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Utility of Gleason pattern 4 morphologies detected on transrectal ultrasound (TRUS)-guided biopsies for prediction of upgrading or upstaging in Gleason score 3 + 4 = 7 prostate cancer

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Abstract

Selected patients with Gleason score (GS) 3 + 4 = 7 prostate cancer (PCa) detected on transrectal ultrasound (TRUS)-guided biopsies may be considered for active surveillance (AS); however, a proportion of these will harbor more aggressive disease. The purpose of this study was to determine if morphologies of Gleason pattern 4 PCa may predict upgrading and/or upstaging after radical prostatectomy (RP). A database search for men with GS 3 + 4 = 7 PCa diagnosed on TRUS-guided biopsy that underwent RP between January 2010 and October 2015 identified 152 patients. Two blinded genitourinary pathologists independently reviewed the biopsies and assessed ill-defined glands (IDG), fused glands, small or large cribriform patterns, and glomerulations. Patient age, serum prostate-specific antigen (PSA), percentage (%) of biopsy sites involved by 3 + 4 = 7 PCa, and overall extent of pattern 4 were also recorded. GS and stage (presence or absence of extraprostatic extension [EPE]) were retrieved from RP reports. Data were compared using independent t tests and chi-square. Inter-observer agreement was calculated using Cohen’s Kappa statistic. Percent of biopsy sites and extent of pattern 4 were compared to statistically significant morphologies using the Spearman correlation. 28.3 % (43/152) of patients were upgraded to GS >3 + 4 = 7 at RP (GS 4 + 3 = 7 [N = 17], GS 4 + 3 = 7 with tertiary pattern 5 [N = 25], and GS 4 + 5 = 9 [N = 1]) and 44.1 % (67/152) showed EPE after RP. PSA was associated with both upgrading (8.5 ± 5.4 vs. 6.9 ± 3.2 ng/mL, [p = 0.04]) and EPE (8.2 ± 4.6 vs. 6.7 ± 3.2 ng/mL, [p = 0.03]). IDG, fused glands, and glomerulations were not associated with upgrading or EPE (p > 0.05) with moderate to strong inter-observer agreement (K = 0.76–0.88). There was strong inter-observer agreement for small and large cribriform formations (K = 0.93 and 0.94, respectively) and both patterns were strongly associated with upgrading (p < 0.001) and EPE (p = 0.02) on RP. Strong associations were observed between increasing number of morphologies and both upgrading (p = 0.0.25) and EPE (p < 0.001). Overall extent of pattern 4 was associated with upgrading (p = 0.009) and EPE (p = 0.019) while percent of sites involved by GS 3 + 4 = 7 was only associated with EPE (p = 0.023). Cribriform morphology correlated to percentage of sites with 3 + 4 and overall extent of pattern 4 (rho = 0.25, p = 0.002, rho = 0.20, p = 0.015, respectively). Presence of cribriform morphology on TRUS-guided biopsy is strongly associated with upgrading and upstaging at RP and shows near-perfect inter-observer agreement whereas IDG, fused glands, and glomerulations were not useful. Cribriform morphology may be of importance when considering treatment plans for patients with intermediate risk PCa.

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Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, Faculty of Medicine, The Ottawa Hospital, The University of Ottawa, 501 Smyth Road, 4th Floor CCW, Ottawa, Ontario, K1H 8L6, Canada

    Trevor A. Flood, Nicola Schieda, Daniel T. Keefe, Rodney H. Breau, Chris Morash, Kevin Hogan, Eric C. Belanger, Kien T. Mai & Susan J. Robertson

  2. Department of Medical Imaging, The Ottawa Hospital, Ottawa, Canada

    Nicola Schieda

  3. Department of Urology, The Ottawa Hospital, Ottawa, Canada

    Daniel T. Keefe, Rodney H. Breau & Chris Morash

Authors
  1. Trevor A. Flood
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  2. Nicola Schieda
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  3. Daniel T. Keefe
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  4. Rodney H. Breau
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  5. Chris Morash
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  6. Kevin Hogan
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  7. Eric C. Belanger
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  8. Kien T. Mai
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  9. Susan J. Robertson
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Correspondence to Trevor A. Flood.

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We confirm that this study is an original unpublished work and is not being submitted for publication elsewhere. All authors have agreed to this submission in its present form and there are no financial or non-financial conflicts of interest. This is a retrospective study that did not involve patient contact and all methodology was approved by our institution’s Research Ethics Board.

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Flood, T.A., Schieda, N., Keefe, D.T. et al. Utility of Gleason pattern 4 morphologies detected on transrectal ultrasound (TRUS)-guided biopsies for prediction of upgrading or upstaging in Gleason score 3 + 4 = 7 prostate cancer. Virchows Arch 469, 313–319 (2016). https://doi.org/10.1007/s00428-016-1981-2

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  • DOI: https://doi.org/10.1007/s00428-016-1981-2

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