A validated genomic classifier score based on 22 prespecified biomarkers is prognostic for the development of clinical metastasis after radical prostatectomy, and could help inform decision making about the timing of subsequent radiotherapy, according to a review of 188 patients who were treated with post–radical prostatectomy radiotherapy.
The findings suggest that patients with a low genomic classifier (GC) score are best treated with salvage radiotherapy (SRT), and those with a high score are best treated with adjuvant radiotherapy (ART), reported Dr. Robert B. Den of Thomas Jefferson University, Philadelphia, and his colleagues. The study was published online Feb. 9 in the Journal of Clinical Oncology.
The 5-year cumulative incidence of metastasis in the study subjects, who were identified from the GenomeDx prostate cancer genomic database, was 0%, 9%, and 29% in those with low (less than 0.4), average (0.4-0.6), and high (greater than 0.6) GC scores, respectively. On multivariable analysis, pre–radical prostatectomy prostate-specific antigen levels and GC were independent predictors of metastasis (hazard ratio, 2.12; hazard ratio, 1.90 for every 10% increase in GC score, respectively). No differences were seen in the cumulative incidence of metastasis when patients with GC scores less than 0.4 were compared based on whether they received ART or SRT, but among those with GC scores of 0.4 or higher, the cumulative incidence of metastasis at 5 years was 6% in those who received ART, and 23% in those who received SRT (J. Clin. Oncol. 2015 Feb. 9 [doi:10.1200/JCO.2014.59.0026]).
Use of the GC scoring model either alone or in combination with the Cancer of the Prostate Risk Assessment Postsurgical (CAPRA-S) scoring model was superior to other clinicopathological models for predicting metastasis, and had “a higher net benefit than clinical models across a wide range of decision threshold probabilities,” they noted.
The patients were men with pT3 or margin-positive prostate cancer who received radiotherapy after radical prostatectomy (post-RP RT) at either Thomas Jefferson University, Philadelphia, or the Mayo Clinic, Rochester, Minn., between 1990 and 2009. They were treated at a median dose of 66.6 Gy with conventional fractionation by either three-dimensional conformal RT or by intensity-modulated RT techniques, and followed for a median of 10 years after radical prostatectomy and 8 years after radiotherapy.
The findings have important implications for the treatment of contemporary prostate cancer patients who harbor adverse pathologic characteristics at the time of radical prostatectomy; these patients are often treated with postoperative radiotherapy alone or with hormonal therapy, but the optimal timing of post-RP RT has been unclear, the investigators explained.
“Advocates for adjuvant RT argue that this treatment modality might maximize cancer control outcomes. However, salvage RT can minimize overtreatment while offering acceptable oncologic outcomes,” they wrote, adding that trials comparing the two are underway, but because of the rarity of data in the field and the unresolved controversy about the best approach to treatment, they “sought to integrate a novel biomarker test to improve clinical decision making regarding post-RP RT.
“We demonstrate that the GC is highly prognostic in the setting of postprostatectomy RT and that the GC may be a predictive marker that can help determine which patient will benefit from ART as opposed to SRT. This supports the importance of local therapy in the setting of presumed occult metastatic disease,” they said, noting that the findings are “particularly intriguing and provide a unique, more individualized approach in the management of postprostatectomy patients with adverse pathologic findings.”
While a biomarker shouldn’t replace shared patient-physician decision making, the use of the GC could provide insight into the aggressiveness of disease and aid in decision making regarding postprostatectomy therapy, they said.
Intensification of therapy in men with a high GC score who are receiving salvage radiotherapy is currently being examined in the Radiation Therapy Oncology Group 9601 randomized, phase III trial comparing SRT with SRT plus high-dose bicalutamide, the noted.
“Given that this cohort consists of high-risk patients by clinicopathologic nomograms and the utilization of a GC allowed for significant downstaging, this study has major ramifications in terms of both potential for overtreatment and substantial cost savings to the U.S. health care system. Thus, the GC is a valuable tool to aid in management of men with prostate cancer undergoing prostatectomy,” they concluded.
Dr. Den and several coauthors disclosed ties with GenomeDx Biosciences, Janssen, Medivation, CE Outcomes, Photocure, Dendreon, Astellas, Celgene, Varian, Merck KGaA, Vertex, Glenview Consulting, Bayer, NRG Oncology, and Myriad Genetics.