Adjuvant radiotherapy following radical hysterectomy for patients with early-stage cervical carcinoma (1984-1996)

Abstract

Background and purpose: The aim of this study was to assess the results of treatment (surgery alone or surgery and postoperative radiotherapy) for early-stage cervical carcinoma and to determine the morbidity associated with adjuvant radiotherapy. A subset of these patients (n=10) was irradiated postoperatively for tumor related negative prognostic factors only and this retrospective analysis was also performed to determine if this decision was right and if the selection for this treatment was based on the right criteria.

Material and methods: From 1984 to 1996, 233 women underwent radical hysterectomy as primary treatment of stage I or IIA cervical carcinoma. One hundred and fifty-six patients were treated with surgery alone (67%) and 77 patients (33%) received adjuvant radiotherapy for a, tumor related negative prognostic factors: the combinaton CLS⊕, tumor size ≥40 mm and poor differentiation grade or the combination tumor size ≥40 mm and depth of invasion ≥15 mm (n=10), or b, positive surgical margins (n=17), and/or c. lymphnode metastases (n=42) and/ or d. parametrial involvement (n=6).

Results: For the entire group the most important prognostic factor for survival and disease free survival was node positivity. Additional factors were depth of invasion and positive surgical margins. Thirty-five patients recurred of which 12 after surgery alone. In all these cases the relapse was in the pelvis (100%). Of the 23 recurrences after surgery and adjuvant radiotherapy 13 were seen in the pelvis (56%) (P=0.003). All patients with negative prognostic factors and N 0, received adjuvant radiotherapy (n=10) and none of these patients recurred. The incidence of severe gastrointestinal radiation related side effects was low (2%). The incidence of lymphedema of the leg was 11% which was similar in the surgery alone group.

Conclusions: The relatively low percentage of radiation related side effects together with 0% recurrence in a subgroup of node negative patients with high risk of recurrence, and a relatively low percentage of recurrence in the surgery alone group lead us to the conclusion that postoperative radiotherapy in special subsets of node negative patients is justified.

Introduction

Although radiation therapy for early cervical cancer is as effective as radical hysterectomy, the standard treatment in many oncology centers is radical hysterectomy with pelvic lymph node dissection, achieving 5-year survival rates of 80–90% [1], [6], [8], [9], [11], [18], [20]. A number of risk factors that predict poor prognosis have been described [1], [5], [6], [8], [9], [11], [18], [20]. They include: age, FIGO- stage, tumor size, depth of tumor invasion into the cervical stroma (DI), histological type of tumor, capillary lymphatic space involvement (CLS), involvement of the lower uterine segment, parametria and surgical margins. Various studies found, with the help of multivariate analysis, different sets of combined factors that identify high risk patients [1], [5], [6], [8], [9], [11], [18], [20]. However, there was no generally accepted rule indicating which factors had to be present in which size or magnitude to turn the scale towards the need of adjuvant radiation treatment. Delgado et al. [6] found clinical tumor size, CLS, and DI to be the combination best predicting prognosis and proposed a scoring system that identifies three separate risk groups for recurrence. Others found adenocarcinoma histology in combination with CLS were the factors associated with recurrence [2] and found no correlation with depth of invasion.

Before 1986 the indications for adjuvant radiotherapy in our center were: lymphnode metastases, parametrial involvement and positive or close surgical margins. In 1986 we decided to extend the indication for the use of postoperative radiotherapy in early cervical cancers: in case of the combination of three factors namely positive CLS, poor differentiation grade and bulky tumor (≥40 mm) or the combination of tumor size ≥40 mm and depth of invasion ≥15 mm. The choice for these factors was partly based on a retrospective analysis of our own unpublished patient material indicating that depth of invasion was an independent prognostic factor for recurrence free survival and partly based on reports from the literature supporting this finding [6], [9], [20]. At the same time, we learned from this retrospective analysis that the adjuvance of pelvic radiotherapy did not significantly increase the morbidity [16] compared to hysterectomy alone – a subject on which the reports in literature are controversial [8], [16], [18], [19]. In the period from 1986 to 1996 inclusive, 233 evaluable patients had a radical hysterectomy in our center of which 77 (33%) were given postoperative adjuvant radiotherapy. The aim of this study was to assess the results of treatment in terms of survival, site and time of recurrence in comparison with surgery alone, and to determine the morbidity associated with adjuvant pelvic radiotherapy. Furthermore we wanted to evaluate if the decision to irradiate a subset of patients with adverse tumor factors only was the right decision and if the selection of these two subgroups for the indication of adjuvant radiotherapy was the right choice.