|Year : 2015 | Volume
| Issue : 4 | Page : 780-785
Clinicopathological characteristics and primary treatment of prostate cancer in a urology unit of Sri Lanka
Anuruddha M Abeygunasekera1, Suranga N Wijayarathna1, Kusal de Silva1, Upayasearam Gobi1, Suvendran Swarna1, Weerasinghe Sujeeva2
1 Department of Urology, Colombo South Teaching Hospital, Dehiwela, Sri Lanka
2 Department of Oncology and Radiotherapy, National Cancer Institute, Maharagama, Sri Lanka
|Date of Web Publication||15-Feb-2016|
Anuruddha M Abeygunasekera
65/11, Anderson Road, Dehiwela
Source of Support: None, Conflict of Interest: None
Aims: The aim was to describe the clinicopathological characteristics of prostate cancer and the primary treatment modality in a cohort of patients seen in a urology unit of Sri Lanka.
Materials and Methods: Data were collected prospectively from all patients with newly diagnosed prostate cancer and managed in a urology unit in Sri Lanka from January 2010 to December 2013. Patient's age, clinical presentation, prostate specific antigen (PSA) level, mode of diagnosis, Gleason sum score, stage of the disease and main modality of treatment were recorded and analyzed.
Results: There were 278 cases of histologically proven prostate cancer. Mean patient age was 70.5 years. About 50% presented with lower urinary tract symptoms. Only 2% were screening detected cases. Five (2%) patients had a first-degree relative who had prostate cancer. About 81% of patients had a serum PSA above 20 ng/ml. Gleason sum score was 8 or more in 44% of patients. Metastases were found at the time of diagnosis in 60% of patients. Forty-eight patients underwent radical radiotherapy, while seven patients had radical prostatectomy. Most (94%) of the 203 patients who required androgen deprivation therapy had surgical orchiectomy.
Conclusions: Sri Lankans appear to be having a low incidence of prostate cancer, but a larger proportion of high-grade cancers in comparison to the UK and USA. Although genetic differences may exist, a dietary or an environmental factor is more likely to be the cause for these changes. The protective effect of this factor appears to wane as South Asians emigrate and live in UK and USA.
Keywords: Clinical profile, pathological characteristics, prostate carcinoma, South Asia
|How to cite this article:|
Abeygunasekera AM, Wijayarathna SN, de Silva K, Gobi U, Swarna S, Sujeeva W. Clinicopathological characteristics and primary treatment of prostate cancer in a urology unit of Sri Lanka. J Can Res Ther 2015;11:780-5
|How to cite this URL:|
Abeygunasekera AM, Wijayarathna SN, de Silva K, Gobi U, Swarna S, Sujeeva W. Clinicopathological characteristics and primary treatment of prostate cancer in a urology unit of Sri Lanka. J Can Res Ther [serial online] 2015 [cited 2020 Jul 5];11:780-5. Available from: http://www.cancerjournal.net/text.asp?2015/11/4/780/140839
| > Introduction|| |
Sri Lanka is an Island nation in South Asia the others being India, Pakistan, Bangladesh, Nepal, Bhutan and Maldives. Twenty-three urological surgeons serve the country's population of 20 million. Therefore, a significant proportion of urological surgical work in Sri Lanka is handled by general surgeons too. Though Sri Lanka is a developing country with a budgetary allocation of 3.5% of the gross domestic product for health (82 US$/person annually), for several decades Sri Lanka has shown better health outcomes compared to countries with similar income levels.  Yet there are deficiencies and hiatuses in the Sri Lankan health system which needs identification and rectification.
