Tai, Yi-Sheng Department of Urology, National Taiwan University Hospital
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Transcript of Tai, Yi-Sheng Department of Urology, National Taiwan University Hospital
SMOKING INCREASED BLADDER TUMOR RECURRENCE RATE IN UPPER TRACT
UROTHELIAL CARCINOMA
吸菸增加上泌尿道泌尿上皮癌之膀胱復發
Tai, Yi-ShengDepartment of Urology, National Taiwan University Hospital
Background & Purpose
Cigarette smoking increases bladder recurrence in bladder UC patients.
Smoking status is a risk factor for recurrence after transurethral resection of non-muscle-invasive bladder cancer. Eur Urol. 2011
Stopping smoking decreases bladder recurrence in bladder UC patients. Stopping smoking might reduce tumour recurrence in nonmuscle-invasive bladder
cancer. BJU Int. 2007
Whether smoking also plays an important role on bladder recurrence in UUC patients?
Materials and Methods
Patient population: Consecutive UUC patients from 2000~2011 All received nephroureterectomies
Exclusion criteria Arsenic endemic residency Previous chemothrapy and radiotherapy for
any reason Insufficient tissue samples for etiology
identification
Materials and Methods
Etiology identification Questionnaire: cigarette smoking and herbs
Renal cortex: aristolactam-DNA adduct (aristolochic acid exposure)
Tumor: TP53 gene sequencing (signature mutation for aristolochic acid-induced UC)
Materials and Methods
Outcome measurement Bladder recurrence: only tumor recurrence 3
months after nephroureterectomy
Tumor recurrence within 3 months was considered as synchronous bladder cancer
excluded from the analysis
Patient demographics
Patient charcteristics No. of patients (%)Patient number 159Median age 66.4 (22-90)Sex
Female 72 (45.3)Male 89 (54.7)
Ever smoking 34 (21.7)Heavy smokers* 27 (17.2)Herbs usage 28 (17.8)AL-DNA adduct 95 (61.3)TP53 mutation, all 84 (55.6)TP53 signature mutation, AA related
49 (31.6)
ESRD 24 (15.5)DM 38 (24.2)Hypetension 66 (42.0)Grade
High 108 (69.2)Low 48 (30.8)
StageTa-1NoMo 74 (48.4)T2-4NoMo 69 (45.1)
nodal or metastatic 10 (6.5)Multiple tumor location 49 (30.8)
Heavy smoker * : greater than 20 pack-year of smoking
Patient demographics stratified by smoking
Heavy smokerNon-heavy
smoker*p value
Median age 66 (45-83) 67 (22-91) 0.483Sex
Female 0 72 (55)Male 27 (100) 58 (45) <0.001
Herbs usage 1 (4) 27 (21) 0.035AL-DNA adduct 14 (52) 81 (64) 0.227All TP53 mutation, 9 (35) 74 (60) 0.017TP53 signature mutation 2 (8) 47 (37) 0.004ESRD 3 (11) 21 (17) 0.471DM 8 (30) 30 (23) 0.469Hypertension 13 (48) 53 (41) 0.48Grade
Low 10 (37) 38 (30)High 17 (63) 89 (70) 0.468
StageTa-1NoMo 13 (48) 61 (49)T2-4NoMo 13 (48) 54 (44)
nodal or metastatic 1 (4) 9 (7) 0.486Multiple tumor location 12 (44) 37 (28) 0.103
Bladder tumor recurrence
Non-heavy smoker
Heavy smoker
Log-rank p=0.034
Bladder tumor recurrence stratified by etiologies
AA-UUC: signature p53 mutation and AL-DNA adduct
Prognostic factors for bladder tumor recurrenceUnivariate Multivariate
Factors HR p value HR p valueMedian age 0.99 0.246 ▬ ▬Sex
Female 1 ▬ ▬ ▬Male 1.56 0.163 ▬ ▬
Ever smoking 1.66 0.151Heavy smokers* 2.24 0.034 3.63 0.002Herbs usage 2.01 0.037 1.52 0.328AL-DNA adduct 0.97 0.924TP53 mutation, all 2.27 0.027 3.11 0.004TP53 signature mutation
0.98 0.954 ▬ ▬
ESRD 1.64 0.209 ▬ ▬DM 2.36 0.008 3.13 0.001Hypetension 1.48 0.205Grade
Low 0.9 0.731 ▬ ▬High 0.9 0.731 ▬ ▬
StageTa-1NoMo 1 ▬ ▬ ▬T2-4NoMo 1.42 0.26 ▬ ▬
Multiple tumor location 2.93 0.001 2.61 0.019
Discussion
Cigarette smoking and bladder cancer
Cigarette smoking and UTUC
Smoking and bladder tumor recurrence in UUC
Cigarette smoking and bladder cancer
Current cigarette smokers have an approximately threefold higher risk of urinary tract cancer than nonsmokers. Cancer. 2000 Aug 1;89(3):630-9.
