Indian Journal of Cancer Medknow Publications on behalf of Indian Cancer Society ISSN: 0019-509X EISSN: 1998-4774 Vol. 47, Num. 4, 2010, pp. 385-390

Indian Journal of Cancer, Vol. 47, No. 4, October-December, 2010, pp. 385-390

Symposium

Complimentary role of FDG-PET imaging and skeletal scintigraphy in the evaluation of patients of prostate carcinoma

BP Tiwari¹, S Jangra¹, N Nair¹, HB Tongaonkar², S Basu¹

¹ Radiation Medicine Centre, Bhabha Atomic Research Centre, TATA Memorial Hospital, Jerbai Wadia Road, Parel, Mumbai - 400 012, India
² Department of Surgery, TATA Memorial Hospital, Jerbai Wadia Road, Parel, Mumbai - 400 012, India

Correspondence Address:
S Basu
Radiation Medicine Centre, Bhabha Atomic Research Centre, TATA Memorial Hospital, Jerbai Wadia Road, Parel, Mumbai - 400 012
India
drsanb@yahoo.com

Code Number: cn10094

PMID: 21131750

DOI: 10.4103/0019-509X.73572

Abstract

Keywords: Bone scan, FDG-PET, prostate carcinoma, scintigraphy

Introduction

Prostate cancer is one of the most common neoplasms in elderly males and is the second most frequent cause of death by cancer ^[1] in this group of patients. The standard method for detection of the disease is digital rectal examination. Serum levels of prostate-specific antigen (PSA) and Gleason′s scoring have been found useful in the evaluation of prostrate adenocarcinoma. ^[2],[3] A noninvasive imaging technique to detect recurrent and metastatic prostate cancer is important for effective management of such patients. The imaging methods, such as ultasonography, computed tomography (CT), magnetic resonance imaging, and imaging with ¹¹¹ In-Protascint, have been used with varying degrees of accuracy. Bone scintigraphy has been utilized to detect skeletal metastases but is nonspecific and can be false positive in a number of benign etiologies.

Positron emission tomography with ¹⁸ F- fluorodeoxyglucose (FDG-PET) has been widely used in the evaluation of various malignancies. ^[4] It is useful in the staging of neoplasm, detection of secondary spread, evaluation of treatment response, and assessing posttherapy changes from residual or recurrent disease. The success of FDG-PET depends on enhanced glucose metabolism in malignant cells due to increased expression of cellular membrane glucose transporters (GLUT), especially GLUT-1 and hexokinase enzyme (HK-II) in the cells.

Early experience using FDG-PET in prostate cancer has demonstrated a relatively poor sensitivity because of low FDG accumulation in primary disease and its metastases.^{[5],[6],[7],[8]} However, some studies and reviews have advocated that FDG-PET may be useful in the evaluation and management of patients with prostate cancer. ^{[9],[10],[11],[12],[13],[14],[15],[16],[17],[18],[19],[20]} The objective of the present study was to evaluate diagnostic utility of FDG-PET in confirmed cases of prostate cancer, especially with regard to the detection of osseous involvement of the disease by comparing the findings with the results of conventional skeletal scintigraphy.

Materials and Methods

We selected 16 patients (mean age, 67.2 years; age range, 55-83 years) with confirmed diagnosis of prostate cancer who were referred to our center for bone scan (BS) and subsequently for FDG-PET study for evaluation of the disease. Prior treatments were provided to 13 patients, which included (1) bilateral orchidectomy in 3 cases, (2) hormonal therapy in 1 case, (3) bilateral orchidectomy and hormonal therapy in 9 cases, and (4) 3 patients had not undergone any treatment. All the patients underwent bone scintigraphy as well as wholebody FDG-PET study at our center. Both studies were carried out within 1-week period for each patient [Table - 1].

Bone scintigraphy was carried out between 3 and 4 h after intravenous injection of 900 MBq 99mTc-methylene diphosphonate and obtaining wholebody anterior and posterior skeletal images on the same film. Detailed images were also obtained when considered necessary for better viewing of suspected regions. A Dual-Head Gamma Camera (Picker International, Inc., Cleveland, OH, USA) attached with parallel-hole high-resolution low-energy collimator was employed for the study. The images were evaluated by 2 experienced Nuclear Medicine Physicians for the presence of skeletal metastases.

