The Evolving Role of Imaging in Identification and Management of Prostate Cancer

Introduction

RIUS0001(Cytogen)_04-12.qxd 12/4/06 13:15 Page S1 INTRODUCTION The Evolving Role of Imaging in Identification and Management of Prostate Cancer David G. McLeod, MD, JD Department of Urology, Walter Reed Army Medical Center, Washington, DC and Center for Prostate Disease Research, Rockville, MD [Rev Urol. 2006;8(suppl 1):S1-S3] © 2006 MedReviews, LLC rostate cancer is the most common cancer in men. The disease is newly diagnosed in more than 230,000 men and responsible for more than 30,000 deaths each year in the United States.1 Recent trends from the National Cancer Institute Surveillance, Epidemiology, and End Results program demonstrate that approximately 90% of prostate cancer patients, regardless of race, were diagnosed with localized prostate cancer between 1995 and 2000.1 However, one of the great challenges of this malignancy is the determination of the extent P VOL. 8 SUPPL. 1 2006 REVIEWS IN UROLOGY S1 RIUS0001(Cytogen)_04-12.qxd 12/4/06 13:15 Page S2 Introduction continued of disease, which remains a critical issue for the selection of appropriate therapy. It is possible to make some predictions about confinement of the disease based on pathologic evaluation of biopsy samples and serum prostate-specific antigen (PSA) values, but these data do not always provide adequate information about exact disease location or extent. Predictive nomograms are useful to prognosticate about local extension or seminal vesicle involvement. The accuracy is much lower for prediction of lymph node involvement, however, because the existing databases rely on tissue from only a limited sample of the potential area of lymphatic spread. Lymph node metastasis is definitely underestimated, when one considers the 4- and 5-year progression-free rates for extended lymph node dissection (39% and 43%, respectively).2,3 Even patients in the low-risk category have a higher rate of lymph node metastasis than predicted by nomograms.3 Various forms of noninvasive imaging have been used to evaluate patients with prostate cancer, but the clinical utility of standard crosssectional imaging is limited because a relatively large volume of disease generally is required for detection. However, several advances in imaging technology are now available, along with new modalities for molecular imaging. In addition, the diagnostic use of light sources may enhance accuracy of prostate cancer localization when combined with advances in imaging resolution, providing significant promise for future improvements in imaging capabilities. Positron emission tomography (PET) measures the metabolism of a radiolabeled analog in tissue, and the higher metabolic rate of neoplasia registers an increased scintigraphic signal, which is more pronounced in highly aggressive tumors. Although the most S2 VOL. 8 SUPPL. 1 2006 commonly used radiotracer for PET is 18 F-fluoro-2-deoxyglucose (FDG), this analog is not particularly useful in evaluating prostate cancer because of the relatively low glycolytic rate of most localized or metastatic prostate cancers.4,5 However, several newer positron-emitting agents have shown some utility for prostate cancer imaging that is not based solely on tumor metabolism. Unlike 18F-FDG, the 11C derivatives of methionine, acetate, and choline avoid renal excretion and artifactual signal in the bladder to allow clearer identification of juxtavesicular disease.6 Co-registration of functional PET images with anatomic computerized tomography (CT) data improves anatomic localization for many tumors, though this has not proven beneficial for prostate cancer detection. Magnetic resonance imaging (MRI) may be significantly enhanced by the use of ultrasmall superparamagnetic iron oxide particles coated with dextran. Lymph nodes with metastatic disease demonstrate persistent highintensity signal in areas of tumor. Performance characteristics of an MRI with lymphotrophic particles when compared with MRI alone are in the high 90 percentiles in recent tissueconfirmed