CC BY-NC-ND
0The Egyptian Rheumatologist (2014) 36, 35-39
Egyptian Society for Joint Diseases and Arthritis The Egyptian Rheumatologist
www.rheumatology.eg.net www.sciencedirect.com
ORIGINAL ARTICLE
Profile of bone metastases of prostate cancer among rheumatology inpatients in Lome (Togo): A single center experience
Kodjo Kakpovi, Owonayo Oniankitan *, Prenam Houzou, Eyram Fianyo, Viwale E.S. Koffi-Tessio, Komi C. Tagbor, Moustafa Mijiyawa
Service de Rhumatologie, CHU Sylvanus Olympio Lomé, BP. 14502 Lomé, Togo
Received 17 April 2013; accepted 30 September 2013 Available online 8 November 2013
Abstract Aim of the work: To determine the epidemiological, clinical, paraclinical and therapeutic profile of bone metastases of prostate cancer.
Patients and methods: This was the study of a series of cases of bone metastases of prostate cancer.
Results: Fifty-eight of 2881 patients (2%) admitted to the Rheumatology department during 21 years suffered from a bone metastasis of prostate cancer. The average age at admission was 64.27 ± 8.9 years while the disease duration was 28.43 ± 44.16 months. Prostate cancer was known in 27% of cases before the metastasis and the metastasis was revealing in 73% of cases. The average time between the diagnosis of prostate cancer and the development of metastasis was 5.4 ± 3.67 years in 27% of the cases. The main manifestations of patients with bone metastases were alteration of general condition (81.03%), inflammatory bone pain (75.86%), voiding disorders (58.62%) and spinal cord compression (36.20%). The spine was the main area of pain (89.65%). An osteosclerosis was the most observed radiological lesion (63.79%). The prostate specific antigen average was 301.87 ± 738.23 ng/ml. Histopathological examination was performed in 18 patients and confirmed adenocarcinoma of the prostate. Hormone therapy, mainly by anti-androgens (86.20%), surgical treatment (32.75%) and orthopedic treatment (29.31%) was administered in our patients. A severe anemia caused the death of seven patients (12.06%) during hospitalization.
Conclusion: Diagnosis of cancer of the prostate is late and takes place in the majority of cases at the stage of metastasis.
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Arthritis.
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KEYWORDS
Prostate cancer; Bone metastases; Black Africa
* Corresponding author. Tel.: +228 90156634; fax: +228 22218595. E-mail address: Owonayo@yahoo.com (O. Oniankitan). Peer review under responsibility of Egyptian Society for Joint Diseases and Arthritis.
1. Introduction
Prostate cancer is by far the most common cancer in men and the second leading cause of cancer death after lung cancer in developed countries [1,2]. Prostate metastases are a common reason for hospitalization in rheumatology. They occur after
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the diagnosis of prostate cancer although they may be revealing. Among the patients with prostate cancer, approximately 70% have a proven clinical metastatic bone at the time of death [3]. In Africa in general, the diagnosis is not always easy and care remains poor due to lack of both technical, financial, and above all the still very limited access to appropriate health care facilities. Prostate cancer ranks first among bone metastasis osteophilic cancers [4,5]. The purpose of this study was to determine the epidemiological, clinical, paraclinical, and therapeutic profile of bone metastases of prostate cancer in a rheu-matological service in Lome;.
2. Patients and methods
This study was retrospectively performed on a series of cases admitted in the Department of Rheumatology, University Hospital Sylvanus Olympio, Lome, Togo's capital between January 1990 and December 2010. The series included all patients diagnosed with bone metastasis of prostate cancer. Most of these patients were diagnosed with the cancer after being admitted in the Rheumatology ward for inflammatory bone pain. The study was approved by the ethics committee and all patients gave an informed consent for a study. The demographic, clinical, paraclinical and therapeutic data of patients were collected from their records. The diagnosis of bone metastasis was based essentially on the clinical picture (inflammatory bone pain and alteration of the general condition) and radiological features (mainly osteosclerosis). The prostatic origin of metastasis was based essentially on the clinical picture (voiding disorders, history of prostate cancer, enlarged and indurated prostate) and serum prostate specific antigen (PSA) concentration >100 ng/ml. For economic reasons, a finger guided biopsy of the prostate was conducted for histo-logical confirmation only when the diagnosis was uncertain (bone lysis, PSA less than 100 ng/ml). Gleason histopatholo-gical grading system has been used for classification of prostatic carcinomas [6]. The grading of prostate adenocarci-noma indicates the histological differentiation of the carcinoma and rises with the severity of the prognosis: from 2 to 6: well differentiated tumor, 7: moderately differentiated tumor and from 8 to 10 undifferentiated tumor [6].
