Long-term survival and late toxicity after chemoradiotherapy for cervical cancer - The Addenbrooke's experience

Aim: To evaluate the long term cause-specific survival and late toxicity of chemoradiotherapy for carcinoma of the cervix treated outside research settings. Materials and methods: Between May 1999 and April 2003, 74 patients with carcinoma of the cervix were treated with radical radiotherapy given concurrently with weekly cisplatin chemotherapy. Three patients died during treatment, leaving 71 patients available for analysis of long-term survival and late toxicity of treatment. In total, 56 patients (78.9%) received chemoradiotherapy as primary radical treatment. Ten patients (14.1%) received chemoradiotherapy as adjuvant treatment after radical surgery. The remaining five patients (7.0%) received chemoradiotherapy as salvage treatment for pelvic recurrences after previous surgery. Forty-seven (66.2%) patients had squamous cell carcinomas, whereas 24 (33.8%) patients had adenocarcinomas. Results: The median follow-up for surviving patients was 64 months. The actuarial 5-year cause-specific survival for the 66 patients undergoing primary treatment (chemoradiotherapy surgery) was 54.6%. The cause-specific survival by International Federation of Gynecology and Obstetrics (FIGO) disease stage was 58.3% for stage I disease, 69.9% for stage II disease and 20.8% for stage III disease. The actuarial 5-year pelvic control rate for the same group of patients was 73.3% overall (stage I = 79.2%, stage II = 89.0%, stage III = 33.3%). Four of the five patients treated for recurrent disease are alive and well with a median follow-up of 70 months. Of the 66 patients undergoing primary treatment, seven (10.6%) had persistent disease after chemoradiotherapy. Of the 22 patients (33.3%) who relapsed >6 months after treatment, eight (36.4%) relapsed within the pelvis alone, 12 (54.5%) had metastatic disease alone, whereas two (9. 1 %) had both local and distant relapse. The overall rates of pelvic and distant relapse were 25.8 and 21.2%, respectively. Eight of 23 patients (34.8%) with adenocarcinomas developed metastatic disease compared with only six of 43 patients (14.0%) with squamous cell tumours. Thirteen patients (18.3%) had at least one complication that was classified as grade 3 or 4. Six patients (8.5%) had grade 3 or 4 urinary complications, five (7.0%) had grade 3 or 4 bowel complications and six (8.5%) had grade 3 or 4 complications affecting other organs. Five patients had grade 3 or 4 complications affecting more than one organ. The actuarial rate for grade 3 or 4 urinary complications was 14.5%, 9.4% for grade 3 or 4 bowel complications and 11.4% for grade 3 or 4 complications affecting other organs. The overall actuarial risk for grade 3 or 4 long-term morbidity in the study group was 28.2%. There were no significant correlations between the incidence of serious late toxicity and disease stage, field arrangement, treatment volumes or postoperative radiotherapy. Conclusions: Our study has shown that the addition of chemotherapy to radiotherapy for cervical cancer probably improves the survival of patients treated outside research settings, but the benefit may not be as large as that obtained in clinical trials and the risk of serious late toxicity is increased. Further developments to improve survival and local control and to minimise toxicity are therefore necessary.