The CAIRO4 study is a clinical trial designed to investigate the impact of upfront primary tumor resection (PTR) on overall survival (OS) in patients with synchronous unresectable metastatic colorectal cancer (mCRC) who do not have severe symptoms from their primary tumor by the Dutch Colorectal Cancer Group and the Danish Colorectal Cancer Group.

This study is crucial because although previous analyses have suggested a potential survival benefit from upfront PTR, we need prospective data to confirm these findings and guide clinical practice. In patients with mCRC, the primary tumor is often left in place when there are distant metastases that are not amenable to curative resection.

The reasoning behind not operating on the primary tumor includes avoiding the complications associated with major surgery, especially when life expectancy is limited due to metastatic disease. However, there has been an ongoing debate about whether resecting the primary tumor might improve survival by reducing the tumor burden, potentially enhancing the effectiveness of systemic therapies, and preventing future complications from the primary tumor, such as bleeding or obstruction.

The CAIRO4 study would typically randomize patients with asymptomatic or minimally symptomatic synchronous mCRC to either immediate PTR followed by systemic therapy or to systemic therapy alone. The primary endpoint would be overall survival, with secondary endpoints possibly including progression-free survival, quality of life, and the rate of primary tumor-related complications.

The results of the CAIRO4 study are expected to provide high-quality evidence to inform the decision-making process regarding the management of the primary tumor in patients with synchronous mCRC. If the study finds that upfront PTR does not confer a survival benefit, this could support the practice of avoiding major surgery in this patient population. Conversely, if a survival benefit is observed, it could lead to a change in clinical guidelines to recommend upfront PTR in selected patients with mCRC.

Pic: freepik. Source: https://www.annalsofoncology.org/article/S0923-7534(24)00722-1/fulltext?rss=yes