Long-term toxicity and health-related quality of life after adjuvant chemoradiotherapy or radiotherapy alone for high-risk endometrial cancer in the randomised PORTEC-3 trial

Background: The survival results of the PORTEC-3 trial showed a significant improvement in both overall and failure-free survival with chemoradiotherapy versus pelvic radiotherapy alone. The present analysis was performed to compare long-term adverse events (AE) and health-related quality of life (HRQOL). Patients and methods: 660 women with high-risk endometrial cancer were randomly assigned to receive chemoradiotherapy (2 concurrent cycles of cisplatin followed by 4 cycles of carboplatin/paclitaxel) or radiotherapy alone. Toxicity was graded using CTCAE v3.0. HRQOL was measured using EORTC QLQ-C30 and CX24/OV28-subscales and compared to normative-data. An as-treated analysis was performed. Results: Median follow up was 74.6 months; 574 (87%) patients were evaluable for HRQOL. At 5 years, grade ≥2 AE were scored for 78 (38%) patients who had received chemoradiotherapy versus 46 (24%) who had received radiotherapy (p=0.008). Grade 3 AE did not differ significantly between the groups (8% vs 5%, p=0.18) at 5 years, and only one new late grade 4 toxicity had been reported. At 3 and 5 years, sensory neuropathy toxicity grade ≥2 persisted after chemoradiotherapy in 6% (vs 0% after radiotherapy, p<0.001) and more patients reported significant tingling or numbness at HRQOL (27% vs 8%, p<0.001 at 3 years; 24% vs 9%, p=0.002 at 5 years). Until 3 years, more patients who had chemoradiotherapy reported limb weakness (21% vs 5%, p<0.001) and lower physical (79 vs 87, p<0.001) and role functioning (78 vs 88, p<0.001) scores. Both treatment groups reported similar long-term global health/QOL scores, which were better than those of the normative-population. Conclusion: This study shows a long-lasting, clinically relevant, negative impact of chemoradiotherapy on toxicity and HRQOL, most importantly persistent peripheral sensory neuropathy. Physical and role functioning impairments were seen until 3 years. These long-term data are essential for patient information and