Morphologic characterization of preoperatively treated prostate cancer: toward a post-therapy histologic classification

Abstract

Background: Preoperative treatment of prostate cancer (PCa) changes morphology of residual tumors so that the Gleason score is no longer valid.

Objective: To codify morphologic features of preoperatively treated PCa and identify potential classifiers predictive of outcome.

Design, setting, and participants: We performed a detailed morphologic evaluation of specimens obtained from 115 patients with high-risk PCa who had preoperative androgen ablation, alone or in combination with chemotherapy.

Measurements: Included hierarchical clustering analysis of morphologic characteristics, associations with other pathologic parameters, and univariate and multivariate analyses in search for associations with disease outcome.

Results and limitations: Based on hierarchical clustering analysis, we categorized pretreated prostate cancer in three morphologically distinct groups: group A, characterized by a predominance of cell clusters, cell cords, and isolated cells; group B tumors, by intact and fused small glands; and group C tumors by any degree of cribriform growth pattern or intraductal tumor spread. Univariate analysis identified associations between this grouping, pathologic tumor stage (p<0.01) and residual tumor volume (p<0.001). Presence of intraductal spread or cribriform pattern in biopsies was associated with group C tumors. The presence of cribriform or intraductal spread morphology and positive surgical margins were stronger predictors of biochemical relapse than pathologic stage on multivariate analysis. The number of specimens evaluated in this study was limited, and a prospective validation is warranted along with molecular studies to validate the proposed morphologic classifier.

Conclusions: If validated, this classification will introduce uniformity in the selection of tissue samples for biomarker studies, facilitate the comparison of trials among different institutions, and may provide a new prognostic tool for preoperatively treated PCa.

Conflict of interest statement

Financial disclosures: I certify that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: None.

Copyright © 2009 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Figures

Fig. 1

Tumor architecture of preoperatively treated prostate cancer: (a) Single cells, cell cords, and cell clusters; (b) small glands; (c) fused glands; (d) cribriform pattern; (e) intraductal spread.

Fig. 2

Proposed grouping. Top: Group A morphology is characterized by the predominance of isolated cells, cell clusters, and cords with complete absence of cribriform pattern or intraductal tumor spread. Middle: Group B morphology is characterized by the predominance of small and/or fused glands with complete absence of cribriform pattern or intraductal tumor spread. Bottom: Group C morphology is defined by the presence of cribriform pattern and/or intraductal tumor spread regardless of other patterns.

Fig. 3

Median volumes of the dominant tumor focus according to morphologic group. Group A: 0.36 cm3 (range: 0.03–2.88 cm3); group B: 1.20 cm3 (range: 0.12–6.00 cm3); group C: 2.48 cm3 (range: 0.14–13.82); p < 0.001 (Kruskal-Wallis test). P < 0.001 for groups A and B combined versus group C.

Fig. 4

Kaplan-Meier estimates of biochemical failure(BCF)–free survival. Dotted lines above and below represent the confidence intervals (CIs). (a) Kaplan-Meier estimates of BCF-free survival overall, median follow-up 55 mo (range: 42–108 mo) (b) by pathologic stage and (c) by morphologic group A, B, C. P = 0.001 for groups A and B combined versus group C (d) by margin status and (e) by biopsy presence versus absence of cribriform pattern and/or intraductal spread (IDS) (n = 85; 30 were missing due to lack of complete biopsy data). Note: Kaplan-Meier estimates include as biochemical failure five patients who died of unrelated causes (two in group C and three in groups A and B).

Fig. 4

Kaplan-Meier estimates of biochemical failure(BCF)–free survival. Dotted lines above and below represent the confidence intervals (CIs). (a) Kaplan-Meier estimates of BCF-free survival overall, median follow-up 55 mo (range: 42–108 mo) (b) by pathologic stage and (c) by morphologic group A, B, C. P = 0.001 for groups A and B combined versus group C (d) by margin status and (e) by biopsy presence versus absence of cribriform pattern and/or intraductal spread (IDS) (n = 85; 30 were missing due to lack of complete biopsy data). Note: Kaplan-Meier estimates include as biochemical failure five patients who died of unrelated causes (two in group C and three in groups A and B).

Fig. 4

Kaplan-Meier estimates of biochemical failure(BCF)–free survival. Dotted lines above and below represent the confidence intervals (CIs). (a) Kaplan-Meier estimates of BCF-free survival overall, median follow-up 55 mo (range: 42–108 mo) (b) by pathologic stage and (c) by morphologic group A, B, C. P = 0.001 for groups A and B combined versus group C (d) by margin status and (e) by biopsy presence versus absence of cribriform pattern and/or intraductal spread (IDS) (n = 85; 30 were missing due to lack of complete biopsy data). Note: Kaplan-Meier estimates include as biochemical failure five patients who died of unrelated causes (two in group C and three in groups A and B).

Fig. 4

Kaplan-Meier estimates of biochemical failure(BCF)–free survival. Dotted lines above and below represent the confidence intervals (CIs). (a) Kaplan-Meier estimates of BCF-free survival overall, median follow-up 55 mo (range: 42–108 mo) (b) by pathologic stage and (c) by morphologic group A, B, C. P = 0.001 for groups A and B combined versus group C (d) by margin status and (e) by biopsy presence versus absence of cribriform pattern and/or intraductal spread (IDS) (n = 85; 30 were missing due to lack of complete biopsy data). Note: Kaplan-Meier estimates include as biochemical failure five patients who died of unrelated causes (two in group C and three in groups A and B).

Fig. 4

Kaplan-Meier estimates of biochemical failure(BCF)–free survival. Dotted lines above and below represent the confidence intervals (CIs). (a) Kaplan-Meier estimates of BCF-free survival overall, median follow-up 55 mo (range: 42–108 mo) (b) by pathologic stage and (c) by morphologic group A, B, C. P = 0.001 for groups A and B combined versus group C (d) by margin status and (e) by biopsy presence versus absence of cribriform pattern and/or intraductal spread (IDS) (n = 85; 30 were missing due to lack of complete biopsy data). Note: Kaplan-Meier estimates include as biochemical failure five patients who died of unrelated causes (two in group C and three in groups A and B).