Additional value of Diffusion Weighted Imaging in the detection and treatment of prostate cancer

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1 Additional value of Diffusion Weighted Imaging in the detection and treatment of prostate cancer Poster No.: C-2000 Congress: ECR 2013 Type: Scientific Exhibit Authors: A. F. Syed abbas hasan, A. J. Clark, C. George, A. D. C. Jacob; Stoke on Trent/UK Keywords: Pathology, Cancer, Staging, Outcomes analysis, Imaging sequences, MR-Diffusion/Perfusion, MR, Pelvis, Oncology, Genital / Reproductive system male DOI: /ecr2013/C-2000 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. Page 1 of 27

2 Purpose Prostate cancer (P ca) is the most common cancer diagnosis among North American and European men and causes significant morbidity and mortality. Recent advances in management of P ca like Active surveillance and focal therapies including Intensity Modulated Radiation Therapy ( IMRT), Cryotherapy and HighIntensity Focused Ultrasound (HIFU) have made accurate tumour detection, staging and delineation of tumour extent all the more important in current practice. 1)The purpose of our study is to assess the additional value of Diffusion Weighted Imaging (DWI) in the detection, treatment and surveillance of prostate cancer. 2)To illustrate the advantages of DWI in a wide range of clinical scenarios with appropriate clinical and histo-pathological correlation. Fig. 21: Quick over view of our presentation Page 2 of 27

3 References: Radiology, National Health Services, University Hospital North Staffordshire - Stoke on Trent/UK Images for this section: Fig. 1 Page 3 of 27

4 Fig. 21: Quick over view of our presentation Page 4 of 27

5 Methods and Materials st st All prostate MRI scans performed over a one year period (1 March 2011 to 1 March 2012) were included. Scans were performed on a 1.5 T Phillips magnet with a standard pelvic coil. Standard MRI sequences included a T1W axial, T2W axial, coronal and sagittal sequences through the pelvis. Diffusion weighted images were acquired using b0, b100, b400 and b800 gradient. Inbuilt Phillips software provided a corresponding ADC map using a mono-exponential gradient. All scans were double read by a panel of Radiologist (AC, CG, AJ) who have a special interest in urogenital radiology. Standard MRI sequences were first assessed. Additional findings identified on review of DWI were documented. These finding were compared with multidisciplinary meeting outcomes, follow up PSA levels, histo-pathological reports and clinical notes. Results 206 patients underwent MRI of the prostate in the study period. 6 patients were excluded due to non-diagnostic MR images. Page 5 of 27

6 Fig. 2 References: Radiology, National Health Services, University Hospital North Staffordshire - Stoke on Trent/UK 127 patients accounting for 62 % had additional finding on DWI that were not obvious on standard MRI sequences. These are categorised and discussed as below: Page 6 of 27

Fig. 3 References: Radiology, National Health Services, University Hospital North Staffordshire - Stoke on Trent/UK Tumour detection: Anterior prostate tumors are difficult to image and biopsy on

7 Fig. 3 References: Radiology, National Health Services, University Hospital North Staffordshire - Stoke on Trent/UK Tumour detection: Anterior prostate tumors are difficult to image and biopsy on TRUS. These contribute largely to the false negative rate of TRUS guided biopsy which has been reported to be between 11 and 25%. Benign prostatic hypertrophy changes in the transitional zone make assessment difficult on conventional T2W MRI. Diffusion weighted imaging has been shown to be useful in detecting prostate cancer and distinguishing it from other benign changes. It helps in targeting the tumour foci on TRUS biopsy with a high yield. Fig. 5 on page 10 Page 7 of 27

In our series 66 MRI scan were performed in patient with previously negative biopsies. MRI identified tumour in 21% of cases that were confirmed on subsequent biopsies.

