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 Table of Contents  
ORIGINAL ARTICLE
Year : 2019  |  Volume : 8  |  Issue : 14  |  Page : 60-63

Incidence of skeletal-related events in advanced and metastatic prostate cancer patients treated with androgen deprivation therapy in a low- and middle-income country


1 Department of Surgery, Division of Urology, College of Health Sciences, University of Abuja, Garki, Abuja, Nigeria
2 Department of Surgery, Division of Urology, University of Abuja Teaching Hospital, Garki, Abuja, Nigeria

Date of Submission01-May-2017
Date of Acceptance01-Feb-2019
Date of Web Publication04-Oct-2019

Correspondence Address:
Dr. Oseremen Inokhoife Aisuodionoe-Shadrach
Aisuodionoe-Shadrach, Department of Surgery, Division of Urology, College of Health Sciences, University of Abuja, PMB 117, Garki, Abuja
Nigeria
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/nnjcr.nnjcr_12_17

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  Abstract 


Context: Skeletal-related events (SREs) occur in men with prostate cancer (CaP) and may result from androgen deprivation therapy (ADT). Aims: The purpose of this study was to determine the incidence of SREs in patients with CaP treated with HT while highlighting the burden of advanced and metastatic CaP in a low- and middle-income country practice. Settings and Design: Eligible cases were newly diagnosed patients with CaP seen at the University of Abuja Teaching Hospital, Abuja, Nigeria between January 2012 and December 2015 with bone metastases and treated with ADT. Subjects and Methods: Data compiled from patient's medical records showed tumor diagnosis, laboratory and radiology results. SREs included spinal cord compression, surgery to bone, pathologic fracture, and radiation to bone. Statistical Analysis Used: The data were analyzed using SPSS version 20 for windows (SPSS INC: Chicago Illinois). Results: Two hundred and nineteen cases of CaP were seen over the period of which 142 (64.8%) cases were first diagnosed as American Joint Committee on Cancer Stage IV CaP and commenced on ADT. More than half the patients on ADT were older >65 years with a mean (standard deviation [SD]) of 68.3 (±9.5) years. Serum prostate-specific antigen range was 1.4–2461.58 ng/ml with a mean (SD) of 113.7 (±288.9) ng/ml. Twenty nine patients (20.5%) had one or more SREs with spinal cord compression (19.1%), pathological fractures (1.4%), and radiotherapy to the affected bone (1.4%) being the most common SREs. ADT was orchiectomy, LHRH, anti-androgens, and complete androgen blockade (orchiectomy plus antiandrogens) in 14 (9.8%), 3 (2.1%), 44 (30.9%), and 81 (57%) patients, respectively. Conclusions: Sixty-five percent of the cases in this series were either advanced or metastatic CaP at first diagnosis majority of whom went on to orchiectomy plus antiandrogens as ADT. This lends credence not only to late presentation and increased morbidity and mortality of CaP in our environment but also to significantly low penetration of radiotherapy services and access to LHRH.

Keywords: Androgen deprivation therapy, low- and middle-income country, prostate cancer, skeletal-related events


How to cite this article:
Aisuodionoe-Shadrach OI, Abu S. Incidence of skeletal-related events in advanced and metastatic prostate cancer patients treated with androgen deprivation therapy in a low- and middle-income country. N Niger J Clin Res 2019;8:60-3

How to cite this URL:
Aisuodionoe-Shadrach OI, Abu S. Incidence of skeletal-related events in advanced and metastatic prostate cancer patients treated with androgen deprivation therapy in a low- and middle-income country. N Niger J Clin Res [serial online] 2019 [cited 2019 Dec 5];8:60-3. Available from: http://www.mdcan-uath.org/text.asp?2019/8/14/60/268526




  Introduction Top


Prostate cancer (CaP) is among the leading causes of cancer mortality in men globally with the bony skeleton being the most common organ to be affected by metastatic CaP.

Adeloye et al.[1] applying the United Nations population estimates for Africa (assuming demographic factors and other population health determinants were fully accounted for), found the pooled CaP incidence rate to be about 25,000 cases of CaP among men aged 40 years and above in Africa in 2015.

