Abstract and Introduction
Abstract
Background: Over the past decades, the therapeutic landscape has markedly changed for patients with metastatic solid cancer, yet few studies have evaluated its effect on population-based survival. The objective of this study was to evaluate the change in survival of patients with de novo metastatic solid cancers during the last 30 years.
Methods: For this retrospective study, data from almost 2 million patients diagnosed with a solid cancer between January 1, 1989, and December 31, 2018, were obtained from the Netherlands Cancer Registry, with follow-up until January 31, 2021. We classified patients as with or without de novo metastatic disease (M1 or M0, respectively) at diagnosis and determined the proportion with M1 disease over time. Changes in age-standardized net survival were calculated as the difference in the 1- and 5-year survival rates of patients diagnosed in 1989–1993 and 2014–2018.
Results: Different cancers showed divergent trends in the proportion of M1 disease and increases in net survival for M1 disease (approximately 0–50 percentage points at both 1 and 5 years). Patients with gastrointestinal stromal tumors saw the largest increases in 5-year survival, but we also observed substantial 5-year survival increases for patients with neuroendocrine tumors, melanoma, prostate cancer, and breast cancer.
Conclusion: Over 30 years, the survival of patients with de novo M1 disease modestly and unevenly increased among cancers. Metastatic cancer still remains a very lethal disease. Next to better treatment options, we call for better preventive measures and early detection to reduce the incidence of metastatic disease.
Introduction
Solid cancers are a major public health problem worldwide, with approximately 16 million new patients and 8.5 million deaths reported in 2020.[1] Approximately 4%-65% of cancers are diagnosed as metastatic disease, which is often associated with a poor prognosis.[2,3] 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]
Population-based cancer survival statistics, including 5-year survival rates, are important metrics for evaluating and prioritizing cancer control policy.[6] Many prior studies have compared survival rates between countries or have assessed the differences in survival between periods irrespective of cancer stage.[6,7] 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]
Systemic therapy constitutes the backbone of treatment for most metastatic cancers. 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. 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] This is an important knowledge gap because clinical trial results may not be representative of the general patient population.[10] Moreover, RCTs do not usually include the cumulative benefit of sequential therapies. 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.
In this study, we investigate the survival trends of patients with metastatic cancers at the time of diagnosis (de novo metastatic cancer [M1]) using data from the nationwide Netherlands Cancer Registry (NCR). We evaluate changes in the survival of patients presenting with a solid cancer between 1989–1993 and 2014–2018, and we discuss this in light of the systemic therapies introduced. Our aim is to determine whether M1 cancer survival has improved during a period in which many novel medicines have been approved.
J Natl Cancer Inst. 2023;115(6):628-635. © 2023 Oxford University Press
