Performance of clinicopathologic models in men with high risk localized prostate cancer: impact of a 22-gene genomic classifier

Jeffrey J. Tosoian ¹,
Samuel R. Birer ²,
R. Jeffrey Karnes ³,
Jingbin Zhang ⁴,
Elai Davicioni ⁴,
Eric E. Klein ⁵,
Stephen J. Freedland ⁶,
Sheila Weinmann ⁷,
Bruce J. Trock ⁸,
Robert T. Dess ²,
Shuang G. Zhao ²,
William C. Jackson ²,
Kosj Yamoah ⁹,
Alan Dal Pra ¹⁰,
Brandon A. Mahal ¹¹,
Todd M. Morgan ¹,
Rohit Mehra ¹²,
Samuel Kaffenberger ¹,
Simpa S. Salami ¹,
Christopher Kane ¹³,
Alan Pollack ¹⁰,
Robert B. Den ¹⁴,
Alejandro Berlin ¹⁵,
Edward M. Schaeffer ¹⁶,
Paul L. Nguyen ¹¹,
Felix Y. Feng ¹⁷,
Daniel E. Spratt ²

¹ Department of Urology, University of Michigan, Ann Arbor, MI, USA ² Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA ³ Department of Urology, Mayo Clinic, Rochester, MN, USA ⁴ Decipher Biosciences, Vancouver, BC, Canada ⁵ Glickman Urological Institute, Cleveland Clinic, Cleveland, OH, USA ⁶ Department of Urology, Cedars-Sinai, Los Angeles, CA, USA ⁷ Center for Health Research, Kaiser Permanente, Portland, OR, USA ⁸ Department of Urology, Johns Hopkins, Baltimore, MD, USA ⁹ Department of Radiation Oncology, Moffitt Cancer Center, Tampa, FL, US ¹⁰ Department of Radiation Oncology, University of Miami, Miami, FL, USA ¹¹ Department of Radiation Oncology, Brigham Women's Hospital, Boston, MA, USA ¹² Department of Pathology, University of Michigan, Ann Arbor, MI, USA ¹³ Department of Urology, University of California San Diego, San Diego, CA, USA ¹⁴ Department of Radiation Oncology, Thomas Jefferson, Philadelphia, PA, USA ¹⁵ Department of Radiation Oncology, Princess Margaret Hospital, Toronto, ON, Canada ¹⁶ Department of Urology and Polsky Urologic Cancer Institute, Northwestern University, Chicago, IL, US ¹⁷ Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA

Abstract

Publication: Prostate Cancer and Prostatic Diseases, March 2020

https://www.nature.com/articles/s41391-020-0226-2

Background

Prostate cancer exhibits biological and clinical heterogeneity even within established clinico-pathologic risk groups. The Decipher genomic classifier (GC) is a validated method to further risk-stratify disease in patients with prostate cancer, but its performance solely within National Comprehensive Cancer Network (NCCN) high-risk disease has not been undertaken to date.

Methods

A multi-institutional retrospective study of 405 men with high-risk prostate cancer who underwent primary treatment with radical prostatectomy (RP) or radiation therapy (RT) with androgen-deprivation therapy (ADT) at 11 centers from 1995 to 2005 was performed. Cox proportional hazards models were used to determine the hazard ratios (HR) for the development of metastatic disease based on clinico-pathologic variables, risk groups, and GC score. The area under the receiver operating characteristic curve (AUC) was determined for regression models without and with the GC score.

Results

Over a median follow-up of 82 months, 104 patients (26%) developed metastatic disease. On univariable analysis, increasing GC score was significantly associated with metastatic disease ([HR]: 1.34 per 0.1 unit increase, 95% confidence interval [CI]: 1.19–1.50, p < 0.001), while age, serum PSA, biopsy GG, and clinical T-stage were not (all p > 0.05). On multivariable analysis, GC score (HR: 1.33 per 0.1 unit increase, 95% CI: 1.19–1.48, p < 0.001) and GC high-risk (vs low-risk, HR: 2.95, 95% CI: 1.79–4.87, p < 0.001) were significantly associated with metastasis. The addition of GC score to regression models based on NCCN risk group improved model AUC from 0.46 to 0.67, and CAPRA from 0.59 to 0.71.

Conclusions

Among men with high-risk prostate cancer, conventional clinico-pathologic data had poor discrimination to risk stratify development of metastatic disease. GC score was a significant and independent predictor of metastasis and may help identify men best suited for treatment intensification/de-escalation.