Evaluation of Distribution Features of Bone Metastases by Bone Scintigraphy in Prostate Cancer

Prostate cancer (PCa) represents the most common non-cutaneous malignancy for men, where an estimated 241,740 new cases will be diagnosed in 2013 in the United States [1]. Whereas most of those new diagnoses will be clinically localized, up to 17% of patients may experience metastatic disease, in which the risk of cancerspecific mortality is increased [2]. In this context, it is well established that, beyond regional lymph nodes, the skeleton represents the most common metastatic site [3]. The study aims to evaluate the pattern of distribution of bone metastases in prostate cancer patients by 99mTcmethylene diphosphonate (99mTc-MDP) bone scintigraphy. It was formed in 150 patients with pathologically proven prostate cancer and presented for bone scans with 99mTc-methylene diphosphonate (99mTc-MDP) for detection and evaluation of bone metastases. It was noted that patients with bone metastases had significantly higher frequency of bone pain when compared with patients without and noted that spine was the most commonly affected site (60.0 %) followed by ribs (52.0 %) and femur (30.0 %). Spread of bony metastases among the bony skeleton has distribution manner not only to the right or to the left. Metastatic bony lesions of prostate cancer are located mainly in spine (58.0%) followed by ribs (52.0 %) and femur (30.0 %). Patients with extensive bone metastasis had significantly higher frequency of skull, spine, scapula, humerous, sternum, ribs, iliac bone, ischium, and femur metastases.


Introduction
Prostate cancer is the most common male cancer diagnosed in Western population. Autopsy studies have shown that with increasing age the majority of men will develop microscopic foci of cancer in populations at both high and low risk. However, only a small percentage of men will develop invasive form of prostate cancer. The cancer cells may metastasize from the prostate to other parts of the body, particularly the bones and lymph nodes [4].
The presence of prostate cancer may be indicated by symptoms, physical examination, prostate-specific antigen (PSA), or biopsy.Prostate-specific antigen testing increases cancer detection but does not decrease mortality [5].
Prostate cancer is the second most frequently diagnosed cancer of men after lung cancer and the fifth most common cancer worldwide [6]. It constitutes 10.6% of cancers of men in sub-Saharan Africa [7]. In the USA the tumor appears to be more common in African-American men than in Caucasian men [8].
Prostate cancer frequently metastasizes to bone but metastases can also be found in other body organs and tissues [9]. They contribute significantly to the morbidity associated with advanced disease [10]. The bone metastases of prostate cancer are usually radiologically osteoblastic. Presentation with diffuse osteolytic bone metastases is rare and only a few case reports exist in the medical literature with this type of metastatic lesion [11,12].
Bone scintigraphy is a sensitive and efficient method for the detection of bone metastases of malignant tumors, although it is considered to be a nonspecific method. Bone scintigraphy has value in determining the stage [13]. Selecting therapeutic schedule, evaluating prognosis [14] and performing follow-up [15] for tumor patients.

Aim of the Work
The aim of the study is to evaluate the pattern of distribution of bone metastases in prostate cancer patients by 99mTc-methylene diphosphonate (99mTc-MDP) bone scintigraphy.

Patient and Methods
This study was performed between August 2014 andAugust 2015. This research was done after faculty committee approval (available upon request). Furthermore, this study is a retrospective study. It included 150 patients with cancer prostate.They had a mean age of 61.2 ± 10.2 years (40 -86 years). They were referred to Clinical Oncology and Nuclear Medicine Departments, Menofyia University for bone scan.

Methods
Whole-body bone scans, anterior and posterior views obtained with a dual detector gamma camera were studied from 150 patients who had undergone scintigraphy , with Tc-99m methylene diphosphonate(600 MBq Tc-99m MDP) because of suspected bone metastatic disease.
All patients were subjected to full history taking, Clinical examination, assessment of PSA, MRI pelvis. CT chest, Biopsy and Gleason score and Staging of all patients.

Diagnostic Criteria of Bone Metastasis
The results of bone scans were interpreted as bone metastasis if radiotracer activity of local bone lesion was greater or less than that of contralateral or adjacent normal bone tissues.
The results of bone scans were considered negative under the following circumstances: a) No abnormal increased radiotracer uptake was detected. b) Radiotracer uptake was characterized by medical& benign disease (e.g. arthritis, fracture, and trauma)

Classification of Bone Metastasis
The lesions in the body were divided into three categories depending on their location: left, center, and right sides. Lesions in the center were located in the vertebrae and chest bone, those on the left side were located on left parts of the body from the middle line, except the vertebrae and chest bone, and those on the right side were located on the right parts of the body from the middle line, except the vertebrae and the chest bone. According to the total number of metastatic bony lesions, patients were divided into three groups: fewer bone metastases, with the total number being one to three; moderate bone metastases, with the total number being four to 10; and extensive bone metastases, with the total number being more than 10 [16].

Data management: Statistical analysis
Data obtained from the present study were computed using SPSS versions 17 under the platform of Microsoft Windows XP, Professional Edition. Continuous data were expressed in the form of mean ± SD while categorical data were expressed in the form of count and percent. Comparison of continuous data were performed utilizing student t test, while categorical data were done using Chi-square test. P value less than 0.05 was considered statistically significant. In the present study, the studied patients had a mean age of 61.  In the present study, it was noted that spine was the most commonly affected site (60.0 %) followed by ribs (52.0 %) and femur (30.0 %) ( Table 1). As regards the grade of bone metastases in the studied patients, we found that the studied patients 61 patients with few bone metastases, 29 patients with moderate metastases and 10 patients with extensive bone metastases (Figure2).

