This Article Abstract Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lecouvet, F. E. Articles by Tombal, B. Search for Related Content PubMed PubMed Citation Articles by Lecouvet, F. E. Articles by Tombal, B. Related Articles Related Correspondence

Magnetic Resonance Imaging of the Axial Skeleton for Detecting Bone Metastases in Patients With High-Risk Prostate Cancer: Diagnostic and Cost-Effectiveness and Comparison With Current Detection Strategies

Frédéric E. Lecouvet, Daphné Geukens, Annabelle Stainier, François Jamar, Jacques Jamart, Bertrand Janne d'Othée, Patrick Therasse, Bruno Vande Berg, Bertrand Tombal

From the Departments of Radiology, Urology, and Nuclear Medicine, Cliniques Universitaires Saint Luc, Université Catholique de Louvain; European Organisation for Research and Treatment of Cancer, Brussels; Center of Biostatistics, Mont Godinne University Hospital, Yvoir, Belgium; and the Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA

Address reprint requests to Frédéric E. Lecouvet, MD, PhD, Saint-Luc University Hospital, Department of Radiology, Hippocrate Ave 10/2942, B-1200 Brussels, Belgium; e-mail: lecouvet{at}rdgn.ucl.ac.be

	ABSTRACT

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION AUTHORS' DISCLOSURES OF... AUTHOR CONTRIBUTIONS REFERENCES

 
Purpose: To evaluate the diagnostic performance, costs, and impact on therapy of one-step magnetic resonance imaging (MRI) of the axial skeleton (MRIas) for detecting bone metastases in patients with high-risk prostate cancer (PCa).

Patients and Methods: Sixty-six consecutive patients with high-risk PCa prospectively underwent MRIas in addition to the standard sequential work-up (SW) of bone metastases (technetium-99m bone scintigraphy [BS] completed with targeted x-rays [TXR] in patients with equivocal BS findings and with MRI obtained on request [MRIor] in patients with inconclusive BS/TXR findings). Panel review of initial and 6-month follow-up MRI findings, BS/TXR, and all available baseline and follow-up clinical and biologic data were used as the best valuable comparator to define metastatic status. Diagnostic effectiveness of MRIas alone was compared with each step of the SW. Impact of MRIas screening on patient management and costs was evaluated.

Results: On the basis of the best valuable comparator, 41 patients (62%) had bone metastases. Sensitivities were 46% for BS alone, 63% for BS/TXR, 83% for BS/TXR/MRIor, and 100% for MRIas; the corresponding specificities were 32%, 64%, 100%, and 88%, respectively. MRIas was significantly more sensitive than any other approach (P < .05, McNemar). MRIas identified metastases in seven (30%) of 23 patients considered negative and eight (47%) of 17 patients considered equivocal by other strategies, which altered the initially planned therapy. Economic impact was variable among countries, depending on reimbursement rates.

Conclusion: MRIas is more sensitive than the current SW of radiographically identified bone metastases in high-risk PCa patients, which impacts the clinical management of a significant proportion of patients.

	INTRODUCTION

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION AUTHORS' DISCLOSURES OF... AUTHOR CONTRIBUTIONS REFERENCES

 
Although bone metastases represent the initial metastatic site in more than 80% of prostate cancer (PCa) patients, there has been no major breakthrough in diagnostic techniques. The detection algorithm of bone metastases still relies on technetium-99m bone scintigraphy (BS), which strikingly lacks diagnostic specificity.^1-4 Regions of increased uptake must be characterized by targeted x-rays (TXR) to distinguish benign (eg, fracture, Paget's disease, degenerative disease, and so on) from metastatic lesions.⁵ This BS/TXR association is imperfect, and the diagnosis often remains equivocal without the additional use of computed tomography (CT) or magnetic resonance imaging (MRI).⁶ Therefore, MRI cost is added to the BS/TXR costs, and this multistep approach can become inconvenient to patients.

