Long-Term Outcome of the Randomized Portec-1 Trial and Quality of Life of the Endometrial Cancer Survivors

Purpose/Objective(s)To determine long-term results of the randomized PORTEC-1 trial for patients with Stage I endometrial carcinoma and evaluate quality of life among the cancer survivors in this trial.Materials/MethodsThe PORTEC trial included 714 patients with FIGO Stages IC Grade 1 or 2 and IB Grade 2 or 3 endometrial cancer (1990–97). After surgery patients were randomly allocated to external beam pelvic radiotherapy (EBRT, 46 Gy, no 3D planning) or no additional treatment (NAT). Long-term quality of life was evaluated in 2008 using a questionnaire combining SF36, EORTC subscales for bladder, bowel and sexual symptoms from PR25, OV28 and CX24, and the Impact of Cancer questionnaire.ResultsAnalyses were done by intention-to-treat. 426 patients were alive at the date of analysis. At a median follow-up of 149 months, 15-year actuarial locoregional recurrence (LRR) rates were 6% in the EBRT group vs. 16% in the control group (p < 0.0001). 15-year overall survival rates for EBRT vs. NAT were 49% vs. 58% (p = 0.14) and failure-free survival 47% vs. 52% (p = 0.93). The majority of LRR in the NAT group were vaginal recurrences (11% of 16%). 15-year rates of distant metastases were 9% vs. 7% (p = 0.26). Second primary cancers were diagnosed in 19% of EBRT patients and 13% for NAT (p = 0.12), with O/E rates of 1.6 (EBRT) and 1.2 (NAT) compared with a matched population. Causes of death were endometrial cancer in 14% vs. 10%, and other disease in 37% vs. 32%. Multivariate analysis confirmed the strong prognostic significance of Grade 3 for both LRR (HR 3.3, p < 0.001) and endometrial cancer death (HR 8.5, p < 0.0001), of age >60 (HR 3.2 and 2.5), and invasion (HR 1.9). Response to the QoL questionnaires was 70%. Patients in the NAT group had QoL scores on SF36 similar to those of an age-matched norm population. In contrast, EBRT patients reported a clinically relevant negative impact on QoL for the SF36 scales of role limitations due to physical health (EBRT 40.7 vs. NAT 58.2 p = 0.005) and physical functioning (50.5 vs. 61.6 p = 0.004). Clinically relevant higher rates of urinary and bowel symptoms were reported after EBRT (28,1 vs. 19,5 and 23.6 vs. 14.1, respectively, both p < 0.001). Increased urinary symptom ratings after EBRT were found for frequency, urgency, and leakage; and higher bowel symptom ratings for diarrhea, fecal leakage and limitation in daily activities.ConclusionsFifteen-year outcomes of PORTEC-1 confirm the main trial results that while EBRT reduces locoregional recurrence, survival is not improved. EBRT should be avoided in patients at low and intermediate risk of recurrence. Quality of life of long-term survivors shows that EBRT is associated with higher levels of urinary and bowel symptoms, leading to more role limitations due to physical health and lower physical functioning, even 10 to 18 years after treatment. Purpose/Objective(s)To determine long-term results of the randomized PORTEC-1 trial for patients with Stage I endometrial carcinoma and evaluate quality of life among the cancer survivors in this trial. To determine long-term results of the randomized PORTEC-1 trial for patients with Stage I endometrial carcinoma and evaluate quality of life among the cancer survivors in this trial. Materials/MethodsThe PORTEC trial included 714 patients with FIGO Stages IC Grade 1 or 2 and IB Grade 2 or 3 endometrial cancer (1990–97). After surgery patients were randomly allocated to external beam pelvic radiotherapy (EBRT, 46 Gy, no 3D planning) or no additional treatment (NAT). Long-term quality of life was evaluated in 2008 using a questionnaire combining SF36, EORTC subscales for bladder, bowel and sexual symptoms from PR25, OV28 and CX24, and the Impact of Cancer questionnaire. The PORTEC trial included 714 patients with FIGO Stages IC Grade 1 or 2 and IB Grade 2 or 3 endometrial cancer (1990–97). After surgery patients were randomly allocated to external beam pelvic radiotherapy (EBRT, 46 Gy, no 3D planning) or no additional treatment (NAT). Long-term quality of life was evaluated in 2008 using a questionnaire combining SF36, EORTC subscales for bladder, bowel and sexual symptoms from PR25, OV28 and CX24, and the Impact of Cancer questionnaire. ResultsAnalyses were done by intention-to-treat. 