The anemia corresponded to a hemoglobin concentration lower than 10 g/dl. A plasma creatinine greater than 12mg/l was considered renal insufficiency. Serum calcium greater than 110mg/l was considered hypercalcemia. Erythrocyte sedimentation rate greater than 20 mm in the first hour was considered accelerated. The combination of fatigue, anorexia, weight loss and pallor or the presence of at least three of these symptoms was considered impaired general condition. A weight loss greater than 10% was considered massive and a weight loss below 10% was considered moderate. A serum PSA level inferior to 4 ng/ml was considered normal. Analgesics were always administered in progressive stages from Tier 1 to Tier 3 (Tier 1: paracetamol, nonsteroidal antiinflammatory drugs; Tier 2: codeine or tramadol; Tier 3: morphine), depending on the intensity of the pain [7]. The pain intensity was measured on a 100 mm visual analog scale for pain (VAS). VAS inferior to 40 mm: moderate pain (Tier 1), from 40 to 70 mm: intense pain (Tier 2), and from 80 to 100 mm: very intense pain (Tier 3). The reduction of pain by 70% was considered as positive effect of flutamide therapy. No patient received bone scan or
magnetic resonance imaging (MRI) due to the absence of scin-tigraphy and MRI in Togo at the time of the study.
3. Results
Of the 2881 rheumatic patients admitted in 21 years, 58 (2%) had bone metastases of prostate cancer. Their average age at admission was 64.27 ± 8.90 years with extremes of 45 and 82 years and the age group most affected was between 65 and 74 years (23 cases, i.e., 39.65%). The mean disease duration was 28.43 ± 44.16 months and the median was 20 months. The mean duration of hospitalization was 38.10 ± 48.20 days and the median was 27 days. Prostate cancer was seen in 16 patients (27%) before metastasis and it was revealing in the remaining 42 (73%). The average time between the diagnosis of prostate cancer and the development of metastasis was 5.4 ± 3.67 years in 27% of the cases. The onset of the disease was insidious in 46 patients (79%) and in 12 others sudden (21%). Alteration of the general condition (47 cases; 81.03%) inflammatory bone pain (44 cases, 75.86%), voiding disorders (34 cases, 58.62%) and spinal cord compression (21 cases; 36.20%) were the main manifestations in our patients (Table 1). The alteration of the general condition was reflected mainly by a massive weight loss in 28 cases (48.27%) and a moderate weight loss in the remaining 19 patients (32.7%). The average body mass index was 21.9 ± 4.48 kg/m2, with a range from 14.69 to 31.14 kg/m2. Only 15% of our patients had a BMI greater than 25 kg/m2. Voiding disorders were represented by urinary frequency, dysuria and dribbling at the end of voiding, respectively in 46.55%, 25.86% and 13.79% of cases. All patients suffered from bone pain and the spine was the main site of pain (52 cases, 89.65%) with a clear preference for the lumbar segment (47 cases, 81.03%). The other sites of spinal pain were thoracic segment (4 cases, 6.89%) and cervical segment (1 case, 1.72%). Most other affected sites were the long bones (10 cases, 17.24%), the pelvis (9 cases, 15.51%) and the ribs (7 cases, 12.06%). An affection of more than one region was revealed in 15.51% cases. Digital rectal examination revealed an abnormality of the prostate in 47 patients. The prostate was enlarged in 42 patients, indurated in 30 patients and irregular in 13 patients. Anemia was found in 28 patients and was microcytic and aplastic with an average hemoglobin level of 7.6 g/dl. Erythrocyte sedimentation rate
Table 1 Distribution of the 58 patients according to the circumstances of discovery of bone metastasis of prostate cancer.
