Page 10 - BladderCancerAbstracts

Bladder Cancer Forum 2023 abstracts

a single-payer healthcare system. A push for the universal use of NAC Clinical complete response as critical predictor for muscle-
will result in improved survival compared to what current rates of use invasive bladder cancer outcomes and survival post-radiation-
achieve but is likely not the best approach considering the drawbacks of based bladder-preservation therapies
chemotherapy, including toxicity and unequal response. This model is Michael C. Tjong , Isis Lunsky , Khaled Ajib , Guan Hee Tan ,
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built upon the available literature and requires further validation prior to Gregory Nason , Annette Erlich , Manjula Maganti , Srikala S. Sridhar ,
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clinical implementation but it demonstrates that personalized medicine Neil Fleshner , Srinivas Raman , Alexandre Zlotta , Alejandro Berlin ,
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is a feasible option. Girish S. Kulkarni , Peter Chung 2
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1 Department of Radiation Oncology, Brigham and Women’s Hospital/
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Genomic dissection of ERBB2 as a predictive biomarker in Dana-Farber Cancer Institute, Boston, MA, United States; Department of
metastatic urothelial carcinoma Radiation Oncology, Princess Margaret Cancer Centre, University Health
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Gillian Vandekerkhove , Andrew Murtha , David C. Müller , Network, Toronto, ON, Canada; Department of Surgical Oncology
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Kimia Rostin , Karan Parekh , Gang Wang , Sunil Parimi , Krista (Urology), Princess Margaret Cancer Centre, University Health Network,
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Noonan , Jenny J. Ko , Daygen Finch , Tilman Todenhöfer , Piet Ost , Toronto, ON, Canada; Department of Biostatistics, University Health
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Peter C. Black , Kim N. Chi , , Bernie Eigl , and Alexander W. Wyatt 1,11 Network, Toronto, ON, Canada; Department of Medical Oncology,
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1 Vancouver Prostate Centre, Department of Urologic Sciences, University Princess Margaret Cancer Centre, University Health Network, Toronto,
of British Columbia, Vancouver, BC, Canada; Department of Medical ON, Canada
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Oncology, BC Cancer, Vancouver, BC, Canada; Department of Urology, Introduction: Bladder preservation using radiotherapy (RT), usually
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University Hospital Basel, University of Basel, Switzerland; Department of with radiosensitizing chemotherapy, for muscle-invasive bladder cancer
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Pathology and Laboratory Medicine, BC Cancer, Vancouver, BC, Canada; (MIBC) is an alternative to radical cystectomy in select patients. This
5 Department of Medical Oncology, BC Cancer, Victoria, BC, Canada; study investigated role of clinical complete response (CR) in predicting
6 Department of Medical Oncology, BC Cancer, Surrey, BC, Canada; disease control and survival in a modern, node-negative MIBC cohort.
7 Department of Medical Oncology, BC Cancer, Abbotsford, BC, Canada; Methods: Between 2003 and 2017, 115 patients with cT2-4N0M0 MIBC
8 Department of Medical Oncology, BC Cancer, Kelowna, BC, Canada; were treated with curative intent RT (50–66 Gy in 20–33fractions) ±
9 Studienpraxis Urologie, Nürtingen, Germany; Department of Human chemotherapy. Post-treatment CR was assessed with cystoscopy and
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Structure and Repair, Ghent University, Ghent, Belgium; Michael Smith imaging. Invasive locoregional recurrence-free survival (LRFS), distant
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Genome Sciences Centre, BC Cancer, Vancouver, BC, Canada metastasis-free survivals (DMFS), and overall survival (OS) at three years in
Introduction: ERBB2 (HER2) alterations are common in urothelial cancer patients with CR vs. non-CR were compared using Kaplan-Meier methods.
(UC) and increase in frequency with disease stage; ~20% of metastatic Univariable (UV) and multivariable (MV) Cox proportional hazards (PH)
tissue samples harbor ERBB2 mutation or amplification. While prior clini- were performed to assess association between outcomes with prognostic
cal trials of HER2-targeted therapies in UC were largely unsuccessful, factors: CR, cT-stage (cT2 vs. cT3-4), carcinoma in situ (CIS) presence,
recent HER2 antibody-drug conjugates show greater promise. Accurate tumor size <5 cm, hydronephrosis, concurrent chemotherapy, (neo)adju-
biomarker-driven patient selection will be critical to enable a new genera- vant chemotherapy, complete TURBT, and ECOG score.
