Prospective Bladder Cancer Infrastructure (ProBCI) - European expansion?

We spoke to Dr. Anke Richters (NL) and Ass. Prof. Richard Meijer (NL) about ProBCI. Dr. Richters is senior researcher and epidemiologist at the Netherlands Comprehensive Cancer Organisation (IKNL) and coordinating researcher of ProBCI. Prof. Meijer is an oncological urologist and Head of Department of Oncological Urology at the University Medical Center Utrecht. Both are closely involved in the project, also supported by Prof. Bart Kiemeney (NL), Professor of Epidemiology at the Radboudumc Urology Department and a board member of the EAU Research Foundation.

What sets ProBCI apart from other cancer registries?
ProBCI provides three unique research opportunities. Firstly, ProBCI forms a nationwide cohort of bladder cancer patients for whom we prospectively collect data, patient-reported outcome measures (PROMs) and biomaterials. This cohort is set up without predefined research questions, with the aim to facilitate a variety of research purposes.

All patients in the cohort are extensively characterised. This allows researchers to efficiently and quickly answer research questions on topics ranging from real-world application outcomes of novel treatments to biomarker validation in blood samples.

Another unique opportunity of ProBCI is that all patients give informed consent to participate in trials-within-cohorts studies (the so-called TwiCs design). This means that patients can be randomised between an experimental arm (treatment, diagnostic pathway, etc), and a standard-of-care arm, where only the experimental arm has to provide additional informed consent. This can be a very efficient design, especially for experimental approaches where patients would be reluctant to receive the standard-of-care. This TwiC design also facilitates novel drug trials, as only an experimental arm has to be accrued and the control group can be selected from the cohort population. There is a near-to-zero dropout rate from the control group, as this group is unaware of any trial comparison.

Thirdly, ProBCI also accommodates additional clinical data collection of all invasive bladder cancer patients in the Netherlands from 2020 onwards, scoping the entire clinical pathway from diagnosis until death. This completely unselected patient cohort provides unique opportunities to study how new developments find their way to usual care, including relevant outcome measures such as metastatic-free survival and overall survival.

How have the infrastructure and the “TwiCs” developed since launch?
Currently, 22 hospitals in the Netherlands are active within ProBCI, with over 1000 inclusions to be reached this year. We believe that TwiCs are a good opportunity to carry out in the context of international collaboration, as it would increase the accrual potential (i.e., shorter timelines) while also increasing the external validity of results for European use. Shorter timelines are likely also advantageous in obtaining funding for a TwiC.

We have been successful in supporting a variety of non-TwiC studies, highlighting the diverse research that can be facilitated by ProBCI. For instance, a single-arm study assessing sequential induction chemo-immunotherapy with locally advanced bladder cancer prior to radical cystectomy uses a concurrent control group from ProBCI centers not enrolling in the experimental arm.

Another study uses tumour tissue, combined with extensive clinical data, from NMIBC patients to validate an RNA-based genomic profile as biomarker for BCG response. Another example is a diagnostic RCT where TURs for suspected MIBC are replaced with multiparametric MRI scans. This RCT is supported by ProBCI through long-term outcome linkage from ProBCI.

There is great potential for collaboration beyond the Netherlands. Could you explain how you envision this?
ProBCI uses the Netherlands Cancer Registry for clinical data collection. Basically, the clinical data collection of ProBCI is an extension of the basic NCR data already collected for each Dutch patient, making this an efficient and very high-quality data collection approach. This does not easily facilitate the inclusion of patients from outside of the Netherlands, where other data collection procedures are in place.

We would advocate for initiatives in other countries that obtain similar data, materials and consent from patients, making use of existing infrastructures in each specific country. Within Europe, we could then collaborate by harmonising sub-study protocols (e.g., TwiCs design) and/or pooling data and materials.

The set-up and maintenance of ProBCI in the Netherlands is funded through contributions from around five pharmaceutical companies. International collaborators aiming to set up a similar platform should acquire funding as well, but protocols and other documents can be shared of course.

As ProBCI can facilitate a wide range of clinical research questions, standardisation of patient care in general is not necessarily required. For some situations, there may be valuable information in different approaches, by comparing outcomes among patients from different countries. For other situations, particular aspects should be similar. However, if ProBCI covers a sufficient range of international settings, collaboration can be sought for specific projects among partners in countries with similar care on the aspects that are relevant to that project.

Currently, all patients in ProBCI are from the Netherlands. However, the set-up of ProBCI accommodates international collaboration, including exchange of patient data and/or patient materials, for research purposes. In collaboration ProBCI also welcomes the use of data by other research groups.

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This article first appeared in the January-February 2024 edition of European Urology Today.