Prostate Cancer: Radiological Diagnosis, Staging, and Detection of Metastasis

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1 Prostate Cancer: Radiological Diagnosis, Staging, and Detection of Metastasis Laura Rosow, HMS III Gillian Lieberman, MD BIDMC Core Clerkship in Radiology February 23, 2009 PACS, BIDMC

2 Outline I. Index patient II. Overview of prostate cancer III. Prostate anatomy IV. Role of imaging in the diagnosis/staging of prostate cancer V. Detecting osseous metastases

3 Part I: Index Patient

4 TM a 69 year-old male Patient TM : Presentation and history On routine lab work at his PCP s office: Prostate specific antigen (PSA): 5.5 ng/ml Increased from 5 years prior, when his PSA was 3.0 ng/ml Calculated PSA velocity: 0.5 ng/ml per year PMH/PSH: s/p Repair of tibial plateau fracture s/p TURP for alleviation of prostatitis no cancer found at that time.

5 On the basis of TM s moderately elevated PSA and PSA velocity, a decision was made to perform a transrectal ultrasound (TRUS)-guided prostate biopsy.

6 Patient TM: TRUS-guided prostate biopsy PROSTATE GLAND PACS, BIDMC 10 core biopsies were taken from throughout the prostate gland.

7 Patient TM: Biopsy findings Left mid-gland adenocarcinoma, Gleason score 6/10, involving 5-10% of core biopsy Right base adenocarcinoma, Gleason score 6/10, involving 30% of core biopsy High-grade prostatic intraepithelial neoplasia (PIN) throughout left base.

8 In order to further characterize the size and extent of TM s prostate cancer, an endorectal MRI was performed.

9 Patient TM: Endorectal MRI PROSTATE GLAND RECTUM (dilated with balloon) T2 Axial Contrast-Enhanced MRI PACS, BIDMC

10 Patient TM: MRI finding #1 Focus of prostate cancer in right peripheral zone. No extracapsular extension. CANCER HEMORRHAGE (normal post-biopsy change) T2 Axial Contrast-Enhanced MRI PACS, BIDMC

11 Patient TM: MRI finding #2 Left lobe mid-gland peripheral zone prostate cancer, 11mm. No extracapsular extension. CANCER T2 Axial Contrast-Enhanced MRI PACS, BIDMC

12 Patient TM: Staging and treatment Given that TM s cancer was bilateral, yet confined to the prostate gland, his cancer was STAGE II. Some of his treatment options included*: Expectant management (aka watchful waiting ) Radical prostatectomy Brachytherapy +/- adjuvant hormonal therapy TM opted for 4 months of hormonal therapy, followed by brachytherapy. 5 months following brachytherapy, a repeat PSA was 0.1 ng/ml. *Schroder FH et al (2008). Clinical Decisions: Management of Prostate Cancer. NEJM:359(24):

13 Part II: Prostate Cancer Overview

14 Prostate cancer statistics Prostate cancer is the second-most common cancer in American men. It is the second-most common cause of cancer-related deaths in men. It is estimated that 1 in 6 men will develop prostate cancer in their lifetime. However, only 1 in 34 men will die from prostate cancer.

15 Classification of prostate cancer TNM Staging Tumor size, Nodal involvement, distant Metastasis Gleason Grade Cancer can be local, locally advanced, or metastatic Further classified by C stage and P stage: C = clinical, determined by DRE and ultrasound exam P = pathological, determined on exam of tissue biopsy Analyzes glandular differentiation and structural architecture of biopsy as an approximation of tumor aggressiveness Scored from 2-10, with 10 being the most aggressive

16 Screening and diagnosis of prostate cancer SCREENING DRE (detects tumors in posterior and lateral prostate gland) PSA general guidelines: Absolute value > 10 BIOPSY Absolute value 4-10 Patient/physician discretion PSA velocity > 2 ng/ml per year BIOPSY Molecular detection in urine* DIAGNOSIS Biopsy: US- or MR-guided * Fradet Y et al (2004). upm3, a new molecular urine test for the detection of prostate cancer. Urology 2004 Aug;64(2):311-5.