8 In our series 66 MRI scan were performed in patient with previously negative biopsies. MRI identified tumour in 21% of cases that were confirmed on subsequent biopsies. More importantly no clinically significant tumour was identified in 59% of cases on MRI with good correlation with subsequent biopsies. Fig. 4 References: Radiology, National Health Services, University Hospital North Staffordshire - Stoke on Trent/UK Tumour volume estimation: Accurate measurement of tumor is important in determining prognosis and aid the clinicians in choosing the best treatment strategy. TRUS biopsies often underestimate the volume of disease especially in the central zone tumors. TW2 MRI alone has been shown to often over estimate volume of P ca. Addition of DWI to T2W MRI significantly improves the accuracy of prostate PZ tumor volume measurement. Fig. 6 on page 10 Page 8 of 27

9 Tumour staging: Post biopsy haemorrhage within the prostate causes significant low signal changes on T2 weighted images. Haemorrhage often exerts focal mass effect resulting in bulging of the capsule and signal distortion within the seminal vesicles. These changes cause considerable interpretational difficulties with frequent over staging as extra capsular spread. Diffusion weighed imaging has been shown to be helpful in detecting tumour within areas of haemorrhage. Fig. 7 on page 11, Fig. 8 on page 12 and Fig. 9 on page 13 Tumour Grade: P ca is graded according to the pathological appearance using gleason score. This is a sum of the primary and secondary pattern and is one of the most important prognostic factors. High Gleason score increases the potential of local spread, early lymphovascular involvement and distant metastases. Needle core biopsies have been known to underestimate the true aggressiveness of tumour. A number of studies have demonstrated a good correlation between ADC values on DWI and the Gleason score. Fig. 10 on page 14 Tumour distribution: IMRT Intensity Modulated Radiation Therapy (IMRT) is a technique of external conformal radiation planning and delivery. Boost doses using fluence maps (i.e., intensity maps) can be used to provide higher dose to the tumour load,with better sparing of surrounding normal tissue. Fusion T2 and high B value images are able to delineate the high risk Clinical Tumour Volume ( CTV) which is vital for treatment planning. Fig. 11 on page 15, Fig. 12 on page 16 and Fig. 13 on page 17 Apical tumours are under sampled on normal TRUS biopsies. Also presence of disease at the apex of the prostate,carries a significant risk of tumour spread along the apical neurovascular bundles. DWI helps delineate the location and extent of tumour which is useful in surgical planning. Fig. 15 on page 19 Page 9 of 27

10 In our case series, 50% of patients with apical tumour,who went on to have radical surgery had positive margins on histology. Extraprostatic findings : Life expectancy in patients with prostate cancer is very good due to natural history of prostate cancer, early detection and advances in treatment. However this cohort still carries the same risk of developing other cancers which often have more serious implications. Diffusion principles are similar in most neoplastic processes. 6 incidental tumours in the rectum, sigmoid and bladder were identified on high B value images which were not apparent of standard sequences. Fig. 18 on page 22, Fig. 19 on page 23 and Fig. 20 on page 24 Images for this section: Fig. 5: Tumour Detection, Anterior tumours are often missed on TRUS biopsy : Representative axial T2W images through the prostate apex (A), midgland (B), and base (C) show heterogeneous T2 signal in the central gland in keeping with BPH changes. There is a low T2 signal area anteriorly at the prostate base (C, green arrow) which shows diffusion restriction [high signal on B800 (E) and low on ADC (F)] in keeping with a cancerous focus. Page 10 of 27

Fig. 6: Tumour Volume Estimation, TRUS biopsies often underestimate the volume of disease, particularly in the central tumours : There is a large area of low T2 signal anteriorly

11 Fig. 6: Tumour Volume Estimation, TRUS biopsies often underestimate the volume of disease, particularly in the central tumours : There is a large area of low T2 signal anteriorly in the central gland (A, green arrow). T2W and B800 fusion image (B) and ADC map (C) show this area to be diffusion restricting in keeping with a large anterior tumour. Page 11 of 27

Fig. 7: Upstage, DW MRI allows for accurate ascertainment of tumour stage which has a bearing on patient management : Axial T1W (B) image through the midgland shows high signal in the peripheral

