Download A clinico epidemiological study of bladder cancer :An eight Year

Epidemiological study of bladder cancer and risk factors in Upper
Egypt
Abeer F Amin
Department of Oncology, Assuit University Hospital
Abstract:
Background and aim: The incidence of bladder cancer is rising throughout the world. The study aims
to know the histopathological aspect of urinary bladder cancer UBC, risk factors, response to treatment in
Assuit University Hospital, oncology department. Materials and methods: Ninety seven cases of
histologicaly proven UBC, data were collected and analyzed during the period (2005- 2012). Results: Male
seven times affected more than female with age distribution 30-91 year,47.7% of cases were smoker, and
bilharzias in 27.8%. Most cases were transitional cell carcinoma TCC 59/97 cases, mainly high grade in
62.7% followed by squamous cell carcinoma SCC 26/97, mainly moderate grade 53.9%. Non-muscle
invasive bladder cancer NMIBC constituted 8.2%while muscle invasive bladder cancer MIBC constituted
76.3%. Treatment response was assed in 77 cases, 5 cases NMIBC treated by transurethral resection
followed by intravesical docetaxel with CR in 80% cases. MIBC treated by: chemo-radiation in 26 cases
with complete response in 50%, radical cyctectomy in 23 cases with CR in 69.6%, or by partial cyctectomy
in 6 cases with 50% complete response. Conclusion: TCC is the most common pathology followed by SCC,
smoking is the main risk factor, flowed by bilharziasis.
Introduction:
Bladder cancer is the 7th most common
cancer in men and the 17th most common in
women worldwide (1). The median age at
diagnosis is over 70 years, and since the
tumor often is related to smoking, many
patients have a substantial number of
coexisting illnesses that pose risks for radical
surgical approaches (2-4).
morbidity secondary to urinary diversion
techniques (6).
Although surgery is considered the
standard therapy, considerable interest in
bladder preservation has led to the use of
radiotherapy as an alternative, particularly in
less
fit
patients.
However,
radical
radiotherapy is associated with a relatively
high rate of incomplete response or local
recurrence (up to 50%), (7) with salvage
cystectomy for treatment failures.
Other risk factors may include positive
family history, exposure to pesticides, bladder
stones, and smoking. These factors seem to
play now more important roles than
schistosomiasis in the development of bladder
cancer, especially in Upper Egypt (3).
Improving bladder-preservation using
chemoradiation treatment could provide
patients with a choice of treatments and
improve quality of life, the concept of
combined administration of chemoradiation is
designed to maximize the interaction between
ionizing radiation and chemotherapeutic
agents (8). Bladder preservation have
equivalent long-term survival with radical
cystectomy (9).
The major prognostic factors depend on
histological type of tumor, degree of
differentiation of tumor (grade), depth of
muscular invasion (stage), age of patient and
mode of therapy. Cellular classification: More
than 90% of carcinoma bladder are
transitional cell carcinoma (Tcc), about 6- 8%
are squamous cell carcinoma (Scc) & 2% are
adenocarcinoma (5).
Materials and methods:
Between 2005-2012, ninety seven cases
with histological proven primary bladder
cancer in Assuit University Hospital,
oncology department data were collected and
analyzed as regard: sex, age, subsite,
Radical cystectomy is the standard
therapy for these patients with an expected 5year survival of 45–60%. However, radical
surgery comes at the cost of long-term
1
pathology, risk factors, grade, stage, treatment
and response.
As regard grade in TCC, 62.7% of
patient were high grade and 37.3% of patient
low grade. Where in SCC, 26.9% were well
differentiated
and
53.9%
moderate
differentiated SCC and 19.2% poorly
differentiated (Table 4).
Results:
Ninety seven case of histological
proven primary urinary bladder tumor data
were collected during the period from (20052012) and analyzed. The patients range in age
from (30-91) year and mean age was 58.34
year(Table1). There were 85 male and 12
female, male: female ratio was7:1(male is
significantly affected more than female(Fig1).
History of smoking was found in 47.3% of
TCC, SCC, TCC with squmaous differentiae
while 27.8% have history of bilharsiasis
(Table2). Location of the tumor within the
bladder mainly as overlapping lesion 46.4%,
followed by lateral wall 27.8%, dome of
bladder in 14.4%(fig2).
TCC stage II, III were found in 43/59
patient, where 7/59 patient presented as noninvasive bladder cancer (stage1), where in
SCC and adenocarcinoma, all are infiltrative.
