Ovarian Cancer Survival Across the Introduction of Targeted Treatment: A Nationwide Analysis by Histotype and Stage

Abstract

Background

Bevacizumab was approved for targeted therapy of ovarian cancer in 2011 by the European Medicines Agency, with the subsequent introduction of PARP (poly[ADP]-ribose polymerase) inhibitors in 2014. Improvements in outcomes of cytoreductive surgery occurred in parallel in many regions.

Objectives

Population-based studies evaluating survival trends in the context of modern treatment are sparse. Our primary objective was to assess variations in net survival trends across grouped calendar periods during the period in which targeted therapies were introduced.

Methods

Nationwide data were derived from the Center for Cancer Registry Data at the Robert Koch Institute. Expected mortality rates were derived from German life tables provided from the Federal Statistical Office of Germany and stratified by age, calendar year and federal state. Cases were diagnosed between January 1, 2010 and December 31, 2023. Survival time was computed as the period between a patient's cancer diagnosis and their death, or December 31, 2023. We defined the following four calendar periods for diagnosis: 2010–2012: largely pre-targeted therapy period; 2013–2016: period following the initial introduction of bevacizumab; 2017–2019: period following the initial introduction of PARP inhibitors; 2020–2023: targeted therapy period. Excess hazard and net survival across the selected periods were estimated using flexible parametric models within a relative survival framework. The models were stratified by histology and included period of diagnosis, stage group (I–II, III–IV), natural splines of age at diagnosis, and area of residence. Net survival and excess hazard were predicted from models for females with median age at diagnosis, residing in the most common area (Central Area) and for each diagnosis period, histological subtype, and stage group.

Results

A total of 62,447 ovarian cancer cases were included. A total of 74% of cases were of high-grade serous histology and 66% of cases were diagnosed at stage III or IV. Excess hazards differed substantially by histotype, and also within histotype by time since diagnosis. Among individuals with the predominant high-grade serous tumours, as well as endometroid tumours, the excess mortality hazard was notably lower in the most recent diagnosis period (2020-2023), as compared to the earliest period (2010-2012). For high-grade serous and endometroid tumours, 3- and 5-years net survival increased over the entire period. Survival patterns over time differed among the other histotypes, with more modest differences across the evaluated time periods.

Conclusions

Ovarian cancer survival in Germany has improved between 2010 and 2023, specifically for the high-grade serous and endometrioid histotypes. This coincides with the introduction of targeted therapies, as well as with improvements in debulking surgery. There remains a need for further studies aimed at enabling earlier diagnosis and improving prognosis in ovarian cancer, as well as for research to develop and refine novel treatments plans tailored to histotypes.