Clinical Assistant Professor Yonsei University College of Medicine
Introduction: PARP inhibitors have shown survival benefits in M-CRPC 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 (NGS) are recommended in men with metastatic prostate cancer. 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. We assessed the incidences and clinical characteristics of HRR genes BRCA1/2 and ATM mutated prostate cancer.
Methods: Our institute has incorporated prostate cancer tissue NGS in clinical practice since Jun 2019. Indications include prostate cancer of high risk (GGG4-5, cT3/4, N1 or M1). Trusight oncology 170/500 panels were used. We 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. T-test (two-sided) with Welch’s correction was used.
Results: We evaluated 126 consecutive prostate cancer tissue NGS data (from Jun 2019 and April 2021). 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). Of metastatic subgroup (N1 or M1, n=62), mean PSA at the time of diagnosis was significantly lower in HRR mutated tumors than wild-type (82ng/mL vs 561ng/mL, p = 0.02). Similar trend was noted in a M-CRPC public dataset (188ng/mL vs 76ng/mL, p = 0.09) (Abida et al., PNAS, 2019). In localized subgroup (N0 and M0, n=64), PSA was not significantly different (58ng/mL vs 26ng/mL, p=0.30).
Conclusions: BRCA1/2 and ATM mutated metastatic prostate cancers may present with low serum PSA.
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