ARTO trial-(NCT03449719): Early results from a phase II randomized trial testing stereotactic body radiation therapy in patients with oligometastatic castration-resistant prostate cancer undergoing I line treatment with abiraterone acetate.
Authors: Francolini Giulio , Detti Beatrice , Di Cataldo Vanessa , Caini Saverio , Alitto Anna Rita , Parisi Silvana , Demofonti Chiara , Bruni Alessio , Ingrosso Gianluca , Timon Giorgia , Allegra Andrea , Aquilano Michele , Ciccone Lucia Pia , Salvestrini Viola , Frosini Giulio , Cerbai Cecilia , Desideri Isacco , Meattini Icro , Mangoni Monica , Livi Lorenzo 
Published: February 2022

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Background: ARTO (NCT03449719) is a multicentre, randomized trial started in January 2019 and currently running in 16 Italian centres, testing the benefit of adding stereotactic body radiation therapy (SBRT) to Abiraterone Acetate (AA) in oligometastatic Castrate Resistant Prostate Cancer (CRPC) patients. Seventy-nine per cent of the target accrual population has been currently enrolled. Here we present a report about early efficacy results of SBRT+AA combination. Methods: Data from patients with ≥ 6 months of follow up were reported. All patients were affected by oligometastatic CRPC, defined as ≤ 3 non-visceral metastatic lesions. Patients were randomized 1:1 to receive either AA alone (control arm) or associated with concomitant SBRT on all sites of disease (treatment arm). Primary endpoint of the trial is rate of biochemical response (BR, defined as a PSA decrease ≥ 50% from baseline measured within 6 months from treatment start). Complete biochemical response (CBR, defined as PSA at 6 months ≤ 0.2 ng/ml) is a secondary endpoint of the trial. Results: Overall, 123 patients have been currently enrolled in ARTO trial. To date, 98 patients had ≥ 6 months of follow-up and were evaluable for the present analysis. BR was detected in 75 (76.5%) patients (82.2% vs. 71.7% in treatment vs. control arm, respectively), with an unadjusted odds ratio (OR) equal to 1.83 (95% CI 0.69-4.82, p-value 0.22). After adjustment for baseline PSA and the number of metastatic sites ( > 1 vs. 1), the OR for BR was 2.23 (95% CI 0.74-6.73, p-value 0.15). CBR was detected in 36 (36.7%) patients (46.7% vs. 28.3% in treatment vs. control arm, respectively), with an unadjusted OR of 2.22 (95% CI 0.96-5.12, p-value 0.06), and an adjusted OR of 2.31 (95% CI 0.90-5.92, p-value 0.08). In multivariable models, baseline PSA and the number of metastatic sites > 1 were non-statistically associated with CBR, with OR equal to 0.92 (95% CI 0.85-1.01, p-value 0.06) and 1.20 (95% CI 0.46-3.09, p-value 0.71), respectively. Conclusions: Results showed promising efficacy of SBRT+AA combination if compared to systemic treatment alone for oligometastatic CRPC, OR for BR and CBR were doubled in treatment vs. control arm, even if statistical significance is not yet reached. Interestingly, baseline burden of disease seems to predict increased outcome after SBRT, suggesting that selection criteria for local treatment may be further refined. Complete results for primary endpoint are awaited in 2022, after enrollment and follow-up completion of whole cohort, and may confirm these early outcomes in a larger population. Clinical trial information: NCT03449719.