Primary tumour asphericity on baseline 18F-FDG PET/CT provides incremental prognostic value beyond stage and metabolic burden in breast carcinoma: association with metastasis, early metabolic response, and survival outcomes

Background Tumour sphericity (TS) and its inverse, tumour asphericity (ASP) = 1 - TS, derived from baseline ¹⁸ F-FDG PET/CT may capture morphologic heterogeneity linked to tumour aggressiveness. Aim To determine whether baseline primary tumour asphericity on ¹⁸ F-FDG PET/CT provides incremental prognostic value beyond clinical stage, molecular subtype, histologic grade, and PET metabolic burden (SUVmax, MTV, TLG) for synchronous distant metastasis and survival outcomes in breast carcinoma. Methods This retrospective study included 202 women (median age 52 years) with biopsy-confirmed breast cancer staged by ¹⁸ F-FDG PET/CT (January 2017 to December 2021) and followed for a median of 48 months. Primary endpoints were synchronous distant metastasis at presentation and overall survival (OS); early metabolic non response and progression-free survival (PFS) were secondary endpoints. Primary tumours were semi automatically segmented (Python; Trimesh) and TS/ASP were computed from 3D surface geometry. Optimal cut offs were identified by ROC analysis. Early metabolic non response was defined as failure to achieve ≥ 30% reduction in primary tumour SUVmax on interim PET/CT (where available). Multivariable logistic and Cox models were adjusted for age, TNM stage, molecular subtype, tumour grade, and PET metabolic metrics (SUVmax, MTV, TLG). Results Median TS was 0.78 (IQR 0.72–0.84); an ASP threshold of 0.25 optimally separated metastatic from non-metastatic cases (AUC 0.78, 95% CI 0.71–0.84). High ASP (> 0.25) independently predicted synchronous distant metastasis (OR 3.1, 95% CI 1.6-6.0; p = 0.001) and was associated with inferior 5 year OS after adjustment (HR 2.4, 95% CI 1.2–4.7; p = 0.010). High ASP (> 0.25; TS < 0.75) increased the likelihood of early metabolic non response (OR 2.5, 95% CI 1.4–4.5; p = 0.002). Associations with PFS were also observed (HR 1.9, 95% CI 1.2–2.9; p = 0.004). In decision curve analysis for 5 year PFS, models including ASP showed higher net benefit than clinical only models across clinically relevant thresholds. Conclusions Baseline tumour asphericity is a reproducible, interpretable biomarker of metastatic dissemination and adverse survival in breast cancer, complementing stage, tumour biology, and metabolic burden. Its association with early metabolic non response supports a role for PET/CT based risk stratification and treatment tailoring, pending multicentre validation.