12 Fig. 7: Upstage, DW MRI allows for accurate ascertainment of tumour stage which has a bearing on patient management : Axial T1W (B) image through the midgland shows high signal in the peripheral zones bilaterally in keeping with post biopsy haemorrhage ( green arrows). There is low signal in the left peripheral zone on T2W (C). There is a further low signal area in the right peripheral zone extending to the right seminal vesicle [better seen on sagittal T2W (A)] which demonstrates diffusion restricting (D,E and F) in keeping with a focus of cancer (T3a) underlying haemorrhage. Page 12 of 27

13 Fig. 8: Downstage : T1W axial image (A) shows high signal in the left peripheral zone in keeping with post biopsy haemorrhage. This area has low signal on T2W (B) with capsular bulge raising suspicion of T3a disease. However ther is no diffusion restriction (C and D), hence can be confidently taken as an area of post biopsy haemorrhage with no underlying tumour. Page 13 of 27

14 Fig. 9: Downstage : Axial T1W image (A) shows high signal in the left seminal vesicle and low signal on corresponding T2W image (B). This area is not diffusion restricting (C and D) and can confidently be taken as an area of post biopsy haemorrhage with no underlying tumour. Page 14 of 27

Fig. 10: Tumour Grade: Representative axial T2W images through the base (A), midgland (D) and apex (G) show almost the entire prostate gland is replaced by low T2 signal, particularly the central

15 Fig. 10: Tumour Grade: Representative axial T2W images through the base (A), midgland (D) and apex (G) show almost the entire prostate gland is replaced by low T2 signal, particularly the central gland on the right. Corresponding fusion ( B,E,H) and ADC images ( C,F,I) show these areas to be diffusion restricting in keeping with prostate cancer. The mean ADC value measured was 0.96 mm(2)/s suggestive of low grade tumour. This was confirmed on prostatectomy which showed Gleason 3+3 disease throughout. Page 15 of 27

Fig. 11: Delineate tumour distribution which is vital in planning Intensity Modulated Radiation Therapy (IMRT): Axial T2W images through the prostate base (A),

16 Fig. 11: Delineate tumour distribution which is vital in planning Intensity Modulated Radiation Therapy (IMRT): Axial T2W images through the prostate base (A), midgland(b)and apex (C) with corresponding fusion images ( D,E, and F). Notice how the fusion images accurately demarcate the tumour distribution. Page 16 of 27

Fig. 12: Delineate tumour distribution which is vital in planning IMRT: Axial T2W (A) image shows a geographic area of low T2 signal in the central gland and the left peripheral zone.

17 Fig. 12: Delineate tumour distribution which is vital in planning IMRT: Axial T2W (A) image shows a geographic area of low T2 signal in the central gland and the left peripheral zone. This area shows high signal on B800 (B) and Fusion (C) images and is low on ADC (D) in keeping with prostate cancer. Notice how well the clinical tumour volume is demarcated on Fusion and ADC images which can be used for planning IMRT. Page 17 of 27

18 Fig. 13: Axial (A), sagittal (B) and coronal (C) Computed Tomography images fused with intensity maps. A combinations of multiple intensity-modulated fields coming from different beam directions produce a custom tailored radiation dose that maximizes tumor dose while also minimizing the dose to adjacent normal tissues. Page 18 of 27

Fig. 14: Surveillance in post radiotherapy patients: Axial T2W image (A, green arrow) shows a intermediate to low signal area in the right peripheral zone which demonstrates diffusion restriction (B

19 Fig. 14: Surveillance in post radiotherapy patients: Axial T2W image (A, green arrow) shows a intermediate to low signal area in the right peripheral zone which demonstrates diffusion restriction (B and C) in keeping with prostate cancer. The patient had radiotherapy (RT) to this area. Post RT images (D,E and F)show low signal in all the sequences in the RT field including the tumour in keeping with scarring( T2 blackout phenomenon). Two years post RT follow up images (G,H and I) show the irradiated area to remain low signal (green arrows), however there is a smaller intermediate to low T2 signal area anterior to it (purple arrows) which demonstrated diffusion restriction (H and I) and is in keeping with a focus of cancer recurrence. Page 19 of 27