Number Percentage (58 cases)
Alteration of the general condition 47 81.03
Inflammatory bone pain 44 75.86
Mixed bone pain 14 24.14
Voiding disorders 34 58.62
Spinal cord compression 21 36.20
Systematic search for visceral metastasis 16 27.58
Externalized bleeding (hematuria: 4 cases, 07 12.06
bleeding per rectum: 3 cases)
* Pain with some features of inflammatory pain and mechanical pain.
Table 2 Distribution of the 58 patients according to the result of the X-ray of the painful bone segment.
Number (58 cases) Percentage
Osteosclerosis 37 63.79
Bone lysis 15 25.86
Vertebral compression 13 22.41
Diffuse bone demineralization 09 15.51
Pathological fracture 04 06.89
Figure 1 Osteosclerosis of the spine.
was elevated in 52 patients. Sedimentation rate average was 86.4 ± 36.74 mm in the first hour with a range from 10 mm to 147 mm. The prostate specific antigen average was 301.87 ± 738.23 ng/ml with a range from 35ng/ml to 5000 ng/ml and the median was 105 ng/ml. Eighteen patients (31.03%) had PSA levels <100 ng/ml. Creatinine was high in four patients with a range from 21 mg/l to 45 mg/l. Hypercalcemia was observed in four (6.89%) of the 34 patients with a range from 121 mg/l to 135 mg/l. Osteosclerosis (37 cases, 63.79%), bone lysis (15 cases, 25.86%) and vertebral compression (13 cases, 22.41%) were the main radiographic lesions observed (Table 2). The locations were mostly the spine (30 cases, 51.72%) (Figs. 1 and 2), followed by the pelvis (17 cases, 29.31%) (Fig3) and the femur (3 cases, 5.17%). Histopatholo-gical examination was performed in 18 patients and showed a grading of the prostate adenocarcinoma higher than or equal to six in all these patients. All the 58 patients received a palliative treatment consisting of analgesics (58 cases), corticoste-roids (9 cases), bisphosphonates (4 cases), and blood transfusion (23 cases) as needed. Analgesics were always administered in progressive stages from Tier 1 to Tier 3, depending on the intensity of the pain. Eight patients were in
Figure 2 Lysis of the fourth cervical vertebra (C4).
Figure 3 Osteosclerosis of the pelvis and the femur.
Tier 1, 40 in Tier 2 and 10 in Tier 3. Morphine was the last resort in Tier 3 patients. Hormonal treatment was administered in 50 patients (86.20%), while only 19 patients (32.75%) had benefited from surgical treatment and 17 patients (29.31%) from orthopedic treatment. Of the 50 patients who received hormone therapy, 41 received flutamide at a dose of 750 mg per day, three received cyproterone acetate at a dose of 300 mg per day, two received tetrasodium fosfestrol at a dose of 900 mg per day, two others received triptorelin at a dose of 11.25 mg every three months, one patient received leuprorelin at a dose of 3.75 mg every month, and one patient received diethylstilbestrol at a dose of 3 mg per day. Of the 41 patients who received flutamide, the effect was positive in 35 patients after 15 days, on an average with a range from 3 days to 31 days and zero in the other six after 21 days. After a mean follow up duration of 36 ± 13.35 months with a range from 14 months to 48 months, three patients had side effects in the form of gynecomastia, sexual impotence and diarrhea. Four patients experienced a loss of effectiveness of the flutamide therapy after 18-24 months. Of the 9 patients who received
hormonal treatment other than flutamide, the effect was positive in four patients after 15 days, and one patient developed gynecomastia. Surgical treatment was performed in 10 patients before the onset of metastasis and in nine others after the onset of metastasis. It consisted mainly of a testicular pulpectomy (12 patients) and a total prostatectomy (7 patients). Of the 17 patients who received orthopedic treatment, it consisted mainly of spinal orthoses. A severe anemia caused the death of seven patients (12.06%) during hospitalization.
