European urology · 2025
Development and Validation of a Multimodal Artificial Intelligence-derived Digital Pathology-based Biomarker Predicting Metastasis Among Patients with Biochemical Recurrence After Radical Prostatectomy in NRG/RTOG Trials.
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Morgan Todd M, Ren Yi, Tang Siyi, Zwerink Wouter, Chen Emmalyn, Mitani Akinori, Huang Huei-Chung, Simko Jeffry P, DeVries Sandy, Pollack Alan, Wilke Derek, Martin André-Guy, Balogh Alexander G, Michalski Jeff M, Greenberg Michael J, Efstathiou Jason A, Bahary Jean-Paul, Ross Ashley E, Esteva Andre, Royce Trevor J, Nguyen Paul L, Hoffman Karen E, Sandler Howard M, Tran Phuoc T, Pugh Stephanie L, Feng Felix Y, Spratt Daniel E
Аннотация
BACKGROUND AND OBJECTIVE: Biochemical recurrence (BCR) after radical prostatectomy (RP) is a heterogeneous disease state in prostate cancer with multiple treatment options. Improved risk stratification could enable more personalized decision-making. We developed and validated a digital pathology-based multimodal artificial intelligence (MMAI) model to predict outcomes in post-RP BCR patients undergoing salvage therapy.
METHODS: An MMAI model was trained to predict distant metastasis (DM) using prostate histopathology image features and clinical variables (pathologic grade group, pathologic T stage, prostate-specific antigen level before salvage radiotherapy [SRT], age, and surgical margin). The locked model was validated in 533 patients from NRG/RTOG 9601 and 0534 treated with SRT ± hormone therapy (HT), using Cox regression and time-dependent area under the receiver operating characteristic curve.
KEY FINDINGS AND LIMITATIONS: With a median follow-up of 9.3 yrs, MMAI score was significantly associated with DM (subdistribution hazard ratio = 2.17 per standard deviation [95% confidence interval 1.65-2.85]; p < 0.001) and remained independently prognostic after adjusting for clinical variables and treatment. The 10-yr time-dependent area under the receiver operating characteristic curve for MMAI was 0.74 compared with 0.68 for a clinical nomogram. Binary risk categorization demonstrated higher 10-yr DM incidence in the MMAI high-risk (25%) than in the low-risk (8.8%) group. The absolute reduction in 10-yr DM incidence with HT plus SRT versus SRT alone was 21% in the high-risk group versus 2.5% in the low-risk group. Limitations include the use of archived trial cohorts.
CONCLUSIONS AND CLINICAL IMPLICATIONS: The post-RP MMAI model provides individualized risk estimates after SRT ± HT and may support shared decision-making about salvage treatment. External and prospective validation are ongoing.
METHODS: An MMAI model was trained to predict distant metastasis (DM) using prostate histopathology image features and clinical variables (pathologic grade group, pathologic T stage, prostate-specific antigen level before salvage radiotherapy [SRT], age, and surgical margin). The locked model was validated in 533 patients from NRG/RTOG 9601 and 0534 treated with SRT ± hormone therapy (HT), using Cox regression and time-dependent area under the receiver operating characteristic curve.
KEY FINDINGS AND LIMITATIONS: With a median follow-up of 9.3 yrs, MMAI score was significantly associated with DM (subdistribution hazard ratio = 2.17 per standard deviation [95% confidence interval 1.65-2.85]; p < 0.001) and remained independently prognostic after adjusting for clinical variables and treatment. The 10-yr time-dependent area under the receiver operating characteristic curve for MMAI was 0.74 compared with 0.68 for a clinical nomogram. Binary risk categorization demonstrated higher 10-yr DM incidence in the MMAI high-risk (25%) than in the low-risk (8.8%) group. The absolute reduction in 10-yr DM incidence with HT plus SRT versus SRT alone was 21% in the high-risk group versus 2.5% in the low-risk group. Limitations include the use of archived trial cohorts.
CONCLUSIONS AND CLINICAL IMPLICATIONS: The post-RP MMAI model provides individualized risk estimates after SRT ± HT and may support shared decision-making about salvage treatment. External and prospective validation are ongoing.