Fig. 15: Delineate tumour distribution, apical Tumours often have positive margins on surgical resection: Sagittal T2W image in the right upper corner of the images shows the cross reference line

20 Fig. 15: Delineate tumour distribution, apical Tumours often have positive margins on surgical resection: Sagittal T2W image in the right upper corner of the images shows the cross reference line passing through the prostate apex. Axial T2W image shows low signal area in the anterior gland (A) which is diffusion restricting on Fusion and ADC images (B and C) in keeping with a large anterior tumour. Page 20 of 27

Fig. 16: 16)Highlight possible bone metastases and lymph-nodal involvement: Axial T1 and T2W images show a low signal area in the right ilium ( A and B, green

21 Fig. 16: 16)Highlight possible bone metastases and lymph-nodal involvement: Axial T1 and T2W images show a low signal area in the right ilium ( A and B, green arrows) which does not restrict diffusion (C and D). This area was cold on subsequent bone scintigraphy and was thought to represent a benign bone island. Page 21 of 27

Fig. 17: Highlight possible bone metastases and lymph-nodal involvement: Axial T1W image shows a low signal intensity area in the right acetabulum (A, green arrow).

22 Fig. 17: Highlight possible bone metastases and lymph-nodal involvement: Axial T1W image shows a low signal intensity area in the right acetabulum (A, green arrow). This area is diffusion restricting (B and C) and proved to be a metastases on bone scintigraphy. Axial B800 inversion (D) image of another patient shows two hot left inguinal lymph nodes(orange arrows). Page 22 of 27

Fig. 18: 18)Additional incidental tumour detection : Axial T2W weighted image shows a incidental focal area of bladder wall thickening in the right posterior wall (A, green arrow) which shows

23 Fig. 18: 18)Additional incidental tumour detection : Axial T2W weighted image shows a incidental focal area of bladder wall thickening in the right posterior wall (A, green arrow) which shows diffusion restriction on Fusion image and ADC map (B and C). This was proven to be a transitional cell carcinoma of the bladder on cystoscopy and biopsy. Images (D,E and F) show a diffusion restricting focus of prostate cancer in the right peripheral zone in the same patient. Page 23 of 27

Fig. 19: Additional incidental tumour detection: Sagittal T2W images in the left corner of the upper row show the cross reference lines 1 and 2 passing through the rectum and the prostate

24 Fig. 19: Additional incidental tumour detection: Sagittal T2W images in the left corner of the upper row show the cross reference lines 1 and 2 passing through the rectum and the prostate respectively. Axial T2W image (A, green arrow) shows a incidental mass in the proximal rectum which is diffusion restricting (B and C) and was proven to represent adenocarcinoma on biopsy. Images of the prostate gland in the same patient show a low T2 signal area in the left peripheral zone(d, green arrow) which is diffusion restricting (E and F) and suggestive of prostate carcinoma. Page 24 of 27

Fig. 20: Additional incidental tumour detection: Sagittal T2W images in the left corner of the upper row show the cross reference lines 1 and 2 passing through the rectum and the prostate

25 Fig. 20: Additional incidental tumour detection: Sagittal T2W images in the left corner of the upper row show the cross reference lines 1 and 2 passing through the rectum and the prostate respectively. Axial T2W image (A) shows a tiny area of eccentric mucosal thickening of the rectum at 3' O clock position (green arrow. This demonstrates diffusion restriction (B and C), and polyp was proven on endoscopy.. Images of the prostate gland show a low T2 signal area in the anterior gland (D, green arrow) which is diffusion restricting (E and F) and in keeping with prostate carcinoma. Page 25 of 27

