German Clinical Trials Register

Acronym/abbreviation of the study

PUCC

URL of the study

http://www.pucc-trial.de

Brief summary in lay language

For patients with colorectal cancer with ≥ 3 lung metastases there is no evidence whether pulmonary metastasectomy in addition to systemic therapy is associated with a better outcome than the standard of care. The guidelines leave room for interpretation, hence both treatment options are currently valid approaches and are generally applied. The main issue of existing data is that the reported favourable survival in patients in whom a pulmonary metastasectomy was performed could be due to a selection bias. There are no control groups with similar predispositions that only undergo systemic treatment. Hence in this trial patients with comparable predispositions are randomised to either undergo pulmonary metastasectomy or standard of care, including medical treatment and Stereotactic Radiation Therapy (SBRT), if indicated, to overcome this issue.

Brief summary in scientific language

There are approximately 65.000 new cases of colorectal cancer diagnosed in Germany each year and up to 50% of the patients develop metastases during the course of disease. Hepatic as well as pulmonary metastasectomy are well established treatments of metastasized colorectal cancer but an oncological or survival benefit has never been proven in prospective trials. Generally, the application of local measures in metastasized cancers, such as surgery or stereotactic body radiation, remains controversial. Some argue that systemic diseases should be treated as such and hence therapy should be confined to medical treatment. Others believe that local control results in a survival benefit and resection of metastases may be advantageous due to cytoreduction and removal of sites which are capable of seeding new metastases and thus result in an additional oncological benefit. The significance of tumour cell release by secondary tumours for further metastasisation remains unclear, however, there is clinical and experimental evidence that aggressive local ablative treatment of oligometastasis has a beneficial effect on further metastasisation. Current guidelines of the European Society of Medical Oncology recommend resection of pulmonary metastases in cases in which R0-resection is feasible, however under consideration of relative biological contraindications. These relative contraindications include presence of a higher number of metastases, meta- vs. synchronicity of metastasisation and a short interval from diagnosis of the primary to first manifestation of metastasis. Due to the lack of strong evidence the interpretation of these relative contraindications is highly variable and the chosen treatment modalities depend largely on the treating institution and discipline. Whilst patients with few metastases generally undergo PM, patients with multiple metastases are often considered oncologically irresectable. Any result from a prospective randomised trial will have a major impact on treatment: If surgical resection in comparison to the current standard of care would proof as superior within the studied patient collective, PM could be implicated as standard of care also in patients with multiple metastases and thus improve long-term survival; a negative finding could result in abandoning the practice of PM at least in a selected cohort.