17 Part III: Prostate Anatomy Review

18 Male reproductive tract Rush University Medical Center

19 Prostate and seminal vesicles U.S. National Cancer Institute

20 Prostate anatomy on digital rectal examination (DRE) ANTERIOR GLAND (not palpable) POSTERIOR GLAND (readily palpable) LATERAL GLAND (usually palpable) UpToDate

21 Prostate anatomy on endorectal MRI Transverse/axial Coronal Sagittal Images courtesy of Nicolas Bloch, MD

22 Prostate anatomy on endorectal MRI: Labeled Transverse/axial Coronal Sagittal PERIPHERAL ZONE CENTRAL GLAND (transition + central zones) SEMINAL VESICLES BASE MID-PROSTATE APEX

23 Part IV: Role of imaging in the diagnosis and staging of prostate cancer

24 Radiologic tests most commonly used for diagnosing/staging prostate cancer Transrectal ultrasound Endorectal MRI Bone scan Arnold Krongrad, MD We will now discuss each of these imaging modalities individually.

25 But first Why is radiological staging of prostate cancer so important?

26 Significance of appropriate radiological staging Different stages of prostate cancer are managed with different treatment modalities. Accurate staging ensures that a patient will receive the most appropriate therapy for his prostate cancer. In addition, it reduces morbidity associated with potentially unnecessary procedures.

27 Transrectal Ultrasound (TRUS) Uses: Biopsy Cancer screening (not recommended due to poor sensitivity) Study: nearly 40% of prostate cancers would be missed if biopsied on the basis of abnormal TRUS alone.* Prostate gland measurement, calculation of PSA density Therapy (brachytherapy seed implantation, cryotherapy) PROS - simple, outpatient procedure - reasonably well-tolerated - inexpensive CONS - low sensitivity, low PPV - large inter-observer variability - transrectal approach intolerable for some * Catalona WJ et al (1994). Comparison of digital rectal examination and serum prostate specific antigen in the early detection of prostate cancer: results of a multicenter clinical trial of 6,630 men. Journal of Urology: 151(5):

28 TRUS as an aid to biopsy PACS, BIDMC This is TM s ultrasound. Only 3 images were captured, as the primary purpose of the ultrasound was to localize the prostate for biopsy. There was little need to capture multiple views.

29 Approach to prostate biopsy = Traditional sextant approach: biopsies are taken from the base, mid-prostate, and apex bilaterally = Extended biopsy: 10 or more biopsies are taken Scientific Electronic Library Online:

30 Companion patient #1: TRUS as a diagnostic tool 60 yo male with PSA of Biopsy later confirmed prostatic adenocarcinoma of the left base. Prostate cancer typically appears as a hypoechoic nodule on TRUS. Greater than 20 images were taken from a multitude of views to aid in diagnosis. PACS, BIDMC

31 DDx: Differential diagnosis of a hypoechoic nodule on TRUS 1. Benign hyperplasia 2. Prostate adenocarcinoma A 2005 study* looked at 472 men suspected of having prostate cancer, all of whom were found to have a hypoechoic nodule on TRUS-guided biopsy: 65.68% had benign findings on histopathology 34.32% had prostate adenocarcinoma * Tang J et al (2005). Correlation between hypoechoic nodules on ultrasonography and benign hyperplasia in the prostatic outer gland. Journal of Ultrasound Medicine 24:

32 Endorectal MRI Uses: Prostate cancer detection Local and distant staging Accuracy in staging prostate cancer ranges from 54-93%* Guide biopsy PROS - Superior detection of tumors in transition zone and anterior prostate - Excellent resolution allows fairly accurate assessment of tumor size, invasion - Multiple scanning paradigms allow for a variety of images CONS - Large inter-observer variability noted* - Time-consuming, uncomfortable - Expensive - Must wait as long as 6-8 weeks postbiopsy, as hemorrhage may hamper tumor detection* *Hricak H et al (2007). Imaging Prostate Cancer: A Multidisciplinary Perspective. Radiology:23(1);28-53

33 Endorectal MRI: Rectal coils Image courtesy of Nicolas Bloch, MD

34 Companion Patient #2 58 year-old male with PSA of 7.2, elevated PSA velocity, and microhematuria. Large central cancer with extracapsular invasion (stage T3b). This appears as an area of lower signal intensity. T2 Axial Contrast-Enhanced MRI PACS, BIDMC

35 Companion Patient #2 58 year-old male with PSA of 7.2, elevated PSA velocity, and microhematuria. BPH T2 Axial Contrast-Enhanced MRI PACS, BIDMC

36 DCEMRI Dynamic Contrast Enhanced MRI (DCEMRI) analyzes contrast wash-in and wash-out rates. Tumor-induced changes in vascular permeability allow us to detect cancerous lesions.* Images courtesy of Nicolas Bloch, MD T2 axial Parametric DCEMRI map Companion patient #3: Patient had an elevated serum PSA and negative TRUS-guided biopsy. Cancer later confirmed on MR-guided biopsy. *Lenkinksi et al (2008). An illustration of the potential for mapping MRI/MRS parameters with genetic over-expression profiles in human prostate cancer. Magn Reson Mater Phys 21:

37 Part V: Detecting osseous metastases

38 Prostate cancer metastasis Bone is the most common site of prostate cancer metastasis 5% of patients have bone mets at presentation Radionuclide bone scan is a sensitive method of detecting osseous metastases, particularly those that are osteoblastic. PSA guidelines: PSA ng/ml 10% incidence of positive bone scan PSA >50 ng/ml 50% incidence Many radiologists recommend reserving bone scanning for symptomatic patients or patients with a PSA >10 ng/ml.* *Hricak et al (2007)

39 Basics: Radionuclide Bone Scan: More information Technitium-99-MDP (methylene diphosphonate) is injected into the patient. This radiotracer is preferentially taken up in areas of active bone formation. Thus, osteoblastic metastases (typical of prostate cancer) appear hot on bone scan. Confirmation: Men who have a positive or equivocal bone scan are often further worked up with plain radiographs or an MRI.

40 Application of the bone scan to TM: our index patient Over a 1-year period following treatment, TM s PSA rose from 0.1 to 14.3 ng/ml. He was asymptomatic. A bone scan was performed and was equivocal. When his PSA remained elevated, a repeat scan was performed 5 months later. This repeat scan showed a new sclerotic focus, consistent with metastatic disease.

41 Patient TM: Bone scans 12 months postbrachytx 17 months postbrachytx Increased uptake at L1 consistent with metastatic disease. PACS, BIDMC PACS, BIDMC

42 Patient TM: further workup and treatment course An MRI was then performed, which confirmed this lesion as an osteoblastic metastasis. TM began a second course of hormonal therapy. His most recent scan showed no lesions (except for a minor compression fracture), compatible with successfully treated metastasis. TM will continue to be monitored regularly for recurrence throughout his treatment. PACS, BIDMC

43 Summary Prostate cancer presents in many different forms and levels of severity, and there are numerous therapeutic options available. Appropriate use of imaging techniques allows for the timely diagnosis and staging of prostate cancer, as well as the formulation of the most appropriate treatment plan for each patient. We have reviewed several imaging modalities and their utility in prostate cancer, including: TRUS: biopsy and diagnosis Endorectal MRI and DCEMRI: biopsy, diagnosis, and staging Radionuclide bone scan: detection of osseous metastases

44 Thank you for your time and attention!

45 Acknowledgments Dr. Gillian Lieberman Radiology Course Director Maria Levantakis Radiology Education Coordinator Dr. Robert Kane for help with TRUS Dr. Nicolas Bloch for help with endorectal MRI, DCEMRI and images Dr. Robert Lenkinski for help with endorectal MRI and DCEMRI Mark Stahlhammer for Photoshop expertise

46 References Catalona WJ, Richie JP, Ahmann FR, Hudson MA, Scardino PT, Flanigan RC, dekernion JB, Ratliff TL, Kavoussi LR, Dalkin BL (1994). Comparison of digital rectal examination and serum prostate specific antigen in the early detection of prostate cancer: results of a multicenter clinical trial of 6,630 men. Journal of Urology; 151(5): Fradet Y, Saad F, Aprikian A, Dessureault J, Elhilali M, Trudel C, Masse B, Piche L, Chypre C (2004). upm3, a new molecular urine test for the detection of prostate cancer. Urology; 64(2): Hricak H, Choyke PL, Eberhardt SC, Leibel SA, Scardino PT (2007). Imaging Prostate Cancer: A Multidisciplinary Perspective. Radiology; 23(1):28-53 Lenkinksi RE, Bloch BN, Liu F, Frangioni JV, Perner S, Rubin MA, Genega EM, Rofsky NM, Gaston SM (2008). An illustration of the potential for mapping MRI/MRS parameters with genetic over-expression profiles in human prostate cancer. Magn Reson Mater Phys; 21: Kantoff P, Taplin ME (2008). Overview of the clinical presentation, diagnosis, and staging of prostate cancer. UpToDate Schroder FH, Roach M 3 rd, Scardino P (2008). Clinical Decisions: Management of Prostate Cancer. NEJM; 359(24): Tang J, Li X, Wang N, Zhang S, Lin Q, Li J, Shi H (2005). Correlation between hypoechoic nodules on ultrasonography and benign hyperplasia in the prostatic outer gland. Journal of Ultrasound Medicine; 24:

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