title: The concordance between the volume hotspot and the grade hotspot: a 3-D reconstructive model using the pathology outputs from the PROMIS trial.
abstract: The rationale for directing targeted biopsy towards the centre of lesions has been questioned in light of prostate cancer grade heterogeneity. In this study, we assess the assumption that the maximum cancer Gleason grade (Gleason grade hotspot) lies within the maximum dimension (volume hotspot) of a prostate cancer lesion.
  
  
  
  3-D histopathological models were reconstructed using the outputs of the 5-mm transperineal mapping (TPM) biopsies used as the reference test in the pilot phase of Prostate Mri Imaging Study (PROMIS), a paired validating cohort study investigating the performance of multi-parametric magnetic resonance imaging (MRI) against transrectal ultrasound (TRUS) biopsies. The prostate was fully sampled with 5 mm intervals; each core was separately labelled, inked and orientated in space to register 3-D cancer lesions location. The data from the histopathology results were used to create a 3-D interpolated reconstruction of each lesion and identify the spatial coordinates of the largest dimension (volume hot spot) and highest Gleason grade (Gleason grade hotspot) and assess their concordance.
  
  
  
  Ninety-four men, with median age 62 years (interquartile range, IQR= 58-68) and median PSA 6.5 ng ml(-1) (4.6-8.8), had a median of 80 (I69-89) cores each with a median of 4.5 positive cores (0-12). In the primary analysis, the prevalence of homogeneous lesions was 148 (76%; 95% confidence interval (CI) ±6.0%). In all, 184 (94±3.2%) lesions showed concordant hotspots and 11/47 (23±12.1%) of heterogeneous lesions showed discordant hotspots. The median 3-D distance between discordant hotspots was 12.8 mm (9.9-15.5). These figures remained stable on secondary analyses using alternative reconstructive assumptions. Limitations include a certain degree of error within reconstructed models.
  
  
  
  Guiding one biopsy needle to the maximum cancer diameter would lead to correct Gleason grade attribution in 94% of all lesions and 79% of heterogeneous ones if a true hit was obtained. Further correlation of histological lesions, their MRI appearance and the detectability of these hotspots on MRI will be undertaken once PROMIS results are released.
authors.affiliation: Division of Surgery and Interventional Science, University College London, London, UK.|Department of Urology, University College London Hospitals NHS Foundation Trust, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: El-Shater Bosaily
authors.affiliation: Division of Surgery and Interventional Science, University College London, London, UK.|Department of Urology, University College London Hospitals NHS Foundation Trust, London, UK.|Department of Urology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Valerio
authors.affiliation: Centre for Medical Image Computing, University College London, London, UK.
authors.forename: Y
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Histopathology, College London Hospitals NHS Foundation Trust, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Freeman
authors.affiliation: Department of Histopathology, College London Hospitals NHS Foundation Trust, London, UK.
authors.forename: C
authors.initials: C
authors.lastname: Jameson
authors.affiliation: Medical Research Council Clinical Trials Unit, University College London, London, UK.
authors.forename: L
authors.initials: L
authors.lastname: Brown
authors.affiliation: Medical Research Council Clinical Trials Unit, University College London, London, UK.
authors.forename: R
authors.initials: R
authors.lastname: Kaplan
authors.affiliation: Department of Urology, Basingstoke Hospital, Hampshire Hospitals NHS Foundation Trust, Hampshire, UK.
authors.forename: R G
authors.initials: RG
authors.lastname: Hindley
authors.affiliation: Centre for Medical Image Computing, University College London, London, UK.
authors.forename: D
authors.initials: D
authors.lastname: Barratt
authors.affiliation: Division of Surgery and Interventional Science, University College London, London, UK.|Department of Urology, University College London Hospitals NHS Foundation Trust, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Emberton
authors.affiliation: Division of Surgery and Interventional Science, University College London, London, UK.|Department of Urology, University College London Hospitals NHS Foundation Trust, London, UK.
authors.forename: H U
authors.initials: HU
authors.lastname: Ahmed
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D006801:Humans; D061705:Image-Guided Biopsy; D021621:Imaging, Three-Dimensional; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology*; D047368:Tumor Burden
chemical_list: D014408:Biomarkers, Tumor