Risks of advancing to metastatic breast cancer including and excluding competing risks: imnterpretation as a policiy versus clinical prognosis measure

Background: To overcome cancer registries' lack of recurrence data, a modeling method was developed to estimate recurrence-free survival both excluding (net survival) and including (crude survival) competing risks. This study aims to report recurrence-free survival for breast cancer (BC) patients diagnosed with early-stage disease using both methods and discuss the suitability of each method/measure as a health policy versus clinical decision measure. Methods: Both methods are based on an illness–death process coupled with a mixture cure model for relative survival. The risk of recurrence is inferred from the estimated survival among the non-cured fraction and survival for patients initially diagnosed with metastatic breast cancer and published data on survival after recurrence. Overall survival from US life tables is used to estimate recurrence-free survival under competing risks. We apply the method to relative survival by stage at diagnosis for women diagnosed with breast cancer between 2000-2018 in the Surveillance, Epidemiology and End Results registries. We compare 5-year recurrence free estimates in the absence and presence of competing risks by age and stage at diagnosis. Results: Recurrence-free survival obtained under the competing risk framework (crude) and assuming women can only die of their cancer (net) were similar for younger women especially at 5 years from diagnosis. However, including risks of dying of other causes produces lower estimates of recurrence-free among older women and longer time since diagnosis. For example, the 5-year recurrence-free survival for women diagnosed with stage II breast cancer at ages 15-59, 60-74 and 75-84 were respectively 87% (net) vs. 86% (crude) (15-59), 90% (net) vs. 86% (crude) (60-74), and 87% (net) vs. 71% (crude) (70-84). The same measure for 10-year recurrence-free survival were 83% (net) and 81% (crude) (15-59), 84% (net) vs. 76% (crude) (60-74), and 76% (net) vs. 45% (crude) (70-84). In the net framework the conditional probabilities of being recurrence-free in the next 5 years given alive 5 years from diagnosis did not vary much by age or stage. Including the risks of dying of other causes, the estimates of the percent of women recurrence-free is very similar to the net estimates for women diagnosed at younger ages 15-59 years and differ considerably for older women. Discussion: These recurrence free survival measures are especially useful for researchers, policy makers, clinicians and patients. However, by including versus excluding risks of dying of competing causes they can answer different questions. Net recurrence-free survival are most appropriate to represent trends, comparisons between different groups of cancer patients and the impact of cancer biology, as changes in competing causes of death could obscure comparisons. As such, net survival best suited to answer questions related to health policy, research, and biology. On the other hand, competing risk survival better describes an individual's chance of survival because it accounts for both the chance of dying from cancer and from competing causes and are most valuable in predictive tools, clinical decision making, and precision medicine. For example, older patients with coexisting comorbidity may have a higher probability of dying from competing causes than of dying from their cancer; in fact, the chance of dying from competing causes may preclude the benefit of cancer treatment. While they may be extremely valuable for a physician, they may provide a more pessimistic prognosis picture for a cancer patient by including their risk of dying of other causes. More research is needed on the communication of survival measures to cancer patients.

Survival

Competing Risk

Cancer

Recurrence

Conditional; Survival

Communication of cancer statistics