Assessing dynamic micromechanical markers for the evaluation of the prostate for cancer
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Date
02/07/2016Item status
Restricted AccessEmbargo end date
31/12/2100Author
Good, Daniel William
Metadata
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.