Impact of Stereotactic Body Radiotherapy after Progression in Castrate Resistant Prostate Cancer Patients Undergoing First Line Abiraterone Treatment. A Subgroup Analysis from ARTO Trial (NCT03449719)

Use of metastasis directed therapy (MDT) through stereotactic body radiotherapy (SBRT) is a well consolidated treatment for oligometastatic/oligoprogressive prostate cancer in clinical practice. Moreover, this approach gained further attention after the publication of several prospective trials testing its benefit both in hormone sensitive (e.g, STOMP, ORIOLE, RADIOSA) or even castrate resistant status with or without androgen receptor pathway inhibitors treatment (e.g, ARTO, EXTEND, GROUQ-PCS9). The biological rationale behind the clinical value of a local treatment of oligometastatic/oligoprogressive disease relies on the eradication of resistant clones of disease, which are able to seed distant metastases and promote further progression of disease. From this point of view, the subgroup analysis of the ARTO trial suggests two main discussion topics.

First, SBRT administered after progression under first line abiraterone, in a selected group of oligoprogressive patients, provided a similar benefit to a second line systemic treatment, and could be considered as a viable treatment option to delay systemic therapy change. On the other side, upfront administration of concomitant SBRT and Abiraterone provided a significant improvement if compared to systemic standard of care, as suggested by original trial results. Overall, this underlines that the best integrated treatment strategy for oligometastatic castrate resistant prostate cancer relies on upfront use of SBRT aimed at early eradication of foci of resistant disease. Indeed, waiting for further progression to include SBRT in the treatment paradigm could be detrimental for these patients. Of note, evidence in favour of SBRT addition to androgen receptor pathway inhibitors (e.g, abiraterone, enzalutamide) is mainly related to castration resistant status, and is based on results of ARTO and GROUQ-PCS9 trials (the latter recently presented at ASCO GU 2025).

Whether this benefit is maintained as well in oligometastatic hormone sensitive prostate cancer is the object of the PERSIAN trial (NCT05717660), a randomized phase II trial testing the addition of SBRT to standard of care androgen deprivation therapy and apalutamide. This trial completed its accrual in November 2024, and early results about the rate of complete biochemical response were presented at ASCO GU 2025, showing a significant advantage in the experimental arm of treatment for patients with <3 metastatic lesions. Overall, the early multidisciplinary approach seems to be the most important tool to improve clinical prognosis of oligometastatic prostate cancer patients.

Written by: Giulio Francolini,¹ Niccolò Bertini,² Vanessa Di Cataldo,¹ Pietro Garlatti,¹ Michele Aquilano,³ Saverio Caini,⁴ Alessio Bruni,⁵ Gianluca Ingrosso,⁶ Rolando Maria D'angelillo,⁷ Luca Tagliaferri,⁸ Matteo Augugliaro,⁹ Luca Triggiani,¹⁰ Silvana Parisi,¹¹ Giorgia Timon,⁹ Fabio Arcidiacono,¹² Giulia Marvaso,¹³ Barbara Alicja Jereczek-Fossa,¹³ Andrea Lancia 14, Ciro Franzese 15, Filippo Alongi 16, Gabriele Simontacchi 1, Daniela Greto 1, Pierluigi Bonomo 1, Mauro Loi 1, Giulio Frosini 2, Luca Burchini 2, Isacco Desideri 2, Icro Meattini 2, Richard K Valicenti 17, Lorenzo Livi 2

Radiation Oncology Unit, Azienda Ospedaliero Universitaria Careggi, University of Florence, Florence, Italy.
Department of Biomedical, Experimental and Clinical Sciences "Mario Serio", University of Florence, Florence, Italy.
Cyberknife Unit, Istituto Fiorentino di Cura ed Assistenza, IFCA, Florence, Italy.
Cancer Risk Factors and Lifestyle Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network (ISPRO), Florence, Italy.
Radiation Oncology Unit, Department of Oncology and Hematology, University Hospital of Modena, Modena, Italy.
Radiation Oncology Section, Department of Medicine and Surgery, University of Perugia, Perugia, Italy.
Radiation Oncology, Department of Biomedicine and Prevention, University of Rome "Tor Vergata", Rome, Italy.
UOC di Radioterapia Oncologica, Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario "A.Gemelli" IRCCS, Rome, Italy.
Unit of Radiotherapy, Azienda USL-IRCCS di Reggio Emilia, Reggio emilia, Italy.
Università degli Studi di Brescia, Department of Radiation Oncology, Brescia University, Brescia, Italy.
Radiation Oncology Unit, Department of Biomedical, Dental Sciences and Morphological and Functional Imaging, University of Messina, Messina, Italy.
Radiation Oncology Centre, S. Maria Hospital, Terni, Italy.
Division of Radiation Oncology, IEO, European Institute of Oncology, IRCCS, Milan, Italy.
Department of Radiation Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
Department of Radiotherapy and Radiosurgery, Humanitas Clinical and Research Center, IRCCS, Rozzano, Milan, Italy.
Department of Advanced Radiation Oncology, IRCCS Sacro Cuore Don Calabria Hospital, Negrar, Verona, Italy.
Department of Radiation Oncology, UC Davis, Sacramento, CA, USA.

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