Nuclear Shape and Architecture in Benign Fields Predict Biochemical Recurrence in Prostate Cancer Patients Following Radical Prostatectomy: Preliminary Findings

Abstract

Background: Gleason scoring represents the standard for diagnosis of prostate cancer (PCa) and assessment of prognosis following radical prostatectomy (RP), but it does not account for patterns in neighboring normal-appearing benign fields that may be predictive of disease recurrence.

Objective: To investigate (1) whether computer-extracted image features within tumor-adjacent benign regions on digital pathology images could predict recurrence in PCa patients after surgery and (2) whether a tumor plus adjacent benign signature (TABS) could better predict recurrence compared with Gleason score or features from benign or cancerous regions alone.

Design, setting, and participants: We studied 140 tissue microarray cores (0.6mm each) from 70 PCa patients following surgery between 2000 and 2004 with up to 14 yr of follow-up. Overall, 22 patients experienced recurrence (biochemical [prostate-specific antigen], local, or distant recurrence and cancer death) and 48 did not.

Intervention: RP was performed in all patients.

Outcome measurements and statistical analysis: The top 10 features identified as most predictive of recurrence within both the benign and cancerous regions were combined into a 10-feature signature (TABS). Computer-extracted nuclear shape and architectural features from cancerous regions, adjacent benign fields, and TABS were evaluated via random forest classification accuracy and Kaplan-Meier survival analysis.

Results and limitations: Tumor-adjacent benign field features were predictive of recurrence (area under the receiver operating characteristic curve [AUC]: 0.72). Tumor-field nuclear shape descriptors and benign-field local nuclear arrangement were the predominant features found for TABS (AUC: 0.77). Combining TABS with Gleason sum further improved identification of recurrence (AUC: 0.81). All experiments were performed using threefold cross-validation without independent test set validation.

Conclusions: Computer-extracted nuclear features within cancerous and benign regions predict recurrence following RP. Furthermore, TABS was shown to provide added value to common predictors including Gleason sum and Kattan and Stephenson nomograms.

Patient summary: Future studies may benefit from evaluation of benign regions proximal to the tumor on surgically excised prostate cancer tissue for assessing risk of disease recurrence.

Keywords: Digital pathology; Field effect; Markers; Prognosis; Prostate cancer; Quantitative histomorphometry; Radical prostatectomy; Recurrence.