studies, and noncontiguous lymph node disease was also detected.7 Imaging with this contrast agent is independent of tumor metabolic activity, unlike PET, which requires high metabolic activity to register signal. Radioimmunoscintigraphy acquires images through the use of a radiolabeled antibody that recognizes prostate tissue. The most studied antigen is prostate-specific membrane antigen (PSMA), which is expressed in prostate cells and upregulated in higher-grade cancer, androgen-insensitive cancer, and metastatic deposits.8-12 The most intensively studied monoclonal antibody conjugate to PSMA is capromab pendetide (ProstaScint ®; Cytogen Corporation, REVIEWS IN UROLOGY Princeton, NJ), a 100-kd type II transmembrane glycoprotein that recognizes an intracellular epitope.13 Several other candidates, primarily with external epitopes, have been evaluated, but none have been approved for general use.14 Despite controversy about the utility of an antibody to an internal epitope, and the question of whether this antibody recognizes live tissue, capromab pendetide has been shown to bind to live cells. This finding has been documented by several studies that show a high correlation between pathologic specimens and scans.15-18 Major advances in image acquisition and image co-registration have significantly enhanced the accuracy of disease detection with the capromab 7E11 radioimmunoconjugate. Dualhead gamma cameras combined with the fusion of functional single-photon emission tomography (SPECT) and an anatomic image (CT or MRI) have now made a dramatic difference in prostate cancer detection.18-20 Localization accuracy has doubled, and tissue confirmation of scan results now demonstrates an accuracy of 83% with fused images.19,20 Clinical outcomes data related to PSMA and capromab pendetide scan results now strengthen the case for use of this radioimmunoconjugate. Overexpression of PSMA in prostate cancer has been associated with higher recurrence rates and a faster time to recurrence.21 The 7-year data on a large patient cohort who received altered radiation dose based on scan results show superior results across all risk categories compared with the 5-year meta-analysis of brachytherapy patients.22 Furthermore, patients with scan-positive findings outside the pelvis had a 3-fold increase in biochemical disease recurrence, regardless of risk category. The suggestion that variations of signal intensity within the prostate may be a guide for RIUS0001(Cytogen)_04-12.qxd 12/4/06 13:15 Page S3 Introduction altering therapeutic dose with either radiation or cryotherapy has led to the initiation of several studies. In addition, recent studies with external beam radiotherapy also suggest that fused scans will be more suitable for patient selection and for localization for targeted therapy in this patient population.23 These fused scans are also now being used for further evaluation in patients with rising PSA levels after prostatectomy, prior to salvage radiation. It is clear that our ability to more accurately detect and appropriately treat prostate cancer depends on enhanced imaging capabilities for selecting patients and monitoring therapy. Fortunately, technological advances and a better understanding of biological mechanisms provide these opportunities. The evaluation of fluorocarbon microbubble ultrasound contrast agents and MRI spectroscopy offer the potential to improve intraprostatic tumor detection. Optical coherence tomography, which uses diffuse reflectance of infrared light to image subepithelial structures, has shown promise in identifying neurovascular tissue and radiation effects. Future applications of technologies such as electron paramagnetic resonance imaging, which detects tumor hypoxia and requires 650 times less energy than MRI, and hyperspectral imaging with multiple wavelengths of light promise further refinements of our ability to image tissues for diagnosis. Imaging is clearly in a dynamic process of evolution, which will have an increasing impact on our ability to detect and manage prostate cancer. This supplement is designed to provide the reader with a glimpse of some of these exciting developments. 