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 a study presented by Pirus Ghadjar, MD, and colleagues at the 2021 Genitourinary Cancers Symposium (Abstract 194). The higher dose also carried the risk of increased gastrointestinal toxicity.

“After radical prostatectomy for localized prostate cancer, biochemical progression occurs in up to, or exceeding, 50% of patients, depending on specific risk factors,” said Dr. Ghadjar, of Charité - Universitätsmedizin Berlin, who presented the results of the SAKK 09/10 randomized phase III trial. “In patients who experience biochemical progression after radical prostatectomy, salvage radiation therapy to the prostate bed is the only available curative treatment option.”

Pirus Ghadjar, MD

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

The SAKK 09/10 TRIAL was a prospective, open-label, prospective, multicenter, randomized, superiority phase III trial. It compared a dose-intensified regimen (70 Gy in 35 daily fractions of 2 Gy) vs a conventional dose regimen (64 Gy in 32 daily fractions of 2 Gy) in patients with biochemical progression (ie, two consecutive rises with the final prostate-specific antigen [PSA] > 0.1 ng/mL or three consecutive rises) following radical prostatectomy.

Patients (n = 350) were randomly assigned 1:1 to receive either the dose-intensification strategy or the conventional dose strategy. Patients were excluded if they had PSA persistence > 0.4 mg/mL, had received any prior hormonal therapy, had a local recurrence on imaging, or any evidence of lymph node metastasis. Primary endpoint was freedom from biochemical progression; 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 arm, who received 64 Gy, and 174 in the dose-intensification group receiving 70 Gy given as 3D conformal radiation or intensity-modulated radiotherapy. The median PSA at random assignment was 0.3 ng/mL, and patients were followed for a median of 6.2 years.

Results

The study did not meet its primary endpoint: median freedom from biochemical 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 between the groups with regard to progression-free survival, and 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. Grade 3 events occurred in 8% and 4% of patients, respectively, and were not significantly different. There was an increase in gastrointestinal late toxicity with the dose-intensified regimen, with only 7% of patients reporting grade 2 events in the 64 Gy group compared with 20% in the 70 Gy group (P = .009). For grade 3 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 in this setting,” concluded Dr. Ghadjar. However, the researchers did add, “Dose-intensified salvage radiotherapy was associated with higher frequencies of late grade ≥ 2 gastrointestinal toxicity.”

Disclosure: For full disclosures of the study authors, visit coi.asco.org.