An international group of experts led by the Comprehensive Cancer Centre (CCC) at MedUni Vienna and University Hospital Vienna has established endpoints for clinical trials in patients with cancer and isolated metastases. The aim is to evaluate the benefits of modern therapies specifically targeting metastases using metrics that are particularly relevant to patients. The consensus paper, now published in the journal The Lancet Oncology, marks a paradigm shift in cancer research.
The consensus paper focuses on oligometastatic cancer. This refers to the stage of the disease between locally confined disease and widely advanced metastasis, which can occur in many types of tumour. A cure is possible at this stage; today, some patients can live for many years with a good quality of life despite having isolated metastases. Metastasis-directed therapies (MDT) are highly precise local treatment methods such as stereotactic ablative radiotherapy (SABR), surgical resection or thermal ablation, which can be used to treat individual metastases in a targeted manner using imaging techniques.
The consensus paper now published in The Lancet Oncology stems from OligoCare, the world’s largest prospective cohort study evaluating SABR in oligometastatic disease across various tumour types, involving more than 3,500 patients. As SABR is used as a local procedure in many of these cases, the consensus project also focused on high-precision radiotherapy. The aim was to define valid primary study endpoints that are relevant from the patient’s perspective and, at the same time, applicable to different cancers at the oligometastatic stage.
The focus was on clinical trials investigating the benefits of the various treatment options in combination with drug therapies. The experts were drawn from the OligoCare consortium of the European Organisation for Research and Treatment of Cancer (EORTC) and the European Society for Radiotherapy and Oncology (ESTRO), and covered the fields of radiotherapy, radiology, epidemiology and statistics; representatives of European patient organisations were also involved.
Repeated removal of metastases possible
In clinical trials, primary endpoints are the key metrics used to assess the efficacy and benefits of a therapy. In addition to established endpoints such as survival with a good quality of life, the expert group agreed on two new metrics that reflect the specific mechanism of action of high-precision ablative therapies and aim to remove the often symptom-free metastases locally. The new standards for clinical trials mark a departure from the previously used endpoint of progression-free survival (PFS), which inadequately reflects the specific benefits of local, high-precision therapies. This allows for the assessment of further factors that are directly relevant to patients – such as treatment-free time and minimal side effects.
New endpoints are being evaluated
The focus is on two new metrics: STFS (Start or Switch of Systemic Therapy–Free Survival), which describes the period without the initiation or change of systemic therapy, and pPFS (polymetastatic Progression–Free Survival), which captures the time until progression to a disease stage with widespread metastasis. Both endpoints take into account the fact that MDT allows individual metastases to be treated in a targeted and repeated manner. For example, if, following the removal of a metastasis in the right lung, another metastasis occurs in the left lung.
"We see this as a genuine paradigm shift in clinical research into oligometastatic disease. Previous endpoints were often unable to adequately demonstrate the benefits of local therapies. With these new, internationally agreed standards, we are establishing a foundation for better interpreting study results and translating them more quickly into clinical practice," explains study lead Joachim Widder (Department of Radiation Oncology and CCC). The broad data set and the international consensus, which includes patient representatives, lend the new endpoints particular relevance for future studies and represent a step towards more precise and patient-centred therapeutic approaches.