For FDG-PET study, the patients were instructed to fast for at least 6 h and maintained blood sugar below 150 mg%. Imaging was performed 45-60 min after intravenous administration of 370-444 MBq (10-12 mCi) of FDG. Wholebody images were acquired on a dedicated PET instrument with full ring Bismuth Germanate (BGO) detectors (NXI, PETAdvance, GE Medical Systems, Milwaukee, WI, USA) in 2D mode. The scanner had axial spatial resolution of 5 mm FWHM (full width half maximum) and 14.5 cm field of view. At each bed position, emission as well as transmission data were acquired and 6-8 bed positions were covered starting from base of skull to distal thigh region. The skull was also included if indicated. Reconstruction of PET images was performed by using ordered subset expectation maximization algorithm and the images were processed with attenuation correction. The images were assessed visually by 2 experienced Nuclear Medicine Physicians after viewing the images in axial, sagittal, and coronal planes in conjunction with the clinical information and close correlation with other available imaging studies.

Skeletal abnormalities evident on FDG-PET study were compared with the findings of the BS on a lesion by lesion basis and vice-versa. Abnormal FDG accumulation in the extraosseous sites was also noted. Abnormal findings of both methods in 3 patients who have not received any management were critically reviewed to understand the role of individual modality in the evaluation of the disease.

Results

Results of BS and comparative FDG-PET findings are shown in [Table - 2]. Totally, 198 lesions of osseous involvement were noted on BSs. A total of 97 skeletal lesions were evident on FDG-PET. In 2 patients, both the studies showed complete concordance for bone metastases. In one patient with normal BS, FDG-PET detected 3 sites of bone involvement. In the remaining 13 patients, FDG-PET showed less number of lesions than in the BS with varying concordance in various regions [Table - 2].

The findings of the FDG-PET demonstrating extra sites of the disease involvement are mentioned in [Table - 3]. Five bone lesions that were observed in 2 patients were not evident on BS. Positive lymph nodes in the mediastinal, iliac, hilar, and inguinal regions were noted in 5, 2, 6, and 1 patients, respectively. Extensive bone marrow involvement was evident in 4 patients. Multiple liver lesions and lung lesion with multiple liver metastases were observed in 2 and 1 patients, respectively.

The description of the abnormalities evident on BS and FDG-PET in 3 untreated patients are separately given in [Table - 4]. One patient (No. 2) had normal bone study. FDG-PET detected 3 bony lesions in addition to abnormal accumulation of FDG in the mediastinal right hilar nodes. In comparison to the skeletal scintigraphy, more number of bone lesions were evident on FDG-PET in patient No. 1. Another patient (No. 3) also showed almost the same number of bony involvement, but the site was different for a few lesions. All the patients had soft tissue involvement as evident on FDG-PET [Figure - 1], [Figure - 2], [Figure - 3].

Discussion

Prostate cancer is one of the major health problems in elderly men. There is a need for reliable and accurate imaging methods for evaluating patients with prostate cancer. Attempts have been made to study the usefulness of PET imaging in prostate cancer and variable results were demonstrated with FDG. Effert et al performed a study using FDG-PET on 48 patients with untreated prostate cancer and concluded that it was not useful for differentiating prostate cancer and benign prostate hyperplasia. ^[9] The accumulation of FDG was positive only in 9 (19%) patients with prostate cancer, and it was not related to the clinical stage or histologic grade. Shreve et al demonstrated a sensitivity of 65% for the detection of skeletal involvement of prostate cancer using this technique. ^[6] In a study by Yeh et al, FDG-PET could identify only 20% of bone metastases in patients with prostate cancer. ^[10] In a study of 22 patients, Salminen et al found FDG-PET having only a limited value for clinical practice because of its low sensitivity and specificity. ^[19] The impact on the management was high in 46% cases, low in 41%, and there was no impact in 14% cases.

