Clinicopathological profile of malignancies treated in a urology unit over a period of five years

There were 386 prostate cancers, 193 bladder tumours, 173 renal tumours, 13 upper urinary tract carcinomas, eight penile cancers, seven testicular malignancies, one urethral carcinoma and two urachal carcinomas during the study period. Gleason score of 8 or more prostate cancers were seen in 164 (42.5%) patients. Metastases were present in 59.8% of patients with prostate cancer. Muscle invasive urothelial cancers constituted 31.4% patients with bladder carcinoma. Primary carcinoma-in-situ of the bladder was seen in only one patient. Average age at diagnosis of renal cell carcinoma was 56.9 years with a male to female ratio of 3.5:1.


Introduction
Total health expenditure as a share of GDP in Sri Lanka is around 3.5% [1].Twenty six Urological surgeons serve the country's population of 20 million.With universal health care and a robust public health network across the country, Sri Lanka has made noteworthy achievements in health outcomes compared to other developing countries [2].With the changes in the socioeconomic parameters of the Sri Lankan society non communicable diseases have become the major health challenge of the new millennium.Malignancies make a significant portion of the non-communicable diseases worldwide as well as in Sri Lanka [3].
Different countries have populations of varying ethnicities with potentially different genetic makeup.In addition to genetic differences, the pattern of cancers differs according to different socio-cultural factors inherent to the index population.In the absence of a comprehensive national cancer registry, data maintained at individual units or at institutional level are useful to identify epidemiological and demographic patterns.Our aim of the study was to identify the clinico-pathological profile of urological malignancies treated in the urology unit of a tertiary care hospital in Sri Lanka.

Materials and methods
A cancer registry was maintained prospectively at the urology init of Colombo South Teaching Hospital.Data related to all newly diagnosed malignancies were recorded prospectively.The data were updated as the patients' follow up continued in the clinic.The data belonging to patients over a period of st st five years from 1 January 2011 to 31 December 2015 were analysed.
Histopathologcal evaluation was done according to the World Health Organisation (WHO) and International Society of Urological Pathology (ISUP) classification 2004 [4].All patients included in the study had their diagnosis confirmed by histopathological evaluation.Tumour staging was done using the TNM classification of the Union for International Cancer Control 2009 [5].Approval for the study was obtained from the Ethics Review Committee of the Institute.There were 193 patients with bladder tumors during the fiveyear period.Average age at diagnosis was 65 years with a male to female ratio of 4.2:1.Histological types of bladder tumours are given in table 3. Infiltrating urothelial carcinoma was seen in 133 patients.There was only one primary carcinoma-in-situ found among the bladder tumours.There were 14 (7.3%) patients with squamous cell carcinoma and five (2.6%) with adenocarcinoma of the bladder.In addition to the above primary malignant neoplasms in the bladder, five patients had metastatic deposits in the bladder during the five year study period.Their primary malignancies were breast carcinoma, papillary renal cell carcinoma -type II, ovarian carcinoma, carcinoma of the stomach and melanoma of the skin.One patient had an inflammatory myofibroblastic tumour of the bladder.The pathological evaluation of the bladder cancers revealed that 47.7% (82/172) were high grade and 31.4% (54/172) were muscle invasive (Table 4).
There were 173 renal tumours (Table 5) out of which, 164 were renal cell carcinomas.The male to female ratio of RCC was 3.5:1.The average age at diagnosis of renal cell carcinoma was 56.9 years.The commonest (81%) renal tumour was clear cell renal cell carcinoma (Table 5).There were 25 papillary renal cell carcinomas.Most (70%) patients had radical nephrectomy as the primary mode of treatment for renal tumours (Table 6).
Facilities for radiofrequency ablation is available at the institute and three patients including one with von Hippel-Lindau disease were treated with radiofrequency ablation.There were eight penile cancers with an average age at diagnosis of 59.8 years.Seven had squamous cell carcinoma while one had a basaloid cell carcinoma.Five of the squamous cell carcinomas were well differentiated while two were moderately differentiated.Pathological stage was pT1 in five, pT2 in two and pT3 in one.Three patients had N1 stage disease and one patient had N2 stage lymph nodes.Mode of surgery included total penectomy in two, partial penectomy in five and glansectomy in one.
There were seven testicular malignancies.The histological types included classic seminoma in three, mixed germ cell tumour in two, choriocarcinoma in one and non-Hodgkins lymphoma in one.When the patient with lymphoma was excluded (who was 79 years old) the average age of patients with testicular malignancies was 31.5 years.The pathological stage was pT1 in five and pT2 in one.One of them had N3 disease while one had lung metastases.
The patient with primary urethral carcinoma had total penectomy and the histology was a squamous cell carcinoma.One male (age 51 years) and one female (age 47 years) patient had urachal carcinomas.Both had partial cystectomy with excision of urachal ligament and umbilicus and pelvic lymphadenectomy.
The histology revealed mucinous type and enteric type of adenocarcinoma in the two patients respectively.
3 The Sri Lanka Journal of Surgery 2016; 34(4): 1-6    When compared with other Asian countries this pattern is similar to that found in China, Hong Kong and Taiwan [6].Whether this is due to the late presentation or due to an unknown risk factor is debatable [8].Only 17.6% were Gleason 6 cancers.Active surveillance is done very rarely due to technical problems like poor compliance and commitment to rigorous follow up.
Surgical orchidectomy is the mostly used (94.3%)form of androgen deprivation therapy which could be considered an attractive option in developing countries with large rural communities [8].Most patients with organ confined disease in our study preferred radical radiotherapy over radical prostatectomy.
Urothelial tumours constituted 89% of bladder malignancies.Muscle invasive tumours were seen in 31.4% indicating delayed presentations or de novo aggressive disease.
Although this is higher than the proportion in the western world, is much less than the 74.1% in China [9].A higher incidence of squamous cell carcinoma (7.3%) compared to the western world and some other Asian countries is evident in this study.
The proportion of squamous cell carcinoma in China is around 1.9% [9].Whether this is related to environmental risk factors that operate in Sri Lanka is unclear [10].Primary carcinoma-in-situ of the bladder is almost unheard of in Sri Lanka.This is so in other south Asian countries like India too [11,12].
However in China, carcinoma-in-situ of the bladder is seen in 2.4% of urothelial carcinomas [9].Although the exact reason is unknown it could be due to the high prevalence of BCG vaccination in Sri Lanka.Intravesical BCG is well known to be effective in treatment of primary carcinoma in situ of the bladder.In 1929 Raymond Pearl reported a lower frequency of cancer in patients with tuberculosis [13].He also showed that cancer survivors had a higher incidence of healed tuberculosis than those who succumbed to malignancy.In late 1950s it was shown that mice infected with BCG were better able to resist inoculation with cancer cells [14].
In 1969 Coe and Feldman observed a strong delayed hypersensitivity type reaction to BCG in guinea pig bladder [15].These observations lead Morales to try intravesical BCG to prevent tumour recurrences of bladder cancer [16].Hence it is reasonable to postulate that widespread BCG vaccination may be a potential reason for the rarity of primary carcinoma in situ in Asia.In Sri Lanka BCG vaccination is mandatory at birth and coverage is more than 90% of the population for most vaccines [2].
Unlike prostate and bladder cancers, renal cancers of our study have been diagnosed at a relatively early stage similar to developed nations [17].This may be due to the widespread availability of abdominal ultrasonography facilities in the country.However the average age at diagnosis of renal cell carcinoma is much lower than in the developed countries of Asia and Europe [15,16].In Japan it is 63.9 years and in Sweden it is 67 years [17,18].The average age at diagnosis of renal cell carcinoma in our study is similar to that of neighbouring India [19].Some postulate whether comparatively poor nutritional status of younger population in developing countries could be responsible for this difference [19].The distribution of histological types of renal cell carcinoma in Sri Lanka is similar to the rest of the world [17,18].
Upper tract urothelial cancers are uncommon and accounts for 5% of urothelial malignancies [20].In our study cohort upper urinary tract urothelial carcinoma occurred at a ratio of 1:10.2, when compared with urothelial carcinomas of the bladder which is similar to worldwide data.
Most of the upper tract urothelial cancers of Sri Lanka are of high grade (61.6%) and are diagnosed at an advanced stage (54% were pT3 stage).However the percentages are similar to those of developed countries in Asia.In Japan 60% of UTUCs are high grade and 49% are pT3 stage [21].Even the average age at diagnosis (69.7 in our study and 70 years in Japan) and male to female ratio (76.9% and 72% men in our study and Japan respectively) of upper urinary tract urothelial carcinoma are similar to that of our study [21].The small number of cases of testicular and penile malignancies in this study is due to the fact that such tumours are managed by general surgeons in the country.Hence referral of such patients to urology units is minimal.
The main limitation of this study is that it is confined to a single urology unit with a specific drainage population which may not be representative of the whole population of Sri Lanka.However National cancer registry of Sri Lanka is based only on basic data collected from patients registered at oncology units of the country.Therefore robust data related to urological cancers in Sri Lanka are sparse.Furthermore publication of Cancer Registry data is delayed by many years.Hence under the circumstances, data and inferences of our study would be useful for health planners and researchers.

