SCRT-CAPEOX-Serplulimab for MSS/pMMR Rectal Cancer With Oligometastases

Background and Significance:

Colorectal cancer (CRC) ranks as the third most common cancer and the second leading cause of cancer-related deaths globally. Despite improved early screening rates, a significant proportion of newly diagnosed CRC patients present with synchronous metastases, predominantly liver metastases. The concept of oligometastases, introduced by Hellman and Weichselbaum in 1995, describes a transitional state between localized disease and widespread metastases, characterized by limited metastatic lesions (typically 1-5) confined to 1-2 organs.

Current Treatment Landscape:

The management of oligometastatic disease combines local therapeutic approaches (surgery, radiotherapy, radiofrequency ablation) with systemic treatments, aiming to achieve No Evidence of Disease (NED) status. The ESMO guidelines officially categorized metastatic CRC into oligometastatic and widespread metastatic states in 2016, emphasizing the importance of integrated local and systemic treatments for oligometastatic colorectal liver metastases (CRLM).

Treatment Evolution and Challenges:

While the EPOC study established CAPEOX neoadjuvant chemotherapy followed by R0 resection as the standard treatment for initially resectable CRLM, patients with synchronous rectal cancer oligometastases present unique challenges due to complex local anatomy and high local recurrence risks. Although various neoadjuvant approaches, including Total Neoadjuvant Therapy (TNT), have been studied, they have not demonstrated significant long-term survival benefits, primarily because distant metastases impact survival more significantly than local recurrence.

Innovative Approach:

Recent success with Immunotherapy-Based Total Neoadjuvant Therapy (iTNT) in microsatellite stable/proficient mismatch repair (MSS/pMMR) locally advanced rectal cancer has shown promising results. Short-course radiotherapy (SCRT) combined with chemotherapy and immunotherapy has demonstrated superior efficacy trends, attributed to radiation's immune-activating effects on both local and distant tumor microenvironments.

Research Objective:

This project aims to evaluate the effectiveness of iTNT combined with SCRT in MSS/pMMR rectal cancer patients with synchronous oligometastases. The novel approach integrates SCRT with CAPEOX chemotherapy and Serplulimab, potentially improving complete response rates, organ preservation opportunities, and overall treatment efficacy while reducing recurrence risks. This pioneering study represents the first investigation of iTNT in synchronous rectal cancer oligometastases, offering a potentially transformative treatment strategy for this challenging patient population.

Research Innovation:

The study uniquely combines SCRT, CAPEOX chemotherapy, and Serplulimab in a neoadjuvant setting for MSS/pMMR synchronous rectal cancer oligometastases, addressing an unmet clinical need and potentially establishing a new treatment paradigm in this field.