Horizon Scanning Technology Briefing National Horizon Scanning Centre Magnetic resonance spectroscopy for prostate cancer August 2006 This technology briefing is based on information available at the time of research and a limited literature search. It is not intended to be a definitive statement on the safety, efficacy or effectiveness of the health technology covered and should not be used for commercial purposes.
Magnetic resonance spectroscopy for prostate cancer Target group Identification and localisation of prostate cancer in men with elevated prostate specific antigen (PSA) or histopathology confirmed prostate cancer prior to prostatectomy. Technology description Magnetic resonance spectroscopy (MRS) is an add-on option to current high-field strength magnetic resonance imaging (MRI) systems. MRS measures the level of specific chemicals (including choline, creatine, citrate and lactate) in the targeted tissue. The MRS software displays a waveform with peaks corresponding to various chemicals being detected. By studying the relative quantities of chemicals in the tissue, cellular activity and the presence of malignant cells can be determined. Following a routine MR scan the MRS region of interest, called a voxel (typically a 1-2 cm cube of tissue), is targeted and the MRS waveform generated for that voxel. Some MRS systems can evaluate multiple voxels simultaneously. Data acquisition takes approximately 15 to 20 minutes. The technical quality of MRS information is improved using higher-field strength magnets (e.g. 1.0, 1.5 or 3.0 Tesla). MRS in men with prostate cancer has been undertaken in most published trials using an endorectal coil, which is invasive and can distort regional anatomy. MRS is used, or has been studied, in the diagnosis, evaluation and management of patients with brain tumours, strokes, oxygen deprivation, epilepsy and multiple sclerosis. High quality research evidence on diagnostic and clinical utility is scarce. 1,2 Innovation and/or advantages Expert opinion is that this technique could be used to detect cancer and perhaps reduce the need for biopsy in men with elevated PSA. Developer Add-on options to current MRI systems are available from several manufacturers including Siemens, Philips Medical Systems and GE Medical Systems. Purpose Diagnosis or identification of disease Prevention e.g. immunisation, public health programme Continuous therapy e.g. dialysis, life support Service delivery changes Investigation, assessment or staging of known disease Screening programme or tests to identify latent or early disease Patient management and pathways of care Other: Susceptibility testing for identifying risk of disease Individual treatment e.g. drug, device, procedure, radiotherapy Rehabilitation Place of use Home care e.g. home dialysis Secondary care e.g. general, non-specialist hospital General public e.g. over the counter Community or residential care e.g. district nurses, physio Tertiary care e.g. highly specialist services or hospital Other: Primary care e.g. used by GPs or practice nurses Emergency care e.g. paramedic services, trauma care Aug 2006 2
Stage of development and availability in EU/UK Phase III clinical trials or Pre-registration in EU (drugs) equivalent Licence or CE mark application in Licence or CE mark application in UK/EU likely within 12 months UK/EU likely within 24 months Launch or use in UK/EU likely Established product, but this is a within 24 months new indication in development CE marked, but not yet launched or available in UK Launch or use in UK/EU likely within 12 months Other: already available in some centres. Add on MRS options will become more widespread in 2007/8 with newer MR machines installed under the cancer plan. Approval and/or availability in the USA and/or Canada Licensed for use in the USA Available for use in USA and/or and/or Canada Canada Details: Fast track designation in USA NHS or Government priority area: Cancer Cardiovascular disease Children Diabetes Chronic conditions Mental health Older people Public health Renal disease Women s health None identified Other: Relevant guidance A NICE clinical guideline on the diagnosis and treatment of prostate cancer is due to be published in November 2007. Clinical need and burden of disease The incidence of prostate cancer has been increasing, and in 