In recent years, the landscape of microsatellite instability (MSI) testing in colorectal cancer (CRC) has undergone significant transformation, reflecting advances in both clinical practice and molecular diagnostics. A groundbreaking study published in BMC Cancer delves into this evolution within a French regional population, offering critical insights on MSI testing trends prior to the release of nationwide official guidelines. This comprehensive analysis showcases the shifting patterns in MSI testing before formal recommendations became standard, highlighting disparities that persisted and the strides made toward systematic implementation.
Microsatellite instability, a genomic condition characterized by hypermutability at microsatellite regions due to defective DNA mismatch repair mechanisms, plays a pivotal role in colorectal cancer pathology. Identifying MSI status not only aids in the detection of Lynch syndrome—an inherited cancer predisposition syndrome—but also informs therapeutic decisions, especially as MSI-high tumors respond differently to chemotherapeutic agents and immunotherapies. Despite this, the pathway to standardized MSI testing has varied widely, making region-specific studies crucial to understanding and addressing barriers in clinical adoption.
The study harnessed data from the Calvados digestive cancer registry, capturing cases diagnosed between 2019 and 2021. This population-based cohort included 1,169 patients, providing a robust framework for assessing MSI testing uptake in real-world settings. Patient demographics such as age, gender, and socioeconomic deprivation were analyzed alongside tumor characteristics including anatomical location, stage at diagnosis, and disease progression. Additional factors like the type of hospital performing surgical interventions and conducting multidisciplinary meetings were also scrutinized to elucidate their influence on testing rates.
One of the most salient findings was that 60 percent of patients underwent MSI testing during the studied timeframe. Intriguingly, younger patients had a markedly higher testing frequency, with 80 percent of those under 65 tested compared to just 57 percent in patients over 80 years of age. This age-based discrepancy points to potential gaps in the healthcare system’s approach to elderly patients, raising questions about equity in access to molecular diagnostics and tailored cancer care.
Stage at diagnosis also greatly influenced MSI testing rates. Patients with advanced disease (stage IV) were more likely to receive testing (70%) compared to those diagnosed at stage I (52%). This trend underscores the complex interplay between tumor burden, clinical urgency, and the prioritization of molecular investigations, suggesting that early-stage patients may be underserved despite potentially benefiting from targeted management strategies informed by MSI status.
The temporal dimension of the study revealed a positive trajectory: MSI testing increased over the years, with 2021 seeing a higher proportion of tested cases relative to 2019 and 2020. This gradual uptake anticipates the arrival of official French national guidelines in late 2021, reflecting a growing clinical consensus on the importance of biomarker-driven personalized care in colorectal oncology.
Tumor localization emerged as another critical determinant. Colon cancers exhibited a significantly higher MSI testing rate (75%) compared to rectal tumors (61%). Given differences in biology and treatment options between colon and rectal cancers, these findings highlight a need for more harmonized testing protocols to bridge gaps and ensure all eligible patients are evaluated comprehensively.
Among the 816 tested patients, MSI prevalence stood at 13.6%, aligning with global estimates which typically report MSI-high status in approximately 10-15% of colorectal cancers. Notably, colon cancer cases demonstrated a higher instability rate (19%) than rectal cancers (2%), reinforcing existing evidence of molecular heterogeneity within colorectal cancer subtypes and emphasizing the clinical relevance of MSI stratification.
When isolating data from 2021 alone—closer to when official recommendations were promulgated—18 percent of cases remained untested, highlighting persistent barriers despite heightened awareness and policy endorsement. However, significant disparities narrowed considerably, with tumor location and stage at diagnosis being the main factors influencing testing. In particular, stage I patients still experienced lower testing rates, suggesting continued challenges in fully embedding MSI evaluation across all patient groups.
This study’s findings resonate beyond regional borders, illuminating broader challenges in the implementation of biomarker testing within oncology. The incremental increase in MSI testing rates illustrates progress fueled by evolving guidelines and clinical evidence. Yet, the presence of disparities grounded in patient age, tumor stage, and site calls for ongoing efforts toward universal testing protocols that can facilitate early detection of hereditary cancer syndromes and optimize treatment strategies.
The implications for clinical practice are profound. Universal MSI testing in colorectal cancer not only facilitates Lynch syndrome identification—enabling cascade testing and preventive care among at-risk relatives—but also influences therapeutic decision-making. Specifically, MSI-high tumors tend to respond favorably to immune checkpoint inhibitors, making MSI status a critical biomarker in precision oncology. As such, bridging testing gaps is imperative to fulfill the promise of personalized medicine.
Moreover, the findings highlight systemic factors that may modulate testing rates. Institutional capacities, expertise at multidisciplinary team meetings, and resource availability in different hospital settings merit attention. Addressing these elements through education, infrastructure development, and policy reinforcement could further expand MSI testing coverage and improve patient outcomes.
From a research perspective, the study underscores the value of population-based cancer registries as instruments for monitoring diagnostic practices and quality-of-care indicators over time. These data repositories enable nuanced analyses that can guide targeted interventions, inform guideline updates, and ultimately catalyze improvements in healthcare delivery.
As MSI testing becomes more entrenched as a standard of care in colorectal cancer, anticipating the next wave of challenges is crucial. These include integrating MSI status with other molecular markers, refining cost-effective screening algorithms, and ensuring equitable access across diverse healthcare systems. Collaboration among clinicians, policymakers, researchers, and patient advocates will be key to realizing these goals.
Looking ahead, continued surveillance post-guideline implementation will be essential to assess adherence and impact on clinical outcomes. The study’s baseline analysis offers a valuable benchmark against which subsequent progress can be measured, elucidating the journey from recommendation to routine practice.
In sum, this ambitious French cohort study sheds light on the evolution of MSI testing in colorectal cancer during a pivotal interval preceding official guidance. It poignantly reveals strides made and challenges remaining in achieving systematic testing—a cornerstone of modern oncology marked by precision and patient-centered care. As cancer diagnostics continue to evolve, integrating molecular profiling seamlessly into clinical workflows remains a vital frontier.
The research spotlights the dynamic interplay between evidence, policy, and practice. Observing how molecular testing paradigms unfold in real-world contexts provides insights for countries embarking on similar transitions, offering lessons on overcoming inertia and disparities.
Ultimately, the increasing adoption of MSI testing heralds a paradigm shift in colorectal cancer management, emphasizing biology-driven strategies that promise improved survival and quality of life. Continued efforts to standardize and expand access will ensure that the benefits of these advances extend broadly and equitably across populations.
Subject of Research: Evolution and frequency of microsatellite instability testing in colorectal cancer patients within a French population-based cohort prior to official national guidelines.
Article Title: Evolution of microsatellite instability testing in a population-based cohort of patients with colorectal cancer in France in the years leading up to official recommendations.
Article References:
Wilson, S., Guittet, L., Gardy, J. et al. Evolution of microsatellite instability testing in a population-based cohort of patients with colorectal cancer in France in the years leading up to official recommendations. BMC Cancer 25, 1450 (2025). https://doi.org/10.1186/s12885-025-14895-2
Image Credits: Scienmag.com
DOI: https://doi.org/10.1186/s12885-025-14895-2