26 Conclusion Diffusion weighted imaging is a robust technique with only 3 % of patients having a non-diagnostic examination. No specialist software is required as DWI is widely used in neuroradiology departments and images are acquired in a short span to time. In our experience 62% of patients had significant additional finding on DWI. DWI proved beneficial in all aspects of the patient journey, ranging from tumour detection, staging, treatment planning and surveillance. We recognise there is a learning curve with this technique and there are variations in image interpretation. Our review demonstrated an interobserver variability of less that 5% and a encouraging trend of corelation with histopathological outcomes. References Bott, S. R. J. R. J., Young, M. P. A. P. A., Kellett, M. J. J., & Parkinson, M. C. C. (2002). Anterior prostate cancer: is it more difficult to diagnose? BJU International, 89(9), doi: /j x x Daneshgari, F., Taylor, G. D., Miller, G. J., & Crawford, E. D. (1995). Computer simulation of the probability of detecting low volume carcinoma of the prostate with six random systematic core biopsies. Urology, 45(4), doi: /s (99)80051-x Hambrock, T., Somford, D. M., Huisman, H. J., van Oort, I. M., Witjes, J. A., Hulsbergen-van de Kaa, C. A., Scheenen, T., et al. (2011). Relationship between apparent diffusion coefficients at 3.0-T MR imaging and Gleason grade in peripheral zone prostate cancer. Radiology, 259(2), Radiological Society of North America. doi: /radiol Lips, I. M., van der Heide, U. A., Haustermans, K., van Lin, E. N. J. T., Pos, F., Franken, S. P. G., Kotte, A. N. T. J., et al. (2011). Single blind randomized phase III trial to investigate the benefit of a focal lesion ablative microboost in prostate cancer (FLAME-trial): study protocol for a randomized controlled trial. Trials, 12(1), 255. doi: / Nagarajan, R., Margolis, D., Raman, S., Sheng, K., King, C., Reiter, R., & Thomas, M. A. (2012). Correlation of Gleason scores with diffusion-weighted imaging findings of prostate cancer. Advances in urology, 2012, doi: /2012/ Nayyar, R., Singh, P., Gupta, N. P., Hemal, A. K., Dogra, P. N., Seth, A., & Kumar, R. (n.d.). Upgrading of Gleason score on radical prostatectomy specimen compared to the pre-operative needle core biopsy: an Indian Page 26 of 27

27 experience. Indian journal of urology#: IJU#: journal of the Urological Society of India, 26(1), doi: / Qayyum, A., Coakley, F. V., Lu, Y., Olpin, J. D., Wu, L., Yeh, B. M., Carroll, P. R., et al. (2004). Organ-confined prostate cancer: effect of prior transrectal biopsy on endorectal MRI and MR spectroscopic imaging. AJR. American journal of roentgenology, 183(4), Retrieved from Sakr, W. A., Tefilli, M. V., Grignon, D. J., Banerjee, M., Dey, J., Gheiler, E. L., Tiguert, R., et al. (2000). Gleason score 7 prostate cancer: a heterogeneous entity? Correlation with pathologic parameters and disease-free survival. Urology, 56(5), Retrieved from Tamada, T., Sone, T., Jo, Y., Yamamoto, A., Yamashita, T., Egashira, N., Imai, S., et al. (2008). Prostate cancer: relationships between postbiopsy hemorrhage and tumor detectability at MR diagnosis. Radiology, 248(2), Nature Publishing Group. doi: /radiol Wu, L.-M., Xu, J.-R., Ye, Y.-Q., Lu, Q., & Hu, J.-N. (2012). The clinical value of diffusion-weighted imaging in combination with T2-weighted imaging in diagnosing prostate carcinoma: a systematic review and meta-analysis. AJR. American journal of roentgenology, 199(1), doi: / AJR Personal Information Page 27 of 27

PI-RADS classification: prognostic value for prostate cancer grading

PI-RADS classification: prognostic value for prostate cancer grading Poster No.: C-1622 Congress: ECR 2014 Type: Scientific Exhibit Authors: I. Platzek, A. Borkowetz, T. Paulus, T. Brauer, M. Wirth, M.