The 2024 ASTRO annual meeting included a session on novel prognostic tools in prostate cancer, featuring a presentation by Dr. Shalini Moningi discussing the examination of the Decipher® prostate genomic classifier in patients with de novo metastatic disease from a large-scale real-world clinical and transcriptomic data linkage. Metastatic prostate cancer is a heterogeneous population, and disease volume and presentation impact patient prognosis:
Prognostic gene expression testing of primary tumor tissue has become widely adopted for localized prostate cancer risk stratification. Recent retrospective analyses of clinical trials have examined such testing in metastatic hormone-sensitive disease but little has been reported outside of this context:
Presented at ESMO 2024, in the STAMPEDE trial of mHSPC patients, high Decipher® classifier identified patients treated with ADT + abiraterone that had a poor prognosis in addition to identifying docetaxel sensitive tumors:
Thus, Decipher® genomic classifier provides a rational biomarker for selecting patients for ADT + ARPI + docetaxel. Decipher® in the metastatic setting may provide further clarity regarding who may benefit from doublet versus triplet treatment intensification:
At the 2024 ASTRO annual meeting, Dr. Moningi and colleagues examined the Decipher® prostate genomic classifier use in the context of routine clinical practice.
Clinical and transcriptomic data from clinical use of the genomic classifier between 2013-2022 were linked with real-world data aggregated from insurance claims, pharmacy records, and electronic health record data. Patients were anonymously linked between datasets by deterministic methods through a de-identification engine using encrypted tokens. A hierarchical claims-based algorithm was used to identify de novo distant metastasis in the patient’s record. De novo metastasis was defined using administrative claims and diagnosis codes within 90 days from initial prostate cancer diagnosis and at least 90 days earlier than non-prostate cancer diagnosis (if present), excluding a set of codes identifying metastases without specification of sites or for pelvic lymph node metastases. The distribution of genomic classifier scores in these samples was compared to localized prostate cancer after matching on baseline clinical and pathological factors drawn from 116,971 patients who received genomic classifier testing. A total of 92,976 patients with Decipher® prostate genomic classifier were successfully linked to real-world data, including 53,871 from biopsy and 39,105 from radical prostatectomy tests. De novo metastases were identified in 194 patients (0.21%; including 114 patients that underwent radical prostatectomy) and compared to a matched set of 13,192 patients with localized disease. Among patients with de novo metastasis, the median age at Decipher® testing was 69 years (IQR 63-75), median percentage of positive cores was 58% (IQR 33-92%), median PSA was 14 ng/mL (IQR 6.3- 47), and 70% had NCCN high or very high-risk disease at diagnosis. Compared to the matched set, 25% of metastatic patients had PSA > 50 versus 5% for localized patients:
In the biopsy cohort, the median Decipher® score for metastatic patients was 0.88 compared to 0.69 and 0.46 in the matched and unmatched localized patient cohorts, respectively. In the post-op cohort, the median Decipher® score for metastatic patients was 0.70 compared to 0.64 and 0.56 in the matched and unmatched localized patient cohorts, respectively. Of note, in both cohorts, mCSPC patients were more likely to have very high-risk scores compared to localized patients:
A Decipher® very high-risk group (> 0.85) is the score threshold used for including in the intensification study (+ ARPI) in NRG GU009 PREDICT-RT phase 3 trial, as well as what was used to identify benefit (+ docetaxel) in the retrospective analysis of the STAMPEDE trial. Moreover, p53 mutation signature was present in nearly 50% of mCSPC patients compared to 10% of localized patients. pTEN deletion signature, representing mTOR activation, was present in nearly 30% of mCSPC patients compared to 8% of localized patients:
Dr. Moningi concluded her presentation discussing the examination of the Decipher® prostate genomic classifier in patients with de novo metastatic disease from a large scale real-world clinical and transcriptomic data linkage with the following take-home points:
- This is the largest linkage of prostate cancer transcriptomic and clinical data to date with algorithms to identify de novo metastatic disease from a cohort of patients tested with Decipher®
- These de novo metastatic disease patients tended to have higher PSA values at presentation, very high Decipher® scores, and enrichment mutations/deletions in key tumor suppressor gene pathways.
- This unique resource could be leveraged to enhance the understanding of de novo metastatic disease biology, patterns of care, and treatment effectiveness.
Presented by: Shalini Moningi, MD, Oncologist, Brigham and Women's Hospital/Dana-Farber, Boston, MA
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2024 American Society for Radiation Oncology (ASTRO) Annual Meeting, Washington, DC, Sun, Sept 29 – Wed, Oct 2, 2024.