Prostate cancer is the second most commonly diagnosed cancer in men worldwide and accounted for 258,000 deaths in 2008.  Despite being a global disease, significant variations in the pattern of incidence and mortality by region and race have been observed. In USA, African American men are at the highest risk of developing prostate cancer with an annual incidence of 178/100,000.  Among Asian Americans the incidence is 88.3/100,000. It is 49.5/100,000 among South Asians residing in the UK.  Although the leading cancer in South Asian men in USA is prostate, the incidence of prostate cancer in native Indians is 9/1,000,000, which is 15-fold less than their counterparts residing in the USA. , These variations may be due to genetics, culture, diet, and other environmental factors.
The age adjusted rate of prostate cancer among Sri Lankan men calculated based on data available at the cancer registry is 5.7/100,000 for 2005.  There were 303 newly diagnosed cases of prostate cancer in 2005. According to the cancer registry maintained by the National Cancer Control Program of Sri Lanka, in 2006 prostate cancer was the eighth commonest cancer among men in Sri Lanka with 321 new cases reported.  Until 2007, the Sri Lankan cancer registry was based on data gathered from oncology units of the country. In essence only those patients who sought treatment from oncology units were included, which lead to significant under-reporting. From 2008 onwards, data from pathology laboratories of hospitals are also included in an effort to improve the accuracy. Hence in 2008, the year with the latest available data, 391 cases of prostate cancer have been reported to the cancer registry (unpublished data). Accurate prostate cancer estimates in less developed countries are often unknown due to incomplete case reporting to tumor registries.  Most metastatic prostate cancers can be managed by surgical orchiectomy as the mode of androgen deprivation therapy (ADT) and hence these patients do not seek oncological services and escape being recorded in cancer registries. Stigma related to cancer in South Asian countries make matters worse as patients and their families shun dedicated oncology services. There are no electronic data storage systems in Sri Lankan hospitals for gathering patient data; hence retrospective studies based on cancer registries are bound to be flawed. Therefore, the true incidence of prostate cancer in Sri Lanka is probably underestimated. Under these circumstances hospital based prospectively collected data are useful to identify morbidity patterns and complement the information available from cancer registries.
Data-related to characteristics and morbidity pattern of Sri Lankan patients with prostate cancer are sparse. ,, Hence, we conducted a prospective hospital based cohort study over a period of 4 years from 2010 to 2013 among newly diagnosed patients with prostate cancer in a single urology unit of a tertiary care hospital in Sri Lanka. The objectives of the study were to describe the clinicopathological characteristics of prostate cancer and the primary treatment modality in a cohort of native Sri Lankan patients seen in a urology unit of a tertiary care hospital in Sri Lanka.
| > Materials and methods|| |
Data were collected prospectively from all patients with newly diagnosed prostate cancer and managed in the urology unit of a tertiary care hospital manned by a single urological surgeon over a period of 4 years (January 1, 2010-December 31, 2013). Data were recorded in individual files maintained in the urology unit as well as electronically and updated as the patient follow-up continued in the outpatient clinic. Every patient was given a booklet containing information regarding the illness written in native Sinhalese and Tamil languages in order to educate them regarding the importance of regular follow-up. Those who defaulted were contacted over the phone or via mail to encourage clinic attendance and data collection. In 2011, Sri Lanka had 87 cellular phone subscribers per 100 population compared to 93 in the USA, which allowed us to contact our patients efficiently.  All patients with histologically proven carcinoma of prostate were included in the study.
Those with acute or chronic urinary retention or severe obstructive lower urinary tract symptoms (LUTS) and a suspicion of prostate cancer underwent transurethral resection of prostate (TURP) which provided histology as well as relief of bladder outflow obstruction [Figure 1]. Those who had clinically unequivocally malignant prostates with little or no bladder outflow obstruction had digital guided trans-rectal biopsies as this mode was less demanding financially. Those with raised prostate specific antigen (PSA) only or with a clinically equivocal prostate on digital rectal examination underwent trans-rectal ultrasound (TRUS) guided trans-rectal core biopsy of prostate. Once histologically proven to have prostate cancer, all patients were advised to have an isotope bone scan. If the bone scan was negative for metastases they underwent cross sectional imaging with a computed tomography (CT) scan or a magnetic resonance imaging (MRI) scan of pelvis/prostate to assess the local spread of the disease. Though a MRI scan was preferred, as there was no MRI scanner available at our hospital only those who could afford it done privately at their expense were able to have a MRI scan to assess the local disease burden. Others had a CT scan assessment.
