Implications of a failed prospective trial of adjuvant therapy after radical hysterectomy for stage Ib-IIa cervical carcinoma with pelvic node metastases

Background: Lymph node metastasis is established as a poor prognostic factor in cervical carcinoma patients undergoing primary surgery. However the optimal postoperative therapy for node-positive patients remains to be defined. Materials and Methods: To determine the role of adjuvant therapy in stage Ib-IIa cervical carcinoma patients who had pelvic node metastases after radical hysterectomy, a single institutional randomized controlled trial with factorial design, comparing concurrent chemo-radiotherapy (CT+RT) versus chemotherapy (CT) or radiotherapy (RT) alone was conducted. Study endpoints included site of recurrence, time to recurrence, relapse-free and overall survivals, and toxicity of treatment. Results: At a median follow-up of 61 months, the 6-year relapse-free and overall survival rates of the 39 patients entered into this trial were 78.2% and 85.2%, respectively. This trial was prematurely closed due to suboptimal accrual and protocol violation. It is inconclusive regarding the efficacy of CT because of the limitation of the sample size and the imbalance of prognostic features by actual treatment. A model for risk group classification of patients with stage Ib-II cervical carcinoma with pelvic node metastases from a retrospective analysis was validated by this prospective cohort. The results of this failed trial suggest that adjuvant CT alone seemed comparable to RT alone or CT+RT in survival but was associated with significantly less morbidity. Conclusion: It is warranted to consider a CT alone arm in comparison with either observation or CT+RT according to risk of recurrence in future prospective trials. However, this important issue can only be addressed by a large multicenter trial.