Assessing dynamic micromechanical markers for the evaluation of the prostate for cancer

Abstract

The diagnostic pathway for prostate cancer involves the blood test prostate specific antigen (PSA) which has high sensitivity but low specificity at age related reference ranges. The resultant clinical consequence is a large number of negative diagnostic studies (transrectal ultrasound guided biopsies - TRUS). There is a need for a secondary screening test to help improve on the current diagnostic pathway. Mechanical markers have been used previously to assess the prostate for disease with numerous ex-vivo reports of differences between benign and malignant prostates. There have been no in-vivo studies with direct elasticity assessment devices for prostate cancer detection. This thesis forms part of work in a collaborative study in conjunction with engineers who have created a microscale device, capable of dynamic elasticity assessment. The specific objectives of this thesis were to a) assess dynamic micromechanical markers for the detection and differentiation of clinically significant from insignificant prostate cancer b) to identify relationships between mechanical and histopathological variables in the ex-vivo and in-vivo environments and c) assess the potential for these markers to differentiate peri-prostatic tissues. A prospective study was set-up with full ethics and management approvals with patients undergoing a systematic mechanical assessment of their prostate using the E-finger device and after prostate excision a systematic ex-vivo mechanical assessment on a calibrated stage. The ex-vivo assessment allowed accurate histopathological and mechanical variable assessment in a controlled environment. 7-Tesla ex-vivo MRI scanning aided in assessing the limitations of mechanical assessment of the prostate. There were clear consistent differences between individual dynamic micromechanical markers for benign and tumour containing measurement areas in both environments. Modelling of these dynamic micromechanical markers yielded encouraging accuracy levels for the detection of prostate cancer and differentiation of significant from insignificant disease. There were associations between individual mechanical markers and important histopathological features associated with cancer (acinar size, tumour volume and reactive stroma). These markers showed promise and utility in the differentiation of prostate from bladder and rhabdosphincter. This work demonstrates the clear potential translational uses for dynamic micromechanical markers in the assessment of the prostate for cancer.