Treatment monitoring in metastatic castrate-resistant prostate cancer has become a hot topic in the androgen receptor pathway inhibitors (ARPIs) era. Patients without increase in their PSA level at the time of imaging progression are not a rare phenomenon. What is the best monitoring strategy in asymptomatic cases represents a salient question. Here we presented 2 case reports involving men with metastatic castration-resistant prostate cancer who experienced disease progression without the anticipated increase in PSA levels. Our 2 cases show that imaging beyond standard PSA determination should be incorporate to monitor disease progression in patients with metastatic castrate-resistant prostate cancer even in the context of an undetectable PSA.