Metastatic bladder cancer were found in
15/97 patients, main site of metastases is bone
12.4%(Fig3).
Treatment response were assed in 77
cases as 20 case were missed, 5 patient
NMIBC all are stage I treated by
transurethral
resection
followed
by
intravesical docetaxel with CR in 80% and
DP in 20%.
As regard pathology: transitional cell
carcinoma TCC was the most predominant
MIBC treated surgicaly by either radical
histological type 60.8%, male is significantly
cystectomy in 23 cases and the main response
affected more than female male to female 7:1
was CR in 69.6%,or partial cystectomy in6
the mean age of TCC was 61.3 year. The
cases and the main response CR in 50%
frequency of squamous cell carcinoma SCC
While Chemo-radiation treatment in 26 cases
were case 26.8%, the mean age of SCC was
with complete response in 50% (Table 5) .
54.3 year. Adenocarcinoma 6.2% all are male
and transitional cell carcinoma with squamous
differentiation 6.2%, male: female ratio 2:1
(Table 3).
Table 1: Age distribution in bladder cancer
Age (years)
< 50
50 - < 60
60 - < 70
≥ 70
Mean ± SD (Range)
Risk factors
Bilharziasis
Smoking
Stone
No risk factors
No. (n= 97)
%
19
19.6
34
35.1
26
26.8
18
18.6
58.34 ± 12.17 (30 – 91)
Table (2): Risk factors in bladder cancer
No. (n= 97)
26
46
3
22
Table (3): Mean age according to pathology
%
26.8
47.4
3.1
22.7
Age (years)
Pathology
Mean ± SD
53.33 ± 10.27
TCC with squamous cell differentiation
2
Range
40 – 66
38 – 91
38 – 62
30 – 80
61.05 ± 12.08
54.00 ± 8.60
54.35 ± 12.22
Transitional cell carcinoma
Adenocarcinoma
Squamous cell carcinoma
Table (4): Pathology and grade distribution in bladder cancer
Pathology
Adenocarcinoma:
Well differentiation
Moderate differentiation
Squamous cell carcinoma:
Well differentiation
Moderate differentiation
Poor differentiation
Transitional cell carcinoma:
High grade
Low grade
TCC with squamous cell differentiation
No. (n= 97)
6
2
4
26
7
14
5
59
37
22
6
%
6.2
33.3
66.7
26.8
26.9
53.8
19.2
60.8
62.7
37.3
6.2
Table (5): Treatment response in bladder cancer
Response to treatment
Complete remission
Partial response
Disease progression
Stationary disease
No. (n= 77)
38
22
12
5
%
49.4
28.6
15.6
6.5
Female
12.4%
Male
87.6%
Figure (1): Sex distribution in bladder cancer
3
46.4
50
45
40
35
27.8
30
% 25
20
14.4
15
10
4.1
4.1
3.1
5
0
Anterior
wall
Dome
Lateral
Figure(2)subsite distribution in bladder cancer
4
Outelet
Overlapping
lesion
Posterior
wall
57.7
60
50
40
% 30
18.6
15.5
20
8.2
10
0
Stage I
Stage II
Stage III
Stage IV
Figure (3): Stage distribution in bladder cancer
Discussions:
In the present study , the transitional
cell carcinoma is the most common bladder
tumor 59/97, while squamous cell carcinoma
constitute only 26/97 of the cases seen over a
period of 8 years duration. This correlates
with the decrease incidence of SCC over past
25 year related to the control of
Schistosomiasis (10).
differentiated Scc was 5,These results may be
slightly different from other studies, this
discrepancy may be attributed to individual
variation of interpretation of tumors grade (15).
Most cases 54/97 presented as invasive
bladder cancer (stage II, III) and 15/97 patient
metastatic. This correlates with decrease
incidence of P2-4 lesions dropped from
92.2% to 64.9% in a study comparing two
central pathology registries that were studied
for the years 2003–2004, while incidence of
non invasive bladder cancer (stage I) were
found in 8.2 %, still low in our study this
may be due to management in urology
department without referral
to our
(16)
department
.
Nearly Fifty percent of TCC, SCC and
TCC with squmaous differentiae were smoker
and this correlates with a study found that risk
factors may include positive family history,
exposure to pesticides, bladder stones, recent
cystitis, and smoking. These factors seem to
play now more important roles than
schistosomiasis in the development of bladder
cancer, especially in Upper Egypt (11).
