Vinnie Y T Liu

Demographic and clinical characteristics of the UPCA referral cohort.

Multimodal artificial intelligence (MMAI) biomarker score distribution by A) NCCN and B) CAPRA risk groups.

Univariable analyses of multimodal artificial intelligence (MMAI) score for biochemical recurrence (BCR) and adverse pathology (AP) at radical prostatectomy within NCCN Subgroup.

Comparison of multimodal artificial intelligence (MMAI) score to individual clinical variables, NCCN risk groups, and CAPRA score.

PURPOSE: Long-term androgen deprivation therapy (ADT) improves survival in men with high-risk localized prostate cancer (PCa) receiving radiotherapy (RT). Predictive biomarkers are needed to guide ADT duration. METHODS: A multimodal artificial intelligence (MMAI)–derived predictive biomarker was trained for long-term (LT) versus short-term (ST) ADT using pretreatment digital prostate biopsy images and clinical data (age, prostate-specific antigen, Gleason, and T stage) from six NRG Oncology phase III randomized radiotherapy trials. The novel MMAI-derived biomarker was developed to predict the differential benefit of LT-ADT on the primary end point, distant metastasis (DM). MMAI predictive utility was validated on a seventh randomized trial, RTOG 9202 (N = 1,192), which randomly assigned men to RT + ST-ADT (4 months) versus RT + LT-ADT (28 months). Fine-Gray and cumulative incidence analyses for DM, and secondarily, death with DM, were performed. Deaths without DM were treated as competing risks. RESULTS: In the validation cohort (median follow-up, 17.2 years), LT-ADT significantly improved DM from 26% to 17% (subdistribution hazard ratio [sHR], 0.64 [95% CI, 0.50 to 0.82], P < .001). A significant biomarker-treatment predictive interaction was observed ( P = .04) for DM, whereby MMAI biomarker–positive men (n = 785, 66%) had reduced DM with LT-ADT versus ST-ADT (sHR, 0.55 [95% CI, 0.41 to 0.73], P < .001), whereas no treatment benefit was observed for MMAI biomarker–negative men (n = 407; sHR, 1.06 [95% CI, 0.61 to 1.84], P = .84). The estimated 15-year DM risk difference between RT + LT-ADT and RT + ST-ADT was 14% in MMAI biomarker–positive men and 0% in MMAI biomarker–negative men. The MMAI biomarker was also prognostic for DM, irrespective of treatment (sHR, 2.35 [95% CI, 1.72 to 3.19], P < .001). CONCLUSION: To our knowledge, the MMAI model is the first validated predictive biomarker to guide ADT duration with RT in localized/locally advanced PCa. Approximately one third of men with high-risk PCa could safely be spared the additional 24 months of ADT and the associated morbidity.

Demographic and clinical characteristics of the UPCA referral cohort.

Univariable analyses of multimodal artificial intelligence (MMAI) score for biochemical recurrence (BCR) and adverse pathology (AP) at radical prostatectomy within NCCN Subgroup.

Purpose:A multimodal artificial intelligence (MMAI) biomarker was developed using clinical trial data from North American men with localized prostate cancer treated with definitive radiation, using biopsy digital pathology images and key clinical information (age, PSA, and T-stage) to generate prognostic scores. This study externally validates the biomarker in a prospective, real-world dataset of men who underwent radical prostatectomy (RP) for localized prostate cancer at a tertiary referral center in Sweden.Experimental Design:Association between the MMAI scores (continuous and categorical) and endpoints of interest was assessed with Fine–Gray and cumulative incidence analyses for biochemical recurrence (BCR) and logistic regression for adverse pathology (AP) at RP.Results:The analysis included 143 patients with evaluable biopsy pathology images and complete clinical data to generate MMAI scores. The median follow-up was 8.8 years. At diagnosis, the median PSA was 7.5 ng/mL, the median age was 64 years, 29% had a Gleason grade group ≥3, and 88 men were evaluable for AP at RP. MMAI was significantly associated with BCR [subdistribution HR, 2.45; 95% confidence interval (CI), 1.77–3.38; P < 0.001] and AP at RP (OR, 4.85; 95% CI, 2.54–10.78; P < 0.001). Estimated 5-year BCR rates for MMAI intermediate to high versus low were 25% (95% CI, 16%–36%) versus 4% (95% CI, 1%–11%), respectively.Conclusions:The MMAI biomarker, previously shown to be prognostic for distant metastasis and prostate cancer–specific mortality in men receiving definitive radiation, was prognostic for post-RP endpoints: BCR and AP. This biomarker validation study further supports the use of MMAI biomarkers in men with prostate cancer outside North America and those treated with RP.

Multimodal artificial intelligence (MMAI) biomarker score distribution by A) NCCN and B) CAPRA risk groups.