Digital Quantification of Five High-Grade Prostate Cancer Patterns, Including the Cribriform Pattern, and Their Association With Adverse Outcome

Abstract

Proper grading of the cribriform prostate cancer pattern has not previously been supported by outcome-based evidence. Among 153 men who underwent radical prostatectomy, 76 with prostate-specific antigen (PSA) failure (≥0.2 ng/mL [0.2 µg/L]) were matched to 77 without failure. Frequencies of high-grade patterns included fused small acini, 83.7%; papillary, 52.3%; large cribriform, 37.9%; small (≤12 lumens) cribriform, 17.0%; and individual cells, 22.9%. A cribriform pattern was present in 61% (46/76) of failures but 16% (12/77) of nonfailures (P < .0001). Multivariate analysis showed the cribriform pattern had the highest odds ratio for PSA failure, 5.89 (95% confidence interval, 2.53–13.70; P < .0001). The presence of both large and small cribriform patterns was significantly linked to failure. The cumulative odds ratio of failure per added square millimeter of cribriform pattern was 1.173 (P = .008), higher than for any other pattern. All 8 men with a cribriform area sum of 25 mm2 or more had failure (range, 33–930). Regrading cribriform cancer as Gleason 5 improved the grade association with failure, although half of all cases with individual cells also had a cribriform pattern, precluding a precise determination of the independent importance of the latter. The cribriform pattern has particularly adverse implications for outcome.

Disease-specific survival of patients with invasive cribriform and intraductal prostate cancer at diagnostic biopsy

“…[2][3][4][5]11,13 To date, only few studies have analyzed the prognostic value of intraductal carcinoma in pre-treatment diagnostic biopsies. [7][8][9] They showed that intraductal carcinoma is associated with high-grade and non-organ-confined prostate cancer in subsequent radical prostatectomies.…”

“…Recent studies have suggested that the broad contemporary definition of the Gleason grade 4 pattern may be one of the explanations for the variable outcomes of patients with Gleason score 7 prostate cancer. [2][3][4][5] Architecturally, four Gleason grade 4 growth patterns are recognized: ill-formed, fused, glomeruloid, and cribriform. 1,6 Recently, cribriform pattern has been associated with adverse outcome after radical prostatectomy in Gleason score 7 prostate cancer.…”

“…1,6 Recently, cribriform pattern has been associated with adverse outcome after radical prostatectomy in Gleason score 7 prostate cancer. [2][3][4][5] In recent years, the clinical relevance of intraductal carcinoma of the prostate-a high-risk lesion defined as malignant epithelium filling large acini or ducts with preservation of basal cells-has been acknowledged. Although not included in the Gleason score, intraductal carcinoma has been associated with high Gleason scores, advanced tumor stage, biochemical relapse, and distant metastasis.…”

“…Studies on the prognostic value of invasive cribriform and intraductal carcinoma have mostly been based on radical prostatectomy specimens. [2][3][4][5]11,13 The aim of this study was to determine the prognostic value of invasive cribriform and intraductal carcinoma in diagnostic biopsies on time to disease-specific death.…”

Does cumulative prostate cancer length (CCL) in prostate biopsies improve prediction of clinically insignificant cancer at radical prostatectomy in patients eligible for active surveillance?

“…This has resulted in a Gleason score 3 + 3 = 6 category that is more homogeneously low risk at the expense of a more biologically heterogeneous Gleason score 3 + 4 = 7 category. Patients with a biopsy Gleason score of 3 + 4 = 7, who previously could have been scored as Gleason score 3 + 3 = 6, may not have as aggressive a cancer as current algorithms might predict [9][10][11][12]. Several recent studies have examined the use of biopsy Gleason score ≤3 + 4 = 7 as inclusion criteria for AS but have had mixed results, probably due to the biological heterogeneity of this group [13][14][15][16][17][18][19][20][21].…”