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
Corresponding Author
Ileana Montoya Perez MSc
Department of Diagnostic Radiology, University of Turku, Turku, Finland
Department of Future Technologies, University of Turku, Turku, Finland
Medical Imaging Centre of Southwest Finland, Turku University Hospital, Turku, Finland
Address reprint requests to: I.M.P., Department of Future Technologies, University of Turku, Agora 4th Floor, Vesilinnantie 5, 20500 Turku, Finland. E-mail: [email protected]Search for more papers by this authorIvan Jambor MD, PhD
Department of Diagnostic Radiology, University of Turku, Turku, Finland
Department of Radiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
Medical Imaging Centre of Southwest Finland, Turku University Hospital, Turku, Finland
Search for more papers by this authorTapio Pahikkala PhD
Department of Future Technologies, University of Turku, Turku, Finland
Search for more papers by this authorAntti Airola PhD
Department of Future Technologies, University of Turku, Turku, Finland
Search for more papers by this authorHarri Merisaari PhD
Department of Diagnostic Radiology, University of Turku, Turku, Finland
Department of Future Technologies, University of Turku, Turku, Finland
Medical Imaging Centre of Southwest Finland, Turku University Hospital, Turku, Finland
Search for more papers by this authorJani Saunavaara PhD
Department of Diagnostic Radiology, University of Turku, Turku, Finland
Medical Imaging Centre of Southwest Finland, Turku University Hospital, Turku, Finland
Search for more papers by this authorSaeid Alinezhad PhD
Department of Biotechnology, University of Turku, Turku, Finland
Search for more papers by this authorRiina-Minna Väänänen PhD
Department of Biotechnology, University of Turku, Turku, Finland
Search for more papers by this authorTerhi Tallgrén MSc
Department of Biotechnology, University of Turku, Turku, Finland
Search for more papers by this authorJanne Verho MD
Department of Diagnostic Radiology, University of Turku, Turku, Finland
Medical Imaging Centre of Southwest Finland, Turku University Hospital, Turku, Finland
Search for more papers by this authorAida Kiviniemi MD
Department of Diagnostic Radiology, University of Turku, Turku, Finland
Medical Imaging Centre of Southwest Finland, Turku University Hospital, Turku, Finland
Search for more papers by this authorOtto Ettala MD, PhD
Department of Urology, University of Turku and Turku University hospital, Turku, Finland
Search for more papers by this authorJuha Knaapila MD
Department of Urology, University of Turku and Turku University hospital, Turku, Finland
Search for more papers by this authorKari T. Syvänen MD, PhD
Department of Urology, University of Turku and Turku University hospital, Turku, Finland
Search for more papers by this authorMarkku Kallajoki MD, PhD
Institute of Biomedicine, University of Turku and Department of Pathology, Turku University Hospital, Turku, Finland
Search for more papers by this authorPaula Vainio MD
Institute of Biomedicine, University of Turku and Department of Pathology, Turku University Hospital, Turku, Finland
Search for more papers by this authorHannu J. Aronen MD, PhD
Department of Diagnostic Radiology, University of Turku, Turku, Finland
Medical Imaging Centre of Southwest Finland, Turku University Hospital, Turku, Finland
Search for more papers by this authorKim Pettersson PhD
Department of Biotechnology, University of Turku, Turku, Finland
Search for more papers by this authorPeter J. Boström MD, PhD
Department of Urology, University of Turku and Turku University hospital, Turku, Finland
Search for more papers by this authorPekka Taimen MD, PhD
Institute of Biomedicine, University of Turku and Department of Pathology, Turku University Hospital, Turku, Finland
Search for more papers by this authorCorresponding Author
Ileana Montoya Perez MSc
Department of Diagnostic Radiology, University of Turku, Turku, Finland
Department of Future Technologies, University of Turku, Turku, Finland
Medical Imaging Centre of Southwest Finland, Turku University Hospital, Turku, Finland
Address reprint requests to: I.M.P., Department of Future Technologies, University of Turku, Agora 4th Floor, Vesilinnantie 5, 20500 Turku, Finland. E-mail: [email protected]Search for more papers by this authorIvan Jambor MD, PhD