|Figure 1: The management plan of patients with prostate cancer. LUTS=Lower urinary tract symptoms, PSA=Prostate specific antigen, TRUS=Trans rectal ultrasound, TURP=Transurethral resection of prostate|
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Patients with metastatic disease decided on the mode of hormonal treatment of their choice. Most opted for surgical orchiectomy as the form of ADT due to financial reasons. The luteinizing hormone-releasing hormone (LHRH) agonists are not available in the National Health Service of Sri Lanka. Those with localized disease were offered surveillance, radical prostatectomy or radical radiotherapy according to the grade of the tumor and patient's wishes. Follow-up included 3 monthly PSA levels initially for 1-year and thereafter 6 monthly.
Approval for the study was obtained from the Ethics Committee of the Institute.
| > Results|| |
There were 278 patients with histologically proven prostate carcinoma. Average age at diagnosis was 70.5 years (range: 48-87 years). Five (2%) patients had a first degree relative who had prostate cancer. Two hundred and nineteen (79%) patients had a clinically malignant prostate on digital rectal examination. The most common presentation was LUTS [Table 1]. Only six (2%) patients were found to be having screening detected prostate cancer, after they had elevated serum PSA levels at routine medical check-ups. Serum PSA was available for 253 patients. More than half (57%) of the patients had a serum PSA more than 50 ng/ml [Table 1]. Histopathology was ascertained by TRUS guided trans-rectal core biopsy in 34%, trans-rectal digital guided prostate biopsy in 34% and TURP chips in 32%. The vast majority (270/278) were acinar adenocarcinomas. There were eight unusual histological types - three ductal carcinomas, two undifferentiated carcinomas, two neuroendocrine tumors and one signet ring cell carcinoma. Gleason sum score was available in 264 patients [Table 1]. The specimen was not adequate to give a Gleason score in 14 patients. Gleason sum score was 8 or more in 44% of the patients.
Stage of the disease was determined at the end of clinical, biochemical and radiological assessment. Doubtful cases were discussed with the oncology team and a decision was arrived at. Accordingly 60% (167/278) had metastatic disease at the time of diagnosis. Nine patients had soft tissue (extra-regional lymph nodes 5, liver 2, lungs 1, brain 1) metastases. Forty eight patients underwent radical radiotherapy while seven patients had radical prostatectomy [Table 2]. Twenty patients decided not to have any intervention. One hundred and fifty-eight patients with metastatic disease and 14 patients with locally advanced disease underwent bilateral orchiectomy. Even among patients who had to have ADT as neoadjuvant therapy before other forms of treatment, most opted for bilateral orchiectomy [Table 2]. Only 13 patients decided to buy LHRH agonists as ADT. Hence 94% patients opted to have surgical orchiectomy as the mode of ADT. The main reason for a large majority undergoing surgical orchiectomy was the nonavailability of LHRH agonists in the National Health Service of Sri Lanka due to high cost.
|Table 2: Different forms of treatment given according to the stage of the disease |
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The median follow-up was 22 months (range: 2-49 months). Thirty-two (11.5%) patients died during the study period. Twenty-two (8%) of them died due to progression of the disease. Twenty (91%) of those died due to disease progression had a Gleason score of 9 or 10.
| > Discussion|| |
Average age (70.5 years) at diagnosis of prostate carcinoma among men in Sri Lanka is higher than that in the developed world where the median age is approximately 67 years.  Incidence of familial cancer was 2% in our patient cohort. Worldwide it is 9%. , Sri Lanka's neighboring country, India has a familial cancer rate of 3% which is closer to the rate of Sri Lanka.  It has been shown that introduction of PSA testing does not appear to alter the familial risk of prostate cancer significantly.  Therefore genetic differences between prostate carcinoma in South Asians and the developed world is a possibility which needs further evaluation.