Up to 90% of men dying from CaP will have bone metastases,[2],[3],[4] which can be associated with skeletal-related events (SREs).

SREs are defined as: a pathologic fracture, spinal cord compression, necessity for radiation to bone (for pain or impending fracture), or surgery to bone[5] and ultimately lead to severe pain, increased risk of death, increased health care costs, and decreased quality of life.

SREs though seen in men with CaP may also result from androgen deprivation therapy (ADT).

Randomized trials in advanced cancer have shown that one of these major skeletal events occurs on an average every 3–6 months, and if untreated, about half of the patients harboring advanced CaP with bone metastasis will experience at least one SRE over a 2-year period[6] The presence of three or more lesions increases a patient risk of SREs, and once a patient experiences an SRE, the risk of subsequent SRE is increased.[7] SREs pose a significant health and economic burden.[8]

The purpose of this study was to determine the incidence of SREs in patients with CaP on hormonal therapy in a low- and middle-income country (LMIC) practice.


  Subjects and Methods Top


This was a 4-year retrospective study patients seen at the University of Abuja Teaching Hospital (UATH), Abuja, Nigeria between January 2012 and December 2015 with a recent diagnosis of CaP with bone metastases and treated with ADT. The data which were compiled from only retrievable patient's medical records showed tumor diagnosis, laboratory, and radiology results.

Recorded SREs included spinal cord compression, surgery to bone, pathologic fracture, and radiation to bone, and the method of ADT was noted.

SPSS (IBM Corp. Released 2011. IBM SPSS Statistics for Windows, Version 21.0. Armonk, NY: IBM Corp.) was used for all analyses.


  Results Top


Over the period under review, a total of 219 cases of CaP were seen. Of the number, 142 (64.8%) cases were first diagnosed as the American Joint Committee on Cancer (AJCC) Stage IV CaP and commenced on ADT.

The serum prostate-specific antigen (PSA) range among these 142 patients with advanced CaP was 1.4–2461.58 ng/ml with a mean (standard deviation [SD]) of 113.7 (±288.9) ng/ml while their mean (SD) age was 68.3 (±9.5) years with more than half of them older than 65 years of age [Table 1].
Table 1: Outline of measured Parameters

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It was observed that 29 of the patients (20.5%) had one or more SREs, with spinal cord compression (19.1%), pathological fractures (1.4%), and radiotherapy to the affected bone (1.4%) being the most common SREs, respectively.

It was further observed that 50 other patients (35.2%) had bone pains which were localized to the lumbosacral spine in more than half of them. There were no records however to show if these bone pains at the time were significant to necessitate radiation to bone either for pain or impending fracture.

The available records show that the only two patients with pathological fractures had both internal fixation and bone radiotherapy, respectively.

The prescribed ADT regimen was either bilateral total orchiectomy in 9.8% (14 cases), subcutaneous LHRH agonist in 2.1% (3 cases), oral anti-androgens in 30.9% (44 cases) while it was complete androgen blockade (CAB) in 57% (81 cases), respectively.

Interestingly, of the 81 patients who had CAB, the therapy was restricted to orchiectomy plus oral antiandrogens in a vast majority of the patients (80.2%, n = 55) as only a fewer number (n = 16, 19.8%) could afford subcutaneous LHRH agonist in addition to oral antiandrogens.


  Discussion Top


Among men who develop metastatic CaP, up to 90% will have osseous metastasis[9] occurring in the axial skeleton and or proximal appendicular skeleton possibly because these bones contain hematological active bone marrow.[10]

SREs may be detected clinically on the basis of symptoms or by reviewing imaging studies because detection through imaging is possible whether or not SREs causes symptoms. In our review, we found fifty other patients who complained of bone pains localized to the lumbosacral spine but in whom there were no records showing that they had radiologic images to confirm the occurrence of an SRE.

