Gleason grading after neoadjuvant hormonal therapy retains prognostic value for systemic progression following radical prostatectomy

S. B. Stewart, J. C. Cheville, T. J. Sebo, I. Frank, S. A. Boorjian, R. H. Thompson, M. T. Gettman, M. K. Tollefson, E. C. Umbriet, S. P. Psutka, E. J. Bergstralh, L. Rangel, Robert Jeffrey Karnes

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Abstract

Background:The Gleason grading system in prostatectomy specimens following receipt of neoadjuvant therapy has been considered inaccurate. However, with continuing expansion of novel therapeutics, it is important to understand whether the Gleason system can be effectively utilized in this setting. The aim of this study was to assess the ability of the Gleason grading system to predict systemic progression among prostatectomy specimens treated with neoadjuvant hormone therapy (NHT).Methods:This was a single-institution retrospective analysis from 1987 to 2009 of 13 427 patients who underwent radical prostatectomy (RP) without NHT and 1148 patients with NHT. NHT consisted of leuprolide alone (n=415), antiandrogen therapy alone (n=400) and combined treatment (n=333). Kaplan-Meier analysis estimated 15-year systemic progression-free survival among NHT and non-NHT patients. Cox proportional hazard regression models estimated risk of systemic progression following RP according to NHT use and nonuse.Results:Median duration of NHT was 3 months (interquartile range (IQR) 2-4) whereas median follow-up after RP was 8.3 years (IQR 5-10.8). NHT patients were more likely to be D'Amico high risk, have locally advanced pathologic T stage (≥pT3), pathologic Gleason scores (GS) of 8-10 and lymph node involvement (P<0.0001 for all). NHT use was associated with lower rates of positive surgical margins, more downgrading to pT0 and less GS upgrading from biopsy (P≤0.001 for all). GS could not be assigned to only 3% of NHT patients. On multivariate analysis, pathologic GS remained a predictor of systemic progression (SP) following NHT (hazard ratio (HR) 1.6, P=0.005), but the association was less strong compared with non-NHT patients (HR 2.9, P<0.0001).Conclusions:Utilization of the Gleason system appears feasible among hormonally pretreated prostatectomy specimens and shows continued prognostication for systemic progression. Confirmatory investigations are needed before the Gleason system can be reliably applied in the setting of neoadjuvant therapy.

Original languageEnglish (US)
Pages (from-to)332-337
Number of pages6
JournalProstate Cancer and Prostatic Diseases
Volume17
Issue number4
DOIs
StatePublished - Dec 13 2014

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Neoadjuvant Therapy
Neoplasm Grading
Prostatectomy
Hormones
Leuprolide
Therapeutics
Androgen Antagonists
Kaplan-Meier Estimate
Proportional Hazards Models
Disease-Free Survival
Multivariate Analysis

ASJC Scopus subject areas

  • Oncology
  • Urology
  • Cancer Research

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Gleason grading after neoadjuvant hormonal therapy retains prognostic value for systemic progression following radical prostatectomy. / Stewart, S. B.; Cheville, J. C.; Sebo, T. J.; Frank, I.; Boorjian, S. A.; Thompson, R. H.; Gettman, M. T.; Tollefson, M. K.; Umbriet, E. C.; Psutka, S. P.; Bergstralh, E. J.; Rangel, L.; Karnes, Robert Jeffrey.

In: Prostate Cancer and Prostatic Diseases, Vol. 17, No. 4, 13.12.2014, p. 332-337.

Research output: Contribution to journalArticle

Stewart, SB, Cheville, JC, Sebo, TJ, Frank, I, Boorjian, SA, Thompson, RH, Gettman, MT, Tollefson, MK, Umbriet, EC, Psutka, SP, Bergstralh, EJ, Rangel, L & Karnes, RJ 2014, 'Gleason grading after neoadjuvant hormonal therapy retains prognostic value for systemic progression following radical prostatectomy', Prostate Cancer and Prostatic Diseases, vol. 17, no. 4, pp. 332-337. https://doi.org/10.1038/pcan.2014.30
Stewart, S. B. ; Cheville, J. C. ; Sebo, T. J. ; Frank, I. ; Boorjian, S. A. ; Thompson, R. H. ; Gettman, M. T. ; Tollefson, M. K. ; Umbriet, E. C. ; Psutka, S. P. ; Bergstralh, E. J. ; Rangel, L. ; Karnes, Robert Jeffrey. / Gleason grading after neoadjuvant hormonal therapy retains prognostic value for systemic progression following radical prostatectomy. In: Prostate Cancer and Prostatic Diseases. 2014 ; Vol. 17, No. 4. pp. 332-337.
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abstract = "Background:The Gleason grading system in prostatectomy specimens following receipt of neoadjuvant therapy has been considered inaccurate. However, with continuing expansion of novel therapeutics, it is important to understand whether the Gleason system can be effectively utilized in this setting. The aim of this study was to assess the ability of the Gleason grading system to predict systemic progression among prostatectomy specimens treated with neoadjuvant hormone therapy (NHT).Methods:This was a single-institution retrospective analysis from 1987 to 2009 of 13 427 patients who underwent radical prostatectomy (RP) without NHT and 1148 patients with NHT. NHT consisted of leuprolide alone (n=415), antiandrogen therapy alone (n=400) and combined treatment (n=333). Kaplan-Meier analysis estimated 15-year systemic progression-free survival among NHT and non-NHT patients. Cox proportional hazard regression models estimated risk of systemic progression following RP according to NHT use and nonuse.Results:Median duration of NHT was 3 months (interquartile range (IQR) 2-4) whereas median follow-up after RP was 8.3 years (IQR 5-10.8). NHT patients were more likely to be D'Amico high risk, have locally advanced pathologic T stage (≥pT3), pathologic Gleason scores (GS) of 8-10 and lymph node involvement (P<0.0001 for all). NHT use was associated with lower rates of positive surgical margins, more downgrading to pT0 and less GS upgrading from biopsy (P≤0.001 for all). GS could not be assigned to only 3{\%} of NHT patients. On multivariate analysis, pathologic GS remained a predictor of systemic progression (SP) following NHT (hazard ratio (HR) 1.6, P=0.005), but the association was less strong compared with non-NHT patients (HR 2.9, P<0.0001).Conclusions:Utilization of the Gleason system appears feasible among hormonally pretreated prostatectomy specimens and shows continued prognostication for systemic progression. Confirmatory investigations are needed before the Gleason system can be reliably applied in the setting of neoadjuvant therapy.",
author = "Stewart, {S. B.} and Cheville, {J. C.} and Sebo, {T. J.} and I. Frank and Boorjian, {S. A.} and Thompson, {R. H.} and Gettman, {M. T.} and Tollefson, {M. K.} and Umbriet, {E. C.} and Psutka, {S. P.} and Bergstralh, {E. J.} and L. Rangel and Karnes, {Robert Jeffrey}",
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T1 - Gleason grading after neoadjuvant hormonal therapy retains prognostic value for systemic progression following radical prostatectomy

