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

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
  2. Persistent PSA ≥1.0 ng/mL
    • Linked to significantly higher risk of both ACM and PCSM
    • Emphasizes the prognostic importance of PSA clearance
  3. 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

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