4. Discussion
Metastasis was the first presentation in 42 of the 58 patients who had bone metastases from prostate cancer. The strict interpretation of the results requires taking into account selection biases and the narrowness of the technical platform. This was a hospital-based study that took into account only patients admitted at the hospital and viewed in the rheumatology department, which constitutes a bias making it impossible to generalize our results. The mean duration of symptoms prior to presentation was 28 months in our study, 10.3 ± 17.1 months in Nigeria [8]. Because the serum prostatic specific antigen (PSA) is routinely performed from the age of 50 years since the late 1980's in France, prostate cancer can be diagnosed before symptom onset [4].The average disease duration in our study reflects on the one hand the limited and late recourse to specialized agencies and on the other hand the lack of medical information of the population without ignoring the impact of unfavorable socio-economic conditions. However, the shortcomings of our study do not alter its epide-miological significance. We noted over a period of 21 years, 58 cases (2%) of bone metastases of prostate cancer. These results are similar to those found in other African studies [9,10]. In the study of Houzou et al. [9], 26/13,517 patients admitted to the rheumatology department in 15 years had bone metastases of prostate cancer and 6/509 patients in the two years study of Daboiko et al. [10]. In the present study, the average age at admission of patients was 64.27 years and the age ranging from 65 to 74 years was the most represented. Many African series [11-13], Asian [14,15], European [16-18] and American [19,20] have found similar results (Table 3). In our study, early signs of cancer were seen in 27% of cases and bone metastasis was revealing prostate cancer in 73% of cases. The same obser-
vation was made in other African series [11-13]. The alteration of the general condition, inflammatory bone pain, voiding disorders and spinal cord compression were the main manifestations, respectively in 81.03%, 75.86%, 58.62%, and 36.20% of the cases. Botto et al. [16] and Rigaud et al. [21] in France found 47.50% and 30% of their patients, respectively to have impaired general condition. Such a difference is probably due to the consistent delay in consultation of patients observed in our African populations [11,21,8]. Botto et al. [16] found 69% and 70% of their patients to have bone pain and voiding disorders, respectively.
Osteosclerosis was the main radiographic finding in 63.79% of cases. This result is consistent with those of Ammani et al. [11] and Vandelcandelaere et al. [17]. Prostate specific antigen (PSA) level increases with the extension of the disease. PSA levels <50 ng/ml indicate usually that the tumor is confined to the prostate. PSA between 50 and 100 ng/ml indicated metastases of cancer prostate in 80% of cases and PSA more than 100 ng/ml indicated bone metastases of cancer prostate [22]. Indeed, Western [23], Asian series [24], and ours found a median PSA greater than 100 ng/ml in patients with metastatic prostate cancer. None of our patients performed a routine PSA. The frequency of mass screening (performing routine PSA and/or biopsy in elderly subjects) is however higher in developed countries [16,23-25]. In our study, treatment had consisted of surgical castration in 32.75% and medical one in 86.20% cases. Hormonal treatment is imposed against surgical castration [26]. In Western studies, the implementation of surgical castration has become limited [15,27]. In our series, at most one surgical castration was made per year. This frequency is very limited due to the fact that most of our patients were diagnosed at the stage of metastasis and that they prefer to keep for a little time their manliness despite the high cost of the hormonal therapy which is at least five times the minimum wage guaranteed in Togo. On the contrary, the frequency of surgical castration is high in studies from Nigeria [28], Taiwan [24], and especially in China [15] due to the cost of chemical castration. Lachand et al. [29] also noted by order of frequency hormonal therapy in 91.54% of cases and surgical castration in 47.88% of cases. In the present study, seven patients (12.06%) died during hos-pitalization due to the late diagnosis and especially the anemic complications. Alteration of the general condition, bone pain, Gleason score of 8 to 10, and visceral metastasis remained as independent risk factors predicting a reduced cancer specific survival in other series [21,24]. In conclusion, diagnosis of cancer of the prostate is late and takes place in the majority of cases at the stage of metastasis.
Conflicts of interest
The authors have no conflict of interest. References
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Table 3 Average age at presentation of patients with prostate
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Authors Origin of Age at presentation
the publication in years
Our series Africa 64.27 (45-82)*
Ammani et al. [11] Africa 71 (53-90)
Eke et al. [12] Africa 71.6 (45-88)
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Peyromaure et al. [15] Asia 72 (49-92)
Botto et al. [16] Europe 71.22 ± 8.25
Vandecandelaere et al. [17] Europe 63 (38-85)
Mohile et al. [20] America 71 (51-81)
* Mean age (range).
** Mean age ±SD.
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