Prostate-specific membrane antigen (PSMA) PET/CT is routinely used to restage prostate cancer (PCa) in patients with biochemical recurrence (BCR), yet negative scans may still harbor subclinical disease. This study investigated whether radiomics features extracted from recurrence-prone organs on negative [¹⁸F]DCFPyL PET/CT can predict clinical progression (CP) and clinical progression-free survival (CPFS).
Materials and Methods: We performed a post-hoc analysis of 132 patients with BCR (mean age, 74.5 years) who had negative [¹⁸F]DCFPyL PET/CT scans and received no further treatment after imaging. Recurrence-prone organs, defined as anatomical sites at highest risk for prostate cancer recurrence (prostate bed, lymph nodes, bones, liver, and lungs), were segmented using nnU-Net (TotalSegmentator), and radiomics features were extracted. Machine learning models (XGBoost) and Cox proportional hazards models were evaluated using nested cross-validation (5-fold outer, 3-fold inner). External validation across two independent centers was performed after ComBat harmonization. The effect of reader-assigned diagnostic certainty on predictive performance was also examined. Only recurrence-prone organs were analyzed, as prior studies have shown that more than 80% of PCa recurrences arise in these regions.
Results: Median PSA at imaging was 0.74 ng/mL. During a median follow-up of 25.5 months, 42 of 132 patients (31.8%) developed progression. The concordance index improved from 0.65 using clinical variables alone to 0.74 when PET, CT, and clinical features were combined (p < 0.05). Predictive performance was strongly influenced by diagnostic certainty, with moderate-certainty negative scans showing higher accuracy than high-certainty negative scans. Radiomics features derived from negative PSMA PET/CT reflected systemic recurrence risk and were associated with early lung metastases. External validation demonstrated less than 10% reduction in performance despite inter-center differences.
Conclusion: Radiomics signatures from recurrence-prone organs on negative PSMA PET/CT may reveal subclinical disease and provide complementary biomarkers for risk stratification in BCR patients.
Biomedical physics & engineering express. 2026 Jun 30 [Epub ahead of print]
Fereshteh Yousefirizi, Sara Harsini, Mobin Mohebi, Ian Alberts, Tahir Yusufaly, Monica Luo, Hamid Abdollahi, Elmira Yazdani, Seyyede Mirabedian, Maziar Sabouri, Parham Geramifar, Peyman Sheikhzadeh, Patrick Martineau, Don Wilson, François Bénard, Carlos Felipe Uribe, Arman Rahmim
BC Cancer Research Centre, Vancouver, Vancouver, British Columbia, V5Z 1L3, Canada., Department of Medical Imaging, University of Toronto, Toronto, Toronto, Ontario, M5S 1A1, Canada., Institut de Biologie Valrose , Inserm, Nice, France, nice, 06108, France., BC Cancer Agency, 675 10th Ave W, Vancouver, Vancouver, British Columbia, V5Z 1G1, Canada., Department of Radiation Medicine and Applied Sciences, University of California San Diego, Moores Cancer Center, 3855 Health Sciences Drive, La Jolla, California, 92093-0865, United States., BC Cancer Research Centre, 675 10th Ave W, Vancouver, Vancouver, British Columbia, V5Z 1L3, Canada., BC Cancer Research Centre, 675 10th Ave W, Vancouver, British Columbia, V5Z 1L3, Canada., Department of Medical Physics, Iran University of Medical Sciences, Tehran, Tehran, 14496-14535, Iran (The Islamic Republic of)., Tehran University of Medical Sciences, Vali-Asr Hospital, Tehran, Tehran, 1416753955, Iran (The Islamic Republic of)., Tehran University of Medical Sciences, Tehran, Tehran, Tehran Province, 1416753955, Iran (The Islamic Republic of)., BC Cancer Agency, 675 10th Ave W, Vancouver, British Columbia, V5Z 1G1, Canada., BC Cancer - Vancouver, 600 W 10th Ave, Vancouver, British Columbia, V5Z 4E6, Canada., BC Cancer Agency, 675 10th Ave W, Vancouver, British Columbia, V5Z 1L3, Canada., Molecular Oncology, BC Cancer Agency, 675 10th Ave W, Vancouver, British Columbia, V5Z 1L3, Canada., Radiology and Physics, The University of British Columbia, 675 10th Ave W, Vancouver, British Columbia, V5Z 1L3, Canada.