title: Toward Prostate Cancer Contouring Guidelines on Magnetic Resonance Imaging: Dominant Lesion Gross and Clinical Target Volume Coverage Via Accurate Histology Fusion.
abstract: Defining prostate cancer (PCa) lesion clinical target volumes (CTVs) for multiparametric magnetic resonance imaging (mpMRI) could support focal boosting or treatment to improve outcomes or lower morbidity, necessitating appropriate CTV margins for mpMRI-defined gross tumor volumes (GTVs). This study aimed to identify CTV margins yielding 95% coverage of PCa tumors for prospective cases with high likelihood.
  
  
  
  Twenty-five men with biopsy-confirmed clinical stage T1 or T2 PCa underwent pre-prostatectomy mpMRI, yielding T2-weighted, dynamic contrast-enhanced, and apparent diffusion coefficient images. Digitized whole-mount histology was contoured and registered to mpMRI scans (error ≤2 mm). Four observers contoured lesion GTVs on each mpMRI scan. CTVs were defined by isotropic and anisotropic expansion from these GTVs and from multiparametric (unioned) GTVs from 2 to 3 scans. Histologic coverage (proportions of tumor area on co-registered histology inside the CTV, measured for Gleason scores [GSs] ≥6 and ≥7) and prostate sparing (proportions of prostate volume outside the CTV) were measured. Nonparametric histologic-coverage prediction intervals defined minimal margins yielding 95% coverage for prospective cases with 78% to 92% likelihood.
  
  
  
  On analysis of 72 true-positive tumor detections, 95% coverage margins were 9 to 11 mm (GS ≥ 6) and 8 to 10 mm (GS ≥ 7) for single-sequence GTVs and were 8 mm (GS ≥ 6) and 6 mm (GS ≥ 7) for 3-sequence GTVs, yielding CTVs that spared 47% to 81% of prostate tissue for the majority of tumors. Inclusion of T2-weighted contours increased sparing for multiparametric CTVs with 95% coverage margins for GS ≥6, and inclusion of dynamic contrast-enhanced contours increased sparing for GS ≥7. Anisotropic 95% coverage margins increased the sparing proportions to 71% to 86%.
  
  
  
  Multiparametric magnetic resonance imaging-defined GTVs expanded by appropriate margins may support focal boosting or treatment of PCa; however, these margins, accounting for interobserver and intertumoral variability, may preclude highly conformal CTVs. Multiparametric GTVs and anisotropic margins may reduce the required margins and improve prostate sparing.
authors.affiliation: Robarts Research Institute, University of Western Ontario, London, Ontario, Canada; Biomedical Engineering, University of Western Ontario, London, Ontario, Canada; Centre for Medical Image Computing, University College London, London, UK; Department of Radiology, Radboud University Medical Centre, Nijmegen, Netherlands.
authors.forename: Eli
authors.initials: E
authors.lastname: Gibson
authors.affiliation: Lawson Health Research Institute, London, Ontario, Canada; Department of Oncology, University of Western Ontario, London, Ontario, Canada. Electronic address: glenn.bauman@lhsc.on.ca.
authors.forename: Glenn S
authors.initials: GS
authors.lastname: Bauman
authors.affiliation: Department of Medical Imaging, University of Western Ontario, London, Ontario, Canada.
authors.forename: Cesare
authors.initials: C
authors.lastname: Romagnoli
authors.affiliation: Department of Medical Imaging, University of Western Ontario, London, Ontario, Canada.
authors.forename: Derek W
authors.initials: DW
authors.lastname: Cool
authors.affiliation: Department of Medical Imaging, University of Western Ontario, London, Ontario, Canada; Queensland Health, Brisbane, Queensland, Australia.
authors.forename: Matthew
authors.initials: M
authors.lastname: Bastian-Jordan
authors.affiliation: Department of Medical Imaging, University of Western Ontario, London, Ontario, Canada.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Kassam
authors.affiliation: Robarts Research Institute, University of Western Ontario, London, Ontario, Canada; Department of Pathology, University of Western Ontario, London, Ontario, Canada.
authors.forename: Mena
authors.initials: M
authors.lastname: Gaed
authors.affiliation: Department of Pathology, University of Western Ontario, London, Ontario, Canada.
authors.forename: Madeleine
authors.initials: M
authors.lastname: Moussa
authors.affiliation: Department of Pathology, University of Western Ontario, London, Ontario, Canada.
authors.forename: José A
authors.initials: JA
authors.lastname: Gómez
authors.affiliation: Lawson Health Research Institute, London, Ontario, Canada; Department of Urology, University of Western Ontario, London, Ontario, Canada.
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Pautler
authors.affiliation: Lawson Health Research Institute, London, Ontario, Canada; Department of Urology, University of Western Ontario, London, Ontario, Canada.
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Chin
authors.affiliation: Robarts Research Institute, University of Western Ontario, London, Ontario, Canada; Lawson Health Research Institute, London, Ontario, Canada.
authors.forename: Cathie
authors.initials: C
authors.lastname: Crukley
authors.affiliation: Department of Medical Imaging, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
authors.forename: Masoom A
authors.initials: MA
authors.lastname: Haider
authors.affiliation: Robarts Research Institute, University of Western Ontario, London, Ontario, Canada; Biomedical Engineering, University of Western Ontario, London, Ontario, Canada; Lawson Health Research Institute, London, Ontario, Canada; Department of Oncology, University of Western Ontario, London, Ontario, Canada; Department of Medical Biophysics, University of Western Ontario, London, Ontario, Canada.
authors.forename: Aaron
authors.initials: A
authors.lastname: Fenster
authors.affiliation: Biomedical Engineering, University of Western Ontario, London, Ontario, Canada; Lawson Health Research Institute, London, Ontario, Canada; Department of Oncology, University of Western Ontario, London, Ontario, Canada; Department of Medical Biophysics, University of Western Ontario, London, Ontario, Canada; Baines Imaging Research Laboratory, London Regional Cancer Centre, London, Ontario, Canada.
authors.forename: Aaron D
authors.initials: AD
authors.lastname: Ward
mesh_terms: D000368:Aged; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000592:standards*; D008297:Male; D000072662:Margins of Excision; D008875:Middle Aged; D064847:Multimodal Imaging / Q000379:methods; D017410:Practice Guidelines as Topic; D011468:Prostatectomy / Q000379:methods; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging* / Q000601:surgery*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D025321:Surgery, Computer-Assisted / Q000592:standards*; D016896:Treatment Outcome; D047368:Tumor Burden