San Antonio, Texas USA (UroToday.com) Neoadjuvant chemotherapy has been a widely accepted part of the treatment algorithm and has level 1 support (Grossman et al, NEJM 2003). There has been a steady uptake in the use of neoadjuvant chemotherapy over the years (Bergerot et al, ASCO 2016).However, up to 40% of patients are not eligible for neoadjuvant therapies due to pre-existing renal dysfunction, poor performance status, and significant hearing loss. Since the approval of Atezolizumab for the treatment of metastatic bladder cancer by the FDA there has been a push for the use of immunotherapy in the neoadjuvant setting.
In this session, Dr. Terence Friedlander (UCSF), presents the rationale on the use of immunotherapy in the neoadjuvant setting for patients with muscle invasive disease (MIBC), and discussed th available data and future clinical trials. Immunotherapy as a neoadjuvant therapy provides several of advantages compared to cytotoxic chemotherapy: an alternative clinical benefit, decrease toxicity, and the ability to further study the biology of the malignancy. Muscle invasive cancer as an ideal candidate for immunotherapy for several reasons: First, it was found to be highly mutated in the TCGA analysis, which has been found to be a predictor of improved immunotherapy efficacy in other solid malignancies such as melanoma and small cell lung cancer. Second, there evidence of improved survival of patients showing T-Cell infiltration in the cystectomy specimens which may provide a clear pathway for the use of immunotherapy. There are however some potential challenges which remain unknown and include the potential delay of surgery in patients with severe adverse side effects, possible healing side effects following surgery. In addition, there is no clear end-point as pT0 appears to be poor surrogate of response with immunotherapy and the effect of PD1 receptor expression on response rates remains to be validated in the neoadjuvant setting.
At the present there is only one published study on the use of immunotherapy in the neoadjuvant setting. The study by Carthon and colleagues (Clin Can Res, 2010) included 12 patients receiving ipilumumab prior to cystectomy. The study showed increase in effector T cells in the cystectomy specimen with 75% of the cohort disease free at 20 months. There were 2 immune related side effects that caused a delay in surgery. There are two ongoing neoadjuvant trials both using Atezolizumab (USCF and Queen Mary Univ London) recruiting patients refusing or unfit to receive cisplatin based chemotherapy. As the results of this trials mature it would be interesting to study the effect on combination cisplatin therapy with immunotherapy as it may further improve survival in this patient population.
In summary, immunotherapy in the neoadjuvant setting may broaden the use of neoadjuvant therapy due to its decrease toxicity, potential improve outcomes for MIBC patients and generate a new platform of study to further understand the biology of the disease.
Presented By: : Terence Friedlander, MD (USCF)
Written By: Andres F. Correa MD, Society of Urologic Oncology Fellow, Fox Chase Cancer Center
17th Annual Meeting of the Society of Urologic Oncology - November 30 -December 2, 2016 – San Antonio, Texas USA