2002 there were almost 28,000 men registered with prostate cancer in England and Wales. There were just over 9,000 deaths from prostate cancer in 2003. For men diagnosed in 2000 or 2001 the 5-year survival around 70%. Existing comparators and treatments Investigation of symptoms: PSA test; digital rectal examination (DRE); clinical examination of the abdomen and inguinal lymph nodes. Confirmation of diagnosis: prostate core needle biopsy for histopathology with transrectal ultrasound for visualisation. Staging and localisation: there are no accepted radiographic tests with a high enough specificity and sensitivity for reliable staging and localisation. CT scanning and MRI can be used, but accuracy can be poor and clinical utility is unknown. Nuclear imaging can be used to detect distant metastases. Clinical utility No published trials evaluating the clinical utility of MRS (i.e. the ability of MRS to change the patient care pathway or outcome) have been identified. Analytical and clinical validity A study in 48 men prior to radical prostatectomy compared MR alone, MR with MRS, and histopathology. 3 The study found false positive lesions associated with MR and MRS systems, and developed a decision rule based on lesion diameter and position to identify false positives. Aug 2006 3
A study in 9 men who had increasing PSA after external-beam radiation therapy compared biopsy, DRE, MR and MRS as methods of identifying local prostate cancer recurrence. 4 MR spectroscopy had a sensitivity of 77% and a specificity of 78%. MR imaging had a sensitivity of 68% and a specificity of over 90%. MR spectroscopy was found to produce false positives. A study of MRS and MRS-guided prostate biopsy in 42 men with an elevated PSA and at least two negative prostate biopsies, found 31 men with metabolic abnormalities on MRS (voxel score 4: scale 1-benign to 5-malignant) suggestive of cancer. 5 Cancer was detected on MRS-guided biopsy in 17 of the 31 men giving a sensitivity of 100%, specificity 44%, positive predictive value 55%, and a negative predictive value 100%. A study of the additional benefit of MR and MRS when added to PSA- and histopathology-based nomograms in detecting prostate-confined cancer in 612 men prior to radical prostatectomy found that the addition of MR contributed significantly to the nomogram, particularly in those at intermediate or high-risk. 6 However, although the accuracy of the prediction was higher with the addition of MRS, the difference was not significant. An abstract of a study of non-invasive external coils for MRS (as opposed to endorectal coils) in 12 men with biopsy-proven prostate cancer, found in the 8 men with evaluable signals, a sensitivity and specificity of 78% and 57% respectively. 7 A study of the additional benefit of MR and MRS to clinical, PSA and histopathology scoring for detecting extracapsular extension of prostate cancer in 344 men prior to surgery, found that MR significantly added to the prediction, but MRS did not. 8 A study investigated the accuracy of a standardised evaluation tool for endorectal MRS in 37 men before radical prostatectomy. 9 Twenty-two had good or excellent MRS data and independent spectroscopists scored the spectra of selected voxels on a 5 point scale: 1 benign to 5-malignant. The specificity of voxel scores 4 and 5 were 84.6% and 89.3% respectively; and sensitivities 90% and 93%. The same patients were used in a study to evaluate the utility of MR and MRS in measuring tumour volume. 10 Tumour volume measurement using MR with MRS was significantly correlated with histolopathological volume post-surgery. The awareness of clinical data significantly improved the tumour detection rate of MRS. 11 A preliminary study of MR and MRS in 21 men with biochemical failure after external beam radiation therapy found that the presence of 3 or more suspicious voxels in a hemiprostate showed a sensitivity and specificity of 89% and 82% respectively for the diagnosis of local recurrence on later biopsy. 12 A case-controlled study evaluated the utility of combined MR and MRS in localising prostate cancer in 16 men receiving neoadjuvant hormone therapy prior to radical prostatectomy and 48 men not receiving hormone therapy prior to surgery. 13 Results showed that there was no difference in the sensitivity or specificity of MR and MRS between the hormone-treated and un-treated men. Aug 2006 4