426 patients were alive at the date of analysis. At a median follow-up of 149 months, 15-year actuarial locoregional recurrence (LRR) rates were 6% in the EBRT group vs. 16% in the control group (p < 0.0001). 15-year overall survival rates for EBRT vs. NAT were 49% vs. 58% (p = 0.14) and failure-free survival 47% vs. 52% (p = 0.93). The majority of LRR in the NAT group were vaginal recurrences (11% of 16%). 15-year rates of distant metastases were 9% vs. 7% (p = 0.26). Second primary cancers were diagnosed in 19% of EBRT patients and 13% for NAT (p = 0.12), with O/E rates of 1.6 (EBRT) and 1.2 (NAT) compared with a matched population. Causes of death were endometrial cancer in 14% vs. 10%, and other disease in 37% vs. 32%. Multivariate analysis confirmed the strong prognostic significance of Grade 3 for both LRR (HR 3.3, p < 0.001) and endometrial cancer death (HR 8.5, p < 0.0001), of age >60 (HR 3.2 and 2.5), and invasion (HR 1.9). Response to the QoL questionnaires was 70%. Patients in the NAT group had QoL scores on SF36 similar to those of an age-matched norm population. In contrast, EBRT patients reported a clinically relevant negative impact on QoL for the SF36 scales of role limitations due to physical health (EBRT 40.7 vs. NAT 58.2 p = 0.005) and physical functioning (50.5 vs. 61.6 p = 0.004). Clinically relevant higher rates of urinary and bowel symptoms were reported after EBRT (28,1 vs. 19,5 and 23.6 vs. 14.1, respectively, both p < 0.001). Increased urinary symptom ratings after EBRT were found for frequency, urgency, and leakage; and higher bowel symptom ratings for diarrhea, fecal leakage and limitation in daily activities. Analyses were done by intention-to-treat. 426 patients were alive at the date of analysis. At a median follow-up of 149 months, 15-year actuarial locoregional recurrence (LRR) rates were 6% in the EBRT group vs. 16% in the control group (p < 0.0001). 15-year overall survival rates for EBRT vs. NAT were 49% vs. 58% (p = 0.14) and failure-free survival 47% vs. 52% (p = 0.93). The majority of LRR in the NAT group were vaginal recurrences (11% of 16%). 15-year rates of distant metastases were 9% vs. 7% (p = 0.26). Second primary cancers were diagnosed in 19% of EBRT patients and 13% for NAT (p = 0.12), with O/E rates of 1.6 (EBRT) and 1.2 (NAT) compared with a matched population. Causes of death were endometrial cancer in 14% vs. 10%, and other disease in 37% vs. 32%. Multivariate analysis confirmed the strong prognostic significance of Grade 3 for both LRR (HR 3.3, p < 0.001) and endometrial cancer death (HR 8.5, p < 0.0001), of age >60 (HR 3.2 and 2.5), and invasion (HR 1.9). Response to the QoL questionnaires was 70%. Patients in the NAT group had QoL scores on SF36 similar to those of an age-matched norm population. In contrast, EBRT patients reported a clinically relevant negative impact on QoL for the SF36 scales of role limitations due to physical health (EBRT 40.7 vs. NAT 58.2 p = 0.005) and physical functioning (50.5 vs. 61.6 p = 0.004). Clinically relevant higher rates of urinary and bowel symptoms were reported after EBRT (28,1 vs. 19,5 and 23.6 vs. 14.1, respectively, both p < 0.001). Increased urinary symptom ratings after EBRT were found for frequency, urgency, and leakage; and higher bowel symptom ratings for diarrhea, fecal leakage and limitation in daily activities. ConclusionsFifteen-year outcomes of PORTEC-1 confirm the main trial results that while EBRT reduces locoregional recurrence, survival is not improved. EBRT should be avoided in patients at low and intermediate risk of recurrence. Quality of life of long-term survivors shows that EBRT is associated with higher levels of urinary and bowel symptoms, leading to more role limitations due to physical health and lower physical functioning, even 10 to 18 years after treatment. Fifteen-year outcomes of PORTEC-1 confirm the main trial results that while EBRT reduces locoregional recurrence, survival is not improved. EBRT should be avoided in patients at low and intermediate risk of recurrence. Quality of life of long-term survivors shows that EBRT is associated with higher levels of urinary and bowel symptoms, leading to more role limitations due to physical health and lower physical functioning, even 10 to 18 years after treatment.