Acta Med. Nagasaki 34 : 24-27
Carcinoma of The Urinary Bladder in Singapore
E. P. C. Tock,' K. T. Foot , K. H. Tung' and E. C. Tan'
Depertment of Pathology * and the Department of Surgery+
National University of Singapore
INTRODUCTION
Carcinoma of the urinary bladder is relatively common in Singapore, being the tenth common- est cancer in the male population (Singapore Cancer Registry 1985) The present study exa- mines the pattern of this malignant disease in the Singapore population, in terms of clinical presentation, pathology, and management. It is based on an analysis of cases of transitional cell carcinoma of the urinary bladder as seen in the Department of Surgery, National Univer- sity of Singapore, over a period of 12 years, from 1973 to 1984 inclusive. The study is divid- ed into two parts ; the first part deals with invasive carcinoma of the urinary bladder, while the second part is concerned with intra- epithelial carcinoma or carcinoma-in-situ.
PART I : INVASIVE CARCINOMA OF
THE URINARY BLADDER
MATERIAL AND METHODS
A retrospective study was made of 73 cases of invasive carcinoma of the urinary bladder seen at the Department of Surgery of the National University of Singapore during the period 1973 to 1978. The cases were identified from the records of the Singapore Cancer Registry at the Department of Pathology and the clinical data were derived from the patients' case records. The authors have also been analy- zing all cases of bladder carcinoma seen after 1978, but the additional data obtained do not throw further light on the subject than what is presented in this paper.
RESULTS AND DISCUSSION Age, Sex and Racial Distribution
Of the 73 patients reviewed, 60 were males and 13 females, giving a male preponderance of 4.6 to 1. The male to female ratio reported in the literature varies from 2.3 : 1 (Anderson, 1973) to 5 : 1 (Westcott, 1966) This male preponderance has been attributed to urothelial carcinogens such as through cigarette smoking and occupational exposure. In Singapore, while there is a much higher incidence of smoking among males than females, there is no known occupation involving exposure to known urothe- lial carcinogens. The use of beta-naphthylamine as an antioxidant in tyre manufacturing has been banned for the last two decades or so. The dyeing industry, seen largely in the batik mak- ing, does not utilise any known carcinogenic dyes. Sixty-four of the 73 patients (or 87.7%) were Chinese. This is consistent with the predominance of Chinese in the Singapore population and therefore does not indicate any ethnic predilection. The majority of the pati- ents (63 out of 73, or 86.3%) were in the fifth, sixth and seventh decades of life. Only 2 pati- ents, both males, were below 40 years of age.
Clinical Presentation
Haematuria was by far the commonest presenting symptom, occurring in about 85%
of patients. Haematuria occurs either as the sole complaint or in conjunction with cystitis and /or outflow obstruction. Hendry and Bloom (1976) have also recorded the over- whelming frequency of haematuria as a
24
1989 CARCINOMA OF THE URINARY BLADDER 25
presellting synlpton1． One patient had a
palpable suprapubic mass。Other symptoms were mainly backache and loin pain。The dura．
tion of haematuria correlated positively with
thestageofthediseasefoundatoperation；
patients presenting with T3and T4tumours had a Iong history of haematuria（for months），
1ηかαUθη0μs Urogrα〃ε F π4加8S
An analys三s was made of the available intra．
venous皿ograms（IVU）of61patients。As
many as15patients（or24．6％）had a norma11 VU．Sixteen patients（or26．2％）had evidence of unilateral or bila．teral ureteric obstruction．
In35patients（or57．4％）the IVU showed・a fillingdefect．In26patients（・r42．6％），the tumour was not outlined．Thus，a normal blad．
der outline did not exclude a bladder tumour．
CZ 1zεcαZ S6α8加8
The illaccuracy of clhlical staging is well known．Hence，histopathological examination of biopsy and resection specimens was used to verify or modify the clinical staging．Thirty．
five cases（or47．9％）were TI tumours．T2tu．
mours accounted for ll ca．ses（or15．0％），T3 for16cases（or21．9％），while6cases（or8．3％）
were stagled T4。
CZ∫1z cαZ S6α8 π8』α1zdl pαむhoZo8 cαZσrαd∫1τ8
A correlation was observed between the clinicarstageandthepathologicalgrade；Tl tumours were usually Grade I or■（well or moderately differentiated），while T3and T4 tumours were generally Grade皿（poorly diffe−
rentiated）．
ノVμ励oro∫Tμ肌oαrs
The majority，520ut of73（or71．3％），of the patients had single tumours；15（or20．5％）
had multiple tumours（1ess than6），while3 patients（or2．19％）presented with papillo．
matosis．
S髭o o∫TμηLOμrs
The lateral walls were the most common sites，
with51patients（or69．8％）presenting with lateral wall tumours，the left and right walls being affected about equally．