13. 14. References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. Jemal A, Murray T, Ward E, et al. Cancer statistics, 2005. CA Cancer J Clin. 2005;55:10-30. Allaf ME, Palapattu GS, Trock BJ, et al. Anatomical extent of lymph node dissection: impact on men with clinically localized prostate cancer. J Urol. 2004;172:1840-1844. Bader P, Burkhard FC, Markwalder R. Disease progression and survival of patients with positive lymph nodes after radical prostatectomy: is there a chance of cure? J Urol. 2003;169:849854. Hain SF, Maisey MN. Positron emission tomography for urological tumours. BJU Int. 2003;92: 159-164. Shvarts O, Han KR, Seltzer M, et al. Positron emission tomography in urologic oncology. Cancer Control. 2002;9:335-342. Schoder H, Larson SM. Positron emission tomography for prostate, bladder, and renal cancer. Semin Nucl Med. 2004;34:274-292. Harisinghani MG, Barentsz J, Hahn PF, et al. Noninvasive detection of clinically occult lymph-node metastases in prostate cancer. N Engl J Med. 2003;348:2491-2499. Horoszewicz JS, Kawinski F, Murphy GP. Monoclonal antibodies to a new antigenic marker in epithelial prostatic cells and serum of prostatic cancer patients. Anticancer Res. 1987;7:927-935. Israeli RS, Powell CT, Fair WR, Heston WD. Molecular cloning of a complementary DNA encoding a prostate-specific membrane antigen. Cancer Res. 1993;53:227-230. Wright GL Jr, Grob BM, Haley C, et al. Upregulation of prostate-specific membrane antigen after androgen-deprivation therapy. Urology. 1996;48: 326-334. Silver DA, Pellicer I, Fair WR, et al. Prostatespecific membrane antigen expression in normal and malignant human tissues. Clin Cancer Res. 1997;3:81-85. Rochon YP, Horoszewicz JS, Boynton AL, et al. 15. 16. 17. 18. 19. 20. 21. 22. 23. Western blot assay for prostate-specific membrane antigen in serum of prostate cancer patients. Prostate. 1994;25:219-223. Troyer JK, Beckett ML, Wright GL Jr. Location of prostate-specific membrane antigen in the LNCaP prostate carcinoma cell line. Prostate. 1997;30:232-242. Smith-Jones P, Vallabhajosula S, Navarro V, et al. Radiolabeled monoclonal antibodies specific to the extracellular domain of prostatespecific membrane antigen: preclinical studies in nude mice bearing LNCaP human prostate tumor. J Nucl Med. 2003;44:610-617. Manyak MJ, Hinkle GH, Olsen JO, et al. Immunoscintigraphy with 111In-capromab pendetide: evaluation before definitive therapy in patients with prostate cancer. Urology. 1999;54: 1058-1063. Barren RJ, Holmes EH, Boynton AL, et al. Monoclonal antibody 7E11.C5 staining of viable LNCaP cells. Prostate. 1997;30:232-242. Hinkle GH, Burgers JK, Neal CE, et al. Multicenter radioimmunoscintigraphic evaluation of patients with prostate carcinoma using indium-111 capromab pendetide. Cancer. 1998;3:739-747. Sodee DB, Nelson AD, Faulhaber PF, et al. Update on fused capromab pendetide imaging of prostate cancer. Clin Prostate Cancer. 2005;3: 230-238. Schettino CJ, Kramer E, Noz M, et al. Impact of fusion of indium-111 capromab pendetide volume data sets with those from MRI or CT in patients with recurrent prostate cancer. AJR Am J Roentgenol. 2004;183:519-524. Wong TZ, Turkington TG, Polascik TJ, Coleman RE: ProstaScint (capromab pendetide) imaging using hybrid gamma camera-CT technology. AJR Am J Roentgenol. 2005;184:676-680. Ross JS, Sheehan CE, Fisher HA, et al. Correlation of primary tumor prostate-specific membrane antigen expression with disease recurrence in prostate cancer. Clin Cancer Res. 2003;9: 6357-6362. Ellis RJ, Kim EY, Zhou H, et al. Seven-year biochemical disease-free survival rates following permanent prostate brachytherapy with dose escalation to biological tumor volumes (BTVs) identified with SPECT/CT image fusion [abstract 121]. Brachytherapy. 2005;4(2):107. Jani AB, Blend MJ, Hamilton R, et al. Radioimmunoscintigraphy for postprostatectomy radiotherapy: analysis of toxicity and biochemical control. J Nucl Med. 2004;45:1315-1322. VOL. 8 SUPPL. 1 2006 REVIEWS IN UROLOGY S3