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IntroductionSurvival in men diagnosed with de novo synchronous metastatic prostate cancer has increased following the use of upfront systemic treatment, using chemotherapy and other novel androgen receptor targeted agents, in addition to standard androgen deprivation therapy (ADT). Local cytoreductive and metastasis-directed interventions are hypothesised to confer additional survival benefit. In this setting, IP2-ATLANTA will explore progression-free survival (PFS) outcomes with the addition of sequential multimodal local and metastasis-directed treatments compared with standard care alone.MethodsA phase II, prospective, multicentre, three-arm randomised controlled trial incorporating an embedded feasibility pilot. All men with new histologically diagnosed, hormone-sensitive, metastatic prostate cancer, within 4 months of commencing ADT and of performance status 0 to 2 are eligible. Patients will be randomised to Control (standard of care (SOC)) OR Intervention 1 (minimally invasive ablative therapy to prostate±pelvic lymph node dissection (PLND)) OR Intervention 2 (cytoreductive radical prostatectomy±PLND OR prostate radiotherapy±pelvic lymph node radiotherapy (PLNRT)). Metastatic burden will be prespecified using the Chemohormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease (CHAARTED) definition. Men with low burden disease in intervention arms are eligible for metastasis-directed therapy, in the form of stereotactic ablative body radiotherapy (SABR) or surgery. Standard systemic therapy will be administered in all arms with ADT±upfront systemic chemotherapy or androgen receptor agents. Patients will be followed-up for a minimum of 2 years. Primary outcome: PFS. Secondary outcomes include predictive factors for PFS and overall survival; urinary, sexual and rectal side effects. Embedded feasibility sample size is 80, with 918 patients required in the main phase II component. Study recruitment commenced in April 2019, with planned follow-up completed by April 2024.Ethics and disseminationApproved by the Health Research Authority (HRA) Research Ethics Committee Wales-5 (19/WA0005). Study results will be submitted for publication in peer-reviewed journals.Trial registration numberNCT03763253; ISCRTN58401737

IntroductionSystemic therapy with androgen deprivation therapy (ADT) and intensification with agents such as docetaxel, abiraterone acetate and enzalutamide has resulted in improved overall survival in men with de novo synchronous metastatic hormone-sensitive prostate cancer (mHSPC). Novel local cytoreductive treatments and metastasis-directed therapy are now being evaluated. Such interventions may provide added survival benefit or delay the requirement for further systemic agents and associated toxicity but can confer additional harm. Understanding men’s preferences for treatment options in this disease state is crucial for patients, clinicians, carers and future healthcare service providers.MethodsUsing a prospective, multicentre discrete choice experiment (DCE), we aim to determine the attributes associated with treatment that are most important to men with mHSPC. Furthermore, we plan to determine men’s preferences for, and trade-offs between, the attributes (survival and side effects) of different treatment options including systemic therapy, local cytoreductive approaches (external beam radiotherapy, cytoreductive radical prostatectomy or minimally invasive ablative therapy) and metastases-directed therapies (metastasectomy or stereotactic ablative body radiotherapy). All men with newly diagnosed mHSPC within 4 months of commencing ADT and WHO performance status 0–2 are eligible. Men who have previously consented to a cytoreductive treatment or have developed castrate-resistant disease will be excluded. This study includes a qualitative analysis component, with patients (n=15) and healthcare professionals (n=5), to identify and define the key attributes associated with treatment options that would warrant trade-off evaluation in a DCE. The main phase component planned recruitment is 300 patients over 1 year, commencing in January 2021, with planned study completion in March 2022.Ethics and disseminationEthical approval was obtained from the Health Research Authority East of England, Cambridgeshire and Hertfordshire Research Ethics Committee (Reference: 20/EE/0194). Project information will be reported on the publicly available Imperial College London website and the Heath Economics Research Unit (HERU website including the HERU Blog). We will use the social media accounts of IP5-MATTER, Imperial Prostate London, HERU and the individual researchers to disseminate key findings following publication. Findings from the study will be presented at national/international conferences and peer-reviewed journals. Authorship policy will follow the recommendations of the International Committee of Medical Journal Editors.Trial registration numberNCT04590976.

TPS5600 Background: Local cytoreductive and metastasis-directed interventions are hypothesised to confer additional survival benefit beyond standard systemic therapy in patients with de novo synchronous metastatic prostate cancer. There is accumulating prospective evidence for local cytoreductive therapy. In particular, the phase III study STAMPEDE which demonstrated improved overall survival in a low burden subgroup of men following cytoreductive radiotherapy. Cytoreductive prostatectomy and minimally invasive ablative therapies (MIAT) are now subject to similar trial evaluation. IP2-ATLANTA will evaluate progression-free and overall survival outcomes with the addition of sequential multi-modal local and metastasis-directed treatments in patients with newly diagnosed metastatic prostate cancer compared to standard care alone. Methods: Phase II, multicentre, three-arm randomised controlled trial using a positive comparator arm ( n=918 ). An internal pilot ( n=80) feasibility phase is incorporated. All men with new histologically diagnosed, hormone sensitive, metastatic prostate cancer, within three months of commencing ADT and of PS 0-2 are eligible. Patients are randomised (1:1:1) to: Control (Standard of Care) OR Intervention 1 (Minimally invasive ablative therapy to the prostate +/- pelvic lymph node dissection [PLND]) OR Intervention 2 (prostate radiotherapy +/- lymph nodes OR Radical prostatectomy +/- PLND). Metastatic burden pre-specified by CHAARTED definition. Men with low-burden disease in intervention arms are eligible for metastasis-directed therapy (stereotactic ablative radiotherapy [SABR] or surgery). Standard systemic therapy given in all arms (incl. docetaxel). Follow-up: min. 2-years; max. 4 years. Primary outcome: progression-free survival (PFS). Secondary outcomes: Overall survival; urinary, sexual & rectal side-effects; patient reported outcome measures. HRA ethical approval (Ref: 19/WA0005). To date, 28/80 (35%) patients have been recruited and randomised across 9 open sites in the internal pilot. Median recruitment rate is 85.7% (IQR 55–86). Internal pilot recruitment expected to be complete by April 2020. IP2-ATLANTA addresses an important research gap in the role of local and metastasis-directed therapy in men with newly diagnosed metastatic prostate cancer. Clinical trial information: NCT03763253 .