Abstract
Invasive cribriform and intraductal carcinoma are associated with adverse clinical outcome in patients with Gleason score 7 prostate cancer. It is yet unclear whether invasive cribriform and intraductal carcinoma of the prostate both have independent prognostic value, or whether field size of invasive cribriform carcinoma has impact on disease outcome. Our objective was to determine the prognostic impact of intraductal and invasive cribriform prostate cancer histological subtypes in radical prostatectomies. We reviewed 420 prostatectomy specimens with ISUP grade 2 prostate cancer, assessed the percentages of Gleason grade 4 and tertiary 5, and performed immunohistochemistry for basal cells to discriminate intraductal from invasive cribriform growth. Small and large invasive cribriform fields were distinguished based on a diameter of at least twice the size of adjacent pre-existent normal glands. Clinicopathological parameters and biochemical recurrence-free survival were used as endpoints. Cribriform architecture was observed in 228 (54.3%) men, 103 (24.5%) of whom had intraductal, 194 (46.2%) small invasive, and 34 (8.1%) large invasive cribriform growth. Large invasive cribriform architecture was associated with older age (P < 0.001), higher percentage Gleason grade 4 (P = 0.001), extraprostatic expansion (P < 0.001), and more frequent lymph node metastases (P = 0.002), when compared with small invasive cribriform and/or intraductal carcinoma. Univariate analysis identified PSA, pT-stage, surgical margin status, and intraductal and invasive cribriform growth as significant predictors for biochemical recurrence-free survival. In multivariable Cox regression analysis, pT-stage (hazard ratio = 1.64, 95% CI: 1.02–2.63, P = 0.04), positive surgical margins (hazard ratio = 3.28, 95% CI: 2.06–5.23, P < 0.001), and large cribriform growth (hazard ratio = 4.36, 95% CI: 2.08–9.17, P < 0.001) were independent predictors for biochemical recurrence-free survival, while intraductal carcinoma, small cribriform growth, and percentage of Gleason grade 4 were not. In conclusion, large cribriform fields represent an aggressive subpattern of invasive cribriform prostate cancer and are an independent predictive factor for biochemical recurrence-free survival in ISUP grade 2 prostate cancer patients.
Highlights
IntroductionThe Gleason score is one of the most important parameters for clinical decision-making in men with prostate cancer
Supplementary information The online version of this article contains supplementary material, which is available to authorized users.The Gleason score is one of the most important parameters for clinical decision-making in men with prostate cancer
While most patients with ISUP grade 2 prostate cancer are treated with radiotherapy and/or surgery, active surveillance is increasingly being considered as alternative strategy for these men [21,22,23,24,25]
Summary
The Gleason score is one of the most important parameters for clinical decision-making in men with prostate cancer. The Gleason grading system is entirely based on tumor architectural growth patterns which are classified into five different grades. While men with biopsy Gleason score 6 are frequently eligible for active surveillance, treatment is warranted in patients with Gleason score 8–10. The optimal therapeutic strategy for individual patients with Gleason score 7 is not yet clear. While most patients with Gleason score 7 undergo radical prostatectomy or radiation therapy, active surveillance is increasingly being considered in this large group of men. There is an urgent need for additional parameters to aid therapeutic decision-making in men with Gleason score 7 prostate cancer
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