Abstract
Background:We examined the ability of a biopsy-based 22-marker genomic classifier (GC) to predict for distant metastases after radiation and a median of 6 months of androgen deprivation therapy (ADT).Methods:We studied 100 patients with intermediate-risk (55%) and high-risk (45%) prostate cancer who received definitive radiation plus a median of 6 months of ADT (range 3–39 months) from 2001–2013 at a single center and had available biopsy tissue. Six to ten 4 micron sections of the needle biopsy core with the highest Gleason score and percentage of tumor involvement were macrodissected for RNA extraction. GC scores (range, 0.04–0.92) were determined. The primary end point of the study was time to distant metastasis. Median follow-up was 5.1 years. There were 18 metastases during the study period.Results:On univariable analysis (UVA), each 0.1 unit increase in GC score was significantly associated with time to distant metastasis (hazard ratio: 1.40 (1.10–1.84), P=0.006) and remained significant after adjusting for clinical variables on multivariable analysis (MVA) (adjusted hazard ratio: 1.36 (1.04–1.83), P=0.024). The c-index for 5-year distant metastasis was 0.45 (95% confidence interval: 0.27–0.64) for Cancer of the Prostate Risk Assessment score, 0.63 (0.40–0.78) for National Comprehensive Cancer Network (NCCN) risk groups, and 0.76 (0.57–0.89) for the GC score. Using pre-specified GC risk categories, the cumulative incidence of metastasis for GC>0.6 reached 20% at 5 years after radiation (P=0.02).Conclusions:We believe this is the first demonstration of the ability of the biopsy-based GC score to predict for distant metastases after definitive radiation and ADT for intermediate- and high-risk prostate cancer. Patients with the highest GC risk (GC>0.6) had high rates of metastasis despite multi-modal therapy suggesting that they could potentially be candidates for treatment intensification and/or enrollment in clinical trials of novel therapy.
Highlights
Radiation and androgen deprivation therapy (ADT) is a standard therapy for contemporary patients with intermediate and high-risk prostate cancer.[1]
Ability of genomic classifier (GC) to predict for metastases and secondary end points On univariable analysis (UVA) of baseline clinical and genomic risk factors we found only GC was a significant predictor of metastasis, associated with a
When adjusting for relevant clinical variables in multivariable analysis (MVA) including stage, Gleason, PSA, percent of positive cores, duration of ADT and year of treatment, we observed a small reduction in the GC hazard ratio (HR: 1.36; 95% confidence interval (CI): 1.04–1.83) but it remained a significant predictor of metastasis (P = 0.024)
Summary
Radiation and androgen deprivation therapy (ADT) is a standard therapy for contemporary patients with intermediate and high-risk prostate cancer.[1] While many men will be cured with this treatment, there remains a proportion of men who will progress after therapy and develop metastatic disease. Because intensification of therapy using longer durations of ADT, second-generation anti-androgens, chemotherapy or novel agents carries risk of additional toxicity, it is critically important to correctly identify the subgroup of patients who may be in need of such intensification While clinical factors such as PSA, T-category and Gleason score have traditionally been used to risk-stratify patients, their accuracy has been significantly enhanced in the last few years by genomic-based tests. CONCLUSIONS: We believe this is the first demonstration of the ability of the biopsy-based GC score to predict for distant metastases after definitive radiation and ADT for intermediate- and high-risk prostate cancer. Patients with the highest GC risk (GC40.6) had high rates of metastasis despite multi-modal therapy suggesting that they could potentially be candidates for treatment intensification and/or enrollment in clinical trials of novel therapy
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