title: Improved prediction of prostate cancer recurrence through systems pathology.
abstract: We have developed an integrated, multidisciplinary methodology, termed systems pathology, to generate highly accurate predictive tools for complex diseases, using prostate cancer for the prototype. To predict the recurrence of prostate cancer following radical prostatectomy, defined by rising serum prostate-specific antigen (PSA), we used machine learning to develop a model based on clinicopathologic variables, histologic tumor characteristics, and cell type-specific quantification of biomarkers. The initial study was based on a cohort of 323 patients and identified that high levels of the androgen receptor, as detected by immunohistochemistry, were associated with a reduced time to PSA recurrence. The model predicted recurrence with high accuracy, as indicated by a concordance index in the validation set of 0.82, sensitivity of 96%, and specificity of 72%. We extended this approach, employing quantitative multiplex immunofluorescence, on an expanded cohort of 682 patients. The model again predicted PSA recurrence with high accuracy, concordance index being 0.77, sensitivity of 77% and specificity of 72%. The androgen receptor was selected, along with 5 clinicopathologic features (seminal vesicle invasion, biopsy Gleason score, extracapsular extension, preoperative PSA, and dominant prostatectomy Gleason grade) as well as 2 histologic features (texture of epithelial nuclei and cytoplasm in tumor only regions). This robust platform has broad applications in patient diagnosis, treatment management, and prognostication.
authors.affiliation: Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: Carlos
authors.initials: C
authors.lastname: Cordon-Cardo
authors.forename: Angeliki
authors.initials: A
authors.lastname: Kotsianti
authors.forename: David A
authors.initials: DA
authors.lastname: Verbel
authors.forename: Mikhail
authors.initials: M
authors.lastname: Teverovskiy
authors.forename: Paola
authors.initials: P
authors.lastname: Capodieci
authors.forename: Stefan
authors.initials: S
authors.lastname: Hamann
authors.forename: Yusuf
authors.initials: Y
authors.lastname: Jeffers
authors.forename: Mark
authors.initials: M
authors.lastname: Clayton
authors.forename: Faysal
authors.initials: F
authors.lastname: Elkhettabi
authors.forename: Faisal M
authors.initials: FM
authors.lastname: Khan
authors.forename: Marina
authors.initials: M
authors.lastname: Sapir
authors.forename: Valentina
authors.initials: V
authors.lastname: Bayer-Zubek
authors.forename: Yevgen
authors.initials: Y
authors.lastname: Vengrenyuk
authors.forename: Stephen
authors.initials: S
authors.lastname: Fogarsi
authors.forename: Olivier
authors.initials: O
authors.lastname: Saidi
authors.forename: Victor E
authors.initials: VE
authors.lastname: Reuter
authors.forename: Howard I
authors.initials: HI
authors.lastname: Scher
authors.forename: Michael W
authors.initials: MW
authors.lastname: Kattan
authors.forename: Fernando J
authors.initials: FJ
authors.lastname: Bianco
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Wheeler
authors.forename: Gustavo E
authors.initials: GE
authors.lastname: Ayala
authors.forename: Peter T
authors.initials: PT
authors.lastname: Scardino
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Donovan
mesh_terms: D002467:Cell Nucleus / Q000378:metabolism; D018572:Disease-Free Survival; D006801:Humans; D008297:Male; D008954:Models, Biological; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology*; D010336:Pathology / Q000379:methods*; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D011944:Receptors, Androgen / Q000378:metabolism; D012680:Sensitivity and Specificity; D015996:Survival Rate; D049490:Systems Biology / Q000379:methods*; D046888:Tissue Array Analysis
chemical_list: D011944:Receptors, Androgen; D017430:Prostate-Specific Antigen