(UroToday.com) The 2022 EAU annual meeting featured a session on improvements in metastatic prostate cancer focusing on imaging and treatment, including a presentation by Dr. Hyunho Han discussing PSA levels at presentation for men with BRCA1/2 and ATM mutated metastatic prostate cancer. PARP inhibitors have previously shown survival benefits in mCRPC patients with homologous recombination repair (HRR) genes (BRCA1/2, and ATM) mutations. Germline panel test of the HRR genes and tumor tissue next generation sequencing are guideline recommended in men with metastatic prostate cancer. Furthermore, the reported incidences of BRCA1/2 and ATM gene mutations are 5-10%, yet it is unclear whether the mutations are enriched in advanced cancer and associated with clinical features. In this study, Dr. Han and colleagues assessed the incidences and clinical characteristics of HRR genes BRCA1/2 and ATM mutated prostate cancer.
The Yonsei University College of Medicine has incorporated prostate cancer tissue next generation sequencing (using Trusight oncology 170/500 panels) in clinical practice since June 2019, with the indication for testing being high-risk prostate cancer (GGG4-5, cT3/4, N1 or M1). In this study, the authors assessed the incidences of BRCA1/2 and ATM mutations (including variant of unknown significance) in the tested population. Clinical characteristics of HRR mutated tumors and wild-type tumors were compared using the T-test (two-sided) with Welch’s correction.
There were 126 consecutive prostate cancer tissue next generation sequencing data (from June 2019 to April 2021) assessed. At the time of diagnosis, cT3/4, N1 and M1 stages were 107 (85%), 54 (43%) and 35 (28%) samples, respectively. BRCA1/2 and ATM mutation frequencies were similar across the stages:
- 32% at T2 vs 34% at T3/4
- 35% at N0 vs 31% at N1
- 32% at M0 vs 37% at M1
HRR mutations tended to be more frequent in GGG 5 than GGG1-4 (41% vs 28%, p = 0.15) tumors. Among the metastatic subgroup (N1 or M1, n = 62), the mean PSA at the time of diagnosis was significantly lower in HRR mutated tumors than wild-type (82 ng/mL vs 561 ng/mL, p = 0.02). Of note, a similar trend was also noted in a mCRPC public dataset (188 ng/mL vs 76 ng/mL, p = 0.09) [1]. In the localized subgroup (N0 and M0, n = 64), PSA was not significantly different (58 ng/mL vs 26 ng/mL, p=0.30) between HRR mutated tumors and wild-type.
Dr. Han concluded his presentation discussing PSA levels at presentation for men with BRCA1/2 and ATM mutated metastatic prostate cancer by emphasizing that these genomically altered cases of prostate cancer may present with low serum PSA.
Presented by: Hyunho Han, PhD, Yonsei University College of Medicine, Urological Science Institute, Dept. of Urology, Seoul, South Korea
Co-Authors: Park C.K.2, Cho N.H.2, Lee J.S.1, Han W.K.1, Ham W.S.1, Choi Y.D.1
Affiliations: 1Yonsei University College of Medicine, Urological Science Institute, Dept. of Urology, Seoul, South Korea, 2Yonsei University College of Medicine, Dept. of Pathology, Seoul, South Korea
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 European Association of Urology (EAU) Annual Hybrid Meeting, Amsterdam, NL, Fri, July 1 – Mon, July 4, 2022.
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