Genomic features of prostate cancer patients with and without ductal adenocarcinoma (DA) based on liquid biopsy.

Abstract

191 Background: Ductal adenocarcinoma (DA) is relatively rare and highly co-existed with prostate adenocarcinoma (AC). This study aims to investigate the distinctive genomic profiles of patients with DA compared to those without it. Methods: Blood samples were obtained from 144 patients (36 with DA and 108 without DA) who were diagnosed with prostate cancer from 2017 to 2023 at West China Hospital. We performed cell-free DNA sequencing to investigate the genomic differences between patients with DA (DA[+]) and those without (DA[-]), and explored the potential associations between their mutational status and prognosis. Pathogenic and likely pathogenic alterations were included for analysis. Results: We identified that AR pathway (16/36 [44.4%] vs 24/108 [22.2%], p=0.017) and WNT pathway (6/36 [16.7%] vs 5/108 [4.6%], p=0.029) mutations were significantly enriched in DA(+) compared to DA(-), with AR pathway featured by FOXA1 (9/36 [25%] vs 5/108 [4.6%], p=0.0012). DDR mutation rate and the HRD scores appeared to be comparable between DA(+) and DA(-). TP53 was associated with a deteriorating prognosis for both DA(+) and DA(-) in terms of castration-free survival (CFS). Conclusions: Our findings provide further genomic insights in prostate cancer with ductal morphology and are instructive for the diagnosis and treatment of DA. Baseline characteristics of the DA (+) and DA (-) cohorts. Variable DA (-), N = 108 1 DA (+), N = 36 1 p-value 2 Treatment line 0.4 HSPC 34 (31%) 7 (19%) CRPC 18 (17%) 6 (17%) Treatment-naive 56 (52%) 23 (64%) Metastasis at detection 0.6 M0 52 (48%) 19 (53%) M1 56 (52%) 17 (47%) Visceral metastasis 8 (7.4%) 8 (22%) 0.028 Bone metastasis 0.7 <5 12 (11%) 6 (17%) ≥5 38 (35%) 12 (33%) 0 55 (51%) 18 (50%) Not available 3 (2.8%) 0 (0%) ISUP 0.055 1 3 (2.8%) 0 (0%) 2 6 (5.6%) 3 (8.3%) 3 16 (15%) 11 (31%) 4 12 (11%) 7 (19%) 5 71 (66%) 15 (42%) Age 68 (61, 73) 68 (61, 73) >0.9 Baseline PSA 0.007 <50 41 (38%) 23 (64%) ≥50 67 (62%) 13 (36%) 1 n (%); Median (IQR). 2 Pearson's Chi-squared test; Fisher's exact test; Wilcoxon rank sum test. DA: dutal adenocarcinoma of the prostate; HSPC: hormone-sensitive prostate cancer; CRPC: castration-resistant prostate cancer; ISUP: International Society of Urological Pathology grading; PSA: prostate-specific antigen.