Prostate-Specific Antigen Persistence After Radical Prostatectomy as a Predictive Factor of Clinical Relapse-Free Survival and Overall Survival: 10-Year Data of the ARO 96-02 Trial

• Published in: International journal of radiation oncology, biology, physics Vol. 91; no. 2; pp. 288 - 294
• Main Authors: Wiegel, Thomas, MD, Bartkowiak, Detlef, PhD, Bottke, Dirk, MD, Thamm, Reinhard, MD, Hinke, Axel, PhD, Stöckle, Michael, MD, Rübe, Christian, MD, Semjonow, Axel, MD, Wirth, Manfred, MD, Störkel, Stephan, MD, Golz, Reinhard, MD, Engenhart-Cabillic, Rita, MD, Hofmann, Rainer, MD, Feldmann, Horst-Jürgen, MD, Kälble, Tilman, MD, Siegmann, Alessandra, MD, Hinkelbein, Wolfgang, MD, Steiner, Ursula, MD, Miller, Kurt, MD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2015
• Subjects: ANTIGENS; Biomarkers, Tumor - blood; COMPARATIVE EVALUATIONS; Disease-Free Survival; Germany - epidemiology; HAZARDS; Hematology, Oncology and Palliative Medicine; HORMONES; Humans; Longitudinal Studies; Male; METASTASES; Middle Aged; Neoplasm Recurrence, Local - mortality; Neoplasm Recurrence, Local - prevention & control; NEOPLASMS; PATIENTS; Prevalence; Prognosis; PROSTATE; Prostate-Specific Antigen - blood; Prostatectomy - mortality; Prostatectomy - statistics & numerical data; Prostatic Neoplasms - blood; Prostatic Neoplasms - mortality; Prostatic Neoplasms - surgery; Radiology; RADIOLOGY AND NUCLEAR MEDICINE; RADIOTHERAPY; REGRESSION ANALYSIS; Reproducibility of Results; Risk Assessment; Sensitivity and Specificity; SURGERY; Survival Rate; Treatment Outcome; Germany
• ISSN: 0360-3016; 1879-355X
• DOI: 10.1016/j.ijrobp.2014.09.039

Objective The ARO 96-02 trial primarily compared wait-and-see (WS, arm A) with adjuvant radiation therapy (ART, arm B) in prostate cancer patients who achieved an undetectable prostate-specific antigen (PSA) after radical prostatectomy (RP). Here, we report the outcome with up to 12 years of follow-up of patients who retained a post-RP detectable PSA and received salvage radiation therapy (SRT, arm C). Methods and Materials For the study, 388 patients with pT3-4pN0 prostate cancer with positive or negative surgical margins were recruited. After RP, 307 men achieved an undetectable PSA (arms A + B). In 78 patients the PSA remained above thresholds (median 0.6, range 0.05-5.6 ng/mL). Of the latter, 74 consented to receive 66 Gy to the prostate bed, and SRT was applied at a median of 86 days after RP. Clinical relapse-free survival, metastasis-free survival, and overall survival were determined by the Kaplan-Meier method. Results Patients with persisting PSA after RP had higher preoperative PSA values, higher tumor stages, higher Gleason scores, and more positive surgical margins than did patients in arms A + B. For the 74 patients, the 10-year clinical relapse-free survival rate was 63%. Forty-three men had hormone therapy; 12 experienced distant metastases; 23 patients died. Compared with men who did achieve an undetectable PSA, the arm-C patients fared significantly worse, with a 10-year metastasis-free survival of 67% versus 83% and overall survival of 68% versus 84%, respectively. In Cox regression analysis, Gleason score ≥8 (hazard ratio [HR] 2.8), pT ≥ 3c (HR 2.4), and extraprostatic extension ≥2 mm (HR 3.6) were unfavorable risk factors of progression. Conclusions A persisting PSA after prostatectomy seems to be an important prognosticator of clinical progression for pT3 tumors. It correlates with a higher rate of distant metastases and with worse overall survival. A larger prospective study is required to determine which patient subgroups will benefit most from which treatment option.