Solid extraintestinal malignancies in patients with inflammatory bowel disease

Table 3 Studies on urinary tract cancer in patients with inflammatory bowel disease

Ref.	Country	Type of study	Patients	Results	Limitations
Bernstein et al[39], 2001	Canada	Population-based-cohort study (1984-1997)	5529 IBD patients; Median F.U. 7.9 yr (3.5-12)	Bladder Ca: CD IRR 1.30 (0.51-3.30) UC IRR 0.67 (0.24-1.85) IBD IRR 0.92 (0.47-1.82). RCC: CD IRR 1.02 (0.31-3.34) UC IRR O.8 (0.25-2.58) IBD IRR 0.89 (0.39-2.06)	Possible confounding factor is socioeconomic status. Maximum F.U 12 yr. Data not analysed by extent of disease
Pasternak et al[22], 2013	Denmark	Cohort study (1997-2008)	45986 patients	AZA: Current users RR 2.8 (1.24-6.51), former users: RR 1.73 (0.70-4.24)	Possibly confounded by indication
Jess et al[75], 2013	Denmark	Population-nested case-control (2002-2006)	1437 UC; 774 CD; Median F.U. UC 15 yr (0-33); CD 14 yr (0-33)	CD SIR 1.69 (0.68-3.49); UC SIR 1.08 (0.56-1.89)	No detailed pharmaco-epidemiological analyses
Jussila et al[30], 2013	Finland	Cohort study (1987-1993 and 2000-2007 and followed up to 2010)	21964 patients with IBD	Urological CD IRR 1.56 (0.58-4.21), RCC CD IRR 1.61 (0.62-4.17)	Possibility of misclassification of IBD, CD, UC, and Ca
Kappelman et al[35], 2014	Denmark	Population-based-cohort study (1978-2010)	48908 IBD patients	Bladder Ca CD SIR 1.1 (0.8-1.6), RCC CD SIR 0.98 (0.77-1.23)	Not age-and sex specific estimates of absolute Ca risk. Detection bias. Data possible lacking. No inpatient encounters prior to 1995
Algaba et al[85], 2015	Spain	Prospective-cohort study (2005-2011)	590 IBD patients; Controls 222219	Bladder Ca RR 5.23 (1.95-13.87)	Small number of cases and limited period of follow-up
Nyboe Andersen et al[94], 2014	Denmark	Cohort study (1999-2012)	56146 IBD patients; Median F.U. 9.3 yr (4.2-14)	Anti-TNF: aHR 1.60 (0.61-4.19)	Confounding by indication, smoking, missing data. Short median F.U. of anti-TNF exposed (3.7 yr). Small number of Ca did not permit subgroup analysis
Bourrier et al[138], 2016 (CESAME study)	France	Prospective-cohort study (2004-2005)	19486 IBD patients (30.1% receiving TP)	Bladder Ca SIR 1.20 (0.44-2.61); RCC SIR 2.05 (0.98-3.77), AZA > 65 yr vs < 50 yr HR 13.26 (3.52-50.03, P = 0.0001), Current users: SIR 3.40 (1.47-6.71; P = 0.006), Ex-users: SIR 0.64 (0.01-3.56)	Smoking is a possible confounding factor. Risk of anti-TNFs not assessed. Short follow-up
Wauters et al[139], 2017	Belgium	Retrospective case–control study (1990-2014)	RCC; Exposed to anti-TNF: 2083 IBD patients (952 men and 1131 women); Un-exposed to anti-TNF: 1952 (977 men and 975 women)	Un-exposed to anti-TNF males SIR 5.4 (2.9-9.2), females SIR 8.5 (3.7-16.8) Exposed to anti-TNF males SIR 7.1(2.3-16.5), females SIR 4.8 (0.6-17.3)	Potential confounding factors were not adjusted. Disease type, severity, and drug exposure of hospitalized patients may not be comparable with the global patient population. Different agents and dose-response for anti-TNF were not studied
Mosher et al[24], 2018	United States	Case-control study Veteran population (1996-2015)	2080 patients with IBD; 271898 without IBD	Bladder Ca 20 yr RR 1.72 (0.86-3.45); RCC 20 yr RR 2.90 (1.46-5.84)	Administrative data. Possible underestimation of Ca incidence (newly diagnosed Ca treated in other centres)
Derikx et al[136], 2015	Holland	Case-control study (1991-2013)	Case control study A: 180 IBD patients with RCC vs 1800 IBD patients; Case control study B: 180 IBD patients with RCC vs 4388 patients with RCC in the general population	Case control A: Montreal E3 UC OR 1.8-2.5 (95%CI: 1.0-5.3), penetrating IBD-CD OR 2.8 (95%CI: 1.3-5.8), IBD related surgery OR 3.7-4.5 (95%CI: 1.6-8.2), male gender OR 3.2-5.0 (95%CI: 1.7-13.2). Case control B: lower age at diagnosis RCC (P < 0.001), lower N-stage (P = 0.025), lower M-stage (P = 0.020), more frequent surgical treatment for RCC (P < 0.001), better survival (P = 0.026; HR 0.7)	Retrospective data collection. Selection bias (different registries and databases)
Biancone et al[26], 2020	Italy	Multi-centre nested case-control study prospective (2011-2017)	403 IBD patients; 806 IBD controls	UC: OR 3.79 (1.27-16.2)	Referral IBD centres included more severe patients compared with community-based centres

IBD: Inflammatory bowel disease; CD: Crohn’s disease; IRR: Incidence rate ratio; CI: Confidence interval; F.U. : Follow-up; Ca: Cancer; UC: Ulcerative colitis; RR: Relative risk; SIR: Standardized incidence ratio; UTC: Urinary tract cancer; RCC: Renal cell carcinoma; aHR: Adjusted hazard ratio; AZA: Azathioprine; TP: Thiopurines; anti-TNF; Anti-tumour necrosis factor; TNF-: Not exposed to anti-TNF; TNF+: Exposed to TNF; N-stage: Lymph node stage; M-stage: Metastatic stage.