Survival outcomes of real world patients with metastatic hormone-sensitive prostate cancer who do not achieve optimal PSA response with intensified androgen deprivation therapy with docetaxel or androgen receptor pathway inhibitors

IntroductionIn patients with metastatic hormone-sensitive prostate cancer (mHSPC) undergoing intensified androgen deprivation therapy (ADT), not achieving an optimal PSA response, defined as PSA nadir >0.2 ng/ml (PSA(subOR)) has been associated with worse survival outcomes in clinical trials ((1)(10)(11)). Here, we externally evaluate, the impact of optimal PSA response on survival outcomes in these patients and provide absolute PFS and OS measures in those with PSA(subOR) in the context of ADT intensification in real world setting.MethodsIn this retrospective study, all consecutive patients with mHSPC who underwent intensified ADT treated at our institution, and whose outcomes data were available, were included. We classified patients based on their PSA nadir on treatment: those with a on treatment PSA(OR) (PSA nadir & LE;0.2 ng/ml) versus PSA(subOR).ResultsA total of 205 patients were eligible: 136 (66.3%) patients achieved PSA(OR) versus 69 (33.7%) patients had PSA(subOR). Patients who experienced a PSA(OR) had significantly improved PFS and OS from the start of intensified ADT versus who did not: PFS was not reached (NR) versus 11 months (hazard ratio (HR) 0.20, P < 0.001) and OS was NR versus 38.9 months (HR 0.21, P < 0.001). Survival outcomes were poor with PSA(subOR) regardless of intensification with docetaxel or an ARPI (absolute PFS and OS measures for each group are provided in the text).ConclusionOur study is the first to explore the negative impact of PSA(subOR) in patients with mHSPC undergoing intensified ADT in the real-world setting, and is the first to provide absolute PFS and OS in patients with PSA(subOR) receiving ADT intensification with ARPIs or docetaxel outside of clinical trial setting. These data will aid with prognostication, patient counseling, and for designing future clinical trials for patients with PSA(subOR) .