The sensitivity of MRI to detect bone metastases in cancer patients has been highlighted for almost 20 years.^5,7 Its superiority over BS has been repeatedly suggested.^6,8-11 It has even been used as the gold standard to evaluate new nuclear medicine techniques for detecting bones metastases and more recently to quantify PCa metastases and measure tumor response to therapy.^4,12,13 However, the use of MRI in first line is often presented as not feasible because of its limited availability, costs, or the limitations of published series validating the method.⁴

This prospective study assessed the diagnostic effectiveness of an MRI study of the axial skeleton (MRIas) used as a straightforward single-step modality for the detection of bone metastases in a homogeneous series of high-risk PCa patients and compared this technique with the current sequential work-up (SW), consisting of BS, BS combined with TXR (BS/TXR) in patients with equivocal BS, and BS/TXR completed by MRI on request (MRIor) in patients with discrepant BS/TXR results (BS/TXR/MRIor). Systematic prospective imaging and clinical and biologic follow-up were used as the best valuable comparator to assess the initial metastatic status.

	PATIENTS AND METHODS

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION AUTHORS' DISCLOSURES OF... AUTHOR CONTRIBUTIONS REFERENCES

 
Patients
Sixty-six consecutive asymptomatic patients with PCa were prospectively enrolled (mean age, 74 years; range, 46 to 85 years). All of the patients were at high risk for bone metastases on the basis of published criteria. Twenty-six patients had newly diagnosed PCa with a biopsy Gleason score 8 and a prostate-specific antigen (PSA) level 20 ng/mL^14,15; 12 patients presented with PSA recurrence within 3 years after radical prostatectomy and a PSA doubling time calculated on three sequential samples of less than 12 months^16,17; and 28 patients presented with an increase in PSA while receiving androgen deprivation therapy and a PSA doubling time of less than 12 months.¹⁸

The routine SW of bone metastases consists of BS, TXR in patients with equivocal BS, and MRIor in patients with a discrepant BS/TXR study (BS uptake with no clear benign or malignant explanation on TXR). In the present trial, all patients underwent an MRIas within 30 days of inclusion. Patients with contraindications to MRI and patients with a previous or concurrent history of other cancers were excluded. The study was approved by the local ethical committee, and informed consent was obtained from all patients.

BS
BS was the first examination to be performed 3 to 5 hours after intravenous bolus injection of approximately 925 MBq of freshly prepared technetium-99m–oxidronate. Scanning was performed in whole-body mode in the anterior and posterior projections using a dual-head gamma camera equipped with a low-energy high-resolution collimator. Additional spot views were performed when appropriate. BS were interpreted without knowledge of other imaging procedures. They were categorized separately by a senior and a senior resident nuclear medicine physician into one of the following three categories according to well-defined published criteria¹⁹: normal/benign: absence of uptake or focal increased uptake typical for a benign origin (eg, fracture, degenerative joint disease, Paget's disease of bone, and so on); positive for bone metastases: presence of either (multi)focal or diffuse (superscan) uptake typical for metastatic disease; and equivocal: image could not be confidently categorized as one of the former two subgroups, hence requiring additional imaging procedures.

TXR
TXRs were directed to equivocal BS areas. The results of the BS/TXR work-up were categorized separately by one senior and one senior resident musculoskeletal radiologist into one of the following three categories: negative or benign; positive for metastases; or equivocal or discrepant when normal radiographs failed to confidently identify either a benign or a malignant explanation to equivocal BS findings.

MRIas
Technical parameters of MRI studies and patterns of metastatic involvement on MRIas have been reported previously.^7,13,20-23 According to this imaging semiology, patients were categorized separately by one senior musculoskeletal radiologist and one senior radiology resident into one of the following three categories: normal or benign; metastatic; or equivocal when only one nonspecific small lesion (< 10 mm) had been detected. These readers were blinded to patients’ clinical and BS (/TXR) findings.

Best Valuable Comparator
Patients were treated according to the final diagnosis and monitored for at least 6 months. In the absence of a histologic gold standard, we used, as the best valuable comparator, a panel of reference consisting of the CT correlation of equivocal MRI findings, prospective systematic follow-up BS and MRI studies at 6 months, and clinical and biologic follow-up obtained during 6 months of follow-up. This material was reviewed afterwards by all of the specialists, who determined in consensus the final diagnosis for each patient in terms of bone metastasis.

Data and Statistical Analyses
Diagnostic effectiveness was compared for two strategies (MRIas used alone v SW). The following three steps were considered for SW: BS alone; BS/TXR in patients with equivocal BS findings; and BS/TXR/MRIor in patients with inconclusive BS/TXR.

