Integrating uPSA into the immediate and continued frequent surveillance of RP patients with organ-confined cancer will improve postop RT outcomes by identifying failures sooner and promoting an early salvage strategy.
Jung Julie Kang, MD, PhD, Robert Reiter, MD, Patrick Kupelian, MD, Michael Steinberg, MD, Christopher R. King, PhD, MD; Department of Radiation Oncology, Department of Urology, UCLA
PURPOSE/OBJECTIVES: Randomized controlled trials have shown that adjuvant radiotherapy (RT) after radical prostatectomy (RP) improves biochemical relapse-free and overall survival in patients with extracapsular disease. However, even patients with organ-confined disease are at risk for failure. This study analyzes postoperative (postop) ultrasensitive prostate-specific antigen (uPSA) in the surveillance of these patients.
MATERIALS AND METHODS: From 1991–2013, 146 patients with pT2N0 disease who were referred for a rise in PSA after RP were identified: 85 were margin-positive (m+), and 61 were margin-negative (m−). Surgical approach (open vs robotic), initial PSA (iPSA), Gleason grade, margin status, and postop uPSA were covariates for analysis. Median first postop PSA and follow-up were 3 and 38 months, respectively. The uPSA threshold was 0.01 ng/mL.
Benign uPSA patterns occurred from 0.01–0.02 ng/mL; thus, ≥ 0.03 ng/mL was defined as uPSA failure. True (conventional) biochemical relapse (tBCR) was defined as PSA ≥ 0.2 ng/mL. Patients were censored at last follow-up or adjuvant therapy. Kaplan-Meier and Cox multivariate analyses were used to compare tBCR rates.
RESULTS: Median time to tBCR for the entire cohort was 50 months. The m+ patients revealed a more indolent course than m− patients (median time to relapse: 86 mo for m+ vs 33 mo for m−; P = .0003). No differences in Gleason grade or iPSA between m+ and m− patients were seen.
On multivariate analysis (MVA), only first postop uPSA ≥ 0.03 ng/mL (hazard ratio [HR] = 4.1; P < .001) and margin status (m−: HR = 5.6; P = .0315) independently predicted for time to tBCR.
First postop uPSA ≥ 0.03 ng/mL discerned tBCR with much greater sensitivity than undetectable first conventional PSA < 0.2 ng/mL (44% vs 19%). First postop uPSA < 0.03 ng/mL vs. ≥ 0.03 ng/mL predicted median tBCR at 61 vs 10 months (P = .0003). Any postop uPSA ≥ 0.03 ng/mL captured all failures missed by analyzing only the first postop value (100% sensitivity).
Using uPSA ≥ 0.03 ng/mL to identify relapse yields a substantial (33 mo) lead time advantage over waiting until conventional relapse at PSA ≥ 0.2 ng/mL (median 17 vs 50 mo in favor of uPSA ≥ 0.03 ng/mL).
CONCLUSIONS: Only first postop uPSA ≥ 0.03 ng/mL and margin status independently predicted biochemical relapse for organ-confined prostate cancer. The m− patients exhibited much earlier failures, suggesting greater biologic aggressiveness.
Biochemical failure can be called at uPSA ≥ 0.03 ng/mL with excellent sensitivity, and adopting it offers an impressive lead time advantage over the conventional failure definition (PSA ≥ 0.2 ng/mL).
Integrating uPSA into the immediate and continued frequent surveillance of RP patients with organ-confined cancer will improve postop RT outcomes by identifying failures sooner and promoting an early salvage strategy.
Proceedings of the 97th Annual Meeting of the American Radium Society - americanradiumsociety.org