Written by Sharmin Begum, science writer
Black patients who were diagnosed with metastatic hormone-sensitive prostate cancer (mHSPC), have been analysed for differences in their clinical and genomic profiles. Implications for the therapeutic management of these patients have been evaluated.
In a retrospective study published by Oxford University Press, researchers from the Tulane Cancer Center (USA), investigated the clinical and treatment outcomes of black patients diagnosed with mHSPC. There is a significant underrepresentation of black patients in historical clinical trials for the treatment of prostate cancer. This is concerning, particularly as previous research indicates tumour heterogeneity and an overall poor prognosis for black patients, when compared to white patients. A multi-institutional analysis was conducted in the USA, assessing the data from black patients who were separated into two treatment groups. Statistical analyses were performed to evaluate baseline characteristics; treatment data; genetic data and clinical outcomes. Insights into somatic and germline mutations were explored, with an emphasis on the development of castrate-resistant prostate cancer (CRPC).
“The black patient underrepresentation along with these paradoxical findings warrants further investigation”, says Meredith Freeman, the lead author of this study.
Previous research in black patients diagnosed with advanced prostate cancer has shown differences in tumour genomic profile, when compared to white patients. In comparison to white patients, black patients have been known to have a higher risk of developing and dying from prostate cancer due to various factors, even with a similar disease burden. The inadequate representation of black patients in clinical trial cohorts for assessing mHSPC therapy is staggering – with 96% of participants from 72 global phase 3 and 4 prostate cancer trials being white. This study reports on the largest known cohort of black mHSPC patients, since the incorporation of chemotherapy and novel hormonal therapies as the standard of care. However, researchers acknowledged that the study was limited due to potential selection bias in terms of restricting patient cohorts to urban environments and only patients with available genetic testing data.
Data was analysed from 7 academic institutions across 7 US states, including 107 black patients diagnosed with stage 4 mHSPC (between 2008 and 2015), with available genetic sequence data. From the time of initial diagnosis, the 2-year survival rate was 93.3% and the median estimated overall survival was 74.9 months.
From the cohort, 54% of patients developed CRPC. The median time to CRPC (46.3 months) and overall survival was favourable for patients given ADT with/without first generation anti-androgens. A statistically weak correlation was found between a shorter time to CRPC observed in patients and either high-volume disease (18.9 months), treatment intensification regimen (23.3 months) or detectable nadir PSA (13.5 months).
Clinical outcomes were assessed in accordance with two regimens of treatment given to patients. The first treatment group was androgen deprivation therapy (ADT) with/without first-generation anti-androgen. The second treatment group was treatment intensification, including ADT with chemotherapy and/or a novel hormonal therapy (e.g., abiraterone acetate, enzalutamide, apalutamide). A significantly higher number of patients were given the treatment intensification regimen (73%) in comparison to treatment with ADT with/without first-generation anti-androgens (27%). The latter treatment group revealed a higher proportion of patients with de novo metastatic disease; high volume disease and initial median prostate-specific antigen (PSA).
The most commonly identified pathogenic germline mutations were BRCA2 (25%), BRCA1 (16.7 %) and PALB2 (16.6%). Next-generation sequencing data revealed that the two most common somatic mutations found in patients were TP53 (24%) and CDK12 (12%). Researchers suggest that TP53 mutations may be attributed to the increased aggressiveness of prostate cancer in black patients. TP53 mutation tumours were also loosely associated with de novo disease, high-volume disease, CRPC development and inferior PSA response rate.
Black patient representation and clinical impact
It is evident from this study that black mHSPC patients treated with ADT-based regimens had favourable clinical outcomes. Data from genetic testing also revealed implications on clinical outcomes and treatments strategies for mHSPC patients. Addressing the significant disparity in the inclusion of different racial and ethnic groups in clinical trials may have a positive impact on understanding the heterogeneity of disease progression and patient management. Researchers acknowledge that the recent increase in efforts to enrol black participants in prostate cancer trials are promising and clinically valuable.
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