PROSTATE CANCER is a heterogeneous disease with outcomes strongly influenced by genomic alterations. Among these, changes in the homologous recombination repair (HRR) pathway, particularly in BRCA1 and BRCA2, are found in roughly 13% of patients and are linked to poorer prognosis in metastatic castration–resistant prostate cancer (mCRPC). These alterations also increase sensitivity to poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors, offering a significant survival advantage when used appropriately.
Limited Uptake of PARP Inhibitors for Prostate Cancer
Despite the proven benefits, real-world uptake of PARP inhibitors is suboptimal. A large US-based study revealed that nearly half of patients with mCRPC and BRCA1/2 alterations are not treated with these therapies. Medicare beneficiaries were more likely to receive PARP inhibitors than patients with commercial insurance, highlighting potential disparities in access. This underuse is concerning given the negative prognostic implications of BRCA1/2 alterations when patients are treated with taxanes or androgen receptor pathway inhibitors (ARPI) instead.
Addressing Access and Awareness Challenges
Barriers to PARP inhibitor use extend beyond prescriber knowledge. Financial challenges, comorbidities, and drug interactions may limit access, while systemic inequities contribute to racial and ethnic disparities. Black patients were observed to have a lower, though non-significant, likelihood of receiving PARP inhibitors, reflecting similar trends seen in ovarian cancer. Improving awareness of survival benefits, reducing financial barriers, and optimising prescription practices are essential steps to ensure equitable access to these life-prolonging therapies.
Future Directions
As PARP inhibitors are investigated in earlier metastatic hormone-sensitive settings, their use is expected to expand. Healthcare providers should prioritise identifying eligible patients with BRCA1/2 alterations and consider early incorporation of PARP inhibitors into treatment strategies. By addressing both educational and systemic barriers, clinicians can better leverage these targeted therapies to improve outcomes in prostate cancer patients.
In conclusion, while PARP inhibitors offer a significant survival benefit in mCRPC with BRCA1/2 alterations, underutilisation remains a critical challenge. Focused efforts to enhance access, awareness, and equitable delivery of care are necessary to translate clinical trial success into real-world improvements for patients.
Reference
Ostrowski M et al. Receipt of PARP inhibitors in patients with metastatic prostate cancer harboring BRCA1/2 alterations. JAMA Netw Open. 2025;8(10):e2534968.
