ASTRO. US: 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 February 1, 2015 issue of the International Journal of Radiation Oncology • Biology • Physics (Red Journal), the official scientific journal of the American Society for Radiation Oncology (ASTRO). This study is a 10-year post-treatment 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 had a
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. Three patients were excluded from the study
because they received immediate hormonal treatment. Prior to reaching an
undetectable PSA post-prostatectomy, 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 post-operative PSA test, a
bone scan and chest radiography. Patients in Arm B received 60 Gy of 3-D
conformal radiation therapy. Patients in Arm C received 66 Gy of 3-D
conformal radiation therapy. Follow-up was conducted for all eligible
patients in the trial quarterly for the first two years, twice a year
from three to six years post-treatment, and annually thereafter. The
median follow-up time was 112 months (9.3 years).
Of the 74 patients in Arm C, 43 (58 percent) also underwent hormone
therapy as a result of 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 percent) experienced distant
metastasis, and in Arm C, 12 patients (16 percent) experienced distant
metastasis.
Patients with detectable PSA post-prostatectomy (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 percent)
reporting grade 3 bladder impairment, and two patients (3 percent)
reporting grade 2 bladder impairment. Fifty patients (68 percent) in Arm
C did not report any genitourinary late toxicity, and 59 patients (80
percent) in Arm C did not report any gastrointestinal late toxicity.
Clinical relapse-free survival (cRFS) was calculated using the
Kaplan-Meier method. In Arm C, patients had a 10-year cRFS rate of 63
percent. Univariate analysis demonstrated that patients in Arm C who had
a Gleason score <8 (p=.0023), pT<3b (p=.0076) or an
extraprostatic tumor extension <2mm (p=.0047) had a better cRFS
rate.
The Kaplan-Meier method was used to analyze overall survival (OS).
Patients in Arm A had a 10-year OS rate of 86 percent, and patients in
Arm B had a 10-year OS rate of 83 percent, compared with patients in Arm
C who had a 10-year OS rate of 68 percent.
“After patients undergo radical prostatectomy, the marker for PSA
should fall below detection limits. Our analysis demonstrates that
patients who have detectable PSA post-prostatectomy 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. “The impact of PSA persistence on 10-year overall survival
is evident based on this new analysis. Improved imaging or surrogate
markers beyond PSA are desirable to distinguish risk groups among men
with PSA persistence. Larger, prospectively randomized clinical trials
should examine additional treatment options to come to a standardized
therapy for prostate cancer patients with PSA persistence.”
For a copy of the study manuscript, contact ASTRO’s Press Office. Learn more about the Red Journal.