Colorectal Pulmonary Metastases: Pulmonary Metastasectomy Versus Stereotactic Ablative Radiotherapy (COPPER)

Colorectal Pulmonary Metastases: Pulmonary Metastasectomy Versus Stereotactic Ablative Radiotherapy: a Phase III Multicenter Randomized Controlled Trial

COPPER is an international, multicenter, parallel-arm, phase III randomized controlled trial comparing two local treatment strategies (SABR or metastasectomy) for patients with an indication for local treatment for limited (max. three) colorectal pulmonary metastases

The study is formally endorsed by the Dutch Society of Lung Surgery (NVvL), the Dutch Society of Cardiothoracic Surgery (NVT), the Dutch Society of Radiation Oncology (NVRO). The main objective of the proposed randomized trial is to compare efficacy of SABR to the efficacy of metastasectomy with regards to the primary endpoint (local recurrence free survival at 5 years) in patients with limited colorectal pulmonary metastases. This will determine the most effective local treatment modality. The investigators hypothesize that patients with limited colorectal pulmonary metastases will have non-inferior overall survival after pulmonary metastasectomy compared to SABR, however metastasectomy will result in superior local recurrence free survival at five years when compared to SABR. In addition, the investigators hypothesize that SABR is associated with lower morbidity, comparable quality of life and comparable health care costs compared to metastasectomy. Recurrent metastases are preferably treated by the index treatment to which the patient was randomized, local recurrent metastases are preferably treated by means of cross-over between both arms. Comparing metastasectomy to SABR for patients with colorectal pulmonary metastases will present the international community the evidence needed to better select patients for local radical treatment, while diminishing uncertainty for patients and care givers.

Colorectal pulmonary metastases, Pulmonary metastasectomy, Stereotactic radiotherapy, Randomized controlled trial, Colorectal cancer metastases

Multicenter, parallel-arm, phase III randomized controlled trial Patients will be randomized in a 1:1 manner to SABR or minimally invasive metastasectomy for the local treatment of three or less colorectal pulmonary metastases

Minimally invasive parenchymal sparing pulmonary metastasectomy Surgical approach by means of video-assisted thoracic surgery (VATS), robot-assisted (RATS), or uniportal VATS

Gross tumor volume = tumor visible on CT (+/- PET) No CTV margin will be added (Clinical target volume (CTV) = Gross target volume (GTV)) Planning Target Volume (PTV): GTV plus margins of 3-5mm (varying depending on site, motion, SABR delivery approach)

Health economic evaluation - Institute for Medical Technology Assessment (iMTA) - iMTA Medical Cost Questionnaire (iMCQ)

Inclusion Criteria: Age ≥ 18 years Eastern Cooperative Oncology Group (ECOG)-Performance status 0 - 2 Willing to provide informed consent Patients with 1 to 3 lung metastases from colorectal cancer eligible for both a minimally invasive surgical resection and SABR, as assessed by the multidisciplinary tumor board (MDT) Radically treated primary colorectal cancer Patient is able and willing to complete the quality-of-life questionnaires Previous liver metastases are radically treated with curative intent Histologically confirmed malignancy with metastatic disease detected on imaging. Biopsy of metastasis is preferred, but not required. Exclusion Criteria: Previous or present metastases outside liver or lungs Concurrent malignant cancer, or history of other malignant cancers within the past 5 years (excluding prespecified low-risk cancers) Hilar or mediastinal lymph node metastases Poor cardiopulmonary function test Inability to treat all colorectal metastases Surgical resection by means of a bilobectomy or pneumonectomy

Data will become available for non-commercial scientific research (open access) after a period of 12 months after the last data collection.

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