A study in 53 men with prostate cancer evaluated the validity of MR, MRS and combined MR/MRS in the detection and localisation of cancer. 14 Sensitivity of MR alone was 77% to 81%; specificity 61% to 46%. Sensitivity of MRS alone was significantly lower at 63%, and specificity significantly higher at 75%. Specificity was up to 91% for combined MR and MRS. Estimated cost and cost impact Expert estimates suggest that a MRI with spectroscopy would cost about 800 per scan. Potential or intended impact speculative Access to MR scanning time is a concern. Patients Reduced morbidity Quicker or more accurate diagnosis Reduced mortality or increased survival Earlier identification of disease Improved quality of life for patients and/or carers Changed pathway of care or outcome Services Increased use e.g. length of stay, out-patient visits Service reorganisation required Staff or training required Decreased use e.g. shorter length of stay, reduced Other: Increased access to MRI is required referrals Costs Increased unit cost compared to alternative Savings: Increased costs: more patients coming for treatment Other: Increased costs: capital investment needed References 1 Jordan HS, Bert R, Chew P, et al. Magnetic resonance spectroscopy for brain tumours. Prepared for the Agency for Healthcare Research and Quality. April 2003. 2 Technology Evaluation Center. Magnetic resonance spectroscopy of revaluation of suspected brain tumor. Blue Cross and Blue Shield Association. Assessment Program 18(1) June 2003. 3 Hom JJ, Coakley FV, Simko JP et al. Prostate cancer: endorectal MR imaging and MR spectroscopic imaging distinction of true-positive from chance-detected lesions. Radiology 2006;238:192-199. 4 Pucar D, Shukla-Dave A, Hricak H et al. Prostate cancer: correlation of MR imaging and MR spectroscopy with pathologic findings after radiation therapy initial experience. Radiology 2005;236:545-553. 5 Prando A, Kurhanewicz J, Borges A et al. Prostatic biopsy directed with endorectal MR spectroscopic imaging findings in patients with elevated prostate specific antigen levels and prior negative biopsy findings: initial experience. Radiology 2005;236:903-910. 6 Wang L, Hricak H, Kattan MW et al. Prediction of organ-confined prostate cancer: incremental value of MR imaging and MR spectroscopic imagine to staging nomograms. Radiology 2005;238:597-603. 7 Hymel EC, Hyslop WB, Kwock L et al. Correlation of prostate MR spectroscopy using external pelvic phased coil assay to histopathology of prostatectomy specimens. American society of Clinical Oncology 2005. Abstract 72. 8 Wang L, Mullerad M, Chen HN et al. Prostate cancer: incremental value of endorectal MR imaging findings for prediction of extracapsular extension. Radiology 2004;232:133-139. 9 Jung JA, Coakley FV, Vigneron DB et al. Prostate depiction at endorectal spectroscopic imaging: investigation of a standardized evaluation system. Radiology 2004;233:701-708. 10 Coakley FV, Kurhanewicz J, Lu Y et al. Prostate cancer tumor volume: measurement with endorectal MR and MR spectroscopic imaging. Radiology 2002;223:91-97. 11 Dhingsa R, Qayyum A, Coakley FV et al. Prostate cancer localization with endorectal MR imaging and MR spectroscopic imaging: effect of clinical data on reader accuracy. Radiology 2004;230:215-220. Aug 2006 5
12 Coakley FV, The HS, Qayyum A et al. Endorectal MR imaging and MR spectroscopic imaging for locally recurrent prostate cancer after external beam radiation therapy: preliminary experience. Radiology 2004;233:441-448. 13 Mueller-Lisse UG, Vigneron DB, Hricak H et al. Localized prostate cancer: effect of hormone deprivation therapy measured by using combined three-dimensional 1 H MR spectroscopy and MR imaging: clinicopathologic case-controlled study. Radiology 2001;221:380-390. 14 Scheidler J, Hricak H, Vigneron DB et al. Prostate cancer: localization with three-dimensional proton MR spectroscopic imaging clinicopathologic study. Radiology 1999;213:473-480. The is funded by the Research and Development Division of the Department of Health, England The, Department of Public Health and Epidemiology University of Birmingham, Edgbaston, Birmingham, B15 2TT, England Tel: +44 (0)121 414 7831 Fax +44 (0)121 414 2269 www.pcpoh.bham.ac.uk/publichealth/horizon Aug 2006 6