MR Apparent Diffusion Coefficient (ADC) Quantification is an Imaging Biomarker Predicting Gleason Score grade in Patients with Prostate Cancer undergoing MRI-guided prostate biopsy
Juan C. Camacho1,2, Nima Kokabi1, Peter A. Harri1, Tracy E. Powell2, and Sherif G. Nour1,2

1Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA, United States, 2Interventional MRI Program, Emory University Hospital, Atlanta, GA, United States

Synopsis

The study objective is to investigate magnetic resonance Apparent Diffusion Coefficient Quantification (ADC) in prostate lesions and to correlate the values with the results of MRI-guided prostate targeted sampling. A prospective cohort of patients presenting with persistently elevated or rising serum prostate specific antigen (PSA) and at least one lesion suspicious for prostate cancer that underwent MRI guided targeted biopsy was evaluated. Thirty-five consecutive patients were recruited presenting with 179 suspicious lesions. ROC curve analysis demonstrates that ADC predicts the presence of malignancy and allows grade stratification and therefore, behaves as a non-invasive imaging biomarker.

Background and purpose

Prostate cancer is the most common solid organ cancer in men (1). The main objective of current non-invasive imaging techniques is to detect early-stage disease that is biologically aggressive in an attempt to offer timely curative treatments. The currently used screening and diagnostic tools include digital rectal examination; serum prostate-specific antigen (PSA) and non-targeted transrectal ultrasound (TRUS)–guided biopsy (3). Because of the limitations and poor specificity of the available diagnostic tools, significant efforts are being made into improving prostate cancer detection. It has been postulated that multiparametric MRI is useful in the detection and risk stratification of prostate cancer (4) and also, that MRI can serve as a real-time guide to adequately sample suspicious lesions in the prostate (5). Therefore, the objective of this study is to investigate magnetic resonance diffusion weighted imaging (DWI) quantification (or Apparent Diffusion Coefficient Quantification (ADC)) in suspicious prostate lesions as an imaging biomarker of malignancy, and to correlate the values with the results of MRI-guided prostate targeted sampling.

Materials and Methods

IRB approved HIPAA compliant retrospective review of a 12-month period prospective cohort of patients presenting with persistently elevated or rising serum prostate specific antigen (PSA) and at least one lesion suspicious for prostate cancer that underwent MRI guided targeted biopsy. Diagnostic and interventional procedures were performed using a 32-element surface pelvic array coil on a 3T MAGNETOM Trio system (Siemens Medical Solutions, Erlangen, Germany). Single shot echo planar DWI was performed with tridimensional diffusion-encoding gradients utilizing b-values of 0, 1000, 1500 and 2000 s/mm2 (TR = 6000 ms / TE = 89 ms / NSA = 7 / FOV = 300 mm / phase over sampling = 50% / slice thickness = 3 mm / BW = 1736 / base resolution = 160 / Ipat = 2 / TA = 7:20 min). Subsequent targeted biopsies of suspicious lesions were performed following transrectal placement of a Dyna-TRIM biopsy system (Invivo, Gainesville, FL). Pre-procedural imaging allowed identification of the transrectal fiducial line, target lesions, and tridimensional trajectory. Pathology results per lesion were correlated to pre-procedural ADC quantification. ADC was measured by placing a region of interest (ROI) in each lesion and in normal prostate tissue within the central and peripheral zones to assure consistency in each patient. Correlation between ADC values of tumors and anatomic pathology was evaluated with paired t-test. Receiver operating characteristic (ROC) curves were made to analyze ADC performance in discriminating low- and high-grade tumors (α=0.05).

Results

Thirty-five consecutive patients were recruited (mean age 63, range 55-82). Average PSA level was 9.3 ng/mL (median 7.76 ng/mL; SD 6.4 ng/mL). 179 suspicious lesions were successfully biopsied (Average number of lesions per patient 5, range 2-8) and all samples were deemed diagnostic. ADC values of the normal tissue in the central zone were significantly lower when compared to the peripheral gland (ADC value of the peripheral zone was 1,27 mm2/sec vs. ADC value of the central gland 0,97 mm2/sec, p<0.001). Overall cancer detection rate was 19/35 (54.2%). Pathology results were benign (inflammation) in 133 lesions (74.3%), and malignant in 43 lesions (24.7%), with low-grade cancer (Gleason score 6) in 12/179 (6.7%); and intermediate to high-grade cancer (Gleason score > 7) in 31/179 (17.3%). ADC values of intermediate and high-grade lesions (mean ADC = 0.685 mm2/sec, SD 0.109 mm2/sec) were significantly lower than low-grade lesions (mean ADC = 0.767 mm2/sec, SD 0.080 mm2/sec; p = 0.01). Also, all grades of prostate cancers demonstrated significantly restricted diffusion compared to benign lesions (mean ADC=0.877 mm2/sec, SD 0.162 mm2/sec; p <0.001). ROC curves are shown below (Figures 1 and 2). Figure 3 illustrates an example of a malignant lesion.

Conclusion

Non-invasive quantitative ADC measurement is a reliable imaging biomarker for predicting malignancy and stratifying cancer risk in patients with persistently elevated or rising serum prostate specific antigen (PSA) levels and suspicious focal prostate abnormalities undergoing targeted tissue sampling under MRI guidance.

Acknowledgements

No financial support was received for this clinical study. The location of the study, the facilities and the study subjects were recruited at Emory University Affiliated Hospitals, Atlanta, Georgia, US.

References

(1) Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin 2010; 60:277–300

(2) Heidenreich A, Bastian PJ, Bellmunt J. Guidelines on prostate cancer. Arnhem, The Netherlands: European Association of Urology, 2012

(3) Barentsz JO, Richenberg J, Clements R, et al.; European Society of Urogenital Radiology. ESUR prostate MR guidelines 2012. Eur Radiol 2012; 22:746–757

(4) Puech P, Sufana Iancu A, Renard B, Villers A, Lemaitre L. Detecting prostate cancer with MRI: why and how. Diagn Interv Imaging 2012; 93:268–278

(5) Robertson NL, Emberton M, Moore CM. MRI-targeted prostate biopsy: a review of technique and results. Nat Rev Urol. 2013 Oct; 10(10): 589-97.

Figures

Figure 1. ROC curve analysis demonstrates that for an AUC of 0.841, the sensitivity and specificity of predicting malignancy tumor with a baseline lesion ADC value of 0.778 mm2/s were 81.4% and 78.9%, respectively.

Figure 2. ROC curve analysis demonstrates that for an AUC of 0.773, the sensitivity and specificity for differentiating low grade vs. intermediate - high grade cancer with a baseline lesion ADC value of 0.741 mm2/s were 74.2% and 81.8%, respectively.

Figure 3. T2W, DWI (b = 2000) and ADC map of a suspicious lesion located within the prostate apex, in the left peripheral zone (Yellow arrow). Pathology confirmed adenocarcinoma (Gleason 4+3=7). Note the significant restriction of the lesion (ADC=0.643 mm2/s)



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
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