σrossハ40甲hoZo8ツoゾTμητoμrs
Forty−two patients （or57．5％）presented withpapillarylesions，19patients（or26％）
had solid tumours，while2patients（or2．7％）
had ulcerative lesions which represented a late stage of the disease。
σrossハ40㌍hoZo＆ソα1ZGどσZ πεcαZ S6α8 η8 Papillary tumours were more likely to early stage，while solid tumours tended to lnvaslve．
be be
伍s亡oZo9 cα1乃PθsoゾTμ肌oμr
The vast majority，sixty．nine，of the patients
（or94．5％）had transitional cell carcinoma、．
There were only2cases of adenocarcinoma（or 2．7％）；there were also2cases（or2。7％）of squamous cell carcinoma，one of which occurr−
ed in a bladder diverticulum．
ハ40dlθs o∫ThθrαPツαπdl RθsμZ6s
A range of treatment modalities had been employed，varying from cystodiathermy alone to total cystectomy．The series therefore lacked a uniform policy of management。For T l tumours，before1976，treatment was by biopsy and cystodiathermy l since1976，transurethral resection became available and was the treat−
ment of choice．This method was also used for T2tumours followed by radiotherapy。For T3 tumours，the recommended treatment was a course of radiotherapy，followed by cystoscopy at4to6weeks later，and，if there was no res．
ponse，a total cystectomy was pereformed．
ForT4tumours，onlypalliativeradiotherapy
was administered．
The overall mortality was46．6％with 34 deaths，of which22（or64．7％）were attribut−
ed directly to carcinoma of the bladder．The majority of the patients succumbed within the first two years。Eight patients with Tl tumours died，but 60f these died of causes other than bladder carcinoma．The malority of patients with invasive carcinoma died of the malignancy．
Carcinoma of the bladder presents with certain specific management problems．The concept of the urothelium as a single continuous membrane lining the urinary tract implies that eradication of a tumour in the bladder does not mean eradication of the disease，since urothe一
26 E．P．C．Tock ▽oど．34
Iia，l tulllourS Illa，y still develop ill otller parts of the urinary tra．ct as long as the aetiologica，I
factor（s）exists．．Also，a problem exists in decidillg oll tho preservatioll of the blεしdder．
LatetUmOUrSaregellerallytreatedmOrera（li−
callythanearlytumours．However，forearly stage，lowgrade lesions，one is confrontedwith the problenl of whether total cystectollly shou1（玉 be perfonlled，bearillg ill Illillcl that about15％
of Tl tumours become invasive later on．Never−
th eIess，because of the good resI）onse of sonle patieIlts to radiotherapy，and thc mortality and morbidityattelldillgcystectomy，selectivity
shoul（i be exerc量sed in perf60nning total cystec−
tomy．Forlowgradetumours（confinedtothe
laminapr・pria），thep・licyad・ptediscyst・sc・一 1）icresectioll．Radiotherapyisgivellilladditioll if there is sul）erficial 111uscle hlvolvelnent．
Multi夏）le small，sul）erficial low grade tumoul・s nlay l）e controlled by illtravesical cytotoxic theral）y．Localisedhighgradetumourses1）ecia−
11y llear the vault of the bladder may be treat−
ed with l）a「rtia，l cystectomy．Papilloma，tosis of the bladder would lleed total cystectonly．Lastly，
because bladder cal℃illo111as tend to be nlultiple not only ill space but also in time，a programme
ofregularchecksfbrrecurrenceshas吃obe
established ；its ratiollale also has to be collvhlcillglyexl）lailledtothel）atiellttoellsure his compliance for regular follow−up checks。
Thlsofcoul・sedoesllotaPl）lytolatestage
disease with l）（）or progllosis regardless of the mO（leOftreatmCllt．
1）ART II ：CARCINOMA−IN−SITU OF THE URINA．RY BLADDER
Carcinoma．h1．sitしI of the urinary bladdel・was first descrjbed i）y Melicow and Hollowelh11弱2；
however，it wa，s not well recognised as a clinical elltity ulltil I970when Utz and his co−workers
describedthel）ligl・tofthepatientwiththis COllditiOl1。ThediagnOSiSOfCarCh10ma−i11−SitU of the bladder is important because of progno．
sticalldtherapcuticconsideratiolls，sinceahigh proportion of cases develop muscle illvasion and become life−threatelling．However，not all patiellts illvariably develop invasive disease，
alld in a sigllif．icallt number of them，the disease 111ay be donllallt alld run a relatively benign
course（Fride且1，1976；』Farrow et a1，1976）．
This poses pl℃blems in management as it is difficult to predict the course of the disease ill a particular patiellt．Nevertheless，、へ・ith a better
ulldersta，ndingofthenaturalhistoryofthe
disease，a general outline in its mana．gemellt would be useful ill order to a、void unclertreat−
ment or overtreatment．This paper serves to illcreaseεしwareness of carcilloma−ill−situ of the bladder ill Singapore，and also proposes a gelle−
ral policy ill the management of the disease．
MATERIAL AND METHODS
Trallsitional cell carcinoma．in−situ Qf the urillary bladder is defined as illtra−epithelial carchlo111a occurrillg ill other、vise nor111al blad−
der mucosa，ill the absence of papillary forma−
