Colorectal cancer (CRC) is one of the most common malignant diseases in the world and has also one of the highest cancer-related mortality rates [
1,
2]. Fortunately, both incidence and mortality from CRC have decreased over the last decades. This is due to several factors, but the most important ones are successful screening and new systemic, as well as progressive surgical treatment options [
3]. Nonetheless, metastatic CRC (mCRC) remains a lethal disease that is present in about 20–25% of patients at diagnosis and 30% will experience a metastatic relapse after initial curative surgical treatment, with or without adjuvant chemotherapy [
4]. In mCRC, estimating survival is difficult, even for experienced oncologists. This directly influences the quality of the communication with patients as information regarding an accurate prognosis is one of the most important pieces of information provided to patients by oncologists [
5]. Sharing information about the course of the disease with patients and estimating survival are challenging issues as is evident by the numerous prognostic and/or predictive factors that have been described over recent years. Socioeconomic factors, supportive treatment enabling adherence to planned treatment procedures, exercise programs and patient reported outcomes play a significant role in prognostication [
6]. Other factors of relevance in clinical practice include the tumor load measured by the number of organs involved in metastasis [
7,
8], patterns of metastatic spread [
9], primary tumor location [
10‐
12] and metachronous or synchronous disease [
13]. Currently, additional molecular markers and even molecular signatures have enriched the traditional family of markers, adding significantly to the complexity of mortality prognosis [
14]. It is now established that
BRAF mutated patients show the worst prognosis among all patients [
15] and the consensus molecular subtypes give a deeper insight into the biology of the disease [
16,
17]. Along with the advent of these modern markers, systemic treatment options targeting angiogenesis, the epidermal growth factor pathway (EGFR) or the
BRAF-pathway have been developed that enable the use of individual treatments [
18]. For example, metastastic left sided colorectal cancer that is
RAS wild-type and treated by an EGFR-antibody combined with chemotherapy shows the longest survival [
19]. In addition, patients who are
BRAF mutated benefit from targeted treatment rather than from chemotherapy [
20].
These improvements in systemic treatments have been accompanied by progressive surgical treatment concepts, which include the resection of metastases, even repeatedly and in more than one organ. For such multimodal treatment concepts, patient selection is the key to success. A multidisciplinarity approach encompassing the experience of specialized oncologists, surgeons and radiologists has become a hallmark of optimal clinical outcomes in the treatment of mCRC resulting in overall survival rates of more than 5 years in the best cases [
21]. The complex prognostic interplay between anatomic, pathological, molecular, and clinical factors cannot be captured in clinical trials. Tools allowing a more accurate prognostication, however, are highly desirable. These are not only helpful in clinical practice, but also support the design of new trials and the evaluation of novel treatments that may play a part in improving routine care. There have been a few contributions to date to fill this gap. Two research groups reported a model tested in large patient populations, however they only include patients treated within clinical trials since 1997, thereby not ideally representing a real-life population of colorectal cancer patients treated with modern, multidisciplinary treatments [
22,
23]. Mortality determinants were also studied in a real-life cohort treated before 2010 and reported single factors associated with a higher relative risk of early mortality, yet representing a patient population before the era of modern oncology [
24,
25]. Ge and colleagues described a nomogram for mCRC patients based on parameters derived from the Surveillance, Epidemiology, and End Results Program (SEER)-database; they identified 13 factors associated with survival at three and 5 years but only treated patients were included and the remarkably high number of prognostic factors limit its clinical utility [
26]. Additionally, the vast majority of patients suffering from mCRC will survive approximately two to 3 years, which has been shown for patients treated either in clinical trials [
27,
28] or in a real-life setting [
9,
29]. To our knowledge, a prognostic model considering this particular survival time in a real-life patient cohort treated by contemporary treatments has not yet been reported.
We therefore aim to validate a mortality prediction model in a representative real-world patient cohort with mCRC by identifying factors directly associated with patient survival at 2 and 3 years. By providing this work, we hope to support oncologists to communicate individualized survival estimation to every patient in daily practice without incurring additional cost.