Background: Approximately 3% of colorectal cancers (CRCs) are due to Lynch syndrome (LS), a hereditary cancer syndrome caused by pathogenic variants (PVs) in the mismatch repair (MMR) genes. Patients with CRC and LS have elevated lifetime risks for a range of cancers and require personalized treatment and targeted surveillance. Relatives of people affected by LS who share the same PV also have elevated cancer risks and can benefit from preventive measures and/or risk-reducing surgeries. Despite this, LS remains vastly underdiagnosed. Universal tumor screening (UTS) for deficient MMR is recommended in diagnosing LS in patients with CRC. This process, when combined with genetic testing (GT) offered within routine cancer care (termed "mainstream GT"), aims to identify individuals at risk efficiently, but integrating UTS and mainstream GT for LS in CRC is a complex endeavor.

Objective: The aim of the proposed scoping review will be to comprehensively explore the literature on diagnostic pathways comprising UTS and mainstream GT for LS among patients with CRC and barriers and facilitators in their implementation.

Methods: The scoping review will follow Arksey and O'Malley's expanded framework. Results will be reported following the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines and summarized quantitatively. A narrative synthesis will also be performed using the Theoretical Domains Framework.

Results: The results will be presented in a forthcoming scoping review, which we expect to publish in a peer-reviewed journal by early 2026.

Conclusions: Aligning UTS with mainstream GT for LS in CRC may boost early diagnosis and prevention while reducing waiting times and other patient burdens. By addressing barriers to and facilitators in diagnostic pathways, health care systems can improve the identification and management of LS, ultimately leading to better outcomes for patients and their families. The insights gained from this scoping review will inform the development of a mixed methods study about implementing diagnostic pathways for LS in CRC that integrate UTS and mainstream GT in Italy.

International registered report identifier (irrid): PRR1-10.2196/70831.

Keywords: Lynch syndrome; Scoping review; barriers; colorectal cancer; diagnostic pathway; facilitators; genetic testing; implementation; mainstreaming; protocol; theoretical domains framework.

©Linda Battistuzzi, Eva Blondeaux, Alberto Puccini, Luca Boni, Federica Grillo, Lucia Trevisan, Liliana Varesco, Maria Stefania Sciallero. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 10.06.2025.

背景：

大约3%的结直肠癌（CRC）是由林奇综合症（LS）引起的，这是一种由错配修复（MMR）基因致病变异（PVs）导致的遗传性癌症综合症。患有CRC和LS的患者在其一生中患上各种癌症的风险较高，并需要个性化的治疗和有针对性的监测。受影响者家族中的亲属如果携带相同的致病变异也有较高的患癌风险，可以从预防措施和/或降低风险的手术中受益。尽管如此，LS仍然被大大低估了。在诊断CRC患者的LS时，推荐进行全肿瘤筛查（UTS）以检测MMR缺陷。当结合常规癌症护理中的基因测试（GT），称为“主流GT”时，这一过程旨在高效地识别有风险的个体，但在结直肠癌中整合UTS和主流GT用于LS是一个复杂的任务。

目标：

本建议的系统综述的目标将是全面探讨包含UTS和主流GT的诊断途径在CRC患者中的文献，并调查其实施过程中存在的障碍和促进因素。

方法：

该系统综述将遵循Arksey和O'Malley扩展框架。结果将根据PRISMA-ScR（系统性回顾和Meta分析的首选报告项目扩展指南）进行报道并定量总结。还将使用理论领域框架进行叙述综合分析。

结果：

结果将在即将发表的系统综述中呈现，我们预计在2026年初之前于同行评审期刊上发布。

结论：

将UTS与主流GT结合用于CRC中的LS诊断可能会提高早期诊断和预防的效果，同时减少等待时间和其他患者负担。通过解决诊断途径中的障碍和促进因素，医疗保健系统可以改善LS的识别和管理，最终为患者及其家庭带来更好的结果。这项系统综述所获得的见解将指导一项关于在意大利整合UTS和主流GT进行LS诊断途径实施的混合方法研究的发展。

国际注册报告标识符（irrid）：

PRR1-10.2196/70831.