Association between waiting time for radiotherapy after surgery for early-stage breast cancer and survival outcomes in Ontario: a population-based outcomes study

摘要

Background: Following surgery for early stage breast cancer, adjuvant radiotherapy decreases the risk of locoregional recurrence and death from breast cancer. It is unclear if delays to the initiation of adjuvant radiotherapy are associated with inferior survival outcomes.Methods: This population-based, prospective cohort study included a random sample of 25% of all women with stage I and II breast cancer treated with adjuvant radiotherapy in Ontario, Canada between September 1, 2001 and August 31, 2002, when due to capacity issues, wait times for radiation were abnormally long. Pathology reports were manually abstracted and deterministically-linked to population-level administrative databases to obtain information on recurrence and survival outcomes. Cox proportional hazard modeling was used to evaluate the association between waiting time and survival outcomes. A composite survival outcome was used to ensure that all possible measurable harms of delay would be captured. The composite outcome, event-free survival, included locoregional recurrence, development of metastatic disease or breast cancer-specific mortality.Results: We identified 1,028 women with Stage I and II breast cancer who were treated with breast-conserving surgery and adjuvant radiotherapy. Among 599 women who were treated with adjuvant radiation without intervening chemotherapy, waiting time ≥12 weeks from surgery to start of radiation appears to be associated with worse event-free survival after a median follow-up of 7.2 years (HR, composite outcome = 1.44, 95% CI: 0.98-2.11; p= 0.07). Among 429 women who received intervening adjuvant chemotherapy, waiting time ≥6 weeks from completion of chemotherapy to start of radiation was associated with worse event-free survival after a median follow-up of 7.4 years (HR 1.50, 95% CI: 1.00-2.22; p= 0.047).Conclusion: Delay to the initiation of adjuvant radiotherapy following breast-conserving surgery is associated with inferior breast cancer survival outcomes. The good prognosis for patients with early stage breast cancer limits the statistical power to detect an effect of delay to radiotherapy. Given that there is no plausible advantage to delay, we agree with Mackillop et al, that time to initiation of radiotherapy should be kept “as short as reasonably achievable.”