Prostate Cancer Risk Stratification in Men With a Clinical Suspicion of Prostate Cancer Using a Unique Biparametric MRI and Expression of 11 Genes in Apparently Benign Tissue: Evaluation Using Machine-Learning Techniques.

Montoya Perez I1,2,3, Jambor I1,4,3, Pahikkala T2, Airola A2, Merisaari H1,2,3, Saunavaara J1,3, Alinezhad S5, Väänänen RM5, Tallgrén T5, Verho J1,3, Kiviniemi A1,3, Ettala O6, Knaapila J6, Syvänen KT6, Kallajoki M7, Vainio P7, Aronen HJ1,3, Pettersson K5, Boström PJ6, Taimen P7.

Author information

1: Department of Diagnostic Radiology, University of Turku, Turku, Finland.
2: Department of Future Technologies, University of Turku, Turku, Finland.
3: Medical Imaging Centre of Southwest Finland, Turku University Hospital, Turku, Finland.
4: Department of Radiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
5: Department of Biotechnology, University of Turku, Turku, Finland.
6: Department of Urology, University of Turku and Turku University hospital, Turku, Finland.
7: Institute of Biomedicine, University of Turku and Department of Pathology, Turku University Hospital, Turku, Finland.

Abstract

BACKGROUND:

Accurate risk stratification of men with a clinical suspicion of prostate cancer (cSPCa) remains challenging despite the increasing use of MRI.

PURPOSE:

To evaluate the diagnostic accuracy of a unique biparametric MRI protocol (IMPROD bpMRI) combined with clinical and molecular markers in men with cSPCa.

STUDY TYPE:

Prospective single-institutional clinical trial (NCT01864135).

SUBJECTS:

Eighty men with cSPCa.

FIELD STRENGTH/SEQUENCE:

3T, surface array coils. Two T2 -weighted and three diffusion-weighted imaging (DWI) acquisitions: 1) b-values 0, 100, 200, 300, 500 s/mm2 ; 2) b-values 0,1500 s/mm2 ; 3) b-values 0, 2000 s/mm2 .

ASSESSMENT:

IMPROD bpMRI examinations were qualitatively (IMPROD bpMRI Likert score) and quantitatively (DWI-based Gleason grade score) prospectively reported. Men with IMPROD bpMRI Likert 3-5 had two targeted biopsies followed by 12-core systematic biopsies (SB); those with IMPROD bpMRI Likert 1-2 had only SB. Additionally, 2-core from normal-appearing prostate areas were obtained for the mRNA expression of ACSM1, AMACR, CACNA1D, DLX1, PCA3, PLA2G7, RHOU, SPINK1, SPON2, TMPRSS2-ERG, and TDRD1 measured by quantitative reverse-transcription polymerase chain reaction.

STATISTICAL TESTS:

Univariate and multivariate analysis using regularized least-squares, feature selection and tournament leave-pair-out cross-validation (TLPOCV), as well as 10 random splits of the data in training-testing sets, were used to evaluate the mRNA, clinical and IMPROD bpMRI parameters in detecting clinically significant prostate cancer (SPCa) defined as Gleason score ≥ 3 + 4. The evaluation metric was the area under the curve (AUC).

RESULTS:

IMPROD bpMRI Likert demonstrated the highest TLPOCV AUC of 0.92. The tested clinical variables had AUC 0.56-0.73, while the mRNA and additional IMPROD bpMRI parameters had AUC 0.50-0.67 and 0.65-0.89 respectively. The combination of clinical and mRNA biomarkers produced TLPOCV AUC of 0.87, the highest TLPOCV performance without including IMPROD bpMRI Likert.

DATA CONCLUSION:

The qualitative IMPROD bpMRI Likert score demonstrated the highest accuracy for SPCa detection compared with the tested clinical variables and mRNA biomarkers.

LEVEL OF EVIDENCE:

1 Technical Efficacy Stage: 2.

KEYWORDS:

PSA; biomarker; biparametric MRI; cross-validation; diffusion weighted imaging; field cancerization effect; gene expression; permutation test; prostate cancer; prostate cancer screening; qRT-PCR; single-institutional trial