Dr. Lotan then discussed that there is a significant problem with understating. He highlighted a series of around 800 patients which showed 23% nodal metastasis and up to 42% of patients can be upstaged after radical cystectomy. He also highlighted that the risk of recurrence in T1-T2 patients is about 20-30% patients, which could be because of micrometastatic disease in these patients. Even though there is level 1 evidence showing that neoadjuvant chemotherapy (NAC) improves survival, but there are problems with understanding, toxicity associated with chemotherapy and current national utilization is only around 20%. Nomograms can be utilized to identify high-risk patients, but they still lack useful information at the molecular level. A potential role for biomarkers is to identify high-risk patients, predict resistance to chemotherapy and identify pathways for targeted therapy.
Dr. Lotan stressed on identifying patients at TUR who have a more aggressive disease than their clinical stage suggests but good evidence is lacking in this area. He highlighted a study which showed that unfavorable biomarker score was independently associated with T-stage upstaging. Dr. Lotan’s group also completed a multicenter study looking at molecular subtyping of clinically localized urothelial cancer using Decipher bladder essay and found that luminal tumors have lower rates of upstaging to non-organ confined disease compared to non-luminal tumors. If validated this data can help inform which patients may need multimodal therapy.
Dr. Lotan then discussed regarding prediction of response to therapy. He highlighted the study from Dr. Plimack’s group showing DNA repair genes can predict response to neoadjuvant cisplatin-based chemotherapy in muscle-invasive bladder cancer. ATM/RB1/FANCC mutation correlated with improved response and survival in discovery and validation sets. He also highlighted a study from Dr. Rosenberg’s group which showed somatic ERCC2 mutation correlated with cisplatin sensitivity in muscle-invasive urothelial cancer and was validated in another study. Multidrug resistance gene 1 (MDR 1) and BRCA 1 have also been studied in this setting. Data derived from TCGA has also been helpful in developing comprehensive molecular characterization. He also pointed to several studies that have looked at basal and luminal subtypes in terms of their response to NAC. The COXEN principle is another study looking at the prediction of treatment outcome using gene expression modeling, which was the basis of SWOG 1314 study.
He concluded his talk by stressing that there is a need to identify which patients are at highest risk of non-organ confined disease and there is also a need to determine which patients will benefit from NAC. Research and trials in this area will lead to personalized medicine.
Presented by: Yair Lotan, MD, The University of Texas Southwestern Medical Center
Written by: Abhishek Srivastava, MD, Society of Urologic Oncology Fellow, Fox Chase Cancer Center, Philadelphia, PA Twitter: @shekabhishek at the 2019 American Society of Clinical Oncology Genitourinary Cancers Symposium, (ASCO GU) #GU19, February 14-16, 2019 - San Francisco, CA