Prostate cancer genomic study shows disparity between Chinese and Caucasians with castration-sensitive disease

A large genomic study involving 1,016 Chinese patients with prostate cancer has revealed important differences in castration-sensitive disease between Chinese and Caucasian patients, but the mutation profile of metastatic castration-resistant prostate cancer (mCRPC) is similar between the populations.

The 1,016 Chinese patients were prospectively enrolled and underwent targeted genetic screening focusing on 41 prostate cancer–related driver genes. Of these patients, 315 had locoregional prostate cancer, 313 had metastatic castration-sensitive prostate cancer (mCSPC), and 388 had mCRPC. Findings from the Chinese patients were compared with publicly available genomic data retrieved from The Cancer Genome Atlas (TCGA), Memorial Sloan Kettering Cancer Center, and Stand Up to Cancer (SU2C) cohorts representative of Caucasian patients. [Wei Y, et al, ESMO Asia 2022, abstract 162MO]

“Comparative analysis across disease stages showed that mutations in TP53, AR, FOXA1, and cell cycle pathway were enriched in mCRPC. Patients with visceral metastasis had more APC mutations than those with bone metastasis,” said Dr Yu Wei of Fudan University Shanghai Cancer Centre, Shanghai, China. “In addition, more than 50 percent of mutations in RAD51D/PALB2/BRCA2 were inherited.”

“Genomic differences between Chinese and Caucasian patients were mainly observed in locoregional prostate cancer and mCSPC, after adjusting for clinical factors such as age and Gleason score,” reported Wei.

“Tumours from Chinese patients with locoregional disease had a higher prevalence of FOXA1 mutations [odds ratio (OR), 3.41; 95 percent confidence interval (CI), 1.69–6.86] and a lower prevalence of TP53 mutations [OR, 0.25; 95 percent CI, 0.13–0.50] compared with their Caucasian counterparts. In Chinese patients with mCSPC, lower prevalence of TP53 [OR, 0.30; 95 percent CI, 0.18–0.49], PTEN [OR, 0.19; 95 percent CI, 0.08–0.48] and APC [OR, 0.15; 95 percent CI, 0.05–0.48] mutations were found compared with Caucasian patients,” he continued. “These findings may partially account for the better prognosis observed in Asian patients in this setting.”

“Unexpectedly, the mutation profile of mCRPC was found to be similar between Chinese and Caucasian patients, after adjusting for clinical factors,” he said.

In the castration-resistant setting, testing of a group of 15 genes responsible for DNA damage and repair, including BRCA1 and BRCA2, has become part of clinical practice following approval of the PARP inhibitor, olaparib, for treatment of mCRPC patients with BRCA1/2 mutations whose disease progressed after prior therapy that included a new hormonal agent. Wei and colleagues found similar rates of mutations predictive of response to PARP inhibitor therapy between Chinese and Caucasian patients, regardless of disease stage.

“This suggests that Chinese patients can equally benefit from PARP inhibitor therapy, provided that they can obtain access to the treatment. Thus, all Asian men with metastatic prostate cancer should receive genomic testing,” he emphasized.

ESMO’s Clinical Practice Guidelines for prostate cancer recommend germline testing for DNA damage and repair genes in all patients with metastatic prostate cancer alongside or following tumour testing, as well as in individuals with a family history of cancer, to facilitate prevention and early diagnosis of cancer in relatives. [Ann Oncol 2020;31:1119-1134]