The sensitivity, specificity, positive predictive value, and negative predictive value of these strategies for the detection of metastatic bone involvement were compared. For the purpose of assessing the accuracy of imaging techniques for the detection of bone metastases, the results were analyzed categorizing the equivocal readings as suggestive for malignancy in patients with no metastasis and categorizing the equivocal readings as benign in patients with metastasis. This pessimistic approach was chosen to obtain threshold sensitivities and specificities of the techniques. The sensitivity and specificity of these approaches were compared using the McNemar test, with P < .05 considered statistically significant.

Cost Evaluation
Cumulative costs of MRIas and SW in the 66 patients were calculated based on reimbursement rates at academic hospitals in Belgium, France, and the United States (Massachusetts) in 2006.

	RESULTS

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION AUTHORS' DISCLOSURES OF... AUTHOR CONTRIBUTIONS REFERENCES

 
Comparison of MRI With Other Approaches
BS was performed in the 66 patients, and TXRs were requested in 37 patients. MRIs were requested in 17 patients to clear inconclusive BS/TXR and performed systematically according to the study protocol in the 49 remaining patients. On the basis of the best valuable comparator, 41 (62%) of 66 patients were metastatic to bone, and 25 (38%) of 66 patients were not. Detection rates by imaging strategy are listed in Table 1.

MRI helped resolve the situation of equivocal BS/TXR work-up and was able to distinguish metastatic (n = 8) from nonmetastatic (n = 9) patients in each of the 17 equivocal readings (Fig 1; Table 2). In addition, MRIas identified metastases in seven of 23 patients considered as having negative readings after BS/TXR and in eight of 17 patients considered equivocal after BS/TXR. In total, MRIas identified metastases in 15 patients (22%) considered negative or equivocal after BS/TXR.

View larger version (43K): [in this window] [in a new window] [PowerPoint Slide for Teaching]   Fig 1. Discrepant bone scintigraphy (BS)/targeted x-ray findings in a patient with increasing prostate-specific antigen 3 years after radical prostatectomy. (A) Anterior-posterior and (B) posterior-anterior BS show isolated focal uptake within L3 (arrows). (C) Spine radiograph does not provide a benign (eg, Paget's disease, fracture) or malignant (eg, osteolysis, sclerosis) explanation for this uptake. (D) Magnetic resonance imaging explains this discrepancy and shows evident metastasis (arrow).

Distribution of the Lesions
On the basis of the BS/TXR survey, 16 of 41 patients with bone metastases had metastatic lesions involving anatomic areas not included in the MRIas work-up (ribs, n = 8; humerus, n = 5; distal femur, n = 3; sternum, n = 2; skull, n = 2; clavicle, n = 1; and tibia, n = 1). Review of the SW and MRIas surveys showed that each of these patients also had spinal, pelvic, and/or femoral metastases detected at MRIas. In the four patients with hot spots at BS exclusively located in areas not explored by MRIas, the causative lesions were benign on the basis of TXRs and prospective follow-up (three rib fractures and one Paget's disease).

Impact of MRI Findings on Patient Management
Overall, initial treatment plans were modified in 15 patients (22%) as a consequence of MRIas results. In 38 patients with newly diagnosed disease or rapid PSA increase after prostatectomy, the number of patients with false-negative results indicates the proportion of patients who would have undergone unnecessary or inappropriate local treatment. MRIas identified metastases in three (21%) of 14 patients with normal BS/TXR findings and two (16%) of 12 patients with equivocal BS/TXR findings (Table 4). These five patients, who were scheduled for local therapy (surgery or radiation therapy), were reoriented to systemic therapy with androgen deprivation and enrolled onto clinical trials to assess bone protection therapy.

Cost Evaluation
Given our gross cost evaluation, the cumulative cost of MRIas screen compared favorably with the cumulative cost of SW in Belgium (16,720 for MRIas v 19,172 for SW) where reimbursement rates of MRI are the lowest. This did not apply to countries with higher reimbursement rates of MRI, such as in France (23,760 for MRIas v 22,680 for SW) or the United States ($46,860 for MRIas v $33,801 for SW).

