The Egyptian Rheumatologist (2014) 36, 35–39

Egyptian Society for Joint Diseases and Arthritis

The Egyptian Rheumatologist

www.rheumatology.eg.netwww.sciencedirect.com

ORIGINAL ARTICLE

Profile of bone metastases of prostate cancer

among rheumatology inpatients in Lome (Togo):

A single center experience

* 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.

Production and hosting by Elsevier

1110-1164 � 2013 Production and hosting by Elsevier B.V. on behalf of Egyptian Society for Joint Diseases and Arthritis.

http://dx.doi.org/10.1016/j.ejr.2013.09.003

Kodjo Kakpovi, Owonayo Oniankitan *, Prenam Houzou, Eyram Fianyo,

Viwale E.S. Koffi-Tessio, Komi C. Tagbor, Moustafa Mijiyawa

Service de Rhumatologie, CHU Sylvanus Olympio Lome, BP. 14502 Lome, Togo

Received 17 April 2013; accepted 30 September 2013Available online 8 November 2013

KEYWORDS

Prostate cancer;

Bone metastases;

Black Africa

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 bonemetastases 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 ofmetastasis was 5.4 ± 3.67 years

in 27% of the cases. The main manifestations of patients with bone metastases were alteration of gen-

eral 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 themajority of cases at the

stage of metastasis.� 2013 Production and hosting by Elsevier B.V. on behalf of Egyptian Society for Joint Diseases and

Arthritis.

1. Introduction

Prostate cancer is by far the most common cancer in men andthe second leading cause of cancer death after lung cancer indeveloped countries [1,2]. Prostate metastases are a common

reason for hospitalization in rheumatology. They occur after

36 K. Kakpovi et al.

the diagnosis of prostate cancer although they may be reveal-ing. Among the patients with prostate cancer, approximately70% have a proven clinical metastatic bone at the time of

death [3]. In Africa in general, the diagnosis is not always easyand 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 metasta-sis osteophilic cancers [4,5]. The purpose of this study was todetermine the epidemiological, clinical, paraclinical, and ther-

apeutic profile of bone metastases of prostate cancer in a rheu-matological service in Lome.

Table 1 Distribution of the 58 patients according to the

circumstances of discovery of bone metastasis of prostate

cancer.

Number

(58 cases)

Percentage

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,

bleeding per rectum: 3 cases)

07 12.06

* Pain with some features of inflammatory pain and mechanical

pain.

2. Patients and methods

This study was retrospectively performed on a series of casesadmitted in the Department of Rheumatology, University

Hospital Sylvanus Olympio, Lome, Togo’s capital betweenJanuary 1990 and December 2010. The series included all pa-tients diagnosed with bone metastasis of prostate cancer. Mostof these patients were diagnosed with the cancer after being

admitted in the Rheumatology ward for inflammatory bonepain. The study was approved by the ethics committee andall patients gave an informed consent for a study. The demo-

graphic, clinical, paraclinical and therapeutic data of patientswere collected from their records. The diagnosis of bonemetastasis was based essentially on the clinical picture (inflam-

matory bone pain and alteration of the general condition) andradiological features (mainly osteosclerosis). The prostatic ori-gin 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, afinger 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 thecarcinoma and rises with the severity of the prognosis: from

2 to 6: well differentiated tumor, 7: moderately differentiatedtumor and from 8 to 10 undifferentiated tumor [6].

The anemia corresponded to a hemoglobin concentrationlower than 10 g/dl. A plasma creatinine greater than 12 mg/l

was considered renal insufficiency. Serum calcium greater than110 mg/l was considered hypercalcemia. Erythrocyte sedimen-tation rate greater than 20 mm in the first hour was considered

accelerated. The combination of fatigue, anorexia, weight lossand pallor or the presence of at least three of these symptomswas considered impaired general condition. A weight loss

greater than 10% was considered massive and a weight loss be-low 10% was considered moderate. A serum PSA level inferiorto 4 ng/ml was considered normal. Analgesics were alwaysadministered 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 theintensity of the pain [7]. The pain intensity was measured on

a 100 mm visual analog scale for pain (VAS). VAS inferiorto 40 mm: moderate pain (Tier 1), from 40 to 70 mm: intensepain (Tier 2), and from 80 to 100 mm: very intense pain (Tier

