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Preoperative treatment of prostate cancer (PCa) changes morphology of residual tumors so that the Gleason score is no longer valid.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

Cribriform growth is highly predictive for postoperative metastasis and disease-specific death in Gleason score 7 prostate cancer

“…The presence of intraductal carcinoma has been associated with high-grade cancer and adverse outcome. [13][14][15] In our study, presence of cribriform pattern was significantly associated with intraductal carcinoma. Two hypotheses of intraductal carcinoma evolution have been proposed.…”

“…In addition, we assessed the presence of tertiary Gleason grade 5 and intraductal carcinoma of the prostate in each specimen as both have been associated with adverse clinical outcome. [13][14][15][16][17] The following Gleason grade 4 growth patterns, as defined by the ISUP-modified Gleason grading scheme, 2 were scored: (1) fused glands included fused well-and poorly formed glands ( Figure 1a). (2) Ill-defined glands comprised glands with poorly formed or absent glandular lumina (Figure 1b).…”

The presence of intraductal carcinoma of the prostate in needle biopsy is a significant prognostic factor for prostate cancer patients with distant metastasis at initial presentation

“…The median serum PSA was 328 ng/ml (range 4.18-10 992 ng/ml). The median-submitted number of cores was six (mean 7.3, range [1][2][3][4][5][6][7][8][9][10][11][12][13][14] and the median number of cancer-positive cores was six (mean 5.8, range [1][2][3][4][5][6][7][8][9][10][11][12][13][14]. Intraductal carcinoma of the prostate was detected in 100 (67%) patients, six with PSA levels o 20 ng/ml and the remaining 94 with PSA levels 420 ng/ml.…”

Treatment of the Primary Tumor in Metastatic Prostate Cancer: Current Concepts and Future Perspectives

“…Data garnered during this time period may provide prognostic information that can be used for risk stratification for trials or possibly predictive factors for selecting subsequent therapy. There have also been efforts to provide a morphologic characterization of patients who received preoperative systemic treatment to provide a post-therapy histologic classification, as Gleason score cannot be used in such a setting [66]. Efstathiou et al [66] provided an indepth histologic classification in such patients based on hierarchical clustering analysis: group A, characterized by a predominance of cell clusters, cell cords, and isolated cells; group B tumors, characterized by intact and fused small glands; and group C, characterized by tumors with any degree of cribriform growth pattern or intraductal tumor spread.…”

“…There have also been efforts to provide a morphologic characterization of patients who received preoperative systemic treatment to provide a post-therapy histologic classification, as Gleason score cannot be used in such a setting [66]. Efstathiou et al [66] provided an indepth histologic classification in such patients based on hierarchical clustering analysis: group A, characterized by a predominance of cell clusters, cell cords, and isolated cells; group B tumors, characterized by intact and fused small glands; and group C, characterized by tumors with any degree of cribriform growth pattern or intraductal tumor spread. A cribriform or intraductal spread morphology and positive surgical margins were stronger predictors of biochemical relapse than pathologic stage in multivariate analysis.…”