	DISCUSSION

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION AUTHORS' DISCLOSURES OF... AUTHOR CONTRIBUTIONS REFERENCES

 
An accurate diagnostic strategy is critical to identify PCa patients who might benefit from bone-targeted therapies (eg, bisphosphonates, endothelin inhibitors, or osteoprotegerin analogs). In absence of quantitative measurement techniques for bone metastases, these compounds have been tested in metastatic patients using clinically driven end points not relying on BS.^24-26 This issue is even more crucial to implement these agents in a preventive setup (ie, to delay onset of bone metastasis). Using BS alone with its limited sensitivity and specificity might lead to misinterpretation of the data.¹⁸ BS indeed detects bone metastases at an advanced stage of tumor infiltration, when osteoblastic reaction to tumor deposits has occurred.^27-29 Technetium-99m–oxidronate is a nonspecific marker of osteoblastic activity that may be observed in degenerative joint disease, benign fractures, and inflammation.^20,30,31 The limited sensitivity and specificity result in additional studies, most frequently TXRs, required to characterize equivocal BS findings. This improves the sensitivity and specificity of BS but represents additional costs, often requires multiple exposures to x-rays, and if residual doubt remains, may require second-line CT or MRI studies.^20,32

This study confirms the weakness of BS for the detection of metastatic disease. The sensitivity and specificity values of BS alone are 46% and 32%, respectively, and are lower than the values found in the literature, which report sensitivities ranging between 62% and 89%.²⁷ This most likely is a result of the large proportion of equivocal interpretations of BS and TXR in our series and of our stringent statistical approach that included these equivocal findings in the most pessimistic category. This confirms that BS must be used in association with TXR, except in obvious diffuse metastatic scans. In the present trial, 56% of the patients required TXR. The addition of TXR in these patients increased the sensitivity and specificity to 63% and 64%, respectively.

The sensitivity of MRI for the detection of bone metastases has been evaluated previously, and its superiority over BS has been emphasized.^7,33-38 MRI has been used as the gold standard to assess the effectiveness of new nuclear medicine techniques for detecting bone metastases.^12,39,40 MRI characteristics of malignant involvement of the bone marrow are well documented.^{11,13,22,30,41} However, many authors still advocate the use of BS on the assumption that MRI would be too clinically involved, time consuming, and costly and that published series are too small, are too heterogeneous, or lack an accurate gold standard.^4,20,30

This study has evaluated MRI as a one-step substitute to BS and TXRs in 66 patients with high-risk PCa. Noticeably, the rate of metastases (62%) was high. This was not surprising to us, considering our previous report on the monitoring of response to therapy.¹³ Previous careful autopsy studies have revealed bone metastases in up to 90% of the patients diagnosed with PCa, notwithstanding stage and grade.^42,43 The superiority of MRI lies in its ability to detect cells seeded into the normal hematopoietic marrow and its fat cells, thus identifying bone metastases at an early stage before osteoblastic reaction becomes visible on BS and/or TXR.^27,30 Therefore, it is not surprising that the rate of bone metastases found by MRI is somewhere between the rates reported with BS and autopsy series. This also parallels the findings of Sanal et al,²¹ who reported an unexpected frequency of bone metastases of 61% when using MRI in stage II to IV breast cancer patients, whereas BS was only positive in 30% of patients.

A major difficulty was the definition of the gold standard. Histologic verification of suspected areas is not feasible and remains ethically unjustifiable.^13,21 Herein, as the best valuable comparator, we have used a multimodality analysis based on initial and follow-up clinical, biologic, and imaging findings during at least 6 months. MRIas showed better sensitivity and specificity than SW. MRIas detected bone metastases in 15 (37.5%) of 40 patients with a negative or inconclusive BS/TXR work-up. This confirms the results of Fujii et al,⁴⁴ who, in 36 patients with suspected metastatic PCa, demonstrated that MRI revealed metastases in six patients with negative BS.

Whether this has added value in routine practice is a matter of debate. In this study, MRIas results led to changes in treatment plan in 22% of the patients. Noteworthy, this happened in 71% of the patients presenting with a rapid PSA increase on androgen deprivation therapy, which highlights a potential relevant bias when these patients are enrolled onto clinical trials investigating new agents to prevent the first occurrence of bone metastasis.

