1767MO - External validation of a digital pathology-based multimodal artificial intelligence (MMAI)-derived model in high-risk localized (M0)/metastatic (M1) prostate cancer (PCa) starting androgen deprivation therapy (ADT) in the docetaxel (Doc) or abiraterone (AAP) phase III STAMPEDE trials

Background

Effective prognostication will allow better targeting of treatment (Rx) combinations for advanced PCa. A MMAI prognostic test (ArteraAI Prostate) was recently developed in localized PCa. We aimed to validate ArteraAI in advanced PCausing final data from 3 STAMPEDE trials (NCT00268476).

Methods

The MMAI model used digitized whole scan images from new H&E core prostate biopsies (PB), local Gleason score (GS), tumor stage (T), age and pre-ADT serum PSA. Fine-Gray/Cox regression adjusted for Rx allocation and cumulative incidence analyses were performed to evaluate associations with endpoints, as defined in STAMPEDE, for both continuous score (per standard deviation increase) and categorical (quartile,Q). PCa-specific mortality (PCSM) was the endpoint of primary interest. Death not from PCa was treated as a competing risk. HR, 95% CI, and p<0.001 (denoted by *) are reported.

Results

Of 3879 patients recruited Oct 2005 – Jan 2014 to ADT +/- radiotherapy (RT) alone or + Doc +/-zoledronic acid or + AAP, 3725 consented to tissue analysis, 2079 had H&E with sufficient tumor of which 1964 had all of GS, T, pre-ADT PSA (918 M0, 1046 M1, median follow-up: 7.8 years, yr). ArteraAI was strongly associated with PCSM (HR 1.67, 1.5-1.84*), overall survival (1.51,1.4-1.63*), failure-free survival (1.48, 1.38-1.59*), and metastatic progression-free survival (1.59, 1.46-1.73*). ArteraAI Q4 v Q1-3 showed similar results for all endpoints, including PCSM (2.27, 1.95-2.65*). Of component clinical variables, p* for PCSM were PSA Q4 v Q1-3 (1.8, 1.54-2.11), Gleason 8-10 v <=7 (1.64, 1.36-1.98), and T4 v T1-2 (1.77, 1.36-2.32). ArteraAI Q4 v Q1-3 had more PCSM events at 5 yr: 16% (11-21) v 6% (4-8) in M0, 58% (52-64) v 40% (36-43) in M1 and notably for M0 treated with ADT +/- RT+ AAP: 18% (9-28) v 2% (0-4%).

Conclusions

ArteraAI successfully validated in STAMPEDE with stronger prognostic associations than individual clinical variables. The MMAI model identified poor prognostic features in PB from high-risk M0 and M1 PCa.

Clinical trial identification

NCT00268476.

Editorial acknowledgement

Legal entity responsible for the study

University College London (UCL) - Professor Gerhardt Attard.

Funding

Prostate Cancer UK, Cancer Research UK, Medical Research Council, The Jean Shanks Foundation, The Pathological Society of Great Britain & Ireland, Janssen, Sanofi.