AU - Stewart, S. B.

AU - Cheville, J. C.

AU - Sebo, T. J.

AU - Frank, I.

AU - Boorjian, S. A.

AU - Thompson, R. H.

AU - Gettman, M. T.

AU - Tollefson, M. K.

AU - Umbriet, E. C.

AU - Psutka, S. P.

AU - Bergstralh, E. J.

AU - Rangel, L.

AU - Karnes, Robert Jeffrey

PY - 2014/12/13

Y1 - 2014/12/13

N2 - Background:The Gleason grading system in prostatectomy specimens following receipt of neoadjuvant therapy has been considered inaccurate. However, with continuing expansion of novel therapeutics, it is important to understand whether the Gleason system can be effectively utilized in this setting. The aim of this study was to assess the ability of the Gleason grading system to predict systemic progression among prostatectomy specimens treated with neoadjuvant hormone therapy (NHT).Methods:This was a single-institution retrospective analysis from 1987 to 2009 of 13 427 patients who underwent radical prostatectomy (RP) without NHT and 1148 patients with NHT. NHT consisted of leuprolide alone (n=415), antiandrogen therapy alone (n=400) and combined treatment (n=333). Kaplan-Meier analysis estimated 15-year systemic progression-free survival among NHT and non-NHT patients. Cox proportional hazard regression models estimated risk of systemic progression following RP according to NHT use and nonuse.Results:Median duration of NHT was 3 months (interquartile range (IQR) 2-4) whereas median follow-up after RP was 8.3 years (IQR 5-10.8). NHT patients were more likely to be D'Amico high risk, have locally advanced pathologic T stage (≥pT3), pathologic Gleason scores (GS) of 8-10 and lymph node involvement (P<0.0001 for all). NHT use was associated with lower rates of positive surgical margins, more downgrading to pT0 and less GS upgrading from biopsy (P≤0.001 for all). GS could not be assigned to only 3% of NHT patients. On multivariate analysis, pathologic GS remained a predictor of systemic progression (SP) following NHT (hazard ratio (HR) 1.6, P=0.005), but the association was less strong compared with non-NHT patients (HR 2.9, P<0.0001).Conclusions:Utilization of the Gleason system appears feasible among hormonally pretreated prostatectomy specimens and shows continued prognostication for systemic progression. Confirmatory investigations are needed before the Gleason system can be reliably applied in the setting of neoadjuvant therapy.

AB - Background:The Gleason grading system in prostatectomy specimens following receipt of neoadjuvant therapy has been considered inaccurate. However, with continuing expansion of novel therapeutics, it is important to understand whether the Gleason system can be effectively utilized in this setting. The aim of this study was to assess the ability of the Gleason grading system to predict systemic progression among prostatectomy specimens treated with neoadjuvant hormone therapy (NHT).Methods:This was a single-institution retrospective analysis from 1987 to 2009 of 13 427 patients who underwent radical prostatectomy (RP) without NHT and 1148 patients with NHT. NHT consisted of leuprolide alone (n=415), antiandrogen therapy alone (n=400) and combined treatment (n=333). Kaplan-Meier analysis estimated 15-year systemic progression-free survival among NHT and non-NHT patients. Cox proportional hazard regression models estimated risk of systemic progression following RP according to NHT use and nonuse.Results:Median duration of NHT was 3 months (interquartile range (IQR) 2-4) whereas median follow-up after RP was 8.3 years (IQR 5-10.8). NHT patients were more likely to be D'Amico high risk, have locally advanced pathologic T stage (≥pT3), pathologic Gleason scores (GS) of 8-10 and lymph node involvement (P<0.0001 for all). NHT use was associated with lower rates of positive surgical margins, more downgrading to pT0 and less GS upgrading from biopsy (P≤0.001 for all). GS could not be assigned to only 3% of NHT patients. On multivariate analysis, pathologic GS remained a predictor of systemic progression (SP) following NHT (hazard ratio (HR) 1.6, P=0.005), but the association was less strong compared with non-NHT patients (HR 2.9, P<0.0001).Conclusions:Utilization of the Gleason system appears feasible among hormonally pretreated prostatectomy specimens and shows continued prognostication for systemic progression. Confirmatory investigations are needed before the Gleason system can be reliably applied in the setting of neoadjuvant therapy.

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