The present MRIas protocol deliberately limits imaging to the axial skeleton. In contrast to whole-body MRI studies promoted by other teams for the screening of bone metastases, this approach ignores the skull, ribs, and limbs.^27,30 As suggested previously, this approach does not result in any significant loss of accuracy in staging patients with PCa.³⁴ The probability of finding metastases in these locations with no metastases in the axial skeleton is indeed negligible, especially in PCa, which predominantly metastasize to the spine and pelvis.^13,45-47 Along with others, we did not detect any single case of isolated peripheral metastasis.⁴⁷ Moreover, the advantages of a whole-body approach have been questioned because of the difficult analysis of the skull and ribs on MRI.²⁷

In the present study, we did not evaluate positron emission tomography (PET) and whole-body CT. PET imaging has shown high sensitivity for the early detection of bone metastases in various malignancies.^12,39,40 The performance of [¹⁸F]fluorodeoxyglucose, the most available PET radiopharmaceutical, remains poor in the setting of PCa metastases. Ghanem et al³⁵ have suggested that [¹⁸F]fluorodeoxyglucose-PET and [¹⁸F]fluoride-PET, used alone or with PET-CT image fusion, are less sensitive than MRI in the detection of bone metastases. Further studies should focus on the comparison between MRI and new radiopharmaceuticals, such as fluor-18 and acetate, for the detection of PCa bone metastases, but these radiopharmaceuticals are much more expensive and less available.^35,39-41 The advent of multidetector spiral technology has reawakened the potential interest of CT for bone metastasis detection. In a recent analysis, Groves et al⁴⁸ investigated the value of this technique to detect bone metastases. On the basis of their preliminary analysis, they concluded that CT with its present performance is unlikely to replace scintigraphy for the screening of bone metastasis. It addition, they also raised questions of radiation protection, especially if this examination has to be repeated to monitor tumor response.¹³

The present study did not address the interobserver reproducibility of MRI for detecting bone metastases. The technical parameters of MRI studies and patterns of metastatic involvement have previously been largely described in the literature and are now widely recognized.^{7,11,13,20,21} But this question of reproducibility could be addressed before definitively validating the prospective use of MRI as a first-line imaging technique.

Our preliminary cost analysis only provides an indication of the economic impact. More robust economic evaluation is warranted to include this critical aspect in the sensitivity-specificity analysis.

In conclusion, MRIas is a sensitive and specific one-step technique to detect bone metastases in patients with high-risk PCa. We believe it will improve the clinical management of patients with locally advanced or recurrent disease by detecting bone involvement in patients who would have been considered negative by the current strategy.

	AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION AUTHORS' DISCLOSURES OF... AUTHOR CONTRIBUTIONS REFERENCES

 
The author(s) indicated no potential conflicts of interest.

	AUTHOR CONTRIBUTIONS

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION AUTHORS' DISCLOSURES OF... AUTHOR CONTRIBUTIONS REFERENCES

 
Conception and design: Frédéric E. Lecouvet, Bertrand Tombal

Provision of study materials or patients: Daphné Geukens, Annabelle Stainier, François Jamar, Jacques Jamart, Bertrand Tombal

Collection and assembly of data: Frédéric E. Lecouvet, Daphné Geukens, Annabelle Stainier, François Jamar, Jacques Jamart, Bertrand Tombal

Data analysis and interpretation: Frédéric E. Lecouvet, Annabelle Stainier, François Jamar, Jacques Jamart, Bertrand Janne d'Othée, Patrick Therasse, Bruno Vande Berg, Bertrand Tombal

Manuscript writing: Frédéric E. Lecouvet, François Jamar, Jacques Jamart, Bertrand Janne d'Othée, Patrick Therasse, Bruno Vande Berg, Bertrand Tombal

Final approval of manuscript: Frédéric E. Lecouvet, Daphné Geukens, François Jamar, Jacques Jamart, Bertrand Janne d'Othée, Patrick Therasse, Bruno Vande Berg, Bertrand Tombal

	NOTES

 
Supported by an educational grant from the nonprofit organization Fondation Saint-Luc (F.E.L. and B.T.).

