More than 1.4 million men were diagnosed with prostate cancer in 2020 worldwide, but the molecular characteristics of the disease remain unexplored for the majority of patients worldwide. In the final days of the Movember campaign, which each November aims to raise awareness of men’s health issues such as prostate cancer, testicular cancer and men’s mental health, in conjunction with the upcoming ESMO Asia Congress 2022 in Singapore, December 2-4, two studies highlight the need for ethnically diverse prostate cancer genomic data and accessible genetic testing.
Prostate cancer is well established as a malignancy associated with the BRCA gene that can develop as a result of an inherited cancer syndrome, and susceptibility to the disease is known to vary among different ethnicities, men of African and Caribbean origin being at increased risk. However, the impact of ancestry on somatic mutations occurring in tumor is only beginning to be understood, likely due to genetic and non-genetic, societal and environmental factors related to ethnicity. “Such race-related differences may condition disease behavior and treatment, but our current knowledge of prostate cancer genomics is largely limited to data from Europe and the United States, in which Asian ethnicities and non-Caucasians are barely represented,” said Dr Rodrigo Dienstmann, Grupo Oncoclínicas, Sao Paulo, Brazil, and Vall d’Hebron Institute of Oncology, Barcelona, Spain, an expert not involved in the research.
A study has now confirmed the existence of variations in the genomic landscape of prostate cancer in Chinese men, by performing targeted genetic sequencing on tumors from 1,016 Chinese patients and comparing the results with publicly available genomic data. from The Cancer Genome Atlas (TCGA), Memorial Sloan Kettering Cancer Center, and Stand Up to Cancer (SU2C) cohorts representative of Caucasian males.
The largest differences we observed were concentrated in castration-sensitive diseases and included lower mutation rates in prostate cancer driver genes such as TP53 and PTEN in Chinese patients compared to Western cohorts, which may partly explain the better prognosis observed in Asian men in this setting.”
Dr Yu Wei, study author, Fudan University Shanghai Cancer Center, China
Wei says this raises the question of whether the benefits demonstrated by current standard therapies in clinical trials with Western patients can be transposed to the Asian population given the variable treatment responses induced by different driver mutations.
In the castration-resistant context, genetic testing for a group of 15 genes responsible for DNA damage and repair (DDR), including BRCA1 and BRCA2, entered clinical practice in 2020 with the approval of the olaparib, a PARP inhibitor, which reduced the risk of death by 30% for patients with metastatic disease. The Chinese study found that mutation rates in genes predictive of response to these therapies were similar across breeds, regardless of disease stage. “This suggests that Chinese patients may also benefit from PARP inhibitors provided they can access the treatment, which is why we are proposing that all Asian men with metastatic prostate cancer receive genomic testing” , Wei said.
Commenting on the results, Dienstmann observed: “The genomic heterogeneity that we observe in metastatic and refractory prostate cancer can be understood as the result of tumor evolution under the pressure of therapy over several years, but it should be note that ethnic variations were also observed in the primary tumor, confirming the existence of basic differences in cancer development between races. These findings are consistent with other recent research on Asian and African populations and emphasize the importance of increasing the diversity of prostate cancer genomic databases to better understand the molecular epidemiology and thus the testing strategies that need to be implemented in countries around the world. »
ESMO clinical practice guidelines for prostate cancer recommend germline genetic testing for BRCA2 and other DDR genes in all patients with metastatic prostate cancer alongside or after tumor testing, but also in people with a family history of cancer in order to allow early identification of mutation carriers and contribute to the prevention and early diagnosis of tumors in relatives. Far from being a reality, however, access to testing could become a factor in worsening health disparities in the future.
From equal representation to equitable access to treatment
The recommended technology in molecular testing for prostate cancer according to ESMO’s Precision Medicine Task Force is next-generation multigene sequencing, which is expensive and requires high-quality testing and complex interpretation. As indicated in the preliminary results of a recent ESMO survey on the availability and accessibility of biomolecular technologies in oncology in Europe, these are currently only available in some academic cancer centers, and practically not at all. in low- and middle-income countries. Developing the necessary infrastructure, which also includes resources and workflows for sample acquisition, preparation, and storage, is a daunting undertaking that is likely to require the involvement of multiple stakeholders.
“Corporate support programs like the one illustrated in a survey of physician testing patterns in India are a good starting point needed to increase patient access to testing. Going forward, information from these programs should be made public to allow a better understanding of local gaps in access to testing, as well as the prevalence of motor mutations in different patient cohorts.However, these programs are not sustainable in the long term, and the authors of the l The study themselves point out that post-testing implications, such as affordability of drugs and availability of genetic counselors, remain major hurdles in India,” Dienstmann said. “National testing programs will need to be implemented. works to support access to medicines, and companies must increasingly engage in public-private partnerships, not only to facilitate sample analysis. overseas, but to help build the local lab ecosystems that can make testing affordable. and accessible to the entire patient population. »
European Society of Medical Oncology (ESMO)
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