Department of Diagnostic Radiology, University of Turku, Turku, Finland
Department of Radiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
Medical Imaging Centre of Southwest Finland, Turku University Hospital, Turku, Finland
Search for more papers by this authorTapio Pahikkala PhD
Department of Future Technologies, University of Turku, Turku, Finland
Search for more papers by this authorAntti Airola PhD
Department of Future Technologies, University of Turku, Turku, Finland
Search for more papers by this authorHarri Merisaari PhD
Department of Diagnostic Radiology, University of Turku, Turku, Finland
Department of Future Technologies, University of Turku, Turku, Finland
Medical Imaging Centre of Southwest Finland, Turku University Hospital, Turku, Finland
Search for more papers by this authorJani Saunavaara PhD
Department of Diagnostic Radiology, University of Turku, Turku, Finland
Medical Imaging Centre of Southwest Finland, Turku University Hospital, Turku, Finland
Search for more papers by this authorSaeid Alinezhad PhD
Department of Biotechnology, University of Turku, Turku, Finland
Search for more papers by this authorRiina-Minna Väänänen PhD
Department of Biotechnology, University of Turku, Turku, Finland
Search for more papers by this authorTerhi Tallgrén MSc
Department of Biotechnology, University of Turku, Turku, Finland
Search for more papers by this authorJanne Verho MD
Department of Diagnostic Radiology, University of Turku, Turku, Finland
Medical Imaging Centre of Southwest Finland, Turku University Hospital, Turku, Finland
Search for more papers by this authorAida Kiviniemi MD
Department of Diagnostic Radiology, University of Turku, Turku, Finland
Medical Imaging Centre of Southwest Finland, Turku University Hospital, Turku, Finland
Search for more papers by this authorOtto Ettala MD, PhD
Department of Urology, University of Turku and Turku University hospital, Turku, Finland
Search for more papers by this authorJuha Knaapila MD
Department of Urology, University of Turku and Turku University hospital, Turku, Finland
Search for more papers by this authorKari T. Syvänen MD, PhD
Department of Urology, University of Turku and Turku University hospital, Turku, Finland
Search for more papers by this authorMarkku Kallajoki MD, PhD
Institute of Biomedicine, University of Turku and Department of Pathology, Turku University Hospital, Turku, Finland
Search for more papers by this authorPaula Vainio MD
Institute of Biomedicine, University of Turku and Department of Pathology, Turku University Hospital, Turku, Finland
Search for more papers by this authorHannu J. Aronen MD, PhD
Department of Diagnostic Radiology, University of Turku, Turku, Finland
Medical Imaging Centre of Southwest Finland, Turku University Hospital, Turku, Finland
Search for more papers by this authorKim Pettersson PhD
Department of Biotechnology, University of Turku, Turku, Finland
Search for more papers by this authorPeter J. Boström MD, PhD
Department of Urology, University of Turku and Turku University hospital, Turku, Finland
Search for more papers by this authorPekka Taimen MD, PhD
Institute of Biomedicine, University of Turku and Department of Pathology, Turku University Hospital, Turku, Finland
Search for more papers by this authorAbstract
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
J. Magn. Reson. Imaging 2020;51:1540–1553.
Supporting Information
| Filename | Description |
|---|---|
| jmri26945-sup-0001-Supinfo.docxWord 2007 document , 230.7 KB | Table S1 Number of patients stratified per each Gleason Grade Group Table S2 Spearman's rank correlation coefficient (ρ) between 11 mRNA transcript expressions and Gleason Grade Groups Table S3 Cross-relation for IMPROD Likert scoring system between Reader A and Reader B with corresponding Receiver operating characteristic curves Table S4 Cross-relation for PI-RADSv2.1 scores between Reader A and Reader B with corresponding Receiver operating characteristic curves Table S5 Cross-relation between IMPROD bpMRI Likert and PI-RADSv2.1 scores for Reader A Table S6 Cross-relation between IMPROD bpMRI Likert and PI-RADSv2.1 scores for Reader B Figure S1 AUC Frequency distribution in 1000 iterations |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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