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

Abstract

Objectives: 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 and methods: 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.

Results: 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.

Conclusion: 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.

Keywords: ablation; cryotherapy; failure; focal therapy; high-intensity focussed ultrasound; prediction model; prostate cancer; radiotherapy; recurrence; salvage.

Fig. 1:

Flow chart detailing the exclusion and inclusion process of men in this study.

Fig. 2:

Kaplan-Meier curves plotting failure-free survival distributions for all patients undergoing salvage focal ablation (A), and stratified by focal ablation energy (B).

Fig. 3:

Calibration curve (A) and decision curve analysis (B) for model predictions of composite failure at 2 years post-salvage focal ablation for all included men undergoing salvage focal ablation. Calibration slope was 1.01. Decision curve analysis compares decision making to offer salvage focal ablation between model-based decision making and strategies of treating all patients and treating no patients. Plots demonstrating net benefit and percentage reduction in salvage focal ablation procedures are shown. Two clinically-reasonable ranges of risk threshold are highlighted: (i) 0.14–0.52 (light grey); and (ii) 0.26–0.36 (dark grey), based on previously-published pooled 2-year recurrence rates probabilities [4].

Fig. 4:

Kaplan-Meier curves curve plotting time-to-failure stratified by risk groups. This is plotted for all included men undergoing salvage focal ablation. Log-rank test demonstrated a significant difference in survival distributions between groups (p<0.0001).

Fig. 5:

Method of risk score calculation, presented with a nomogram presenting probability of failure-free survival by 2 years corresponding to the range of possible risk scores.