Prostate cancer patients with detectable prostate specific antigen (PSA) following radical prostatectomy should receive earlier, more aggressive radiation therapy treatment, according to a study published in the International Journal of Radiation Oncology * Biology * Physics (2015; doi:10.1016/j.ijrobp.2014.09.039).
This study is a 10-year posttreatment analysis of the German ARO 96-02 trial, a prospective clinical trial that compared a wait-and-see approach versus an adjuvant radiation therapy approach for patients with node-negative prostate cancer who underwent prostatectomy.
ARO 96-02 accrued 388 patients from 1997 to 2004 with pT3-4pN0 prostate cancer with positive or negative margins who had already undergone radical prostatectomy. Twenty-two centers in Germany participated in the trial.
Prior to reaching an undetectable PSA postprostatectomy, 159 patients were randomized to a wait-and-see approach (Arm A) and 148 patients were randomized to receive adjuvant radiation therapy (Arm B). Seventy-eight patients who did not achieve an undetectable PSA were moved to Arm C. Four of the patients in Arm C refused treatment, and 74 patients were treated with salvage radiation therapy in Arm C.
All patients in the study had a pre- and postoperative PSA test, a bone scan, and chest radiography. Patients in Arm B received 60 Gy of 3D conformal radiation therapy. Patients in Arm C received 66 Gy of 3D conformal radiation therapy. Follow-up was conducted for all eligible patients in the trial quarterly for the first 2 years, twice a year from 3 to 6 years posttreatment, and annually thereafter. The median follow-up time was 112 months (9.3 years).
Of the 74 patients in Arm C, 43 (58%) also underwent hormone therapy due to recurrence (at the discretion of the attending physician). Seven patients in Arm C, of the 48 who had data available, reached an undetectable PSA after completion of salvage radiation therapy. In Arms A and B, 20 patients (7%) experienced distant metastasis and 12 patients (16%) in Arm C experienced distant metastasis.
Patients with detectable PSA postprostatectomy (Arm C) experienced limited side effects as a result of radiation therapy. Patients in Arm C did not report any grade 3 or grade 4 acute toxicities. Seven patients experienced severe late effects, with five patients (7%) reporting grade 3 bladder impairment and two patients (3%) reporting grade 2 bladder impairment. Fifty patients (68%) in Arm C did not report any genitourinary late toxicity, and 59 patients (80%) in Arm C did not report any gastrointestinal late toxicity.
Clinical relapse-free survival (cRFS) was 63% at 10 years in Arm C. Overall survival was 86% in Arm A, 83% in Arm B, and 68% in Arm C.
“After patients undergo radical prostatectomy, the marker for PSA should fall below detection limits. Our analysis demonstrates that patients who have detectable PSA postprostatectomy may benefit from more aggressive, early, and uniform treatment that could improve survival outcomes,” said Thomas Wiegel, MD, director of the radiation oncology department at University Hospital Ulm in Ulm, Germany, and lead author of the study.