Washington, DC (UroToday.com) In today’s Adjuvant therapy for localized renal cancer session at the 2015 Society of Urologic Oncology, Dr Uzzo Robert from Fox Chase Cancer center presented the difficulties in finding effective adjuvant therapy for RCC. Dr Uzzo called adjuvant treatment for RCC “the elusive holy grail of surgery” as it will hopefully bridge the gap between incompletely effective surgical therapy and completely effective systemic therapy.
Many trials were conducted in order to find an effective adjuvant treatment for RCC, nearly all were not effective. One trial that examined the efficacy of tumoral vaccine was only marginally effective. The biggest trial to date was the ASSURE trial that examine the effect of sunitinib and surafenib compared to placebo in the adjuvant setting. The results were negative for RFS and OS. So, adjuvant treatment for RCC does not work.
Does it work in other malignant diseases? A database search performed by urologic oncology fellow Dr Ristau Ben and Dr Uzzo revealed that the best RFS and OS benefit of adjuvant treatments was 11% and 6% respectively for breast cancer. So adjuvant treatment appears to marginally effective even in FDA approved settings in 2015.
Why is that? Dr Uzzo offered 3 possible explanations:
- Timing – there are 2 models for metastatic progression. The first, offered by halsted, claims that the progression is happening is a sequential manner. Tumor is first stage 1, then progresses to stage 2,3 and finally 4. In this model, adjuvant treatment will be most effective if given late in the course of the disease and after circulating tumor cells left the primary tumor. The second, offered by Fisher, states that micro metastatic subclinical disease is present from the beginning. In this model adjuvant treatment will be effective early in the course of the disease. “we have no tools for timing of adjuvant treatment” says Dr Uzzo.
- Biology- part of the malignant process is gaining different mutations so there is marked heterogeneity between different cells of the same tumor. Can a single drug attack all the tumoral cells? Probably not.
- Mechanism of TKI’s-this family of drugs work mainly on the endothelium and attack neovascularization of tumors. These drugs probably cannot work on CTC’s which have no blood supply.
Dr. Uzzo ended his talk in a pessimistic note. “Adjuvant treatment is at best minimally effective and right now all we can do is simple wait.
Robert Uzzo, MD.
Fox Chase Cancer Center
Dr. Miki Haifler, MD. from the Society of Urologic Oncology Meeting - December 2 - 4, 2015 – Washington, DC.
Fox Chase Cancer Center