Prospective Dutch colorectal cancer cohort: an infrastructure for long-term observational, prognostic, predictive and (randomized) intervention research

Abstract

Background: Systematic evaluation and validation of new prognostic and predictive markers, technologies and interventions for colorectal cancer (CRC) is crucial for optimizing patients' outcomes. With only 5-15% of patients participating in clinical trials, generalizability of results is poor. Moreover, current trials often lack the capacity for post-hoc subgroup analyses. For this purpose, a large observational cohort study, serving as a multiple trial and biobanking facility, was set up by the Dutch Colorectal Cancer Group (DCCG). Methods/design: The Prospective Dutch ColoRectal Cancer cohort is a prospective multidisciplinary nationwide observational cohort study in the Netherlands (yearly CRC incidence of 15 500). All CRC patients (stage I-IV) are eligible for inclusion, and longitudinal clinical data are registered. Patients give separate consent for the collection of blood and tumor tissue, filling out questionnaires, and broad randomization for studies according to the innovative cohort multiple randomized controlled trial design (cmRCT), serving as an alternative study design for the classic RCT. Objectives of the study include: 1) systematically collected long-term clinical data, patient-reported outcomes and biomaterials from daily CRC practice; and 2) to facilitate future basic, translational and clinical research including interventional and cost-effectiveness studies for both national and international research groups with short inclusion periods, even for studies with stringent inclusion criteria. Results: Seven months after initiation 650 patients have been enrolled, eight centers participate, 15 centers await IRB approval and nine embedded cohort-or cmRCT-designed studies are currently recruiting patients. Conclusion: This cohort provides a unique multidisciplinary data, biobank, and patient-reported outcomes collection initiative, serving as an infrastructure for various kinds of research aiming to improve treatment outcomes in CRC patients. This comprehensive design may serve as an example for other tumor types.

The impact of postoperative complications on health-related quality of life in older patients with rectal cancer; a prospective cohort study

“…This observational study was conducted within the Dutch Prospective Data Collection Initiative on Colorectal Cancer (in Dutch: Prospectief Landelijk ColoRectaal Carcinoom cohort (PLCRC) ClinicalTrials.gov: NCT02070146) which has been approved by the Medical Research Ethics Committee of the University Medical Center (UMC) Utrecht, the Netherlands [31]. PLCRC includes adult patients with histological proven colorectal cancer of all stages.…”

Don't forget about the “R” in cmRCT: reply to Groenwold and van Smeden

“…In a simulation study [1], we identified possible dependence between trial results when conducting multiple trials within a cohort multiple randomized controlled trial (cmRCT) setting [2]. In their letter, Verkooijen et al [3] argue that contrary to our results, there is ''no concern for dependency'' as long as eligible patients for any given new trial are randomly selected into either of its arms.…”

“…global/use-of-the-design). An example of scenario 4 is seen in the PLCRC cohort of colorectal cancer patients [2]. Here, participants of the cohort-based BOOST trial (impact of a radiation boost on pathological response in rectal cancer) may subsequently participate in the SPONGE trial (impact of a retractor sponge on postoperative complications) [3,4].…”

U-CAN: a prospective longitudinal collection of biomaterials and clinical information from adult cancer patients in Sweden

“…In comparison to WCB, U-CAN is enriched with brain tumors and hematological malignancies but does not encompass the same wide range of tumor types. Of the initiatives in the Netherlands [15], the Dutch Colorectal cancer cohort has a very similar infrastructure to U-CAN [16]. In comparison with these initiatives, the unique aspects of U-CAN are its high inclusion frequency at participating hospitals and the systematic longitudinal blood sampling.…”