ASCO GU 2021: 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

( Radical prostatectomy (RP) is a standard treatment for patients with localized prostate cancer. A proportion of patients will experience biochemical recurrence following surgery. In these cases, salvage radiotherapy (ideally, early salvage radiotherapy) is indicated. During the plenary abstract presentation in the Prostate Cancer - Advanced Disease Poster Session at the 2021 American Society of Clinical Oncology (ASCO) Genitourinary (GU) Cancers Symposium, Dr. Pirus Ghadjar and colleagues report the results of the European SAKK 09/10 randomized Phase III trial comparing the effectiveness and tolerability of conventional vs. dose-intensified salvage radiation therapy (RT).

The SAKK 09/10 trial (NCT01272050) is an open-label, multicenter, randomized Phase III trial performed in 24 centers in Switzerland, Germany, and Belgium. The authors recruited men with biochemical progression (two consecutive rises with the final prostate-specific antigen (PSA) > 0.1 ng/mL or three consecutive rises) after RP with a PSA nadir of ≤ 0.4 ng/mL, with a PSA ≤ 2 ng/mL at randomization. Further, patients had to have no evidence of macroscopic disease and no nodal involvement at radical prostatectomy.

Following enrollment, patients were randomly assigned to receive either conventional-dose RT (64 Gy in 32 fractions) or dose-intensified RT (70 Gy in 35 fractions) directed to the prostate bed. Both 3-dimensional conformal RT and intensity-modulated RT/rotational techniques were used. The authors assessed the primary endpoint of freedom from biochemical progression (PSA ≥ 0.4 ng/mL and rising), as well as secondary endpoints of clinical progression-free survival, time to hormonal treatment, overall survival, acute and late toxicity (according to the National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v4.0) and quality of life (according to the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ]-C30 and PR25).

Between February 2011 and April 2014, a total of 350 patients were randomly assigned to conventional-dose RT (64 Gy) (n = 175) or dose-intensified RT (70 Gy) (n = 175). Among these 350 patients, 344 patients (aged 48 to 75 years) were assessable for the intention-to-treat population.

intention to treat convential doese RT

At the time of randomization, the median PSA was 0.3 ng/mL (range, 0.03-1.61 ng/mL), in keeping with relatively early salvage radiotherapy.

As of a data cut-off of July 3, 2020, the median follow-up was 6.2 years (IQR 5.5-7.2) and 138 biochemical progression events had occurred. The estimated 6-year freedom from biochemical progression was 62.3% (95% confidence interval [CI] 54.2-69.4%) among patients in the conventional dosage arm and 61.3% (95% CI 53.4-68.3%) among patients in the dose-intensified arm. After adjustment for stratification factors, there was no difference in freedom from biochemical progression (hazard ratio [HR] 1.14, 95% CI 0.82-1.60; log-rank p = 0.44).

difference in freedom from biochemical progression

This effect was consistent across subgroups.

subgroup difference in freedom from biochemical progression

Assessing secondary efficacy endpoints, there were no significant differences found for clinical progression-free survival, time to hormonal treatment, and overall survival. In fact, Kaplan Meier survival curves for these outcomes were nearly entirely superimposed.

Similarly, rates of late grade 2 and 3 genitourinary toxicity did not significantly differ though late grade 2 and 3 gastrointestinal toxicity was more common in patients receiving dose-intensified RT (35 (20%) and 4 (2.3%) vs. 12 (7.3%) and 7 (4.2%); p=0.009). Assessing patient-reported quality of life, no differences were noted between the two arms.

The authors concluded that dose-intensification at the time of salvage radiotherapy is not associated with oncologic improvements but does have higher rates of late grade 2 and 3 gastrointestinal toxicity.

Presented by: Pirus Ghadjar, MD, Attending Physician, Department of Radiation Oncology, Charité Hospital, Berlin, Germany

Written by: Christopher J.D. Wallis, MD, PhD, Urologic Oncology Fellow, Vanderbilt University Medical Center, Nashville, Tennessee, Twitter: @WallisCJD during the 2021 ASCO Genitourinary Cancers Symposium (ASCO GU), February 11th to 13th, 2021

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