Association of a post-prostatectomy digital pathology–based multimodal artificial intelligence (MMAI) biomarker with nodal and extrapelvic metastasis on PET/CT at the time of biochemical recurrence and event-free survival following salvage radiotherapy.

378 Background: Clinical prostate cancer variables have limited ability to predict patterns of recurrence or outcomes after radical prostatectomy (RP). In this analysis, we evaluated the performance of a digital pathology multimodal artificial intelligence (MMAI) algorithm in predicting patterns of recurrence at the time of post-RP biochemical recurrence (BCR) and oncologic outcomes following PET-guided salvage radiotherapy (RT). Methods: The EMPIRE-1 (NCT01666808) and -2 (NCT03762759) randomized trials evaluated the association of PET-guided salvage RT on event-free survival (EFS) in men experiencing BCR following RP. A subset of patients with available digitized histopathologic images from the prostatectomy specimen was identified. A locked MMAI model (post-RP MMAI v1.1), which uses digital histopathology images and routine clinical data, was applied to generate MMAI scores (continuous and categorized high- vs. low-risk). The primary aim was to evaluate the association of MMAI score with 18 F-fluciclovine or 68 Ga-PSMA-11 PET uptake (defined as prostate bed PB, pelvic lymph node PLN, or extrapelvic EP uptake) at the time of BCR. The secondary aim was to examine the association of MMAI score with EFS (defined as freedom from biochemical/clinical/radiographic recurrence or initiation of systemic therapy) following salvage RT in a contemporary cohort managed with PET/CT and early salvage therapy. Results: Of the 223 patients enrolled on EMPIRE-1 or 2 who underwent PET scan, 92 had digital prostatectomy histopathology images available for MMAI analysis. Median (IQR) PSA at the time of PET/CT was 0.3 (0.2-0.7) ng/mL. MMAI score (continuous or categorized) was not associated with PB uptake on PET. MMAI score was significantly associated with PLN uptake on PET (continuous score per 1 SD increase: OR 2.68, 95% CI 1.57-4.98, P<.001; high vs. low group: OR 4.05, 95% CI 1.37-15.03, P=0.02). MMAI score was significantly associated with EP uptake on PET (continuous score: OR 4.63, 95% CI 1.92-14.47, P=0.003), with EP PET positivity only observed in MMAI high patients. These associations remained significant after pN-stage adjustment. After a median follow-up of 2.0 years, n=15 patients experienced an EFS event following post-RP salvage RT. Among these patients, 12 (80%) had an MMAI-high score. Post-RP MMAI score was significantly associated with EFS (HR 1.80 per SD increase, 95% CI 1.02-3.19, P=0.04). Conclusions: MMAI score from a post-RP model is associated with pelvic lymph node and extrapelvic PET uptake at the time of BCR, even with a low PSA at the time of PET/CT. This MMAI model was also prognostic for EFS following PET-guided early salvage RT.