The increase mean age in this study
(61.3 year in Tcc and 54.3 year in Scc) and
the male predominance ( the male: female
ratio 7:1) are in agreement with other reports
(10,12,13,14)
.
Treatment for muscle-invasive bladder
cancer, which constitutes almost two-thirds of
cases in Egypt, remains a challenge. This is
because it aims at local disease control,
elimination of micro metastases, and
maintenance of the best possible quality of
life without compromising survival.
Tumor grading shows that TCC grade in
37 patients were high grade and 22 low grade.
while in SCC, the frequency of well
differentiated Scc was 7 and of moderate
differentiated SCC was 14 and of poorly
Treatment response were assed in 77
cases as 20 case were missed, deeply invasive
tumors treated by radical cystectomy in
29.9% with a high response CR in 69.6%,
and this agree with the fact that radical
5
8- Sherwood BT, Jones GD, Mellon JK,
Kockelbergh RC, Steward WP, Symonds RP.
Concomitant chemoradiotherapy for muscleinvasive bladder cancer: the way forward for
bladder preservation? Clin Oncol (R Coll
Radiol) 2005;(3):160–6.
9- Grossman HB, Natale RB, Tangen CM, et al.
Neoadjuvant chemo-therapy plus cystectomy
compared with cystectomy alone for locally
ad-vanced bladder cancer. N Engl J Med.
2003;349 (9):859-866.
10- Gouda, N. Mokhtar, D. Bilal, T. El-Bolkainy,
M.N. El-Bolkainy. Bilharziasis and bladder
cancer: a time trend analysis of 9843 patients
J Egypt Nat Cancer Inst, 19 (2) (2007), pp.
158–162.
11- H. Yang, K. Yang, A. Khafagi, Y. Tang, T.E.
Carey, A.W. Opipari, et al. Sensitive
detection of human papillomavirus in
cervical, head/neck, and schistosomiasisassociated bladder malignancies Proc Natl
Acad Sci, 102 (21) (2005, 24), pp. 7683–
7688.
12- El. Bolkaing MN. Mokhter NM; Ghoneim
MA;etal. The impact of scistosomiasis on
pathology of bladder carcinoma. cancer 1981
; 48 ;2643.
13- Gho neim MA; Awad HK; result of treatment
in carcinoma of bilharzial bladder. J urol
1980;123;850.
14- Katta S;Yousef A; Ounora V; Patil. M; AL
Jasser; AL.Ariyan R. Clinico pathological
features of bladder carcinoma among Saudi s
in Riyadh central hospital. Auu Saudi Med
1994;14; 114.
cystectomy is still the treatment of choice in
most cases of muscle-invasive bladder cancer
worldwide. It is associated with a 5-year
disease-free survival rate of 30–50% (17).
Partial cystectomy and chemo-radiation
have an encouraging result in comparison
with radical cystectomy and improved quality
of life this may explain higher incidence in
this study, Platinum-based combination
chemotherapy has proven benefit in palliating
symptoms and prolong survival in responsive
metastatic
disease (stage IV) ,GC
combination have the same response and less
toxicity than MVAC.
References:
1- Ferlay J, Shin HR, Bray F, Forman D, Mathers
C, Parkin DM. GLOBOCAN 2008, Cancer
incidence and mortality worldwide: IARC
CancerBase No. 10 [Internet]. Lyon, France:
International Agency for Research on Cancer;
2010. Available from: http://globocan.iarc.fr.
Accessed May 6, 2012.
2- Grossman HB, Natale RB, Tangen CM, et al.
Neoadjuvant chemotherapy plus cystectomy
compared with cystectomy alone for locally
advanced bladder cancer. N Engl J Med
2003;349:859-866[Erratum, N Engl J Med
2003;349:1880].
3- Stein JP, Lieskovsky G, Cote R, et al. Radical
cystectomy in the treatment of invasive bladder
cancer: long-term results in 1,054 patients. J
Clin Oncol 2001;19:666-675
4- Rodel C, Grabenbauer GG, Kuhn R, et al.
Combined-modality treatment and selective
organ preservation in invasive bladder cancer:
long-term results. J Clin Oncol 2002;20:30613071
5- Tomatis, L. Aitio. A., Day. N. E.. Heseltine, E..
Kaldor, J., Miller A. Parkin, D. M. and Riboli,
E. (eds.). Cancer: causes, occurrence and
control. IARC. Sci. PubI. No. 100. Lyon,
France: IARC, 1990.