Figure 2.
Grade of bone metastases in the studied patients.In the current study, we found that patients with bone metastases had significantly higher frequency of bone pain when compared with patients without ( Table 2). In the current study, patients with extensive bone metastasis had significantly higher frequency of skull, spine, scapula, humerous, sternum, ribs, iliac bone, ischium, and femur metastases when compared with patients with moderate metastases (Table 3).

Discussion
Skeletal scintigraphy has long been a cornerstone of disease assessment in prostate cancer. 99mTc-methylene diphosphonate (99mTc-MDP) bone scans are widely used and provide an indirect measure of tumor activity because they detect tracer deposition by osteoblasts along bone mineralization fronts. Prostate cancer bone metastases can be imaged this way because they are associated with elevated activity by both osteoblasts and osteoclasts. Further, 99mTc-MDP bone scans are an established component of disease assessment in prostate cancer clinical trials [17].
The indication for bone scintigraphy can be a routine examination at the time of the diagnosis of cancer, but bone pain is also a common reason to perform an examination [18].
Many scholars have studied radionuclide bone imaging of prostate cancer, but their analysis in spreading regularity of bone metastasis is still not specific enough [19].
In the present study, the studied patients had a mean age of 61.2 ± 10.2 years. Among the studied patients, 67 patients (44.7 %) had irritative symptoms while 25 patients (16.7 %) had obstructive symptoms and 95 patients (63.3 %) had bone pain. These data are differs from that found by the study of [20] who aimed to report the pattern of prostate cancer presentation in Alexandria University. In this study, the most common clinical presentation was irritative symptoms. This may be explained by the high frequency of patients with bone metastases in the present study.
Regarding PSA levels, we found that among the studied patients, 84 (56.0 %) had a PSA of less than 10 and 66 patients (44.0 %) had PSA ≥ 10. In respect to Gleason score, 40 (26.7 %) had a Gleason score of less than 6, 33 patients (22.0 %) had a score from 6-7 and 77 patients (51.3 %) had a score more than 7. This is in agreement with the study of [21].
In the current study, 100 patients (66.7 %) out of screened 150 had metastatic bone disease. This figure is lower than that found by the study of [22]. In this study, the authors systematically described the most common sites of metastases in a contemporary cohort of PC patients. Overall, 74,826 patients with metastatic PCa were identified. The most common metastatic sites were bone (84%).In the present study, it was noted that spine was the most commonly affected site (60.0 %) followed by ribs (52.0 %) and femur (30.0 %). This is in accordance with the study of [16] . In their study, the authors investigated the distribution characteristics of bone metastases in breast and prostate carcinomas. Bone scintigraphies were performed in 504 cancer patients. They found that spine was the most common bone metastases site in patients with prostate cancer. This is also in agreement with the study of [23] who tried to investigate the distribution of bone metastases in common cancers using bone scintigraphy. 160 consecutive patients with malignancy (prostate cancer: 32, breast cancer: 107, lung cancer:8, and gastrointestinal cancers: 13) underwent bone scan. In patients with cancer prostate, the most frequently involved area was the spine, followed by ribs and pelvic bones.
As regards the grade of bone metastases in the studied patients, we found that the studied patients 61 patients with few bone metastases, 29 patients with moderate metastases and 10 patients with extensive bone metastases. This varied from the findings of [16]. In their study, the authors explored the distribution features of metastatic bony lesions in prostate cancer. Bone scans with 99mTc-methylene diphosphonate were performed in 144 patients with pathologically proven prostate cancer, and distribution regularity of metastatic bony lesions was analyzed retrospectively. Among the 144 patients, 31 presented fewer bone metastases with a total of 58 lesions, 26 presented moderate bone metastases with a total of 161 lesions, and 45 presented extensive bone metastases with a total of 1781 lesions.
In the current study, we found that that patients with bone metastases had significantly higher frequency of bone pain when compared with patients without in agreement with the study of [18] who examined the relation between pain and bone metastases in a group of patients with prostate or breast cancer that had been referred for bone scintigraphy. Wholebody bone scans, anterior and posterior views obtained with a dual detector gamma camera were studied from 101 consecutive patients who had undergone scintigraphy (600 MBq Tc-99m MDP) because of suspected bone metastatic disease. In patients with prostate cancer, they found metastases in 47% (18 ⁄ 38) of the patients with pain, but only in 12% (2 ⁄ 17) of the patients without pain.
In the current study, patients with extensive bone metastasis had significantly higher frequency of skull, spine, scapula, humerous, sternum, ribs, iliac bone, ischium, and femur metastases when compared with patients with moderate metastases. This agrees with the study of [16] .

Conclusions
Prostate cancer frequently develops into bone metastasis. This study indicates that spine was the most commonly affected site by bone metastases followed by ribs and femur and shows that patients with bone metastases had significantly higher frequency of bone pain when compared with patients without. Our results show no significant differences between the studied groups regarding PSA levels and patients' age. patients with extensive bone metastasis had significantly higher frequency of skull, spine, scapula, humerous, sternum, ribs, iliac bone, ischium, pubis and femur metastases when compared with patients with moderate and few metastases. Spine was the most commonly affected site by bone metastases followed by ribs and femur. Patients with bone metastases had significantly higher frequency of bone pain when compared with patients without.