It has been shown that FDG-PET, however, may be useful to detect clinically advanced prostate cancer in patients with a higher Gleason score and serum PSA levels. ^[14] Increased localization of FDG may be due to enhanced rate of tumor growth in comparison to tumors showing low Gleason score. Seltzer et al demonstrated that FDG-PET could be better than 111In-Prostascint imaging in the detection of metastases in patients with higher serum PSA levels. ^[20] It has been well documented that FDG-PET is more useful to detect soft tissue metastases compared with those having skeletal involvement. ^{[10],[14],[17]} In a study by Jadvar et al., FDG-PET clearly localized nodal metastases, whereas CT showed nondiagnostic subcentimeter lymph nodes.^[20]

In the present study, we made an attempt to evaluate the role of FDG-PET in a small number of prostate cancer patients who were in different stages of the disease and compared the findings with BS results. Putting together the data of all the patients, FDG-PET underestimated the extent of osseous metastases as compared with BS [Table - 2]. A lower sensitivity of FDG-PET is reported for sclerotic skeletal metastases, particularly in prostate cancer, which predominantly produces this type of skeletal metastasis. The reason for this is still unclear, although a plausible explanation is that sclerotic metastases are relatively acellular and harbor only small amounts of viable tumor cells, and therefore have a low FDG uptake. However, we believe, this should be interpreted with caution, as we now know that metabolic response precedes osteoblastic response. This is further substantiated by the equivalent or even superior performance of FDG-PET imaging in patients who had not received any treatment previously. Similar concerns do exist in some of the previous studies that had examined patients with prostate carcinoma in its various stages, especially when they have been administered prior therapy. It is important to investigate whether this is the major reason for the apparent lower sensitivity of FDG-PET in these clinical settings. Although prostate cancer typically yields false-negative results on FDG-PET, it is worthwhile to investigate the clinical significance of FDG-PET-negative and BS-positive lesions in this group of patients.

Interestingly, FDG-PET clearly localized the nodal and soft tissue metastatic disease, a few skeletal lesions, and bone marrow disease, which were not localized by skeletal scintigaphy [Table - 2]. Histopathologic correlation of the results could not be done for obvious ethical and practical reasons. The findings of FDG-PET and BS together in this group of patients at various stages of management enabled us to understand the extent of the disease with better sensitivity.

Looking at the findings of both the modalities in the various groups [Table - 1] separately, we observed better lesion detection efficiency of FDG-PET in 3 untreated prostate cancer patients even for bone metastases [Table - 4]. FDG-PET alone may probably play a very important role in the evaluation of freshly diagnosed patients. However, it needs further exploration in a larger number of patients.

Although this study was carried out with FDG, other PET radiopharmaceuticals, such as 11C-acetate, 11C-choline, 11C-methionine and 16beta- ¹⁸ F-fluoro-5alpha-dihydro-testosterone, have been found to be more advantageous than FDG for imaging evaluation of prostate cancer. ^{[15],[21],[22],[23]} The results of recent studies demonstrate the promising role of (18)F-fluoride PET-CT for the detection of bony metastases from prostate cancer. ^{[24],[25],[26],[27]} In a study ^[25] involving 38 patients, the sensitivity, specificity, and accuracy of PET-CT in the detection of bone metastases in prostate cancer was 81%, 93%, and 86% for (18)F fluoride and 74% (P = 0.12), 99% (P = 0.01), and 85%, respectively, for fluorocholine (FCH). (18)F FCH PET-CT led to a change in the management in 2 out of the 38 patients due to the early detection of bone marrow metastases. In another preclinical study ^[27] using small-animals, PET-CT scans were able to detect biologic activity of cells that induced an osteoblastic lesion 2 weeks earlier than plain radiographs. (18)F-FDG lesions strongly correlated with soft tissue measurements, whereas (18)F-fluoride ion activity correlated with bone volume measured on histomorphometric analysis (P < 0.005). The investigators concluded that both (18)F-FDG and (18)F-fluoride ion PET-CT scans can be useful tools in characterizing pure osteolytic and osteoblastic lesions induced by human prostate cancer cell lines. Combining ¹⁸ F-fluoride and FDG in a single scan is also interesting and has generated significant debate in the recent times with regard to their precise clinical use in the oncologic setting. ^[26],[27]

The present study results with subset analysis demonstrate that where the aforementioned PET tracers are not available, imaging with FDG can play a valuable complimentary role to the conventional skeletal scintigraphy in this malignancy, especially in the detection of bone marrow disease and soft tissue involvement. It can be particularly useful with regard to monitoring treatment response where FDG imaging can be superior to the conventional skeletal scintigraphy in demonstrating therapeutic response and is likely to be negative earlier than BS. Hence, in a comparison between the 2 modalities, the history of previous administration of therapy is essential for correct comparison of the 2 techniques. The other important aspect is the prediction of tumor biology. FDG-negative lesions are postulated to run an indolent course but this requires to be examined by further correlative studies between tumor uptake and Gleason score, and overall survival in these patients.

References

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