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

	REFERENCES

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION AUTHORS' DISCLOSURES OF... AUTHOR CONTRIBUTIONS REFERENCES

 
1. Rigaud J, Tiguert R, Le Normand L, et al: Prognostic value of bone scan in patients with metastatic prostate cancer treated initially with androgen deprivation therapy. J Urol 168:1423-1426, 2002[CrossRef][Medline]

2. Soloway MS, Hardeman SW, Hickey D, et al: Stratification of patients with metastatic prostate cancer based on extent of disease on initial bone scan. Cancer 61:195-202, 1988[CrossRef][Medline]

3. Jacobson AF, Fogelman I: Bone scanning in clinical oncology: Does it have a future? Eur J Nucl Med 25:1219-1223, 1998[CrossRef][Medline]

4. Schirrmeister H, Guhlmann A, Kotzerke J, et al: Early detection and accurate description of extent of metastatic bone disease in breast cancer with fluoride ion and positron emission tomography. J Clin Oncol 17:2381-2389, 1999[Abstract/Free Full Text]

5. Gosfield E III, Alavi A, Kneeland B: Comparison of radionuclide bone scans and magnetic resonance imaging in detecting spinal metastases. J Nucl Med 34:2191-2198, 1993[Abstract/Free Full Text]

6. Nakanishi K, Kobayashi M, Takahashi S, et al: Whole body MRI for detecting metastatic bone tumor: Comparison with bone scintigrams. Magn Reson Med Sci 4:11-17, 2005[CrossRef][Medline]

7. Daffner RH, Lupetin AR, Dash N, et al: MRI in the detection of malignant infiltration of bone marrow. Am J Roentgenol 146:353-358, 1986[Abstract/Free Full Text]

8. Engelhard K, Hollenbach HP, Wohlfart K, et al: Comparison of whole-body MRI with automatic moving table technique and bone scintigraphy for screening for bone metastases in patients with breast cancer. Eur Radiol 14:99-105, 2004[CrossRef][Medline]

9. Frat A, Agildere M, Gencoglu A, et al: Value of whole-body turbo short tau inversion recovery magnetic resonance imaging with panoramic table for detecting bone metastases: Comparison with 99MTc-methylene diphosphonate scintigraphy. J Comput Assist Tomogr 30:151-156, 2006[CrossRef][Medline]

10. Ghanem N, Altehoefer C, Kelly T, et al: Whole-body MRI in comparison to skeletal scintigraphy in detection of skeletal metastases in patients with solid tumors. In Vivo 20:173-182, 2006[Medline]

11. Vande Berg BC, Lecouvet FE, Michaux L, et al: Magnetic resonance imaging of the bone marrow in hematological malignancies. Eur Radiol 8:1335-1344, 1998[CrossRef][Medline]

12. Schirrmeister H, Guhlmann A, Elsner K, et al: Sensitivity in detecting osseous lesions depends on anatomic localization: Planar bone scintigraphy versus 18F PET. J Nucl Med 40:1623-1629, 1999[Abstract/Free Full Text]

13. Tombal B, Rezazadeh A, Therasse P, et al: Magnetic resonance imaging of the axial skeleton enables objective measurement of tumor response on prostate cancer bone metastases. Prostate 65:178-187, 2005[CrossRef][Medline]

14. Lee N, Fawaaz R, Olsson CA, et al: Which patients with newly diagnosed prostate cancer need a radionuclide bone scan? An analysis based on 631 patients. Int J Radiat Oncol Biol Phys 48:1443-1446, 2000[CrossRef][Medline]

15. Thurairaja R, McFarlane J, Traill Z, et al: State-of-the-art approaches to detecting early bone metastasis in prostate cancer. BJU Int 94:268-271, 2004[CrossRef][Medline]

16. Dotan ZA, Bianco FJ Jr, Rabbani F, et al: Pattern of prostate-specific antigen (PSA) failure dictates the probability of a positive bone scan in patients with an increasing PSA after radical prostatectomy. J Clin Oncol 23:1962-1968, 2005[Abstract/Free Full Text]

17. Freedland SJ, Humphreys EB, Mangold LA, et al: Risk of prostate cancer-specific mortality following biochemical recurrence after radical prostatectomy. JAMA 294:433-439, 2005[Abstract/Free Full Text]

18. Smith MR, Kabbinavar F, Saad F, et al: Natural history of rising serum prostate-specific antigen in men with castrate nonmetastatic prostate cancer. J Clin Oncol 23:2918-2925, 2005[Abstract/Free Full Text]

19. McCall I, Beharry N: Imaging of malignant bone disorders, in Peeters A (ed): Nuclear Medicine in Radiological Diagnosis. London, United Kingdom, Martin Dunitz, 2003, pp 37-53

