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

Abstract

ObjectivesTo evaluate the impact of a genomic classifier (GC) test for predicting metastasis risk after radical prostatectomy (RP) on urologists' decision-making about adjuvant treatment of patients with high-risk prostate cancer.Subjects and MethodsPatient case history was extracted from the medical records of each of the 145 patients with pT3 disease or positive surgical margins (PSMs) after RP treated by six high-volume urologists, from five community practices. GC results were available for 122 (84%) 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 case, the study participants were asked to make 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 the presentation of case histories was randomised to minimise recall bias.ResultsA total of 110 patient case histories were available for review by the study participants. The median patient age was 62 years, 71% of patients had pT3 disease and 63% had PSMs. The median (range) 5-year predicted probability of metastasis by the GC test for the cohort was 3.9 (1–33)% and the GC test classified 72% of patients as having low risk for metastasis. A total of 51 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 RPs/year and 55% were from community-based practices. Without GC test result knowledge, observation was recommended for 57% (n = 303), adjuvant radiation therapy (ART) for 36% (n = 193) and other treatments for 7% (n = 34) of patients. Overall, 31% (95% CI: 27–35%) of treatment recommendations changed with knowledge of the GC test results. Of the ART recommendations without GC test result knowledge, 40% (n = 77) changed to observation (95% CI: 33–47%) with this knowledge. Of patients recommended for observation, 13% (n = 38 [95% CI: 9–17%]) were changed to ART with knowledge of the GC test result. Patients with low risk disease according to the GC test were recommended for observation 81% of the time (n = 276), while of those with high risk, 65% were recommended for treatment (n = 118; P < 0.001). 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 (odds ratio 8.6, 95% CI: 5.3–14.3%; P < 0.001).ConclusionsKnowledge of GC test results had a direct effect on treatment strategies after surgery. Recommendations for observation increased by 20% for patients assessed by the GC test to be at low risk of metastasis, whereas recommendations for treatment increased by 16% for patients at high risk of metastasis. These results suggest that the implementation of genomic testing in clinical practice may lead to significant chan...

Influence of a genomic classifier on post-operative treatment decisions in high-risk prostate cancer patients: results from the PRO-ACT study

“…This indicates that implementation of the GC test in clinical practice carries the potential to improve allocation of healthcare resources by ensuring that adjuvant therapy is targeted for use by those patients who are truly at higher risk of disease progression. These results are consistent with the ASSESS-D study, which showed that the GC test may result in reductions in treatment intensity after surgery for the majority of patients tested 15 .…”

“…The ASSESS-D study found, among patients classified as low risk by the GC test (72%), observation was recommended 81% of the time, on the basis of reviewing both GC test results and clinical variables. Treatment was planned 65% of the time for patients with GC test results, indicating increased risk of progression; also test results were highly correlated with the chosen treatment intensity (e.g., observation to treatment including multimodal therapy) 15 .…”

A Genomic Classifier Improves Prediction of Metastatic Disease Within 5 Years After Surgery in Node-negative High-risk Prostate Cancer Patients Managed by Radical Prostatectomy Without Adjuvant Therapy

“…The results of this study suggest that Decipher can be used as a standard tool to better risk-stratify patients based on clinical and pathologic risk factors. Recent studies show that Decipher influences physician postoperative decision making in the adjuvant setting and lowers the discrepancy in decision making between urologists and radiation oncologists [38][39][40].…”

Clinical relevance of prostate cancer genetic characterization: literature review

“…Тем не менее некоторые генетические подписи, аппробированные на большом клиническом материале, показали многообещающие результаты при оценке в послеоперационном периоде у больных РПЖ высокого риска, но эти результаты нуждаются в дальнейшей оценке в масштабных проспективных исследованиях [23]. Однако на этапе биопсии ткани (первый минимально-инвазивный контакт с опухолью) проблема ее генети-ческой характеристики на сегодняшний день не решена.…”