Albeit Elumelu et al.[11] found significant positive correlation between PSA levels and total body bone scan (TBS) findings in their study; they failed to provide PSA cutoff at which a TBS is required advising that TBS be performed in all diagnosed CaP regardless of the PSA levels, with or without bony symptoms. With the finding of a high mean (SD) serum PSA of 113.7 (±288.9) ng/ml in our review, we are not surprised that 64.8% of the cases had advanced diseases (AJCC IV CaP) with twenty-nine of the patients having radiological evidence of an SRE. This figure would have been higher if all the additional fifty patients with lumbosacral spine bone pains had imaging studies report. This is because Cumming et al. had showed in their report that significant differences in the pattern of spread in axial skeleton with CaP more to the vertebrae can be explained by Batson's vertebral venous plexus.[12]

The most common site of bone metastasis in CaP is the spine, followed by femur, pelvis, ribs, sternum, skull, and humerus. As a result, CaP is second only to lung cancer as a cause of metastatic spinal cord compression in men.[13]

Small et al. in their review of four large series of prostate metastasis to the spine concluded that patients had four initial presentations: pain, weakness, autonomic dysfunction, and sensory loss. In most cases, pain is the initial presentation of spinal metastasis.[14] This finding may further strengthen the observation in our review that the 50 other patients (35.2%) who had bone pains localized to the lumbosacral spine in more than half of them may already have spinal metastasis even though they had no records of radiologic evidence of metastasis.

Back pain often heralds the diagnosis of spinal cord compression, an oncologic emergency which occurs in 7% of men with CaP.[13] In our series, we observed that spinal cord compression in 27 patients (19.1%) was the most common recorded SRE. This is not a surprisingly high incidence considering that >60% of our patients as alluded to earlier were seen with AJCC IV CaP at initial presentation. Perhaps, who knows if the other fifty patients with lumbosacral spinal pain (most of whom are usually lost to follow-up after diagnosis is established) went on to develop spinal cord compression?

Surgery to the bone in patients with CaP may be required to treat pain, pathologic fracture, or other complications. Our series revealed that only two patients (1.4%) with pathological fractures had both internal fixation and bone radiotherapy, respectively. These figures are not surprising as orthopedic implants procedures are expensive and access to radiation oncology services is severely limited in our environment, hence only an insignificant few could afford both therapeutic procedures. This is quite revealing and perhaps not unconnected with the socioeconomic milieu of our practice.

Finally, we observed that the most commonly administered solitary ADT regimen was oral antiandrogens in 30.9%, n = 44 cases. This was closely followed by surgical ADT (bilateral total orchiectomy) in (9.8%, n = 14) while the use of the more expensive subcutaneous LHRH agonist was only seen in 2.1% (n = 3 cases). Of the 81 patients who had CAB which is a combination ADT, the therapy was mainly orchiectomy plus oral antiandrogens in a vast majority of the patients (80.2%, n = 55) as only a fewer number (n = 16, 19.8%) could afford subcutaneous LHRH agonist in addition to oral antiandrogens.

Access to cancer chemotherapy in our environment is limited while cancer-specific therapy (such as surgery for cancer and radiotherapy) and cancer-specific investigations (such as magnetic resonance imagings, computed tomography scans, and radionuclide scans) are expensive and are not usually affordable because of the socioeconomic limitations of most of the citizenry. This situation is reflected in our findings that oral anti-androgens being the cheapest drug for CaP were the most commonly prescribed while the more commonly used LHRH agonist in other climes are sparsely utilized in a LMIC like ours.

Albeit some clinical trials[14] have found that between 36% and 41% of high-risk metastatic CaP patients developed SREs during 3 years of follow-up, this review of our hospital-based cohort of patients with CaP receiving ADT did not show such a similarly high incidence of SREs. Long-term follow-up of these category of patients and of most hospital patients generally in our environment is a challenge, and this perhaps may account for the currently reported lower incidence of SRE's. Additional studies to explore the incidence of SREs in patients deliberately followed up over a longer period as well as of those with metastatic hormone-refractory CaP in our environment may be relevant.

