Otherwise, tumors are classified by the extent of the disease (EoD) as local, regional, or distant. In most tumors, the stage is coded according to the Union for International Cancer Control tumor, node, metastasis (TNM) classification (4th-8th edition). Staging methods are considered when determining the stage at diagnosis, but no information is recorded on the modalities used or the outcomes. The International Classification of Diseases for Oncology is used for coding topography and morphology. Data managers record data on patient, tumor, and initial treatments directly from patient files. The NCR reached national coverage in 1989 and has an estimated completeness of more than 95% of all malignancies in the Netherlands ( 11). This study was approved by the NCR’s Ethics Committee (written informed consent was not required). Patients with multiple primary tumors were grouped by their first tumor only and were excluded if the first tumor was diagnosed before 1989. We excluded patients diagnosed on the date of death. Information on patients’ vital status was available until January 31, 2021. We included adult patients aged 18 years and older, diagnosed with a solid primary cancer between 19. Additionally, we report on the trends in the proportion of patients with M1 disease (from 1989 to 2018). We divided the data into 2 cohorts (18) to ensure comparison of periods before and after the implementation of novel medicines. The primary outcomes of this study were the changes in the 1-year and 5-year net survival of patients with distant M1 disease. We performed a retrospective cohort study based on data from the NCR between 19. ![]() Our aim is to determine whether M1 cancer survival has improved during a period in which many novel medicines have been approved. We evaluate changes in the survival of patients presenting with a solid cancer between 18, and we discuss this in light of the systemic therapies introduced. In this study, we investigate the survival trends of patients with metastatic cancers at the time of diagnosis (de novo metastatic cancer ) using data from the nationwide Netherlands Cancer Registry (NCR). Analysis of the changes in population-based survival over several decades while considering the systemic therapies that have been introduced might offer valuable insights into the overall impact of new medicines for metastatic cancer. Moreover, RCTs do not usually include the cumulative benefit of sequential therapies. This is an important knowledge gap because clinical trial results may not be representative of the general patient population ( 10). Although randomized controlled trials (RCT) have demonstrated the safety and efficacy of each of these new medicines, the impact on survival in unselected population-based samples has been inadequately studied ( 9). ![]() Historically, this primarily included cytotoxic chemotherapy and hormonal therapy, but in recent decades, the therapeutic landscape has rapidly changed because of the approval of several targeted and immune therapies. Systemic therapy constitutes the backbone of treatment for most metastatic cancers. However, nationwide studies focusing on changes in the survival of patients with distant metastases are scarce because many existing cancer registries have no or incomplete data on stage at diagnosis ( 8). Many prior studies have compared survival rates between countries or have assessed the differences in survival between periods irrespective of cancer stage ( 6, 7). Population-based cancer survival statistics, including 5-year survival rates, are important metrics for evaluating and prioritizing cancer control policy ( 6). Although the approval of over 80 novel systemic therapies since 1990 has expanded the treatment options for most metastatic tumors ( 4), improving survival for these patients remains a challenge ( 5). Approximately 4%-65% of cancers are diagnosed as metastatic disease, which is often associated with a poor prognosis ( 2, 3). ![]() Solid cancers are a major public health problem worldwide, with approximately 16 million new patients and 8.5 million deaths reported in 2020 ( 1).
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