A dose-intensified approach to salvage radiotherapy failed to show superiority to a conventional-dose strategy in patients with biochemically recurrent prostate cancer who had undergone radical prostatectomy, according to the phase III SAKK 09/10 trial presented at the 2021 Genitourinary Cancers Symposium.1 The higher dose also was associated with a risk of increased gastrointestinal toxicity.
Pirus Ghadjar, MD
“After radical prostatectomy for localized prostate cancer, biochemical disease progression occurs in up to, or exceeding, 50% of patients, depending on specific risk factors,” said Pirus Ghadjar, MD, of the Charité Universitätsmedizin Berlin, Germany, who presented these study findings. “In patients who experience biochemical disease progression after radical prostatectomy, salvage radiation therapy to the prostate bed is the only available curative treatment option.”
The optimal dosing strategy for radiation therapy in this setting has been debated, but prior to this study, evidence was limited to retrospective studies.
Study Details and Results
The SAKK 09/10 trial was a prospective, open-label, prospective, multicenter, randomized, superiority trial comparing a dose-intensified regimen (70 Gy in 35 daily fractions of 2 Gy) and a conventional-dose regimen (64 Gy in 32 daily fractions of 2 Gy). All study patients had biochemical disease progression (ie, two consecutive rises in prostate-specific antigen [PSA] value, with the final PSA value > 0.1 ng/mL, or three consecutive rises) after radical prostatectomy.
A total of 350 men were randomly assigned in a 1:1 ratio to receive either the dose-intensification strategy or the conventional-dose strategy. Patients were excluded if they had a PSA value persistently above 0.4 mg/mL, had received any prior hormonal therapy, had local recurrence on imaging, or displayed any evidence of lymph node metastasis. The primary endpoint was freedom from biochemical disease progression; the secondary endpoints were clinical progression-free survival, time to hormonal treatment, overall survival, acute and late toxicity, and quality of life.
The intent-to-treat analysis was based on 170 patients in the conventional-radiotherapy arm (64 Gy) and 174 patients in the dose-intensification group (70 Gy given as three-dimensional conformal radiation therapy or intensity-modulated radiotherapy). The median PSA value at random assignment was 0.3 ng/mL, and patients were followed for a median of 6.2 years.
The study did not meet its primary endpoint: the median freedom from biochemical disease progression was 8.2 years with 64 Gy and 7.6 years with 70 Gy. No differences were observed across a number of subgroups, although Dr. Ghadjar noted that some subgroups had very small numbers of patients. There was also no significant difference reported between the groups with regard to progression-free survival, nor for another secondary endpoint, time to androgen-deprivation therapy.
Grade 2 genitourinary toxicity was observed in 21% of patients receiving 64 Gy and in 26% of those receiving 70 Gy. As for grade 3 genitourinary toxicity, the corresponding rates were 8% and 4%, respectively, and were not significantly different.
There was an increase in late gastrointestinal toxicity with the dose-intensified regimen, with just 7% reporting grade 2 events in the 64-Gy group compared with 20% in the 70-Gy group (P = .009). As for grade 3 gastrointestinal events, those rates were 4% and 2%, respectively. Quality-of-life measures did not differ between the dose regimens, with similar reports of changes in bowel and urinary symptoms from baseline.
“Dose-intensified salvage radiation therapy was not superior to conventional-dose radiation therapy in this setting,” Dr. Ghadjar concluded.
DISCLOSURE: Dr. Ghadjar has served as a consultant or advisor to Dr. Sennewald Medizuntechnik GmbH and Bytec Medizintechnik GmbH and has received research funding from Oncotherm GmbH.
1. Ghadjar P, Hayoz S, Bernhard J, et al: Dose-intensified versus conventional dose-salvage radiotherapy for biochemically recurrent prostate cancer after prostatectomy: Six-year outcomes of the SAKK 09/10 randomized phase III trial. 2021 Genitourinary Cancers Symposium. Abstract 194. Presented February 11, 2021.
Richard K. Valicenti, MD
Invited discussant of the SAKK 09/10 trial, Richard K. Valicenti, MD, of the University of California, Davis, commented: “These results bring us closer to a more individualized approach than using PSA dynamics and conventional imaging. It does not appear that historic ...