tioll， The degree of differentiatioll ls poor，
con・esponding to Grade 皿 in the W．H．O．
ClassificatiOl1．
For the five−year period froln 1980to 1984，
130cas（ヤs of tra．nsitiollal cell ca1℃illonla，of tho bladdcr were soen at the Department of Surgery ofthe National Ulliversity ofSillgapo1・e．Eighty−
two （or63％）of the cases wore staged as superficial carcinoma （T l growths），while48
（or 37％） were diagIIosed as nluscle illvasive cancer（T2，T3andT4gr・wths）。Am・11gthe82
cases o f superficial carciIlonla， 12 （or 15％）
were（：onfirmed histologically to have tfallsitio−
nal cell carcinoma−il1−situ；all l2cases were foulld ill a，ssociation with overt papillary carcinoma cither at the same time or at sul）se（luentfollow−upcystoscopy．Therewere
llo cases of isolated carcillon■a＿in−situ in this serles．
The pathological specimens of all the12cases were reviewed by one of the authors（E．P．C．
Tock）．
RESULTS AND DISCUSSION
Thepe were10males and2females，giving a maleprep・nderancerati・・f5二1．Th・ages・f thepatientsrangedfrom30t・73yearswitha
meall of57years．All etllllic groups were affect−
ed with no obvious predilection．The majority
（100ut of l2cases）were djagnosed in the past 1％years．Allthe patients exceptone had gross
！989 CARCINOMA OF THE URINARY BLADDER 27
haematuria．On cystoscopy，carcinoma−in−situ
（on correlation with histological confirmation）
most commonly appeared as flat areas of hyperaemia，best described as velvety areas，
with no papillary lesion．These areas had ill．
defined margins and were best appreciated with the bladder about one−third full．Occasionally，
carcinoma−in−situ apPeared normal on cystosco−
py，and random biopsy of such normal lookingr mucosa have shown carcinoma−in．situ in some instances．
Cytological smears of bladder washing in all cases showed malignant cells，illcluding those patients who at the time of cytological exami−
nation had no obvious papillary， solid or ulcerative lesions． Our findings illustrate the point that the overt papiIlary lesion tends to attract more attention than the flat lesion of carcinon験一ill−situ and if llo biopsy of the latter or cytology is done，the lesion will be missed．
Our c皿rent routine practice is to do random biopsies of normal looking mucosa as we11，in all cases of bladder tumour．
Once a diagnosis of carcinoma．in−situ has been made，close follow．up of the patient is mandatory，because of the tendency of the lesion to progress to invasion，Management of carcinoma−in−situ of the bladder is problematic because its natural history is not quite well understood and its treatment is still controver．
sia1．Utz at the Mayo Clinic has advised that if on initial diagnosis，the patient is sympto−
matic and the lesion is diffuse involving the trig・neand／・rpr・staticurethra，thent・tal cystectomy should be performed．If the lesion is localised to less than3cm in diameter，and the patient is relatively asymptQmatic，then intravesical chemotherapy should be g・iven． If after6to9months of intravesical therapy，
there is no improvement，then total cystectomy should be done，if the patient is reasonably fit．
We feel that a period of6to9months may
betooshortatimetoassessanyparticular
individual with carcinoma．in．situ of the bladder
becauseofitslongnaturalhistorybeforeit
becomes invasive。（Fridell，1976）．Such patients，
including thos♀with a diffuse lesion，could be given a trial of chemotherapy．A number of intravesical chemotherapeutic agents are now available such as thiotepa，mitomycin C，
adriamycin，and，more recently，BCG．It appears justifiable to try intravesical treatment with the various agents，a．t、the same time keeping a close watch on the patient．？erhaps conserva．
tive management could be continued until such time、as all available effective intravesical agents have been exhausted or when there is invasi6n．With greater awareness of the disease，
more cases ill future will be diagnosed earlier，
and hopefully with early institution of intra−
vesical chemotherapy，progression to muscle invasion can be prevented，and the number of cases requiring cystectomy minimised．
REFERENCES
1）Anderson，C．K．：Currenttopicsinthepatho。
10gy of bladder cancer．Proc．Roy．Soc．Med。
66：283，1973．
2）Fridell，G．H．：Carcinoma，carcinoma−in．
situ，and early lesions ofthe uterine cervix and the urinary bladder． Introduction and definition．Cancer Res．36：2482，1976．
3）Hendry，W。F。＆Bloom，H．」．G。：Urothelia．1 neoplasia：Present position and prospects in recent advances in urology，1976．
4）Melicow，M．N．＆Hollowel，」。W．：In㌻壌㏄o−
thelial cancer，carcinoma−in−situ．Bowen s disease of the urinary system：Discussion of 30eases，」．UroL68：763，1952．
5）Singapore Cancer Registry，1985。
6）Utz，D．C．，HanashK。A．＆Farrow，G．：The plight of the patient with carcinoma of the urinary bladdeL103：160，1970．
7）Westcott，」．W．l The prophylactic use of thiotepa in transitional cell carcinoma of the bladder．」．UroL93：96，1966．
