Persistent PSA After Radical Prostatectomy: A Marker of Mortality Risk?

A large cohort study published in JAMA Oncology examines the implications of persistent prostate-specific antigen (PSA) levels after radical prostatectomy (RP), raising important questions about monitoring duration and treatment timing in prostate cancer. 

🎯 Objective 

To determine if persistent PSA levels post-RP predict increased mortality risk, and whether the current monitoring window (1.5–2.0 months) is sufficient. 

🧪 Study Design 

• 43,298 patients (clinical stage T1N0M0 to T3N0M0 prostate adenocarcinoma) 
• Treated between 1992–2020 at two academic centers 
• Primary outcomes: All-cause mortality (ACM) and prostate cancer-specific mortality (PCSM) 
• Follow-up: Until Nov 2023 
• Analyses: Jul 2024 – Jan 2025 

📊 Key Findings 

1. Pre-RP PSA >20 ng/mL 

• Surprisingly, associated with better outcomes in the context of persistent PSA 
• Suggests prognostic value of pre-surgical PSA 

1. Persistent PSA ≥1.0 ng/mL 

• Linked to significantly higher risk of both ACM and PCSM 
• Emphasizes the prognostic importance of PSA clearance 

1. Timing Matters 

• Many patients may achieve undetectable PSA levels after 3 months 
• Early intervention could lead to overtreatment 

🩺 Clinical Implications 

• Recommend extending post-RP PSA monitoring to at least 3 months before starting salvage therapy 
• Avoid premature decisions based on early PSA measurements 
• Reassess thresholds for intervention in light of these findings 

🔬 Future Directions 

• Explore genomic classifiers and AI to personalize PSA monitoring and escalation decisions 
• Study the long-term effects of monitoring strategies on survival and quality of life 

🧠 Takeaway: Persistent PSA post-RP is a red flag, especially if levels ≥1.0 ng/mL persist. But acting too soon may lead to overtreatment. Longer monitoring = better decisions. 

Full article: JAMA Oncology – Persistent PSA & Mortality Risk