Improved Prostate Cancer Biopsy Grading by Incorporation of Invasive Cribriform and Intraductal Carcinoma in the 2014 Grade Groups

Abstract

E U R O P E A N U R O L O G Y 7 7 ( 2 0 2 0 ) 1 9 1 -1 9 8 a v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m j o u r n a l h o m e p a g e : w w w . e u r o p e a n u r o l o g y . c o m Abstract Background: Grade groups (GGs) are an important parameter for therapeutic decision making in prostate cancer (Pca) patients. Invasive cribriform and/or intraductal carcinoma (CR/IDC) has an independent prognostic value for disease outcome, but are not included in the GG limiting their clinical use. Objective: To perform a proof-of-principle study incorporating CR/IDC in the current GG. Design, setting, and participants: All prostate biopsies of 1031 men with screen-detected Pca between 1993 and 2000 were reviewed for the current GG (ranging from 1 to 5) and CR/IDC. The cribriform grade (cGrade) was equal to the GG if CR/IDC was present and GG minus 1 if not. GG1 was cGrade1 if intraductal carcinoma was absent. Intervention: Biopsy review for GG and CR/IDC. A total of 406 patients had received radical prostatectomy (RP), 508 radiotherapy (RT), 108 surveillance, and eight hormonal therapy, and the treatment was unknown for one patient.Outcome measurements and statistical analysis disease-specific survival (DSS), metastasisfree survival (MFS), and biochemical recurrence-free survival (BCRFS) after 15.1 yr (interquartile range 10.9-19.7 yr) follow-up were compared using Harrell's C-statistic. Results and limitations: The biopsy GGs were 486 GG1, 310 GG2, 104 GG3, 64 GG4, and 67 GG5; cGrade distributions were 738 cGrade1, 102 cGrade2, 91 cGrade3, 58 cGrade4, and 42 cGrade5. The cGrade had a better discriminative value than the GG for DSS (C-index 0.79; 95% confidence interval 0.74-0.83 vs 0.76; 0.71-0.82) and MFS (0.79; 0.74-0.84 vs 0.77; 0.72-0.82). The discriminative value for BCRFS after RP and RT was similar for both models. Different diagnostic, such as use of sextant biopsies, and therapeutic strategies in the 1990s are the limitations of this study. Conclusions: The cGrade is a simple Pca grade modification with better discriminative values for DSS and MFS than the GG, particularly impacting decision making in men with current GG2 Pca. Patient summary: Microscopic grading is an important factor for decision making in prostate cancer (Pca) patients. We show that [ 4 5 _ T D $ D I F F ] a simple grade modification better predicts Pca outcome and might improve treatment choices.

Clinical outcome comparison of Grade Group 1 and Grade Group 2 prostate cancer with and without cribriform architecture at the time of radical prostatectomy

“…Furthermore, recent studies have indicated that biopsies have a moderate sensitivity of 43–47% for detecting cribriform architecture 21,22 . Despite moderate concordance of growth patterns between biopsy and radical prostatectomy specimens, incorporation of cribriform architecture into the Grade Groups has better discriminative value for disease‐specific survival and metastasis‐free survival 20 . In biopsies, we previously demonstrated that subtraction of one point of the Grade Group if no cribriform architecture was present was a simple and valuable modification of the current prostate cancer grading scheme.20…”

“…In previous sextant biopsy studies with long‐term follow‐up, biopsy GG2− patients had similar biochemical recurrence‐free and disease‐specific survival as GG1 patients 16,17 . Therefore, it has been proposed that patients without cribriform architecture might be eligible for active surveillance 15–20 . However, prostate biopsies are subject to significant sampling errors with tumour undergrading in up to 40%, and there is low sensitivity for detection of cribriform architecture 21–23 .…”

Grading of prostate cancer: the impact of including intraductal carcinoma on the overall Grade Group assigned in diagnostic biopsies

“…Van Leenders et al recently proposed an alternative method of incorporating IDCP into the current GrG scheme by modifying the grade on the basis of the presence of any amount of IDCP and/or cribriform carcinoma. 16 In a large series of RP specimens, Kato et al found that incorporating the presence of IDCP, regardless of extent or morphological type, into the GrG system was predictive of biochemical recurrence. 17 Both of these studies propose integrating the presence of any amount of IDCP into the grading system to improve prognostication.…”

Prostate cancer growth patterns beyond the Gleason score: entering a new era of comprehensive tumour grading

“…Our group has defined cribriform architecture as an epithelial sheet (a) in which the majority of tumour cells do not contact the surrounding stroma, (b) with a gland-like space surrounding less than half of the sheet circumference, and (c) with regular intercellular lumens clearly visible on haematoxylin and eosin (H&E)stained sections (Figure 2). 55,56 The first criterion (a) distinguishes a cribriform pattern from complex fused glands in which most if not all tumour cells are still in direct contact with subtle connective tissue cores present within the lesion. The second criterion (b) arbitrarily distinguishes a cribriform from a large glomeruloid pattern in which gland-like spaces surround more than half of the central protrusion.…”