Page 22 - CUA 2020_Onco_Bladder

2020 CUA ABSTRACTS

Moderated Poster Session 8: Bladder Cancer

MP-8.1 4. Skeldon S, Semotiuk K, Aronson M, et al. Patients with Lynch syndrome
Risk of bladder cancer and upper tract urothelial carcinoma mismatch repair gene mutations are at higher risk for not only upper
in Lynch syndrome patients with DNA mismatch repair gene tract urothelial cancer but also bladder cancer. Eur Urol 2013;63:379-
mutations: An update 85. https://doi.org/10.1016/j.eururo.2012.07.047
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Karla Rebullar , Otto Hemminki , Sean Skeldon , Kara Semotiuk , Melyssa 5. Jemal A, Siegel R, Ward E, et al. Cancer statistics 2009. CA Cancer J
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Aronson , Cynthia Kuk , Steven Gallinger , Zane Cohen , Alexandre Zlotta 2,4 Clin 2009;59:225-49. https://doi.org/10.3322/caac.20006
1 Division of Urology, Department of Surgery, University of Toronto, Toronto,
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ON, Canada; Surgical Oncology, Urology, Princess Margaret Hospital, MP-8.2
University Health Network, Toronto, ON, Canada; Familial Gastrointestinal Oncological long-term benefit of re-transurethral resection in
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Cancer Registry, Zane Cohen Center for Digestive Diseases, Mount Sinai primary T1 bladder cancer: A population-based cohort study
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Hospital, Toronto, ON, Canada; Urology, Mount Sinai Hospital, Toronto, from Ontario
ON, Canada Marian S. Wettstein 1,2,3,4 , Nancy N. Baxter , Rinku Sutradhar , Muhammad
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Introduction: Lynch syndrome (LS) is an autosomal dominant syndrome caused Mamdani , Song Pham , Syed R. Qadri , Kathy Li , Ning Liu , Theodorus
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by mutations in DNA mismatch repair (MMR) genes, which increases risk for van der Kwast , Thomas Hermanns , Girish S. Kulkarni 1,2,3
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developing several types of cancer. Prior studies have shown an increased 1 Division of Urology, Department of Surgery, Princess Margaret Cancer
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risk for upper tract urothelial carcinoma (UTUC) in this population. We Centre, University Health Network, University of Toronto, Toronto, ON,
have previously described an increased risk for bladder urothelial carcinoma Canada; Institute of Health Policy, Management and Evaluation, University
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(UC) in LS patients with MSH2 mutations. Herein, we update our previous of Toronto, Toronto, ON, Canada; ICES, Toronto, ON, Canada; Department
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findings and assess the risk of bladder UC and UTUC in patients with MMR of Urology, University Hospital of Zurich, University of Zurich, Zurich,
mutations by analyzing a larger cohort of LS patients within the Familial Switzerland; Department of Pathology, Princess Margaret Cancer Centre,
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Gastrointestinal Cancer Registry (FGICR) in Toronto. University Health Network, University of Toronto, Toronto, ON, Canada
Methods: Cancer data from 1980 to present were obtained from the FGICR Introduction: A second transurethral resection (TUR) within 2–6 weeks
for 1349 LS patients with confirmed MMR mutations (MSH2, MLH1, after the initial resection, a so-called re-TUR, is recommended for patients
MSH6, PMS2). Among mutation carries, the majority had MSH2 (559) diagnosed with primary T1 bladder cancer, as prior studies suggest a thera-
and MLH1 (417) mutations. Standardized incidence ratio (SIR) was used peutic, diagnostic, and prognostic benefit. Results on mortality endpoints,
to compare cancer risk in MSH2 patients with the general population. however, are sparse and conflicting. Hence, we aimed to provide real-world
Results: Among the 559 patients in the registry with a confirmed MSH2 evidence by investigating the oncological long-term benefit of re-TUR at
mutation, bladder UC was found in 28 patients (5.0%), significantly above the population level.
the expected rate in the general population. Seven of 417 (1.8%) patients Methods: Retrospective population-wide observational cohort study based on
with MLH1 mutation, one patient with PMS2 and 0 for MSH6 were found pathology reports linked to health administrative data. We identified patients
to have bladder UC. UTUC was found in 26 patients with a confirmed who were diagnosed with primary T1 bladder cancer in the province of
MSH2 mutation (4.7%), in five patients with MLH1 mutation (1.2%), and Ontario (January 2001to December 2015) and used billing claims to ascertain
in five with MSH6 (2.0%). whether they received re-TUR within 2–10 weeks. The time-dependent effect
Mean age at diagnosis was 58.9 and 63.9 for bladder UC and UTUC, of re-TUR on survival outcomes was modeled by Cox proportional hazards
respectively, with a male:female (M:F) ratio of 0.64 for both cancers, com- regression (HR) (unadjusted and adjusted numerous assumed patient- and
pared to a mean diagnosis age of >70 and M:F ratio of 3 for both cancers in surgeon-level confounders). Potential residual confounding was verified by
the general population. 5 a trace outcome (time to cataract surgery). Effect measures were presented
Conclusions: A similar high incidence (5%) of bladder UC and UTUC as hazard ratios and 95% confidence intervals (CI).
was found in patients with MSH2 mutation. Tumors were detected at an Results: We identified 7666 patients with non-missing covariates, of which
earlier age and, in contrast with sporadic cases, were more common in 2162 (28.7%) underwent re-TUR after a median time of 45 days (inter-
females. Urologists should be encouraged to recognize LS, as genetic testing quartile range 35–56 days). During any time of followup, patients who
can benefit patients and family members, leading to tailored surveillance received re-TUR were less likely to die from any causes (HR 0.68; 95% CI
and risk reduction measures. 0.63–0.74; p<0.001) or from bladder cancer (HR 0.65; 95% CI 0.57–0.76;
References p<0.001). After adjusting for all measured confounders, re-TUR was still
1. Vasen HF, Moslein G, Alonso A, et al. Guidelines for the clinical man- associated with a lower rate of death (overall survival HR 0.88; 95% CI
agement of Lynch syndrome (hereditary non-polyposis can- cer). J Med 0.82–0.95; p=0.002; cancer-specific survival HR 0.87; 95% CI 0.75–1.02;
Genet 2007;44:353-62. https://doi.org/10.1136/jmg.2007.048991 p=0.08). Based on the trace outcome, the suspicion for substantial residual
2. Goecke T, Schulmann K, Engel C, et al. Genotype-phenotype com- confounding is low.
parison of German MLH1 and MSH2 mutation carriers clinically Conclusions: This population-wide study represents one of the largest data-
affected with Lynch syndrome: A report by the German HNPCC sets of T1 tumors assembled and provides real-world evidence supporting
Consortium. J Clin Oncol 2006;24:4285-92. https://doi.org/10.1200/ the use of re-TUR in primary T1 bladder cancer.
JCO.2005.03.7333
3. Geary J, Sasieni P, Houlston R, et al. Gene-related cancer spectrum
in families with hereditary non-polyposis colorectal cancer (HNPCC).
Fam Cancer 2008;7:163-72. https://doi.org/10.1007/s10689-007-
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CUAJ • June 2020 • Volume 14, Issue 6(Suppl2) S127
© 2020 Canadian Urological Association