Conclusion
Characteristics of urological cancers appear to vary among Asian countries.Renal cancers in Sri Lanka occur at an earlier age than the developed countries.They are diagnosed at an early stage similar to the developed world in contrast to the late diagnosis of prostate and bladder malignancies in Sri Lanka.Most prostate cancers are high grade with a Gleason score of 8 or more.Primary carcinoma-in-situ of bladder is extremely rare in Sri Lanka.

Table 2 .
Characteristics of patients with prostate carcinoma

Table 3 .
Histopathological types of bladder tumours

Table 1 .
Distribution of tumours according the site of origin Only 12 (3%) patients had screening detected prostate cancer.One hundred and sixty four (42.5%) patients had Gleason score 8 or more cancers.Two hundred and thirty one (59.8%)patients had evidence of metastases at the time of diagnosis.Out of the 299 patients who required androgen deprivation therapy, 282 (94.3%) patients opted to have surgical orchidectomy.

Table 6
Upper tract urothelial tumours were seen in 13 patients during the five year study period.All of them were urothelial carcinomas.Ten (76.9%) of them were men.Average age of patients with upper tract urothelial carcinoma was 69.7 years.Eight of them had high grade urothelial carcinoma, while five had low grade disease.Pathological stage was pT1 in six cases and pT3 in seven patients.Twelve of them underwent nephroureterectomy and one had segmental resection of the lower ureter with Boari flap reconstruction as he had a single functioning kidney.

Table 5 .
Histopathological types of renal tumours

Table 6 .
Primary treatment modality of all renal tumours

Table 7 .
Pathological stage of renal cell carcinomas after surgery ( n = 154 )