tion of clinical trials and optimize the clinical benefit of HER2-targeted Results: Median age was 76 (IQR 66–82) years. Median followup was 3.3
therapy. Previously, we demonstrated that ERBB2 alterations in circulating (IQR .2–6.7) years. Most patients had cT2 (77%), 17% had cT3, and 6%
tumor DNA (ctDNA) can reflect clinically relevant tumor characteristics, had cT4 disease. Concurrent chemotherapy was received by 72%, neo-
including high HER2 protein expression. Here, we aimed to evaluate the adjuvant in 28%, and adjuvant in 2% patients. CR was achieved in 64%
heterogeneity of ERBB2-altered tumors via ctDNA, and to reveal criti- of patients. At three years, patients with CR had superior LRFS (90.0% vs.
cal genomic variables that could modulate response to HER2-directed 44.0%), DMFS (87.9% vs. 44.7%), and OS (92.0% vs. 63.2%) (all log-
strategies in UC. rank p<0.001). Non-CR was the strongest significant predictor of worse
Methods: In this retrospective analysis, we used a custom targeted outcomes in UV (all p<0.001) and adjusted MV analyses: LRFS: hazard
sequencing panel covering >50 UC relevant genes to profile 412 plasma ratio (HR): 5.26 (95% confidence interval [CI] 2.76–18.61, p<0.001);
cell-free DNA samples from 236 metastatic UC patients. Patient-matched DMFS: HR: 5.36 (95% CI 2.29–12.57, p<0.001); and OS: HR: 5.60 (95%
leukocyte DNA was profiled for all patients as a germline control. CI 2.14–14.65, p<0.001). CIS presence also predicted LRFS: HR: 2.95
Results: 77% of patients had evidence of ctDNA in ≥1 blood collection. (95% CI 1.32–6.63, p=0.009); but CR was the sole significant DMFS and
Protein-altering ERBB2 mutations were identified in 14% of evaluable OS predictor in MV analyses. Concurrent chemotherapy use was the
patients; 61% fell in known oncogenic hotspot loci. ERBB2 copy ampli- sole factor significantly associated with CR (odds ratio 3.43, p=0.011).
fication was detected in 8% of patients, or 9% when excluding patients Conclusions: Post-treatment non-CR predicted for worse locoregional/
with low tumor fractions, precluding accurate evaluation of copy num- distant recurrence and survival in this MIBC cohort. Concurrent chemo-
ber. Leveraging genome-wide and dense targeted probes, in a subset of therapy with RT improves CR rates. Non-CR patients may benefit from
patients we resolved ploidy and ERBB2 locus amplification structure, further treatments, such as post-treatment immunotherapy and consider-
revealing genomic breakpoints on chromosome 17 and cases of tandem ation for salvage cystectomy.
duplication resulting in >50 copies of ERBB2. Clonality and allele-specific
imbalance analyses are in progress. Multi-omic profiling of metastatic urothelial carcinoma in patients
Conclusions: Here, we demonstrated the feasibility of a ctDNA-based exhibiting exceptional response to systemic chemotherapy
approach for determination of nuanced ERBB2 biomarker status in meta- Alberto Contreras-Sanz , Mathieu Roumiguié , Joshua Scurll ,
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static UC. Ongoing work is comparing ctDNA results to mRNA and immu- Emilia Chen , Morgan E. Roberts , Htoo Z. Oo , Kenichiro Ikeda ,
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nohistochemistry from archival tumor tissue samples. Moving forward, Cyrus Chehroudi , Jack V.W. Bacon , Gillian Vandekerkhove ,
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consideration of ERBB2 as a non-binary biomarker will be important for Alexander W. Wyatt , Peter C. Black 1
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a refined understanding of response to HER2-targeted therapy. 1 Vancouver Prostate Centre, Department of Urologic Sciences, Vancouver,
BC, Canada; Service d’Urologie, CHU de Toulouse, Université de
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Toulouse, France
Introduction: Metastatic urothelial carcinoma (mUC) is an aggressive
malignancy with limited therapeutic options and poor prognosis; how-
ever, a small subset of mUC patients have durable responses to sys-
temic chemotherapy. We molecularly profiled tumors in a cohort of
mUC patients with exceptional response (ER) to treatment (ER-mUC) to
understand potential therapeutic vulnerabilities. We aimed to establish
S8 CUAJ • MARCH 2023 • VOLUME 17, ISSUE 3(SUPPL1)