ASTRO 2022: Tertiary Gleason Pattern 5 and a High Genomic Classifier Score Better Predicts Lymph Node Invasion at Radical Prostatectomy in 20,441 Intermediate-Risk Disease Patients

(UroToday.com) The 2022 ASTRO annual meeting featured an improving prostate cancer survival session, including a presentation by Dr. Skyler Johnson discussing the impact of tertiary Gleason pattern 5 and high Genomic Classifier Score on predicting lymph node invasion at the time of radical prostatectomy in patients with intermediate-risk disease. The POP-RT¹ and SSPORT trial² showed that pelvic lymph node radiation therapy can improve prostate or bed-only oncologic outcomes. Grade group 2 or Grade group 3 and tertiary Gleason pattern 5 are heterogeneous patient groups with varied prognoses. Genomic classifiers may provide additional information essential to identifying optimal pelvic radiotherapy candidates. Dr. Johnson and colleagues hypothesized that tertiary Gleason pattern 5, and a Genomic classifier, could improve prognostication of lymph node invasion after radical prostatectomy over traditional clinicopathologic risk factors alone.

The Decipher GRID database (Veracyte, San Diego, CA) contains de-identified Genomic classifiers testing and pathology results for patients tested between November 2015 and March 2020. Intermediate risk patients with Grade group 2 or Grade group 3 were included in the analysis of continuous Genomic classifiers scores (range 0-1) and Genomic classifiers risk groups (low, intermediate, and high). Multivariable logistic regression was used to quantify the relationship between lymph node invasion with Genomic classifiers, tertiary Gleason pattern 5, and other clinicopathologic features (age, race, extraprostatic extension, seminal vesicle invasion, bladder neck invasion).

There were 20,441 patients included (11,934 with Grade group 2 (58.4%) and 8,507 (41.6%) with Grade group 3 disease) in this study. Of those with Grade group 2 and Grade group 3 disease, 1,451 (12.2%) and 2,911 (34.2%) had tertiary Gleason pattern 5, respectively. Patients with tertiary Gleason pattern 5 had a significantly higher Genomic classifiers score (median: 0.39 [IQR 0.24-0.61] vs 0.53 [IQR 0.32-0.75], p<0.001 for Grade group 2 and median: 0.58 [IQR 0.35-0.81] vs 0.66 [IQR 0.43-0.86], p<0.001 for Grade group 3).

In multivariable analysis adjusted for clinicopathologic features, tertiary Gleason pattern 5 and higher Genomic classifiers score were independently associated with the presence of lymph node invasion in both Grade group 2 (tertiary Gleason pattern 5: OR 1.60, 95% CI 1.07-2.38, p=0.02 and Genomic classifier: OR 1.20 per 0.1 increase, 95% CI 1.11-1.29, p<0.001) and Grade group 3 (tertiary Gleason pattern 5: OR 1.47, 95% CI 1.16-1.87, p<0.01 and Genomic classifier: OR 1.13 per 0.1 increase, 95% CI 1.07-1.19, p<0.001) patients. Tertiary Gleason pattern 5 patients with Grade group 2 or Grade group 3 and high Genomic classifiers have a 3.8 and 1.8 fold risk of lymph node invasion over those with a low Genomic classifiers, respectively. Patients with Genomic classifiers high and Grade group 2 or Grade group 3 have a 2.7 and 1.8 fold risk of lymph node invasion over those with or without tertiary Gleason pattern 5, respectively:

ASTRO 2022 Skyler B. Johnson_1

Dr. Johnson concluded his presentation discussing the impact of tertiary Gleason pattern 5 and high Genomic Classifier Score on predicting lymph node invasion at the time of radical prostatectomy in patients with intermediate-risk disease with the following take-home messages:

Tertiary Gleason pattern 5 was associated with higher Genomic classifiers scores and adverse clinicopathologic features
Tertiary Gleason pattern 5 and higher Genomic classifiers are independently associated with lymph node invasion while controlling for other clinicopathologic risk factors, demonstrating their importance in future studies of pelvic RT treatment intensification or de-intensification for these patients

Presented by: Skyler B. Johnson, MD, Department of Radiation Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT

Co-Authors: E. Davicioni², J. Proudfoot³, Y. Liu⁴, and J. D. Tward¹; 1Department of Radiation Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, 2Veracyte Inc., San Diego, CA, 3UCSD, La Jolla, CA, 4Decipher/Veractye, San Francisco, CA

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2022 American Society of Radiation Oncology (ASTRO) Annual Hybrid Meeting, San Antonio, TX, Sat, Oct 22 – Wed, Oct 26, 2022.

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