Improved access to cancer-specific investigations and therapy in LMICs will no doubt improve the clinical outcome of cancer treatment generally and of CaP treatment specifically.


  Conclusions Top


Additional studies to explore the incidence of SREs in patients deliberately followed up over a longer period as well as of those with metastatic hormonerefractory CaP in our environment may be relevant. Improved access to cancerspecific investigations and therapy in LMICs will no doubt improve the clinical outcome of cancer treatment generally and of CaP treatment specifically.

Acknowledgment

We acknowledge doctors Magnus FE, Ugwu CC, and Kolo F., of the Division of Urology, Department of Surgery, UATH, Gwagwalada, FCT, Nigeria for their tireless efforts and invaluable contributions in the data acquisition from the patients' medical records.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Adeloye D, David RA, Aderemi AV, Iseolorunkanmi A, Oyedokun A, Iweala EE, et al. An estimate of the incidence of prostate cancer in Africa: A systematic review and meta-analysis. PLoS One 2016;11:e0153496.  Back to cited text no. 1
    
2.
Petrylak DP, Tangen CM, Hussain MH, Lara PN Jr., Jones JA, Taplin ME, et al. Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med 2004;351:1513-20.  Back to cited text no. 2
    
3.
Scher HI, Morris MJ, Kelly WK, Schwartz LH, Heller G. Prostate cancer clinical trial end points: “RECIST”ing a step backwards. Clin Cancer Res 2005;11:5223-32.  Back to cited text no. 3
    
4.
Tannock IF, de Wit R, Berry WR, Horti J, Pluzanska A, Chi KN, et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med 2004;351:1502-12.  Back to cited text no. 4
    
5.
Ibrahim A, Scher N, Williams G, Sridhara R, Li N, Chen G, et al. Approval summary for zoledronic acid for treatment of multiple myeloma and cancer bone metastases. Clin Cancer Res 2003;9:2394-9.  Back to cited text no. 5
    
6.
Saad F, Gleason DM, Murray R, Tchekmedyian S, Venner P, Lacombe L, 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 2004;96:879-82.  Back to cited text no. 6
    
7.
Tchekmedyian NS, Chen YM, Saad F. Disease progression increases the risk of skeletal-related events in patients with bone metastases from castration-resistant prostate cancer, lung cancer, or other solid tumors. Cancer Invest 2010;28:849-55.  Back to cited text no. 7
    
8.
Weinfurt KP, Li Y, Castel LD, Saad F, Timbie JW, Glendenning GA, et al. The significance of skeletal-related events for the health-related quality of life of patients with metastatic prostate cancer. Ann Oncol 2005;16:579-84.  Back to cited text no. 8
    
9.
Kakhki VR, Anvari K, Sadeghi R, Mahmoudian AS, Torabian-Kakhki M. Pattern and distribution of bone metastases in common malignant tumors. Nucl Med Rev Cent East Eur 2013;16:66-9.  Back to cited text no. 9
    
10.
Wang C, Shen Y. Study on the distribution features of bone metastases in prostate cancer. Nucl Med Commun 2012;33:379-83.  Back to cited text no. 10
    
11.
Elumelu TN, Jatto JB, Abdus-Salam AA, Adenipekun AA. Correlation between prostate specific antigen and total bone scan findings of prostate cancer patients. N Y Sci J 2016;9:46-52.  Back to cited text no. 11
    
12.
Cumming J, Hacking N, Fairhurst J, Ackery D, Jenkins JD. Distribution of bony metastases in prostatic carcinoma. Br J Urol 1990;66:411-4.  Back to cited text no. 12
    
13.
Chen TC. Prostate cancer and spinal cord compression. Oncology (Williston Park) 2001;15:841-55.  Back to cited text no. 13
    
14.
Small EJ, Smith MR, Seaman JJ, Petrone S, Kowalski MO. Combined analysis of two multicenter, randomized, placebo-controlled studies of pamidronate disodium for the palliation of bone pain in men with metastatic prostate cancer. J Clin Oncol 2003;21:4277-84.  Back to cited text no. 14
    



 
 
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