Ex- and current smoking result in significantly shorter recurrence-free survival than non-smoking
Eur Urol 60 (2011) (713 - 720)
Chen et al. - Benefit of smoking cessation on bladder cancer
recurrence. - Continued smokers have a 2.2-time increased risk
than cessation BJU Int. 2007 Aug;100(2):281-6
Cigarette smoking and UTUC
Cigarette smoking : risk factor for the development of UTUC
- 3.1-fold higher risk in smokers
- 7.2-fold higher risk in long-term smokers
CANCER RESEARCH 52, 254-257. January 15, 1992
Associated with advanced disease stages, disease recurrence, and cancer-specific mortality in patients treated with RNU for UTUC. Eur Urol. 2012 Jun 22.
Smoking cessation >10 yr seems to mitigate
some detrimental effects. Eur Urol. 2012 Jun 22.
Smoking and bladder tumor recurrence in UUC
Few published studies focued on the smoking as prognostic factors for bladder cancer recurrence after nephroureterectomy.
Terakawa et al. Pathologic stage and tumor multifocality as
independent predictors for recurrent bladder
Urology. 2008 Jan;71(1):123-7
Simsir et al. smokers had higher cancer-specific
mortality and bladder recurrence rates. not provide a multivariable analysis
Int Urol Nephrol. 2011 Dec;43(4):1039-45
Smoking and bladder recurrence in UUC: this study
Heavy smoking, TP53 mutation, DM and multiple tumor location are independent factors on bladder tumor recurrence after NUx
Aristolochic acid-related UUC: insignificant
Heavy smoking inversely associated with TP53 mutation.
Conclusions
Heavy smokers UUC patients, > 20 pack-years, had more bladder tumor recurrence than non-smokers
and aristolochic acid-related UUC patients
Heavy smoking is an independent factor predicting bladder recurrence in UUC patients and inversely associated with TP53 mutation.
ThanksForYourAttention
A series of studies has demonstrated a significant association between the number of cigarettes smoked per day and p53 nuclear overexpression Cancer Epidemiol Biomarkers Prev. 1994 Jan-Feb;3(1):19-24 as well as between the p53 point mutations and the number of years of smoking in bladder cancer. Carcinogenesis. 2000 Jan;21(1):101-6.
p53 mutation is associated with high-stage disease and p53 overexpression was correlated with advanced tumor stage and grade , and was forwarded as a significant negative predictor of survival . Int J Cancer 53 : 365-370 , J Natl Cancer Inst 85 : 53-58 , Science 252 : 706-709, Cancer, 82 (1998), pp. 715–723
More recently, p53 nuclear accumulation in bladder carcinomas cells was found to correlate with the mitotic index and vascular invasion. J. Urol., 162 (1999), pp. 1496–1501
The detection of nuclear p53 was a independent predictor significantly associated with an increased risk of recurrence of bladder cancer and with decreased overall survival. N Engl J Med. 1994 Nov 10;331(19):1259-64.
Rey et al. were the first to investigate the prognostic role of proteins involved in cell-cycle regulation in 83 patients with UTUC [100].
The authors showed that the overexpression of p53 was significantly associated with tumor aggressiveness and patient survival, even after adjustment for several patient and disease characteristics.
More recently, the impact of p53 on survival was investigated by a Japanese single-center study (n = 66) and a European single-center study (n = 53) [101,102].
According to these studies, while p53 was a predictor of survival in univariable analyses, it did not emerge as an independent prognostic factor after adjustment for other clinical and pathologic characteristics.
TP53 mutation (rate and pattern) in UUC patients(overall)