6- B.T. Sherwood, G.D. Jones, J.K. Mellon, R.C.
Kockelbergh, W.P. Steward, R.P. Symonds
Concomitant chemoradiotherapy for muscleinvasive bladder cancer: the way forward for
bladder preservation? Clin Oncol (R Coll
Radiol) (3) (2005), pp. 160–166.
7- Cooke PW, Dunn JA, Latief T, Bathers S,
James ND, Wallace DM. Long-term risk of
salvage cystectomy after radiotherapy for
muscle-invasive bladder cancer. Eur Urol
2000; 38: 279-286.
15. Ooms Ecm,Anderson WAD,Alons cl,Boon
ME,Veldhuizen RW,Analysis of performance
of pathologist in the grading of bladder
tumors.Hum path 1983;14;140. 15. El sebai I.
Cancers of bilharizial bladder. Urol Res
1978;6;233.
16- N. Mohktar, I. Gouda, I. Adel. Malignant
urinary system tumors Cancer pathology
registry, Department of Pathology, National
Cancer Institute, Cairo University, El Sheraaa
for Advertising (2007).
17- M. Ghonein, M.M. EL Mekresh, M.A. El Baz,
I.A. El-Attar, A. Ashamallah Radical
cystectomy for carcinoma of the bladder:
critical evaluation of the result in 1026 cases J
Urol, 158 (2) (1997), pp. 393–399.
6
‫الملخص العربي‬
‫دراسة بيئيه لمرض سرطان المثانة واألسباب المحتملة في الصعيد‬
‫عبير فائق أمين‬
‫كليه الطب قسم عالج األورام مستشفى أسيوط الجامعي‬
‫نسبه االصابه بمرض سرطان المثانة في تزايد علي مستوى العالم لذا يهدف هذا البحث إلى معرفه أكثر األنواع شيوعا واهم‬
‫األسباب المحتملة واالستجابة للعالج وذلك من خالل دراسة مرجعيه لحاالت سرطان المثانة بقسم عالج األورام مستشفى أسيوط‬
‫الجامعي خالل الفترة (‪5002‬وحتى ‪.) 5005‬‬
‫تضمنت الدراسة ‪ 79‬حاله ممن اثبت باثولوجيا إصابتهم بسرطان المثانة وقد وجد أن عمر المرضى يتراوح بين ‪10‬الى ‪ 70‬عاما‬
‫ومتوسط أعمارهم ‪ 25‬عاما تقريبا وان نسبة االصابه في الرجال سبعة أضعاف النساء كما أن نسبه المدخنين كانت ‪ 4‬و‪%49‬‬
‫ونسبه االصابه بالبلهارسيا ‪ 5‬و‪. %59‬‬
‫على مستوى الباثولوجي وجد أن معظم الحاالت سرطان خاليا انتقاليه ‪ 5‬و‪ % 00‬يتبعه سرطان الخاليا الحرشفية ‪5‬و‪%50‬‬
‫وبعض األنواع األخرى األقل شيوعا مثل سرطان الخاليا الغديه ‪5‬و‪ %0‬وسرطان الخاليا االنتقالية وبه خاليا حرشفية ‪.‬وان معظم‬
‫الحاالت اخترقت العضالت‪ 1‬و‪ %90‬في حين األورام التي لم تخترق العضالت‪ 5‬و‪ %5‬فقط ‪.‬‬
‫تم تقيم تأثير العالج( الجراحي و االشعاعى و االشعاعى الكيميائي المتزامن و الكيميائي) في ‪ 99‬حاله فقط حيث أن ‪ %50‬فقدت‬
‫أثناء ا لعالج وكانت النتائج كما يلي‪:‬الشفاء الكامل في ‪ 4‬و ‪ %47‬و استجابة جزئيه في‬
‫‪ 0‬و ‪ %55‬في حين ظل المرض كما هو في ‪ 2‬و‪ %0‬وتطور في ‪ 0‬و‪. %02‬‬
‫وقد خلصت الدراسة إلى سرطان الخاليا االنتقالية أكثر شيوعا يتبعه سرطان الخاليا الحرشفية وان التدخين السبب المحتمل‬
‫الرئيسي في معظم الحاالت وان الحاالت التي تم عالجها بالعالج االشعاعى الكيميائي المتزامن أعطت نفس النتائج للعالج الجراحي‬
‫مع حياه أفضل عن الجراحة ‪.‬‬
‫‪7‬‬