Cancer Centre, Hamilton, ON, Canada, ¹⁸Summa Health Medical Group, Barberton, OH, ¹⁹Massachusetts General Hospital, Boston, MA, ²⁰The American College of Radiology, Philadelphia, PA, ²¹NRG Oncology Statistics and Data Management Center, Philadelphia, PA, ²²Department of Radiation Oncology, Brigham and Women’s Hospital/Dana-Farber Cancer Institute, Boston, MA

Purpose/Objective(s):

We hypothesized the immunoinflammatory state of intact prostate cancer (PCa) is associated with poor outcomes. We analyzed the hallmark interferon alpha response pathway (IFN-alpha) on biopsy samples using a commercially available transcriptomic platform.

Materials/Methods:

Whole-transcriptome gene expression profiles of patient samples from NRG/RTOG 9202, 9413, 9902, 0126, and 0521 phase III trials were analyzed. NRG/RTOG 9202, 9413, and 9902 were combined into a single high-risk cohort. The performance of an IFN-alpha 97 gene set was evaluated for biochemical failure (BF) by Phoenix criteria, disease progression (DP), distant metastasis (DM), metastasis-free survival (MFS), prostate cancer-specific mortality (PCSM), and overall survival (OS) by univariable and multivariable analysis (MVA). As no pre-defined cut point exists for this marker, the IFN-alpha response signature was analyzed as a continuous and dichotomized variable (split at the median). Pretreatment PSA in RTOG 9202/9413/9902 was log-transformed. Cox and Fine and Gray models (in the presence of competing risks) were used for analysis.

Results:

663 samples (RTOG 0126 n=215, RTOG 0521 n=183, RTOG 9202/9413/9902 n=265) were analyzed. For RTOG 0126 and RTOG 0521, no baseline characteristics were associated with IFN-alpha signature; for RTOG 9202/9413/9902, more patients with IFN-alpha(high) had Gleason score 8-10 (56% v. 34%, p=0.007).

In RTOG 0126, MVA was adjusted for Gleason score, PSA and RT modality. As a continuous variable, IFN-alpha response was significantly associated with BF (sHR [95% CI] per 1 unit increase 1.74 [1.15-2.64], p=0.009), and DP (sHR 1.51 [1.02-2.24], p=0.04). Patients with higher IFN-alpha signature had improved outcomes from RT dose escalation with respect to BF, receipt of salvage therapy, and DP, but no significant treatment interactions were observed.

In RTOG 0521, MVA was adjusted for risk group, treatment arm, and age. IFN-alpha(high) was significantly associated with MFS (high vs. low sHR 1.74 [1.05-2.88], p=0.003) and OS (sHR 1.84 [1.05-3.21], p=0.03). No significant treatment interactions were observed.

In RTOG 9202/9413/9902, MVA was adjusted for age, log(pretreatment PSA), T stage, and Gleason score. Patients with IFN-alpha(high) derived significant benefits from long-term vs. short term androgen deprivation therapy (ADT) for BF (sHR 0.25 (95% CI 0.14-0.44), p<0.001) compared to marginal benefit in those with lower IFN-alpha (sHR 0.71 (95% CI 0.42-1.20), p=0.20, p-int=0.005). Similar trends were identified for DM (p-int=0.18) and PCSM (p-int=0.19).

Conclusion:

IFN-alpha response signatures hold prognostic and predictive value for localized PCa treated with RT. These findings require further validation.