20. Hamaoka T, Madewell JE, Podoloff DA, et al: Bone imaging in metastatic breast cancer. J Clin Oncol 22:2942-2953, 2004[Abstract/Free Full Text]

21. Sanal SM, Flickinger FW, Caudell MJ, et al: Detection of bone marrow involvement in breast cancer with magnetic resonance imaging. J Clin Oncol 12:1415-1421, 1994[Abstract]

22. Vande Berg BC, Malghem J, Lecouvet FE, et al: Classification and detection of bone marrow lesions with magnetic resonance imaging. Skeletal Radiol 27:529-545, 1998[CrossRef][Medline]

23. Vande Berg BC, Malghem J, Lecouvet FE, et al: Magnetic resonance imaging of the normal bone marrow. Skeletal Radiol 27:471-483, 1998[CrossRef][Medline]

24. Carducci MA, Padley RJ, Breul J, et al: Effect of endothelin-A receptor blockade with atrasentan on tumor progression in men with hormone-refractory prostate cancer: A randomized, phase II, placebo-controlled trial. J Clin Oncol 21:679-689, 2003[Abstract/Free Full Text]

25. Dearnaley DP, Sydes MR, Mason MD, et al: A double-blind, placebo-controlled, randomized trial of oral sodium clodronate for metastatic prostate cancer (MRC PR05 Trial). J Natl Cancer Inst 95:1300-1311, 2003[Abstract/Free Full Text]

26. Saad F, Gleason DM, Murray R, et al: Long-term efficacy of zoledronic acid for the prevention of skeletal complications in patients with metastatic hormone-refractory prostate cancer. J Natl Cancer Inst 96:879-882, 2004[Abstract/Free Full Text]

27. Daldrup-Link HE, Franzius C, Link TM, et al: Whole-body MR imaging for detection of bone metastases in children and young adults: Comparison with skeletal scintigraphy and FDG PET. Am J Roentgenol 177:229-236, 2001[Abstract/Free Full Text]

28. Condon BR, Buchanan R, Garvie NW, et al: Assessment of progression of secondary bone lesions following cancer of the breast or prostate using serial radionuclide imaging. Br J Radiol 54:18-23, 1981[Abstract]

29. Pollen JJ, Gerber K, Ashburn WL, et al: Nuclear bone imaging in metastatic cancer of the prostate. Cancer 47:2585-2594, 1981[CrossRef][Medline]

30. Eustace S, Tello R, DeCarvalho V, et al: A comparison of whole-body turboSTIR MR imaging and planar 99mTc-methylene diphosphonate scintigraphy in the examination of patients with suspected skeletal metastases. Am J Roentgenol 169:1655-1661, 1997[Abstract/Free Full Text]

31. Rybak LD, Rosenthal DI: Radiological imaging for the diagnosis of bone metastases. Q J Nucl Med 45:53-64, 2001[Medline]

32. Ghanem N, Altehoefer C, Hogerle S, et al: Comparative diagnostic value and therapeutic relevance of magnetic resonance imaging and bone marrow scintigraphy in patients with metastatic solid tumors of the axial skeleton. Eur J Radiol 43:256-261, 2002[CrossRef][Medline]

33. Avrahami E, Tadmor R, Dally O, et al: Early MR demonstration of spinal metastases in patients with normal radiographs and CT and radionuclide bone scans. J Comput Assist Tomogr 13:598-602, 1989[Medline]

34. Freedman GM, Negendank WG, Hudes GR, et al: Preliminary results of a bone marrow magnetic resonance imaging protocol for patients with high-risk prostate cancer. Urology 54:118-123, 1999[CrossRef][Medline]

35. Ghanem N, Uhl M, Brink I, et al: Diagnostic value of MRI in comparison to scintigraphy, PET, MS-CT and PET/CT for the detection of metastases of bone. Eur J Radiol 55:41-55, 2005[CrossRef][Medline]

36. Kattapuram SV, Khurana JS, Scott JA, et al: Negative scintigraphy with positive magnetic resonance imaging in bone metastases. Skeletal Radiol 19:113-116, 1990[Medline]

