External validation of a risk model predicting failure of salvage focal ablation for prostate cancer.

To externally validate a published model predicting failure within 2 years after salvage focal ablation in men with localised radiorecurrent prostate cancer using a prospective, UK multicentre dataset.

Patients with biopsy-confirmed ≤T3bN0M0 cancer after previous external beam radiotherapy or brachytherapy were included from the FOcal RECurrent Assessment and Salvage Treatment (FORECAST) trial (NCT01883128; 2014-2018; six centres), and from the high-intensity focussed ultrasound (HIFU) Evaluation and Assessment of Treatment (HEAT) and International Cryotherapy Evaluation (ICE) UK-based registries (2006-2022; nine centres). Eligible patients underwent either salvage focal HIFU or cryotherapy, with the choice based predominantly on anatomical factors. Per the original multivariable Cox regression model, the predicted outcome was a composite failure outcome. Model performance was assessed at 2 years post-salvage with discrimination (concordance index [C-index]), calibration (calibration curve and slope), and decision curve analysis. For the latter, two clinically-reasonable risk threshold ranges of 0.14-0.52 and 0.26-0.36 were considered, corresponding to previously published pooled 2-year recurrence-free survival rates for salvage local treatments.

A total of 168 patients were included, of whom 84/168 (50%) experienced the primary outcome in all follow-ups, and 72/168 (43%) within 2 years. The C-index was 0.65 (95% confidence interval 0.58-0.71). On graphical inspection, there was close agreement between predicted and observed failure. The calibration slope was 1.01. In decision curve analysis, there was incremental net benefit vs a 'treat all' strategy at risk thresholds of ≥0.23. The net benefit was therefore higher across the majority of the 0.14-0.52 risk threshold range, and all of the 0.26-0.36 range.

In external validation using prospective, multicentre data, this model demonstrated modest discrimination but good calibration and clinical utility for predicting failure of salvage focal ablation within 2 years. This model could be reasonably used to improve selection of appropriate treatment candidates for salvage focal ablation, and its use should be considered when discussing salvage options with patients. Further validation in larger, international cohorts with longer follow-up is recommended.

BJU international. 2023 Jun 29 [Epub ahead of print]

Alexander Light, Max Peters, Deepika Reddy, Abi Kanthabalan, Marjorie Otieno, Menelaos Pavlou, Rumana Omar, Sola Adeleke, Francesco Giganti, Chris Brew-Graves, Norman R Williams, Amr Emara, Athar Haroon, Arash Latifoltojar, Harbir Sidhu, Alex Freeman, Clement Orczyk, Ashok Nikapota, Tim Dudderidge, Richard G Hindley, Jaspal Virdi, Manit Arya, Heather Payne, Anita V Mitra, Jamshed Bomanji, Mathias Winkler, Gail Horan, Caroline Moore, Mark Emberton, Shonit Punwani, Hashim U Ahmed, Taimur T Shah

Imperial Prostate, Department of Surgery and Cancer, Imperial College London, London, UK., Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, The Netherlands., Division of Surgery and Interventional Sciences, University College London, London, UK., Department of Statistical Science, University College London, London, UK., Department of Oncology, Guy's and St Thomas' NHS Foundation Trust, London, UK., Division of Medicine, Faculty of Medicine, University College London, London, UK., Department of Urology, Basingstoke and North Hampshire Hospital, Hampshire Hospitals NHS Foundation Trust, Basingstoke, UK., Institute of Nuclear Medicine, University College London Hospitals NHS Foundation Trust, London, UK., Department of Histopathology, University College London Hospital NHS Foundation Trust, London, UK., Sussex Cancer Centre, Royal Sussex County Hospital, University Hospitals Sussex NHS Foundation Trust, Brighton, UK., Department of Urology, University Hospital Southampton NHS Foundation Trust, Southampton, UK., Department of Urology, The Princess Alexandra Hospital NHS Trust, Harlow, UK., Imperial Urology, Charing Cross Hospital, Imperial College Healthcare NHS Trust, London, UK., Department of Oncology, University College London Hospital NHS Foundation Trust, London, UK., Department of Oncology, Queen Elizabeth Hospital, The Queen Elizabeth Hospital King's Lynn NHS Foundation Trust, King's Lynn, UK.