Review of the real-world prevalence of mHSPC, nmCRPC, mCRPC, and gene alterations associated with HRR in prostate cancer (PC).

Abstract

229 Background: The clinical journey of PC is evolving rapidly. New hormonal agents (NHA) have demonstrated clinical efficacy in metastatic hormone sensitive prostate cancer (mHSPC), non-metastatic castrate-resistant prostate cancer (nmCRPC) and metastatic castrate-resistant prostate cancer (mCRPC). A shift in the treatment landscape considering precision medicine, recently supported by the phase III PROFOUND study, suggests updates to the currently limited clinical guideline recommendations for genomic testing. Better understanding of the patient pathway and respective proportion of patients to support patient care is needed. The objective of this SLR was to summarize published literature on the prevalence of mHSPC, nmCRPC, mCRPC and HRR gene alterations. Methods: An SLR was conducted across nine databases in OVID to capture English language studies published 01/2009–05/2019 on global epidemiology and clinical practice trends for mHSPC, nmCRPC, mCRPC and HRRm. 4,732 papers were identified which were systematically screened for inclusion. Grey literature searches included 10 conference proceedings from 2014–2019. Results: In total, 244 observational publications met the inclusion criteria - 4 studies reported the prevalence of mCRPC, 3 on nmCRPC and 0 on mHSPC. From these, the estimated prevalence of mCRPC and nmCRPC is 1.6–2.1 and 1.1–2.1 per 100 PC cases, respectively. HRRm were investigated in 13 publications with next generation sequencing of tissue and blood samples being reported as the most frequent method. Of the HRR gene alterations examined, BRCA2 were found to have the highest prevalence with a range of 4.5–9.3 and 1.1–15.1 per 100 overall PC cases for germline and somatic gene alterations, respectively. Other prevalent HRR gene alterations included germline ATM, BRCA1 and CHEK2. Conclusions: Limited data are available evaluating the prevalence of mHSPC, nmCRPC and mCRPC required to quantify the burden of these populations suggesting a lag in the published literature following updates to US treatment guidelines. Our review also shows that HRR gene alterations, specifically BRCA2, are prevalent in PC consistent with recently published data on PROFOUND population.