Incremental prognostic value of baseline 18F-FDG PET/CT tumour asphericity in breast carcinoma: association with de novo metastatic disease and survival outcomes

Background Tumour asphericity (ASP), derived from baseline 18F-FDG PET/CT, may capture morphologic heterogeneity linked to aggressive biology and adverse outcomes. Aim To evaluate the incremental value of baseline ASP for de novo metastatic disease at presentation and survival outcomes in breast carcinoma beyond clinical stage, receptor-derived subtype, Ki-67 and metabolic tumour burden. Methods Patient-level data (n = 180) were analysed. De novo metastasis (stage IV) was modelled using multivariable logistic regression with 5-fold cross-validated ROC analysis; model calibration was assessed using observed versus predicted risk. PFS and OS were analysed using Kaplan-Meier, log-rank tests and multivariable Cox proportional hazards regression. Results De novo metastatic disease was present in 37/180 patients (20.6%). In multivariable logistic regression, ASP (per 0.1 increase) independently predicted baseline metastasis (OR 3.60, 95% CI 2.02 to 6.43, p < 0.001) along with ln(TLG) (natural logarithm transformed TLG; OR 2.47, 95% CI 1.32 to 4.63, p = 0.0047). Out-of-fold AUC for metastasis prediction was 0.80 for ASP alone and 0.82 for the full model including ASP; calibration was satisfactory (calibration slope 1.00; Brier score 0.117). Higher ASP was also associated with treatment non-response (OR 1.99 per 0.1, p = 0.00033). On unadjusted analysis over full follow-up (not administratively censored), ASP > 0.30 (vs ASP ≤ 0.30) was associated with shorter PFS (median 24.7 vs 9.6 months; log-rank p = 0.0017) and OS (median 28.2 vs 10.8 months; log-rank p = 0.00011). Conclusion Baseline tumour asphericity derived from ¹⁸ F-FDG PET/CT is a simple, interpretable geometric biomarker that outperforms conventional metabolic indices and biomarker variables for baseline metastasis discrimination and is associated with treatment non-response and shorter median PFS and OS on unadjusted survival analysis. Prospective multicentre validation is warranted.