CRIS Bladder Cancer Project

Adults Project

Principal Investigator: Dr. Enrique Grande
Centre: Fundación MD Andersen Center, Madrid


Bladder cancer is a relatively common tumour, with an estimated 10,233 new cases a year in the UK. It is more common with ageing, with 70% of cases occurring in patients over the age of 65 years. It is a type of cancer that is often fairly aggressive and is in fact the 9th most common cause of cancer death, if we consider both genders (with around 4,400 deaths in 2018), and the 6th most deadly among men (with around 3,514 deaths in 2020).  

Seventy percent of cases can be cured using surgery followed by some type of therapy (such as chemotherapy or radiotherapy) to stop the tumour from returning. However, 30% of cases are aggressive and invasive, requiring complete removal of the bladder by radical surgery. In order to allow part of the bladder to be saved and improve the patient’s quality of life, it is possible to administer chemotherapy prior to the surgery to reduce the size of the tumour and remove a smaller portion of the bladder. This type of chemotherapy is called neoadjuvant therapy. Even so, these operations do not always slow down the reappearance of tumours and a large percentage of tumours recur.  

Many immunotherapy drugs have been developed over recent years that have had very positive results in a large number of cancers, which could be of interest in bladder cancer patients. The main problem, however, is that these do not work for all patients and there are no clear methods at this time for predicting who the best candidates for immunotherapy are.  

There are several things that may affect how patients respond to immunotherapy: the tumour microenvironment, the immune system cells present in that environment and the many other cells and components surrounding the tumour cells. Based on the presence or absence of many of these characteristics, an immune signature can be defined, which classifies tumours as immunologically cold or hot. Immunologically hot tumours have characteristics that should, in principle, make them more responsive to immunotherapy.  

In this context, Dr Enrique Grande and an esteemed group of physicians have proposed the DUTRENEO trial, which aims to assess the use of immunotherapy in patients with invasive bladder cancer prior to surgery and compare it with the use of chemotherapy.  

The project:  

The DUTRENEO trial proposes that the prognosis of patients with aggressive bladder cancer can be improved by administering immunotherapy prior to surgery, especially if those patients with immunologically hot tumours are first identified.  

The name of the DUTRENEO trial comes from DU (DUrvalumab), TRE (TREmelimumab) and NEO (NEOadjuvant setting). Durvalumab and tremelimumab are the immunotherapy drugs that will be used in this clinical trial. Neoadjuvant, as we said before, describes therapies that are used to reduce the tumour prior to surgery. 

The trial involves patients with invasive bladder tumours whose tumours are classified according to their characteristics as immunologically hot or cold. Although this trial has several objectives, the main objective is to compare whether immunotherapy (with durvalumab and tremelimumab) works better than chemotherapy in patients with immunologically hot tumours.  

This is a multicentre trial, i.e. it involves many hospitals located in different cities in Spain (Madrid, Barcelona, Seville, Valencia, etc.). 

CRIS supports this trial as the trial sponsor, i.e. by providing a vital management structure for this clinical trial.  

Project Status 

The trial and its results have so far been presented at several of the most relevant international conferences. One good example of this is the American Society for Clinical Oncology (ASCO) Annual Meeting, the most important oncology conference in the world, which attracts more than 30,000 professionals every year. The paper by Dr Grande’s team was selected as one of the meeting’s oral presentations due to its quality and relevance.  

One of the most outstanding results of this trial is that treatment with durvalumab and tremelimumab is safe in patients with invasive bladder tumours classified as immunologically hot. However, chemotherapy works considerably better in patients with immunologically cold tumours than in patients with immunological hot tumours given chemotherapy.  

Although the trial has not yet finished and it is too soon to reach definitive conclusions, this type of trial highlights the importance of studying the molecular and immune characteristics of patients with bladder cancer in order to be able to provide them with safer treatments and the highest chance of success. To summarise, the molecular study of tumours and personalized therapy is bringing us nearer to safer, more effective therapies.