Statistics of the National Cancer Control Program of Sri Lanka are used for planning strategies and allocating resources to both curative and preventive aspects of cancers in Sri Lanka. At present, data collection is done through patient registries maintained at Oncology and Pathology Departments of the country. According to the latest cancer registry data, the total number of prostate cancer in 2008 was 391. According to our study, in a unit manned by a single urological surgeon there have been 68 cases of prostate cancer a year on average. Patients with prostate cancer are managed by all twenty-three urological surgeons working in Sri Lanka and by the general surgeons too, especially the patients with metastatic disease. Therefore, cancer registry data in relation to prostate cancer appears to be underestimated, and the urological community in Sri Lanka and the health planners should formulate a better strategy to compile a proper database of prostate cancer in order to collect robust data which can be used for more meaningful planning and resource allocation to control and treat the disease.
Screening for prostate cancer is not recommended in India where the incidence is estimated to be 9/100,000.  Age adjusted rate of prostate cancer in Sri Lankan men is 5.7/100,000.  Even with allowances for under-reporting and lack of widespread PSA testing Sri Lankan incidence should be closer to that of India rather than the Europe and USA, as serum PSA testing will cause an increase in prostate cancer incidence by only about 81%.  Therefore it is reasonable to assume that Sri Lanka belongs to the category of countries with a low incidence of prostate cancer and PSA screening is not warranted as a national preventive program. Yet medical personnel will continue to use serum PSA widely, especially among people with LUTS and during medical checkups based on insurance schemes. This together with a rapidly ageing population and change in dietary habits will contribute to more case detection and prostate cancer will be ranked as a much commoner cancer in Sri Lanka in a not too distant future.  Therefore prostate cancer should receive more attention and made a priority in the National Cancer Control Program of Sri Lanka.
Seventy-nine percent of the patients in our study had locally advanced (19%) or metastatic disease (60%) at the time of diagnosis. According to a study done in India from 2003 to 2005, 71.1% had metastases at the time of diagnosis.  In the west before the advent of serum PSA, two-thirds of patients had locally extensive or metastatic disease at the time of diagnosis.  These figures remain same for nonscreened groups in the Europe even now.  In countries with widespread testing of PSA, only 12-16% will present with locally advanced (T3 or T4) and metastatic disease now. ,
Nearly half (44%) of our patients had a high grade malignancy (Gleason sum score of 8 or more). In the UK and mainland Europe, it is about 16-20%. ,, Two previous studies involving a total of 47 patients had shown that most (66%) prostate cancers in Sri Lanka are high grade tumors with a Gleason score of 8 or more. , Among native Indians, 72.1% had a Gleason score of 7 or more at the time of diagnosis.  However, South Asian migrants in UK and USA have a much lower incidence of high grade tumors. ,, According to the PROCESS study done in late 1990s only 5% of South Asians with prostate cancer had a Gleason score of 8 or more.  During this time serum PSA was not widely used in the UK for early detection of prostate cancer and only about 10% of patients had screening detected cancers. Hence differences cannot be due to widespread PSA usage. Among Asians living in USA prostate cancer with Gleason score of 8 or more is 18% in a study done from 2004 to 2006.  Another study showed that the proportion of poorly differentiated prostate cancer among south Asians was similar to those of whites in USA.  The PROCESS study further shows that incidence of prostate cancer among South Asians residing in UK was 6-7 times higher than their native counterparts living in India. , These findings suggest that incidence of prostate cancer is lower in South Asia, but the proportion of high grade cancers is more. With the migration of South Asians to UK and USA, these differences tend to reverse leading to a much higher overall incidence with a reduction in high grade cancers.
