Phase II Randomized Trial of Radiation Therapy in Oligometastatic mCRPC Prostate Cancer (ARTO)

Summary

Metastatic castration resistant prostate cancer causes approximately 258400 deaths annually worldwide. In the presence of metastatic disease, systemic treatment remains the main clinical option. However, since the introduction of highly sensitive imaging techniques, a new clinical entity of metastatic patients with a limited number of lesions has been defined: oligometastatic patients. Although a clear benefit has yet to be demonstrated in this group of patients, the use of stereotactic body radiotherapy (SBRT) or other local therapies directed against all active lesions has been suggested as a possible salvage treatment. Irradiation of metastatic foci may delay the emergence of castration resistance because irradiation is effective against both ADT¬ sensitive and ADT ¬resistant prostate cancer cells as shown in re-biopsy studies. Stereotactic body radiation therapy has been used in this setting to defer the initiation of ADT in patients with oligometastatic prostate cancer with notable results. Abiraterone acetate is a first class inhibitor of cytochrome P ¬450c17, a critical enzyme in extragonadal and testicular androgen synthesis. Abiraterone plus low dose prednisone improves survival in patients with metastatic castration ¬resistant prostate cancer who have already received docetaxel and the combination therapy has received regulatory approval for this indication. Furthermore, Abiraterone acetate is approved also in patients who did not undergo to docetaxel chemotherapy, after the results from the COU-AA 302 study; Results from this phase III trial confirmed the benefit in chemo-naïve patients treated with abiraterone acetate both in terms of overall and radiological progression free survival, if compared to placebo. In oligometastatic CRPC, the rationale to use SBRT is that the addition of a local ablative treatment could improve disease control in mCRPC patients treated with a systemic therapy. The current phase II randomized trial,"Ablative Radiation Therapy in patients with Oligometastatic castration resistant prostate cancer (ARTO trial)" aims to evaluate the difference in PSA response rate between the experimental arm (AA+SBRT) and control arm (AA) in metastatic castration-resistant prostate cancer patients

Timeline

Start

2018-05-01

Primary completion

2021-09-01

Completion

2022-05-01

Publications

• Francolini G, Di Cataldo V, Caini S, Garlatti P, Aquilano M, Bertini N, Bruni A, Ingrosso G, D'Angelillo RM, Tagliaferri L, Jereczek-Fossa BA, Augugliaro M, Triggiani L, Parisi S, Masieri L, Campi R, Valicenti RK, Simontacchi G, Greto D, Bonomo P, Loi M, Tang C, Livi L; ARTO Working Group. SBRT plus abiraterone acetate and ADT versus abiraterone acetate and ADT in oligometastatic castrate-resistant prostate cancer (ARTO): long-term, unplanned overall survival analysis of an open-label, randomised, phase 2 trial. Lancet Oncol. 2026 Jul;27(7):830-838. doi: 10.1016/S1470-2045(26)00178-6.
• Francolini G, Allegra AG, Detti B, Di Cataldo V, Caini S, Bruni A, Ingrosso G, D'Angelillo RM, Alitto AR, Augugliaro M, Triggiani L, Parisi S, Facchini G, Banini M, Simontacchi G, Desideri I, Meattini I, Valicenti RK, Livi L; ARTO Working Group members. Stereotactic Body Radiation Therapy and Abiraterone Acetate for Patients Affected by Oligometastatic Castrate-Resistant Prostate Cancer: A Randomized Phase II Trial (ARTO). J Clin Oncol. 2023 Dec 20;41(36):5561-5568. doi: 10.1200/JCO.23.00985. Epub 2023 Sep 21.
• Francolini G, Di Cataldo V, Detti B, Simontacchi G, Loi M, Valzano M, Desideri I, Meattini I, Mangoni M, Livi L. Killing two birds with a stone: how to maximise benefit from metastasis-directed therapy and modern systemic treatment in oligometastatic hormone sensitive prostate cancer. Clin Exp Metastasis. 2022 Dec;39(6):841-843. doi: 10.1007/s10585-022-10187-2. Epub 2022 Oct 15.
• Francolini G, Loi M, Detti B, Desideri I, Mangoni M, Simontacchi G, Meattini I, Livi L. Integrating stereotactic body radiation therapy (SBRT) and systemic treatments in oligoprogressive prostate cancer: new evidence from the literature. Clin Exp Metastasis. 2021 Apr;38(2):227-230. doi: 10.1007/s10585-021-10072-4. Epub 2021 Jan 20.

Drugs

Indications

No indication recorded.