Genomic Classifier May Help Predict Metastasis Following Prostatectomy and SRT

Genomic Classifier May Help Predict Metastasis Following Prostatectomy and SRT

October 23, 2015

Clinicians may now have a better tool for guiding therapy in men with prostate cancer who have had a prostatectomy and salvage radiation therapy (SRT).

Clinicians may now have a better tool for guiding therapy in men with prostate cancer who have had a prostatectomy and salvage radiation therapy (SRT). Investigators calculated genomic classifier (GC) scores for 166 patients based on genomic analysis of their own tumor tissue. They found this approach may enable clinicians to better personalize treatment options.

Study authors reported at the American Society for Radiation Oncology’s (ASTRO) 57th Annual Meeting, “Validation of a Genomic Classifier for Prediction of Metastasis Following Postoperative Salvage Radiation Therapy” on Wednesday, October 21, 2015, in San Antonio, that GC scores may be able to distinguish the patients for whom aggressive therapy is beneficial from those for whom SRT on its own is likely the best choice (scientific session, part of abstract 306).

“Our findings are particularly intriguing and provide a unique, more individualized approach to managing men receiving SRT after radical prostatectomy (RP),” said lead study author Robert Den, MD, who is an assistant professor of radiation oncology at Sidney Kimmel Medical College at Thomas Jefferson University in Philadelphia.

Whether these patients need androgen deprivation therapy (ADT) following recurrence may be dictated by a host of factors. However, a high prostate-specific antigen (PSA) level alone is not an ideal indicator of future metastatic disease. Dr. Den and colleagues analyzed GC scores as a validated predictor of metastasis. The goals were to see if these scores could distinguish the patients for whom additional aggressive therapy is beneficial from those for whom SRT on its own is adequate.

The cohort included 166 prostate cancer patients; 53 (32%) were African American and 113 (68%) were Caucasian. All the men received SRT between 1990 and 2010 at three separate sites. GC scores were calculated for each patient based on genomic analysis of their own tumor tissue. A tissue sample was removed from the prostatectomy specimen from the area containing the highest Gleason score and compared to the patient’s Cancer of the Prostate Risk Assessment Postsurgical (CAPRA-S) scores. The investigators used survival c-index, competing-risks and Cox regression analysis for the prediction of metastasis.

They found that a patient’s GC score was the most significant factor in predicting the development of metastases 5 years after SRT. The study demonstrated that with GC low-risk patients the incidence rate of metastases at 5 years was 2.8%, in GC average-risk patients the incidence rate was 5.8%, and in GC high-risk patients, it shot up to 33.5%. Those finding were significantly different than the CAPRA-S scores.

The researchers found the incidence rate was 17% for low CAPRA-S scores, 2.3% for average-risk, and 15% for high-risk. The researchers conducted a univariable analysis and found that only GC, extraprostatic extension, and pre-RT PSA levels were significant predictors of metastasis. However, in multivariable analyses with clinical risk factors or the CAPRA-S nomogram, they found that GC was the only independent predictor of metastasis with a hazard ratio of 1.59 for a 10% unit increase in risk score.

In summary, patients with low GC scores have a good prognosis with SRT and may avoid concurrent hormonal therapy. Patients with a high GC risk are at an increased risk for metastatic disease and SRT failure, and may benefit from systemic therapy.