Disclosure

C.T.A. Parker: Financial Interests, Institutional, Licensing Fees, My employer (UCL) may gain commercially from licensing data to Artera: Artera AI. V. Liu: Financial Interests, Personal, Full or part-time Employment, I am currently employed by ArteraAI: ArteraAI; Financial Interests, Personal, Stocks/Shares, I have stocks/shares as part of my compensation, but none have vested/I have not exercised my rights as of today's date (May 5/2023): ArteraAI; Other, Other, I was previously employed (in the last 2 years) by Decipher Biosciences/Veracyte Inc: Decipher Biosciences. D. Van der Wal: Financial Interests, Personal, Full or part-time Employment: Artera AI. J.R. Griffin: Financial Interests, Institutional, Full or part-time Employment: ArteraAI; Financial Interests, Institutional, Stocks/Shares: ArteraAI; Non-Financial Interests, Leadership Role: ArteraAI; Non-Financial Interests, Institutional, Proprietary Information: ArteraAI. E. Chen: Financial Interests, Institutional, Full or part-time Employment: Artera; Financial Interests, Institutional, Stocks/Shares: Artera. P.T. Tran: Financial Interests, Personal, Advisory Board: Janssen, Myovant, AstraZeneca, Natsar Pharmaceuticals, RefleXion Medical, Bayer, Regeneron, Lantheus; Financial Interests, Personal, Royalties: Natsar Pharmaceuticals; Financial Interests, Institutional, Funding: Bayer, Janssen, Medivation Inc-Astellas Pharma Inc; Non-Financial Interests, Leadership Role: NRG Oncology, ASTRO, Movember; Non-Financial Interests, Institutional, Proprietary Information: Veracyte, Artera. M.K. Parmar: Financial Interests, Institutional, Full or part-time Employment, Director at MRC Clinical Trials Unit at UCL: Medical Research Council Clinical Trials Unit at UCL; Financial Interests, Institutional, Research Grant: AstraZeneca, Astellas, Janssen, Clovis; Non-Financial Interests, Advisory Role, Euro Ewing Consortium: University College London; Non-Financial Interests, Advisory Role, rEECur: University of Birmingham; Non-Financial Interests, Advisory Role, CompARE Trial: University of Birmingham. M.R. Sydes: Financial Interests, Personal, Invited Speaker, Speaker fees at clinical trial statistics training sessions for clinicians (no discussion of particular drugs): Janssen; Financial Interests, Personal, Invited Speaker, Speaker fees at clinical trial statistics training session for clinicians (no discussion of particular drugs): Eli Lilly; Financial Interests, Personal, Other, Educational lecture not associated with any products: Eisai; Financial Interests, Institutional, Research Grant, Educational grant and drug for STAMPEDE trial: Astellas, Janssen, Novartis, Pfizer, Sanofi; Financial Interests, Institutional, Research Grant, Educational grant and biomarker costs for STAMPEDE trial: Clovis Oncology. L.C. Brown: Financial Interests, Institutional, Research Grant, £170k educational grant for the FOCUS4-C Trial from June 2017 to Dec 2021: AstraZeneca; Financial Interests, Institutional, Funding, Various grants awarded to my institution for work undertaken as part of the STAMPEDE Trial: Janssen pharmaceuticals; Financial Interests, Institutional, Funding, Grant funding to my institution for the STAMPEDE2 trial: Novartis AAA; Non-Financial Interests, Other, I am a member of the CRUK CERP funding advisory panel and my Institution also receive grant funding from CRUK for the STAMPEDE and FOCUS4 trials: Cancer Research UK. A. Esteva: Financial Interests, Personal, Officer, CEO: Artera AI. F. Feng: Financial Interests, Personal, Advisory Role: Artera AI. N.D. James: Financial Interests, Personal, Advisory Board, Advice around PARP inhibitors: AstraZeneca; Financial Interests, Personal, Advisory Board, Prostate cancer therapies: Janssen, Clovis, Novartis; Financial Interests, Institutional, Advisory Board, Assisted with submissions regarding licensing for abiraterone: Janssen; Financial Interests, Personal, Advisory Board, Docetaxel: Sanofi; Financial Interests, Institutional, Advisory Board, Providing STAMPEDE trial data to facilitate license extensions internationally for docetaxel: Sanofi; Financial Interests, Personal, Advisory Board, Bladder cancer therapy: Merck; Financial Interests, Personal, Advisory Board, Advice around novel hormone therapies for prostate cancer: Bayer; Financial Interests, Personal, Invited Speaker, Lecture tour in Brazil August 2022 - speaking on therapy for advanced prostate cancer: Merck Sharp & Dohme (UK) Limited; Financial Interests, Institutional, Coordinating PI, Funding for STAMPEDE trial: Janssen, Astellas; Financial Interests, Institutional, Coordinating PI, Funding for RADIO trial bladder cancer: AstraZeneca. G. Attard: Financial Interests, Personal, Invited Speaker: Janssen, Astellas, AstraZeneca; Financial Interests, Personal, Advisory Board: Janssen, Astellas, Novartis, Bayer, AstraZeneca, Pfizer, Sanofi, Sapience, Orion, Novartis; Financial Interests, Personal, Royalties, Included in list of rewards to discoverers of abiraterone: Institute of Cancer Research; Financial Interests, Institutional, Advisory Board: Artera, Veracyte; Financial Interests, Institutional, Research Grant: Janssen, Astellas, Novartis; Financial Interests, Institutional, Coordinating PI: Janssen; Financial Interests, Institutional, Local PI: Novartis, Pfizer; Non-Financial Interests, Principal Investigator: Janssen, Astellas; Non-Financial Interests, Advisory Role: Janssen, AstraZeneca; Non-Financial Interests, Project Lead: Artera, Veracyte. All other authors have declared no conflicts of interest.