Association between prostate-specific antigen (PSA) level <0.2 ng/mL and risk of radiological progression in patients (pts) with nonmetastatic castration-resistant prostate cancer (nmCRPC): Follow-up analysis of ARAMIS.

5022 Background: In pts with nmCRPC, metastatic progression was not consistently associated with PSA progression in a prior analysis of ARAMIS (Morgans AK, et al. J Clin Oncol 2022;40:5044). We evaluated prostate cancer (PC)-specific survival in ARAMIS, and the patterns of disease progression were determined overall and for pts who achieved PSA <0.2 ng/mL. Methods: Pts with nmCRPC received darolutamide (DARO n=955) or placebo (PBO n=554) + ADT in ARAMIS. Using the primary data cutoff (Sept 2018) excluding pts with baseline metastases, PC-specific survival accounting for other deaths as competing risk was analyzed. Treatment group–generated state sequence plots characterized pts by different events: radiological progression, PSA progression, or death. Based on PSA levels and conventional imaging q16 weeks during ARAMIS, the cumulative incidence of time to radiological progression was compared between pts with PSA <0.2 ng/mL and those without. In pts with PSA <0.2 ng/mL and who experienced radiological progression, we evaluated PSA levels at the time of radiological progression. Results: DARO increased overall survival in ARAMIS vs PBO (HR 0.69; 95% CI 0.53–0.88) and notably reduced PC-related deaths. PC was the leading cause of death in pts with nmCRPC in both treatment arms. Fewer pts receiving DARO vs PBO had PSA progression alone (7.8% vs 35.9%) or both PSA and radiological progression (5.4% vs 21.4%) at 12 months. Pts on DARO vs PBO had lower PSA levels at the time of radiological progression (median, 2.4 vs 3.7 ng/mL). DARO led to deep and durable PSA response vs PBO, with 25.1% vs 0.5% of pts achieving PSA <0.2 ng/mL, and DARO delayed time to PSA progression overall (median, 33.2 vs 7.3 months; HR 0.13; 95% CI 0.11–0.16). DARO pts with PSA <0.2 ng/mL had a lower risk of radiological progression vs those with PSA ≥0.2 ng/mL, with rates of 8.7% vs 33% at 24 months. At 36 months, the cumulative incidence of radiological progression remained at 8.7% for DARO pts with PSA <0.2 ng/mL and increased to 50% in pts with PSA ≥0.2 ng/mL. For the 11 pts with PSA <0.2 ng/mL and radiological progression, PSA levels at the time of radiological progression (range, 0.02–438.46 ng/mL) and time to radiological progression (4–22 months) did not follow any patterns. Conclusions: In pts with nmCRPC by conventional imaging, DARO increased overall survival vs PBO. Adding DARO to ADT resulted in deep and durable PSA response vs ADT alone. DARO was associated with low rates of PSA progression ± radiological progression. In DARO pts with PSA <0.2 ng/mL, the risk of radiological progression ± PSA progression was low over 24 months and did not increase through the end of the study. These post hoc results may raise questions about the frequency of conventional imaging for disease progression in pts with nmCRPC. Clinical trial information: NCT02200614 .