The potential for adjuvant therapy in early-stage cervical cancer

Abstract

Adjuvant therapy may potentially improve prognosis in women with early-stage cervical cancer who are at high risk of relapse after primary therapy. Patients with lymph node involvement at surgery are at high risk of recurrence and may benefit from adjuvant therapy, but many patients are treated with radical radiotherapy. At present there is no method of accurately identifying patients at high risk of recurrence in the latter group. A retrospective analysis of 141 surgically managed cases with stage I/II a cervical cancer is presented. The study aims were to characterize patients at high risk of relapse, identify independent prognostic variables predicting for relapse and, using these variables, develop a model, that would accurately predict high-risk patients. Univariate analysis identified depth of invasion, substage, lymph node involvement, lymphatic and blood vessel invasion and tumour differentiation as significant prognostic variables. After stratification for depth of invasion, which did not conform to the proportional hazards assumption implicit in the Cox model, Cox regression analysis showed substage, lymphatic and vascular invasion and histological tumour type to be independent prognostic variables. Using these variables, classification models were constructed that would be applicable to patients treated with either surgery or radiotherapy. Applying the models to 110 cases with greater than 18 months follow-up, 11/18 (61%) and 11/19 cases (58%) predicted as being at high risk of relapse have developed recurrence. Highly active chemotherapy is now available for this disease. We have demonstrated that combined bleomycin, ifosfamide and cisplatin (BIP) is one of the most active regimens in this disease. BIP produces cytoreduction in around 70% of patients with recurrent and primary advanced disease. Responses are achieved rapidly and acute radiotherapy toxicity is not enhanced by giving chemotherapy prior to radical local radiotherapy. A multicentre, prospective randomized trial testing the role of BIP as adjuvant therapy in patients with positive nodes at radical hysterectomy is now in progress. A complementary study testing the role of adjuvant chemotherapy in high-risk patients treated with radical radiotherapy is in preparation.