Morphologic characterization of preoperatively treated prostate cancer: toward a post-therapy histologic classification.
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Preoperative treatment of prostate cancer (PCa) changes morphology of residual tumors so that the Gleason score is no longer valid.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.


METHODS
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.


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


CONCLUSIONS
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.
University of Texas, M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
Eleni
E
Efstathiou
Neil A
NA
Abrahams
Rita F
RF
Tibbs
Xuemei
X
Wang
Curtis A
CA
Pettaway
Louis L
LL
Pisters
Paul F
PF
Mathew
Kim-Anh
KA
Do
Christopher J
CJ
Logothetis
Patricia
P
Troncoso
D000328:Adult; D000368:Aged; D000726:Androgen Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016000:Cluster Analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D011467:Prostate / Q000187:drug effects / Q000473:pathology*; D017430:Prostate-Specific Antigen / Q000097:blood*; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology* / Q000601:surgery; D012189:Retrospective Studies
D000726:Androgen Antagonists; D000970:Antineoplastic Agents; D017430:Prostate-Specific Antigen