Stereotactic prostate radiotherapy with or without androgen deprivation therapy, study protocol for a phase III, multi-institutional randomized-controlled trial

Marco Lorenzo Bonù; Alessandro Magli; Davide Tomasini; Francesco Frassine; Domenico Albano; Stefano Arcangeli; Alessio Bruni; Stefano Ciccarelli; Martina De Angeli; Giulio Francolini; Ciro Franzese; Paolo Ghirardelli; Luigi Grazioli; Andrea Guerini; Andrea Lancia; Giulia Marvaso; Matteo Sepulcri; Luca Eolo Trodella; Vittorio Morelli; Andrea Georgopulos; Anastasiya Oleksandrivna Domina; Lorenzo Granello; Eneida Mataj; Fernando Barbera; Luca Triggiani

doi:10.1259/bjro.20220032

Stereotactic prostate radiotherapy with or without androgen deprivation therapy, study protocol for a phase III, multi-institutional randomized-controlled trial

BJR Open. 2022 Nov 29;4(1):20220032. doi: 10.1259/bjro.20220032. eCollection 2022.

Authors

Marco Lorenzo Bonù¹, Alessandro Magli², Davide Tomasini¹, Francesco Frassine¹, Domenico Albano³, Stefano Arcangeli⁴, Alessio Bruni⁵, Stefano Ciccarelli⁶, Martina De Angeli⁷, Giulio Francolini⁸, Ciro Franzese⁹, Paolo Ghirardelli¹⁰, Luigi Grazioli¹¹, Andrea Guerini¹, Andrea Lancia¹², Giulia Marvaso¹³, Matteo Sepulcri¹⁴, Luca Eolo Trodella¹⁵, Vittorio Morelli¹, Andrea Georgopulos¹, Anastasiya Oleksandrivna Domina¹, Lorenzo Granello¹, Eneida Mataj¹, Fernando Barbera¹, Luca Triggiani¹

Affiliations

¹ Department of Radiation Oncology, Istituto del Radio O.Alberti, University of Brescia and Spedali Civili Hospital, Brescia, Italy.
² Department of Radiation Oncology, AULSS 1 Belluno, Belluno, Italy.
³ Department of Nuclear Medicine, University of Brescia and Spedali Civili Hospital, Brescia, Italy.
⁴ Department of Radiation Oncology, ASST Monza Ospedale San Gerardo, Monza, Italy.
⁵ Department of Radiation Oncology, Azienda Ospedaliera Universitaria Policlinico di Modena, Modena, Italy.
⁶ Department of Radiation Oncology, ASST - Cremona, Cremona, Italy.
⁷ Department of Radiation Oncology, Fondazione Policlinico Tor Vergata, Rome, Italy.
⁸ Department of Radiation Oncology, Azienda Ospedaliera Universitaria Careggi, Firenze, Italy.
⁹ Department of Radiation Oncology, Humanitas Research Hospital, Rozzano, Milano, Italy.
¹⁰ Department of Radiation Oncology, Humanitas Gavazzeni Hospital, Bergamo, Italy.
¹¹ Department of Radiology, ASST Spedali Civili di Brescia, Brescia, Italy.
¹² Department of Radiation Oncology, Fondazione IRCCS Policlinico, San Matteo, Italy.
¹³ Department of Radiation Oncology, Istituto Europeo di Oncologia (IEO), Milano, Italy.
¹⁴ Department of Radiation Oncology, Istituto Oncologico Veneto IOV-IRCCS, Padua, Italy.
¹⁵ Department of Radiation Oncology, Policlinico Universitario Campus Bio-Medico, Roma, Italy.

Abstract

Objective: The therapeutic landscape for localized prostate cancer (PC) is evolving. Stereotactic radiotherapy (SRT) has been reported to be at least not inferior to standard radiotherapy, but the effect of androgen deprivation therapy (ADT) in this setting is still unknown and its use is left to clinical judgment. There is therefore the need to clarify the role of ADT in association with SRT, which is the aim of the present study.

Methods: We present a study protocol for a randomized, multi-institutional, Phase III clinical trial, designed to study SRT in unfavorable intermediate and a subclass of high-risk localized PC. Patients (pts) will be randomized 1:1 to SRT + ADT or SRT alone. SRT will consists in 36.25 Gy in 5 fractions, ADT will be a single administration of Triptorelin 22.5 mg concurrent to SRT. Primary end point will be biochemical disease-free survival. Secondary end points will be disease-free survival, freedom from local recurrence, freedom from regional recurrence, freedom from distant metastasis and overall survival (OS); quality of life QoL and patient reported outcomes will be an exploratory end point and will be scored with EPIC-26, EORTC PR 25, IPSS, IIEF questionnaires in SRT + ADT and SRT alone arms. Moreover, clinician reported acute and late toxicity, assessed with CTCAE v. 5.0 scales will be safety end points.

Results: Sample size is estimated of 310 pts. For acute toxicity and quality of life results are awaited after 6 months since last patient in, whereas, for efficacy end points and late toxicity mature results will be available 3-5 years after last patient in.

Conclusion: Evidence is insufficient to guide decision making concerning ADT administration in the new scenario of prostate ultra-hypofractionation. Hence, the need to investigate the ADT role in SRT specific setting.

Advances in knowledge: The stereotactic prostate radiotherapy with or without ADT trial (SPA Trial) has been designed to establish a new standard of care for SRT in localized unfavorable intermediate and a subclass of localized high risk PC.