Genomic Classifier Score Identifies Risk of Metastasis and Benefit of Adjuvant Radiotherapy After Radical Prostatectomy


Key Points

  • Genomic classifier score was significantly associated with risk of metastasis.
  • Genomic classifier score was predictive of benefit from adjuvant radiotherapy.

In a study reported in the Journal of Clinical Oncology, Den et al found that a 22-biomarker genomic classifier score was predictive of a greater risk of metastasis and benefit of adjuvant vs salvage radiotherapy after radical prostatectomy for prostate cancer.

Metastasis Risk

The study involved genetic classifier scores (GenomeDx PCa genomic database) from 188 patients with pT3 or margin-positive prostate cancer who received radiotherapy after radical prostatectomy at Thomas Jefferson University and Mayo Clinic between 1990 and 2009.

The cumulative incidence of metastasis at 5 years after radiotherapy was 0%, 9%, and 29% for low, average, and high genomic classifier scores (P = .002). By comparison, 5-year cumulative incidence rates in patients with low, average, and high Cancer of the Prostate Risk Assessment Postsurgical scores (CAPRA-S) were 13%, 2%, and 14% (P =.04). On multivariate analysis including the two approaches, hazard ratios (HRs) were 1.69 (P < .001) per 0.10-unit increase in genomic classifier score and 1.28 (P = .0282) per 1-unit increase in CAPRA-S.

On univariate analysis, genomic classifier score, preoperative prostate-specific antigen (PSA) level, and radiotherapy modality were significant predictors of metastasis. On multivariate analysis not including CAPRA-S, genomic classifier score and presurgery PSA level (HR = 2.12, P = .0022) were independent predictors of metastasis. Genomic classifier score was associated with HRs for metastasis of 1.90 for every 0.10-unit increase (P < .001) and 9.58 (P = .013) for high vs low score.

Adjuvant Radiotherapy

Within the low genomic classifier score group (score < 0.4), there was no difference in cumulative incidence of metastasis with adjuvant vs salvage radiotherapy (P = .79). However, for patients with higher scores (≥ 0.4), the cumulative incidence at 5 years was 6% vs 23% (P < .01) for adjuvant vs salvage radiotherapy.

The investigators concluded: “In patients treated with post-[radical prostatectomy radiotherapy], [genomic classifier score] is prognostic for the development of clinical metastasis beyond routine clinical and pathologic features. Although preliminary, patients with low [genomic classifier] scores are best treated with salvage [radiotherapy], whereas those with high [genomic classifier] scores benefit from adjuvant therapy. These findings provide the first rational selection of timing for post-[radical prostatectomy radiotherapy].”

Robert B. Den, MD, of Sidney Kimmel Medical College at Thomas Jefferson University, is the corresponding author of the Journal of Clinical Oncology article. Dr. Den and Kasra Yousefi, MSc, of GenomeDx Biosciences, Vancouver, contributed equally to the article.

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