37. Soderlund V: Radiological diagnosis of skeletal metastases. Eur Radiol 6:587-595, 1996[Medline]

38. Vanel D, Bittoun J, Tardivon A: MRI of bone metastases. Eur Radiol 8:1345-1351, 1998[CrossRef][Medline]

39. Schirrmeister H, Kuhn T, Guhlmann A, et al: Fluorine-18 2-deoxy-2-fluoro-D-glucose PET in the preoperative staging of breast cancer: Comparison with the standard staging procedures. Eur J Nucl Med 28:351-358, 2001[CrossRef][Medline]

40. Uematsu T, Yuen S, Yukisawa S, et al: Comparison of FDG PET and SPECT for detection of bone metastases in breast cancer. Am J Roentgenol 184:1266-1273, 2005[Abstract/Free Full Text]

41. Even-Sapir E, Metser U, Mishani E, et al: The detection of bone metastases in patients with high-risk prostate cancer: 99mTc-MDP planar bone scintigraphy, single- and multi-field-of-view SPECT, 18F-fluoride PET, and 18F-fluoride PET/CT. J Nucl Med 47:287-297, 2006[Abstract/Free Full Text]

42. Bubendorf L, Schopfer A, Wagner U, et al: Metastatic patterns of prostate cancer: An autopsy study of 1,589 patients. Hum Pathol 31:578-583, 2000[CrossRef][Medline]

43. Saitoh H, Hida M, Shimbo T, et al: Metastatic patterns of prostatic cancer: Correlation between sites and number of organs involved. Cancer 54:3078-3084, 1984[CrossRef][Medline]

44. Fujii Y, Higashi Y, Owada F, et al: Magnetic resonance imaging for the diagnosis of prostate cancer metastatic to bone. Br J Urol 75:54-58, 1995[Medline]

45. Batson O: The function of the vertebral veins and their role in the spread of metastases. Ann Surg 112:138-149, 1940[Medline]

46. Cumming J, Hacking N, Fairhurst J, et al: Distribution of bony metastases in prostatic carcinoma. Br J Urol 66:411-414, 1990[Medline]

47. Traill ZC, Talbot D, Golding S, et al: Magnetic resonance imaging versus radionuclide scintigraphy in screening for bone metastases. Clin Radiol 54:448-451, 1999[CrossRef][Medline]

48. Groves AM, Beadsmoore CJ, Cheow HK, et al: Can 16-detector multislice CT exclude skeletal lesions during tumour staging? Implications for the cancer patient. Eur Radiol 16:1066-1073, 2006[CrossRef][Medline]

Submitted October 8, 2006; accepted April 27, 2007.

Related Correspondence

• MRI or Bone Scan or Both for Staging of Prostate Cancer?
  Ramachandran Venkitaraman, Aslam Sohaib, and Gary Cook
  JCO 2007 25: 5837-5838 [Full Text]
• Magnetic Resonance Imaging Versus Bone Scan in High-Risk Prostatic Carcinoma: Some Methodological Considerations
  Filip F.A.Y. Gemmel and Frank W. De Geeter
  JCO 2008 26: 1189-1190 [Full Text]

This article has been cited by other articles:

				F. E. Lecouvet, B. C. Vande Berg, F. Jamar, B. Tombal, J. Jamart, and B. Janne d'Othee In Reply J. Clin. Oncol., March 1, 2008; 26(7): 1190 - 1191. [Full Text] [PDF]

				F. F.A.Y. Gemmel and F. W. De Geeter Magnetic Resonance Imaging Versus Bone Scan in High-Risk Prostatic Carcinoma: Some Methodological Considerations J. Clin. Oncol., March 1, 2008; 26(7): 1189 - 1190. [Full Text] [PDF]

				R. Venkitaraman, A. Sohaib, and G. Cook MRI or Bone Scan or Both for Staging of Prostate Cancer? J. Clin. Oncol., December 20, 2007; 25(36): 5837 - 5838. [Full Text] [PDF]

				F. E. Lecouvet, B. C. Vande Berg, F. Jamar, and B. Tombal In Reply: J. Clin. Oncol., December 20, 2007; 25(36): 5838 - 5839. [Full Text] [PDF]

				Using MRI to Detect Bone Metastases in High-Risk Prostate Cancer Patients Journal Watch Oncology and Hematology, August 21, 2007; 2007(821): 1 - 1. [Full Text]

This Article Abstract Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lecouvet, F. E. Articles by Tombal, B. Search for Related Content PubMed PubMed Citation Articles by Lecouvet, F. E. Articles by Tombal, B. Related Articles Related Correspondence