3). The reduction of pain by 70% was considered as positiveeffect 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 and82 years and the age group most affected was between 65and 74 years (23 cases, i.e., 39.65%). The mean disease dura-

tion was 28.43 ± 44.16 months and the median was20 months. The mean duration of hospitalization was38.10 ± 48.20 days and the median was 27 days. Prostate can-

cer was seen in 16 patients (27%) before metastasis and it wasrevealing in the remaining 42 (73%). The average time betweenthe diagnosis of prostate cancer and the development of metas-

tasis was 5.4 ± 3.67 years in 27% of the cases. The onset of thedisease was insidious in 46 patients (79%) and in 12 otherssudden (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 (21cases; 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 amoderate 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 patientshad a BMI greater than 25 kg/m2. Voiding disorders were rep-resented by urinary frequency, dysuria and dribbling at the endof voiding, respectively in 46.55%, 25.86% and 13.79% of

cases. All patients suffered from bone pain and the spine wasthe main site of pain (52 cases, 89.65%) with a clear preferencefor the lumbar segment (47 cases, 81.03%). The other sites of

spinal pain were thoracic segment (4 cases, 6.89%) and cervicalsegment (1 case, 1.72%). Most other affected sites were thelong bones (10 cases, 17.24%), the pelvis (9 cases, 15.51%)

and the ribs (7 cases, 12.06%). An affection of more thanone region was revealed in 15.51% cases. Digital rectal exam-ination revealed an abnormality of the prostate in 47 patients.

The prostate was enlarged in 42 patients, indurated in 30 pa-tients and irregular in 13 patients. Anemia was found in 28 pa-tients and was microcytic and aplastic with an averagehemoglobin level of 7.6 g/dl. Erythrocyte sedimentation rate

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.

Figure 2 Lysis of the fourth cervical vertebra (C4).

Figure 3 Osteosclerosis of the pelvis and the femur.

Profile of bone metastases of prostate cancer among rheumatology 37

was elevated in 52 patients. Sedimentation rate average was86.4 ± 36.74 mm in the first hour with a range from 10 mmto 147 mm. The prostate specific antigen average was301.87 ± 738.23 ng/ml with a range from 35 ng/ml to

5000 ng/ml and the median was 105 ng/ml. Eighteen patients(31.03%) had PSA levels <100 ng/ml. Creatinine was highin four patients with a range from 21 mg/l to 45 mg/l. Hyper-

calcemia was observed in four (6.89%) of the 34 patients witha range from 121 mg/l to 135 mg/l. Osteosclerosis (37 cases,63.79%), bone lysis (15 cases, 25.86%) and vertebral compres-

sion (13 cases, 22.41%) were the main radiographic lesions ob-served (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 agrading of the prostate adenocarcinoma higher than or equalto six in all these patients. All the 58 patients received a palli-

ative treatment consisting of analgesics (58 cases), corticoste-roids (9 cases), bisphosphonates (4 cases), and bloodtransfusion (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

Tier 1, 40 in Tier 2 and 10 in Tier 3. Morphine was the last re-sort in Tier 3 patients. Hormonal treatment was administered

in 50 patients (86.20%), while only 19 patients (32.75%) hadbenefited 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 mgper day, three received cyproterone acetate at a dose of300 mg per day, two received tetrasodium fosfestrol at a dose

of 900 mg per day, two others received triptorelin at a dose of11.25 mg every three months, one patient received leuprorelinat a dose of 3.75 mg every month, and one patient receiveddiethylstilbestrol at a dose of 3 mg per day. Of the 41 patients

who received flutamide, the effect was positive in 35 patientsafter 15 days, on an average with a range from 3 days to31 days and zero in the other six after 21 days. After a mean

follow up duration of 36 ± 13.35 months with a range from14 months to 48 months, three patients had side effects in theform of gynecomastia, sexual impotence and diarrhea. Four

patients experienced a loss of effectiveness of the flutamidetherapy after 18–24 months. Of the 9 patients who received