Although some of these differences could be due to poor access to health care services in South Asian countries, the possibility of dietary or an environmental factor that reduces the overall incidence of prostate cancer in South Asia while increasing the number of high-grade tumors is a real possibility. Five-alpha-reductase inhibitors, finasteride and dutasteride, are known to reduce the number of prostate cancers.  At the same time, men taking these drugs are diagnosed to have more higher Gleason score tumors.  Therefore, a similar substance in the South Asian diet rich in spices or an effect via exposure to sunlight are potential explanations, which need further study. , Though prostate cancer is known to dedifferentiate in the post PSA detection period,  large differences shown in our study is unlikely to be due to this effect alone. Furthermore even in unscreened European populations, the proportion of high-grade tumors remains much lower than in South Asians living in their native countries.  Similarly, only a small number of patients in the POCESS study had PSA detected cancers, hence widespread use of PSA is unlikely to be the reason for the differences.
In European countries only about 20% of patients who need ADT opt for bilateral orchiectomy.  In our series, 94% (190/203) of them underwent surgical orchiectomy as the mode of ADT. Though the reasons for this were mainly availability and financial, it has been shown that rates of myocardial infarction and cerebrovascular accidents are more after medical forms of ADT (both LHRH agonists and anti-androgens), while no such increased association is seen after surgical orchiectomy.  Even psychological morbidity appears to be minimal after surgical orchiectomy. , Furthermore, the size of the testes become significantly smaller even after medical means of orchiectomy making long-term cosmetic differences negligible.  Elimination of compliance issues and low cost are more relevant to a country like Sri Lanka where resources are scarce and the rural population is large. Additional benefits of surgical castration include certainty in achieving castrate levels of testosterone so that subsequent monitoring of serum testosterone becomes unnecessary. , Therefore surgical orchiectomy can be recommended as a cost saving, yet a scientifically acceptable option of ADT in resource poor settings like Sri Lanka.
Most urological surgeons in Sri Lanka perform TURP as a means of obtaining tissue for diagnosis as well as to relieve significant bladder outflow obstruction in patients already suspected of having prostate cancer by digital rectal examination and elevated serum PSA. This has been our practice too and nearly one-third of our patients had the histological diagnosis by TURP chips. This is the more plausible reason for a higher incidence of prostate cancer in prostatic chips after TURP as reported in a previous study rather than to a change in the incidence or biological behavior of prostate cancer in Sri Lankan patients as hypothesized.  Our explanation is further supported by the results of two studies done in Sri Lanka where the incidence of incidental prostate cancer among TURP done for clinically benign disease was around 10% which is the world average. ,
Although single-center series are naturally prone to selection bias, in the absence of a robust electronic data collecting system and the cancer registry being incomplete and late in publishing its data our study provides the best possible collection of data under the circumstances. The ideal investigation protocol could not be performed in all patients in our study cohort due to difficulty in access to a MRI scanner. Another limitation was that the histological grade was based on needle biopsy specimen and was not reviewed by a central pathologic committee.
The biggest strengths in our study were its prospective nature and the relatively large number of the sample. This minimized the bias attributed to retrospective studies based on poorly maintained patient records in developing countries as well as deficiencies of secondary analysis of data obtained from incomplete cancer registries.
| > Conclusions|| |
Sri Lankans like other South Asians appear to be having a low incidence of prostate cancer, but a larger proportion of high-grade cancers in comparison to the UK and USA. Although genetic differences may exist, a dietary or an environmental factor is more likely to be the cause for these changes. The protective effect of this factor appears to wane as South Asians emigrate and live in UK and USA. This observational study data should be reviewed as preliminary and hypothesis generating.
| > Acknowledgment|| |
Dr. Neelamani Paranagama, National Cancer Control Program, Sri Lanka. Prof. Srinath Chandrasekera, University of Sri Jayawardenapura, Sri Lanka.
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[Table 1], [Table 2]