Intraductal carcinoma and cribriform architecture as novel prognostic factors in patients with prostate cancer treated with dose-escalated radiotherapy.

Abstract

101 Background: Intraductal carcinoma (IDC) and cribriform architecture (CA) represent distinct pathohistological variants of high-grade prostate cancer associated with aggressive disease and poor clinical outcome. We evaluated impact of IDC and/or CA (IDC/CA) as a prognostic marker in patients with prostate cancer who underwent contemporary image-guided, dose-escalated, intensity-modulated radiotherapy (IMRT). Methods: Radiotherapy and clinical records of 379 patients with localized prostate cancer treated from 2005 to 2012 with prostate IMRT with 78 Gy in 39 fractions were retrospectively reviewed. Original diagnostic prostate biopsy slides were centrally reviewed by an expert genitourinary pathologist and scored for presence of IDC/CA. The impact of IDC/CA and other pre-treatment and treatment-related factors on biochemical relapse-free survival (BRFS) was evaluated. Results: IDC/CA was present in 19.3% of patients. After median follow-up of 56 months, 39 (10.3%) and 10 (3.6%) patients experienced biochemical failure and distant metastasis, respectively. On univariate analysis, the presence of IDC/CA was associated with decreased BRFS (HR 4.1 (95% CI: 2.2-7.8), p < 0.0001) and metastasis-free survival (HR = 4.7 (95% CI: 1.4-15.6), p = 0.013). On multivariate analysis, IDC/CA was associated with decreased BRFS (HR = 2.3 (95% CI: 1.2-4.7), p = 0.02) together with NCCN risk group (overall p = 0.0004), Gleason score (overall p = 0.016) and percent of positive biopsy cores (HR = 5.78 (95% CI: 1.4-23.9), p = 0.015). Within intermediate risk patients, presence of IDC/CA was associated with decreased BRFS (HR = 3.3 (95%CI: 1.5-7.1), p = 0.031) and was able to further stratify GS 4+3 patients (HR = 4.5, (95% CI: 1.6-13.0), p = 0.0045). Conclusions: The presence of IDC/CA in the prostate biopsy has negative prognostic impact in patients treated with dose-escalated radiotherapy. Furthermore, the prognostic significance of IDC/CA, even among unfavorable intermediate-risk patients, suggests that these pathological features should be considered in existing risk stratification tools for this patient group.