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PurposeThe sequencing of androgen-deprivation therapy (ADT) with radiotherapy (RT) may affect outcomes for prostate cancer in an RT-field size-dependent manner. Herein, we investigate the impact of ADT sequencing for men receiving ADT with prostate-only RT (PORT) or whole-pelvis RT (WPRT).Materials and methodsIndividual patient data from 12 randomized trials that included patients receiving neoadjuvant/concurrent or concurrent/adjuvant short-term ADT (4-6 months) with RT for localized disease were obtained from the Meta-Analysis of Randomized trials in Cancer of the Prostate consortium. Inverse probability of treatment weighting (IPTW) was performed with propensity scores derived from age, initial prostate-specific antigen, Gleason score, T stage, RT dose, and mid-trial enrollment year. Metastasis-free survival (primary end point) and overall survival (OS) were assessed by IPTW-adjusted Cox regression models, analyzed independently for men receiving PORT versus WPRT. IPTW-adjusted Fine and Gray competing risk models were built to evaluate distant metastasis (DM) and prostate cancer-specific mortality.ResultsOverall, 7,409 patients were included (6,325 neoadjuvant/concurrent and 1,084 concurrent/adjuvant) with a median follow-up of 10.2 years (interquartile range, 7.2-14.9 years). A significant interaction between ADT sequencing and RT field size was observed for all end points (P interaction < .02 for all) except OS. With PORT (n = 4,355), compared with neoadjuvant/concurrent ADT, concurrent/adjuvant ADT was associated with improved metastasis-free survival (10-year benefit 8.0%, hazard ratio [HR], 0.65; 95% CI, 0.54 to 0.79; P < .0001), DM (subdistribution HR, 0.52; 95% CI, 0.33 to 0.82; P = .0046), prostate cancer-specific mortality (subdistribution HR, 0.30; 95% CI, 0.16 to 0.54; P < .0001), and OS (HR, 0.69; 95% CI, 0.57 to 0.83; P = .0001). However, in patients receiving WPRT (n = 3,049), no significant difference in any end point was observed in regard to ADT sequencing except for worse DM (HR, 1.57; 95% CI, 1.20 to 2.05; P = .0009) with concurrent/adjuvant ADT.ConclusionADT sequencing exhibits a significant impact on clinical outcomes with a significant interaction with field size. Concurrent/adjuvant ADT should be the standard of care where short-term ADT is indicated in combination with PORT.

BackgroundMost breast cancer patients die of non-cancer causes. The risk of death from heart disease, a leading cause of death, is unknown. The aim of this study is to characterize the long-term risk of fatal heart disease in breast cancer patients.MethodsThis retrospective study used the Surveillance, Epidemiology, and End Results (SEER) database. Standard mortality ratios (SMR) were calculated for breast cancer patients diagnosed from 1992 to 2014. Patients were stratified by receipt of radiotherapy and/or chemotherapy, disease laterality, and diagnosis era. Hazard ratios (HRs) and odds ratios (ORs) were calculated to compare the risk of death from heart disease among other breast cancer patients.ResultsThere were 1,059,048 patients diagnosed with breast cancer from 1992 to 2014, of which 47,872 (4.6%) died from heart disease. The SMR for death from heart disease at 10+ years for patients who received only radiotherapy was 2.92 (95% CI 2.81–3.04, p < 0.001) and in patients who received only chemotherapy was 5.05 (95% CI 4.57–5.55, p < 0.001). There was no statistically significant difference in SMR for death from heart disease for left-sided vs. right-sided disease. At 10+ years, heart disease made up 28% of deaths from non-primary cancer. HRs and ORs showed that the risk of death from heart disease was highest in patients older than 70 years of age and with longer follow-up.ConclusionThe risk of fatal heart disease was highest in older breast cancer patients with longer follow-up (i.e., >5–10 years) and who received chemotherapy. These patients should be referred to cardio-oncology clinics to mitigate this risk.