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EAU 2018

EAU 2018: Impact of molecular sub types in muscle-invasive bladder cancer on predicting response and survival after neoadjuvant chemotherapy

Copenhagen, Denmark (UroToday.com) Neoadjuvant chemotherapy (NAC) has been shown to confer a small but significant survival advantage to patients undergoing radical cystectomy (RC) for muscle invasive bladder cancer (MIBC), and it is regarded as the standard of care today. However, 60% of patients at RC will still have MIBC, and 45% of them will still die, despite receiving NAC. Real world data demonstrate that despite it being standard of care, NAC is utilized very poorly with only 16% of tertiary centers administering NAC to patients. An important question left unanswered is if NAC is beneficial and meaningful to all patients in the same way.

It has been shown that the ERCC2 mutation has a clear correlation to cisplatin response. This has been shown in a discovery cohort from MSKCC and has been validated in a cohort from the Fox Chase center (Figure 1). Furthermore, mutation in the ATM/RB1/FANCC DNA repair genes have been shown to predict a response to cisplatin. Lastly, urothelium with Luminal characteristics (as opposed to urothelium with basal characteristics) has been shown to confer improved survival without chemotherapy. However, with added NAC, patients with basal urothelium do as well as those with the luminal type. Therefore, basal tumors in the absence of NAC are characterized as high-risk disease, but they have a favorable prognosis to NAC, resulting in an improved overall survival.

To get more data on this topic, we will need to patiently await the results of the SWOG S1314 study, which is a Randomized Phase II Study of CO-eXpression ExtrapolatioN (COXEN)-directed Neoadjuvant Chemotherapy for Localized, Muscle-Invasive Bladder Cancer. The primary focus of this study is to see if looking at tumor biomarkers may predict a patient's response to chemotherapy before surgery. In this study, patients will either receive gemcitabine and cisplatin or methotrexate, vinblastine, doxorubicin, cisplatin, and filgrastim (or pegfilgrastim).

Speaker: R. Seiler, Bern (CH), Y. Allory, Créteil (FR)

Written by: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre, Twitter:@GoldbergHanan, at the 2018 European Association of Urology Meeting EAU18, 16-20 March, 2018 Copenhagen, Denmark