Tumor evolution metrics predict recurrence beyond 10 years in locally advanced prostate cancer.
Javier Fernández-MateosGeorge D CresswellNicholas TrahearnKatharine WebbChirine SakrAndrea LampisChristine StuttleCatherine M CorbishleyVasilis StavrinidesLuis ZapataInmaculada SpiteriTimon HeideLewis GallagherChela JamesDaniele RamazzottiAnnie GaoZSofia Kote-JaraiAhmet AcarLesley TruelovePaula Z ProszekJulia MurrayAlison ReidAnna WilkinsMichael HubankRosalind A EelesDavid P DearnaleyAndrea SottorivaPublished in: Nature cancer (2024)
Cancer evolution lays the groundwork for predictive oncology. Testing evolutionary metrics requires quantitative measurements in controlled clinical trials. We mapped genomic intratumor heterogeneity in locally advanced prostate cancer using 642 samples from 114 individuals enrolled in clinical trials with a 12-year median follow-up. We concomitantly assessed morphological heterogeneity using deep learning in 1,923 histological sections from 250 individuals. Genetic and morphological (Gleason) diversity were independent predictors of recurrence (hazard ratio (HR) = 3.12 and 95% confidence interval (95% CI) = 1.34-7.3; HR = 2.24 and 95% CI = 1.28-3.92). Combined, they identified a group with half the median time to recurrence. Spatial segregation of clones was also an independent marker of recurrence (HR = 2.3 and 95% CI = 1.11-4.8). We identified copy number changes associated with Gleason grade and found that chromosome 6p loss correlated with reduced immune infiltration. Matched profiling of relapse, decades after diagnosis, confirmed that genomic instability is a driving force in prostate cancer progression. This study shows that combining genomics with artificial intelligence-aided histopathology leads to the identification of clinical biomarkers of evolution.
Keyphrases
- prostate cancer
- copy number
- artificial intelligence
- radical prostatectomy
- mitochondrial dna
- locally advanced
- deep learning
- free survival
- clinical trial
- genome wide
- single cell
- machine learning
- squamous cell carcinoma
- rectal cancer
- neoadjuvant chemotherapy
- dna methylation
- big data
- palliative care
- phase ii study
- high resolution
- radiation therapy
- papillary thyroid
- convolutional neural network
- randomized controlled trial
- young adults
- study protocol
- mass spectrometry