Effect of a genomic classifier test on clinical practice decisions for patients with high-risk prostate cancer after surgery.

Badani KK1, Thompson DJ, Brown G, Holmes D, Kella N, Albala D, Singh A, Buerki C, Davicioni E, Hornberger J.

Author information

Abstract

OBJECTIVES:

To evaluate the impact of a genomic classifier (GC) test for predicting metastasis risk after radical prostatectomy (RP) on urologists' decision-making for adjuvant treatment of high-risk prostate cancer patients.

SUBJECTS AND METHODS:

Patient case histories were extracted from medical records of 145 patients with pT3 or positive surgical margin (SM+) disease after radical prostatectomy treated by six high-volume urologists from five community practices. GC results were available for 122 of these patients. US board-certified urologists (n=107) were invited to provide adjuvant treatment recommendations for 10 cases randomly drawn from the pool of patient case histories. For each patient case history, study participants were asked to render an adjuvant therapy recommendation without (clinical variables only) and with knowledge of the GC test results. Recommendations were made without knowledge of other participants' responses and presentation of case histories was randomized to minimize recall bias.

RESULTS:

One hundred ten patient case histories were available for review by the study participants. Median patient case age was 62 years; 71% had pT3 and 63% SM+ disease. The median 5-year predicted probability of metastasis by the GC test in the cohort was 3.9% (range, 1%-33%) and GC classified 72% as 'low risk' for metastasis. Fifty-one urologists consented to the study and provided 530 adjuvant treatment recommendations without and 530 with knowledge of the GC test results. Study participants performed a mean of 130 RP/year and 55% were from community-based practices. Without GC, observation was recommended for 57% (n=303), adjuvant radiation (ART) for 36% (n=193) and other treatments for 7% (n=34) of patient case histories. Overall, 31% (95% CI: 27-35%) of treatment recommendations changed with knowledge of GC. Among ART recommendations without GC, 40% (n=77) changed to observation (95% CI: 33-47%) with GC. For patient case histories recommended for observation, 13% (n=38) (95% CI: 9%-17%) were changed to ART with GC. Case histories with low GC risk were recommended observation 81% of the time (n=276), while for those with high GC risk, 65% were recommended for treatment (n=118, p<0.0001). Treatment intensity was strongly correlated with the GC-predicted probability of metastasis (p<0.001) and the GC test was the dominant risk factor driving decisions in multivariable analysis (OR=8.6, 95% CI: 5.3-14.3%, p<0.0001).

CONCLUSIONS:

Knowledge of GC test results had a direct effect on treatment strategies following surgery. Recommendations for Observation increased by 20% for case histories assessed by the GC test to be at low risk of metastasis whereas recommendations for Treatment increased by 16% for cases at high risk of metastasis. These results suggest that the implementation of genomic testing in clinical practice may lead to significant changes in adjuvant therapy decision-making for high-risk prostate cancer.