38 K. Kakpovi et al.

hormonal treatment other than flutamide, the effect was posi-tive in four patients after 15 days, and one patient developedgynecomastia. Surgical treatment was performed in 10 patients

before the onset of metastasis and in nine others after the onsetof 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 consistedmainly of spinal orthoses. A severe anemia caused the deathof 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 strictinterpretation of the results requires taking into account selec-tion biases and the narrowness of the technical platform. This

was a hospital-based study that took into account onlypatients admitted at the hospital and viewed in the rheumatol-ogy department, which constitutes a bias making it impossibleto 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 prostaticspecific antigen (PSA) is routinely performed from the age of

50 years since the late 1980’s in France, prostate cancer canbe diagnosed before symptom onset [4].The average diseaseduration in our study reflects on the one hand the limited

and late recourse to specialized agencies and on the other handthe lack of medical information of the population withoutignoring 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, 58cases (2%) of bone metastases of prostate cancer. These resultsare similar to those found in other African studies [9,10]. In the

study of Houzou et al. [9], 26/13,517 patients admitted to therheumatology department in 15 years had bone metastases ofprostate cancer and 6/509 patients in the two years study of

Daboiko et al. [10]. In the present study, the average age atadmission of patients was 64.27 years and the age rangingfrom 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, earlysigns of cancer were seen in 27% of cases and bone metastasiswas revealing prostate cancer in 73% of cases. The same obser-

Table 3 Average age at presentation of patients with prostate

cancer in our series and in others series.

Authors Origin of

the publication

Age at presentation

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)

Gueye et al. [13] Africa 69 (52–88)

Cooperberg et al. [14] Asia 66.2 ± 8.7**

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.

vation was made in other African series [11–13]. The alterationof the general condition, inflammatory bone pain, voiding dis-orders and spinal cord compression were the main manifesta-

tions, respectively in 81.03%, 75.86%, 58.62%, and 36.20% ofthe cases. Botto et al. [16] and Rigaud et al. [21] in Francefound 47.50% and 30% of their patients, respectively to have

impaired general condition. Such a difference is probably dueto the consistent delay in consultation of patients observed inour African populations [11,21,8]. Botto et al. [16] found 69%

and 70% of their patients to have bone pain and voiding dis-orders, 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 lev-els <50 ng/ml indicate usually that the tumor is confined to the

prostate. PSA between 50 and 100 ng/ml indicated metastasesof cancer prostate in 80% of cases and PSA more than100 ng/ml indicated bone metastases of cancer prostate [22]. In-

deed, Western [23], Asian series [24], and ours found a medianPSA greater than 100 ng/ml in patients with metastatic prostatecancer. None of our patients performed a routine PSA. The fre-

quency of mass screening (performing routine PSA and/orbiopsy in elderly subjects) is however higher in developed coun-tries [16,23–25]. In our study, treatment had consisted of surgi-cal 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 castra-tion has become limited [15,27]. In our series, at most one sur-

gical castration was made per year. This frequency is verylimited due to the fact that most of our patients were diagnosedat the stage of metastasis and that they prefer to keep for a little

time their manliness despite the high cost of the hormonal ther-apy which is at least five times the minimumwage guaranteed inTogo. On the contrary, the frequency of surgical castration is

high in studies from Nigeria [28], Taiwan [24], and especiallyin China [15] due to the cost of chemical castration. Lachandet al. [29] also noted by order of frequency hormonal therapyin 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 anemiccomplications. Alteration of the general condition, bone pain,

Gleason score of 8 to 10, and visceral metastasis remained asindependent risk factors predicting a reduced cancer specificsurvival in other series [21,24]. In conclusion, diagnosis of can-

cer of the prostate is late and takes place in the majority of casesat the stage of metastasis.

Conflicts of interest

The authors have no conflict of interest.

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