A Randomized Trial of Surgical Decision-Making Guided by TDTP-RECIST

Intrahepatic cholangiocarcinoma (iCCA) is a highly aggressive malignancy with a poor prognosis, and a majority of patients are ineligible for curative surgery upon initial diagnosis. Although the GOLP conversion therapy regimen, pioneered by our research team, has demonstrated promising results in preliminary studies-achieving an 80% objective response rate and a 63% R0 resection rate-its clinical value requires validation through high-level evidence-based medicine. Concurrently, the conventional RECIST 1.1 criteria are inadequate for accurately assessing treatment response in iCCA, leading to challenges in surgical decision-making. To address this, we have developed the innovative TDTP-RECIST evaluation system, which preliminary data suggest can more precisely predict surgical opportunities and survival benefits.

This multicenter randomized controlled trial aims to primarily validate the clinical value of the GOLP regimen as conversion therapy for locally advanced intrahepatic cholangiocarcinoma (iCCA), thereby providing high-level evidence-based medical support for its establishment as a standard treatment protocol. Furthermore, the study seeks to verify the efficacy and superiority of the TDTP-RECIST evaluation system in guiding surgical decision-making following conversion therapy for iCCA. The ultimate goals are to establish an individualized treatment pathway based on TDTP-RECIST assessments, optimize the timing of surgery, reduce unnecessary surgical interventions and healthcare resource waste, and consequently offer a reliable decision-making framework for the conversion therapy of locally advanced iCCA. This will provide a precise and powerful tool to facilitate the transition from "unresectable" to "curable" disease.

Inclusion criteria

-

Subjects eligible to participate in this study must meet all of the following criteria:

• Male or female aged 18-75 years;
• Patients must provide signed informed consent prior to enrollment, demonstrating the ability to understand and willingness to sign the written informed consent form;
• Pathologically confirmed diagnosis of intrahepatic cholangiocarcinoma;
• Locally advanced disease, failure to achieve R0 resection, and absence of distant metastasis;
• At least one measurable lesion;
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0;
• Child-Pugh class A liver function;

Exclusion criteria

-

Subjects who meet any of the following exclusion criteria are not permitted to enroll in this study:

• Pathologically diagnosed hepatocellular carcinoma, combined hepatocellular-cholangiocarcinoma, or other non-cholangiocarcinoma malignant components;
• Patients with postoperative recurrence, or those who have previously received PD-1/PD-L1 antibodies, CTLA-4 antibodies, lenvatinib, or chemotherapy;
• History or current diagnosis of other malignancies;
• Active tuberculosis infection;
• Active, known, or suspected autoimmune disease;
• History of interstitial lung disease, or non-infectious pneumonitis requiring steroid treatment;
• Significant clinically significant bleeding symptoms within 3 months prior to enrollment, or clear bleeding tendency;
• Suspected allergy to the investigational drug(s).