title: Nanocytological field carcinogenesis detection to mitigate overdiagnosis of prostate cancer: a proof of concept study.
abstract: OBJECTIVE
  To determine whether nano-architectural interrogation of prostate field carcinogenesis can be used to predict prognosis in patients with early stage (Gleason 6) prostate cancer (PCa), which is mostly indolent but frequently unnecessarily treated.
  
  
  METHODS
  We previously developed partial wave spectroscopic microscopy (PWS) that enables quantification of the nanoscale intracellular architecture (20-200 nm length scale) with remarkable accuracy. We adapted this technique to assess prostate needle core biopsies in a case control study from men with Gleason 6 disease who either progressed (n = 20) or remained indolent (n = 18) over a ~3 year follow up. We measured the parameter disorder strength (Ld) characterizing the spatial heterogeneity of the nanoscale cellular structure and nuclear morphology from the microscopically normal mucosa ~150 histologically normal epithelial cells.
  
  
  RESULTS
  There was a profound increase in nano-architectural disorder between progressors and non-progressors. Indeed, the Ld from future progressors was dramatically increased when compared to future non-progressors (1±0.065 versus 1.30±0.0614, respectively p = 0.002). The area under the receiver operator characteristic curve (AUC) was 0.79, yielding a sensitivity of 88% and specificity of 72% for discriminating between progressors and non-progressors. This was not confounded by demographic factors (age, smoking status, race, obesity), thus supporting the robustness of the approach.
  
  
  CONCLUSIONS
  We demonstrate, for the first time, that nano-architectural alterations occur in prostate cancer field carcinogenesis and can be exploited to predict prognosis of early stage PCa. This approach has promise in addressing the clinically vexing dilemma of management of Gleason 6 PCa and may provide a paradigm for dealing with the larger issue of cancer overdiagnosis.
authors.affiliation: Department of Medicine, Boston University Medical Center, Boston, Massachusetts, United States of America.
authors.forename: Hemant K
authors.initials: HK
authors.lastname: Roy
authors.affiliation: Department of Surgery, NorthShore University HealthSystem, Evanston, Illinois, United States of America.
authors.forename: Charles B
authors.initials: CB
authors.lastname: Brendler
authors.affiliation: Biomedical Engineering Department, Northwestern University, Evanston, Illinois, United States of America.
authors.forename: Hariharan
authors.initials: H
authors.lastname: Subramanian
authors.affiliation: Biomedical Engineering Department, Northwestern University, Evanston, Illinois, United States of America.
authors.forename: Di
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Biomedical Engineering Department, Northwestern University, Evanston, Illinois, United States of America.
authors.forename: Charles
authors.initials: C
authors.lastname: Maneval
authors.affiliation: Biomedical Engineering Department, Northwestern University, Evanston, Illinois, United States of America.
authors.forename: John
authors.initials: J
authors.lastname: Chandler
authors.affiliation: Biomedical Engineering Department, Northwestern University, Evanston, Illinois, United States of America.
authors.forename: Leah
authors.initials: L
authors.lastname: Bowen
authors.affiliation: Department of Pathology, NorthShore University HealthSystem, Evanston, Illinois, United States of America.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Kaul
authors.affiliation: Department of Surgery, NorthShore University HealthSystem, Evanston, Illinois, United States of America.
authors.forename: Brian T
authors.initials: BT
authors.lastname: Helfand
authors.affiliation: Department of Surgery, NorthShore University HealthSystem, Evanston, Illinois, United States of America.
authors.forename: Chi-Hsiung
authors.initials: CH
authors.lastname: Wang
authors.affiliation: Department of Surgery, NorthShore University HealthSystem, Evanston, Illinois, United States of America.
authors.forename: Margo
authors.initials: M
authors.lastname: Quinn
authors.affiliation: Department of Surgery, NorthShore University HealthSystem, Evanston, Illinois, United States of America.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Petkewicz
authors.affiliation: Department of Pathology, NorthShore University HealthSystem, Evanston, Illinois, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Paterakos
authors.affiliation: Biomedical Engineering Department, Northwestern University, Evanston, Illinois, United States of America.
authors.forename: Vadim
authors.initials: V
authors.lastname: Backman
mesh_terms: D000368:Aged; D063646:Carcinogenesis / Q000473:pathology*; D016022:Case-Control Studies; D055088:Early Detection of Cancer; D006801:Humans; D008297:Male; D000069342:Medical Overuse; D008875:Middle Aged; D060787:Neoplasm Grading; D011379:Prognosis; D011467:Prostate / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000473:pathology