Genitourinary Cancer

SS 28 - GU 3 - New Insights Into Treatment Intensification Strategies for Prostate Cancer

201 - A Biopsy Based Genomic Classifier Predicts Biochemical Failure and Metastasis After Definitive Radiation without Hormone Therapy in a Prospective Cohort of Intermediate-Risk Prostate Cancer

Tuesday, October 23
3:05 PM - 3:15 PM
Location: Room 007 A/B

A Biopsy Based Genomic Classifier Predicts Biochemical Failure and Metastasis After Definitive Radiation without Hormone Therapy in a Prospective Cohort of Intermediate-Risk Prostate Cancer
M. L. K. Chua1, R. G. Bristow2, J. Murgic3, A. Hosni Abdalaty4, A. Salcedo5, S. Kamel-Reid6, M. Fraser5, J. Zhang7, Q. Wang8, C. Ch'ng9, S. Deheshi10, E. Davicioni11, T. Van der Kwast12, P. Boutros5, and A. Berlin13; 1National Cancer Centre Singapore, Bukit Merah, Singapore, 2Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, ON, Canada, 3Sisters of Charity Hospital Zagreb, Zagreb, Croatia, 4Princess Margaret Cancer Center, Toronto, ON, Canada, 5Ontario institute of cancer research, Toronto, ON, Canada, 6Princess Margaret Cancer Centre, Toronto, ON, Canada, 7GenomeDx Biosciences Inc., Vancouver, BC, Canada, 8GenomeDx Biosciences, Inc., Vancouver, BC, Canada, 9GenomeDx Biosciences Inc. (Vancouver, BC), Vancouver, BC, Canada, 10GenomeDx Biosciences Inc. (Vancouver, BC), Vancouer, BC, Canada, 11GenomeDx Biosciences, Vancouver, BC, Canada, 12University Health Network, Toronto, ON, Canada, 13Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada

Purpose/Objective(s): Clinical practice guidelines recommend radiation therapy (RT) for intermediate (int)-risk prostate cancer (PCa) combined with 4-6 months of androgen deprivation therapy (ADT). Treatment with combined modality therapy has demonstrated improved survival outcomes mainly for unfavorable int-risk PCa, as defined by Zumsteg-Spratt classification recently endorsed by the NCCN. Here we investigate whether a 22-feature genomic classifier (GC) could improve risk stratification and guide treatment intensification for these men beyond conventional clinical and pathological risk factors.

Materials/Methods: Tissue specimens were prospectively collected from a single institution’s registry (REB 06-0822-CE) of dose-escalated (78Gy in 39 fractions) image-guided intensity modulated radiation therapy (IG-IMRT) monotherapy between 2005-2011. The genomic risk scores were calculated based on a locked random forest model. Uni- and multivariable survival analysis was performed using continuous scores (range 0-1) and GC low (<0.45), int (0.45-0.6) and high (>0.6) risk group categories. The primary and secondary endpoints were biochemical failure (BCF) and metastasis, respectively. BCF was defined as PSA nadir + 2ng/ml.

Results: The cohort comprised of 121 patients with NCCN favorable (27.3%) and unfavorable (71.9%) int-risk PCa. With a median follow up of 7.5 years, we observed 24 BCF and 5 metastasis events. GC stratified 81.8%, 9.1%, and 9.1% of the NCCN favorable int-risk men and 69.0%, 17.2%, and 13.8% of the NCCN unfavorable int-risk men into low, int and high-risk groups, respectively; 5-year risk of BCF were 4.7%, 16.7%, 45.2%, respectively, in the GC subgroups (p=0.002). Risk of BCF was not differentially stratified by NCCN favorable and unfavorable risk subcategories (p <0.23). Hazard ratio for BCF was 1.36 (95% CI 1.09-1.71, P=0.007) per 10% unit-increase in GC score after adjusting for conventional NCCN clinical and pathological risk factors on multivariable analysis. GC predicted BCF and metastasis at 5-years with an AUC of 0.78 (95% CI 0.70-0.83) and 0.86 (95% CI 0.80-0.92), respectively.

Conclusion: GC improved risk stratification of int-risk PCa and predicted BCF and metastasis after RT, independent of conventional clinical and pathological risk factors. In this study of survival outcomes after dose-escalated IG-IMRT monotherapy, while most men were NCCN unfavorable int-risk, GC classified over 70% as low genomic risk. Five-year BCF for this subgroup was <5% and none developed metastasis during study follow up. In contrast, men with higher genomic risk—wherein five-year BCF risk was 10-fold higher compared to low genomic risk subgroup–had suboptimal outcomes with IG-IMRT alone, and may benefit from intensification with combined hormonal therapy.

Author Disclosure: M. Chua: Stock; Merrimack, Pluristerm. R.G. Bristow: None. J. Murgic: None. A. Hosni Abdalaty: None. A. Salcedo: None. S. Kamel-Reid: None. J. Zhang: None. Q. Wang: None. E. Davicioni: Stock; GenomeDx Biosciences. CSO; GenomeDx Biosciences. T. Van der Kwast: None. P. Boutros: Patent/License Fees/Copyright; University Health NetworkOntario Institute For Cancer Research (Oicr).

Melvin Lee Kiang Chua, MD, PhD

National Cancer Centre Singapore

Disclosure:
Ownership
Merrimack: Stock; Pluristerm: Stock

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201 - A Biopsy Based Genomic Classifier Predicts Biochemical Failure and Metastasis After Definitive Radiation without Hormone Therapy in a Prospective Cohort of Intermediate-Risk Prostate Cancer



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