Comparative Healthcare Research Outcomes of Novel Surgery in prostate cancer (IP4-CHRONOS): A prospective, multi-centre therapeutic phase II parallel Randomised Control Trial.

Focal therapy (FT) targets individual areas of cancer within the prostate, providing oncological control with minimal side-effects. Early evidence demonstrates encouraging short-medium-term outcomes. With no randomized controlled trials (RCT) comparing FT to radical therapies, Comparative Healthcare Research Outcomes of Novel Surgery in prostate cancer (CHRONOS) will compare the cancer control of these two strategies.

CHRONOS is a parallel phase II RCT for patients with clinically significant non-metastatic prostate cancer, dependent upon clinician/patient decision, patients will enrol into either CHRONOS-A or CHRONOS-B. CHRONOS-A will randomize patients to either radical treatment or FT. CHRONOS-B is a multi-arm, multistage RCT comparing focal therapy alone to FT with neoadjuvant agents that might improve the current focal therapy outcomes. An internal pilot will determine the feasibility of, and compliance to, randomization. The proposed definitive study plans to recruit and randomize 1190 patients into CHRONOS-A and 1260 patients into CHRONOS-B.

Primary outcome in CHRONOS-A is progression-free survival (transition to salvage local or systemic therapy, development of metastases or prostate-cancer-related mortality) and in CHRONOS-B is failure-free survival (includes the above definition and recurrence of clinically significant prostate cancer after initial FT). Secondary outcomes include adverse events, health economics and functional outcomes measured using validated questionnaires. CHRONOS is powered to assess non-inferiority of FT compared to radical therapy in CHRONOS-A, and superiority of neoadjuvant agents with FT in CHRONOS-B.

CHRONOS will assess the oncological outcomes after FT compared to radical therapy and whether neoadjuvant treatments improve cancer control following one FT session.

Contemporary clinical trials. 2020 Apr 14 [Epub ahead of print]

Deepika Reddy, Taimur T Shah, Tim Dudderidge, Stuart McCracken, Manit Arya, Chris Dobbs, Mark Emberton, Francesca Fiorentino, Emily Day, A T Prevost, John Staffurth, Matthew Sydes, Mathias Winkler, Hashim U Ahmed

Imperial Prostate, Division of Surgery, Department of Surgery and Cancer, Imperial College London, London, UK; Imperial Urology, Charing Cross Hospital, Imperial College Healthcare NHS Trust, London, UK. Electronic address: ., Imperial Prostate, Division of Surgery, Department of Surgery and Cancer, Imperial College London, London, UK; Imperial Urology, Charing Cross Hospital, Imperial College Healthcare NHS Trust, London, UK., Department of Urology, University Hospital Southampton NHS Trust, Southampton, UK., Department of Urology, Sunderland Royal Hospital, Sunderland, UK; Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK., Imperial Urology, Charing Cross Hospital, Imperial College Healthcare NHS Trust, London, UK; Department of Surgery and Interventional Sciences, University College London, University College Hospital, London, UK., Patient and Public Representative, UK., Department of Surgery and Interventional Sciences, University College London, University College Hospital, London, UK., Imperial Clinical Trials Unit, Imperial College London, London, UK., School of Medicine, Cardiff University, Cardiff, UK., Medical Research Council Clinical Trials Unit at University College London, London, UK.