FIGO IIIB squamous cell carcinoma of the cervix: an analysis of prognostic factors emphasizing the balance between external beam and intracavitary radiation therapy

Abstract

Purpose: To define patient, tumor, and treatment factors that influence the outcome of patients with FIGO Stage IIIB squamous cell carcinoma of the intact uterine cervix.

Methods and Materials: The records of 1,096 patients treated with radiation therapy between 1960 and 1993 for FIGO Stage IIIB squamous cell carcinoma of the intact uterine cervix were reviewed retrospectively. Of these, 983 (90%) were treated with curative intent and 113 were treated only to achieve palliation of symptoms. Of 907 patients who completed the intended curative treatment, 641 (71%) were treated with a combination of external beam irradiation (EBRT) and intracavitary irradiation (ICRT) and 266 (29%) were treated with EBRT only. The median duration of treatment for these 907 patients was 51 days. Between 1966 and 1980, only 52% of patients who completed treatment with curative intent received ICRT, compared with 92% of patients treated during 1981–1993, an increase that reflects an evolution in the philosophy of treatment for advanced tumors. In general, the intensity of ICRT correlated inversely with the dose of EBRT to the central pelvis. Median follow-up of surviving patients was 134 months.

Results: For 983 patients treated with initial curative intent, disease-specific survival (DSS) was significantly worse for those who were < 40 years old, had experienced more than a 10% weight loss, or had a hemoglobin level < 10 g/dl before or during radiation therapy. Tumor factors that correlated with a relatively poor DSS were bilateral pelvic wall involvement, clinical tumor diameter ≥ 8 cm, hydronephrosis, lower vaginal involvement, and evidence of lymph node metastases on lymphangiogram (p < 0.01 in all cases). For the 907 patients who completed treatment with curative intent, 641 who had ICRT had a DSS of 45% at 5 years, compared with 24% for those treated with EBRT alone (p < 0.0001). Those who received > 52 Gy of EBRT to the central pelvis had DSS rates of 27–34%, compared with 53% for patients treated with lower doses of EBRT to the central pelvis and more intensive ICRT (p < 0.0001). At 5 years, the actuarial risk of major complications was also greater for patients treated with > 52 Gy of EBRT to the central pelvis (57–68%), compared with those who had 48–52 Gy (28%) and those who had ≤ 47 Gy of EBRT to the central pelvis (15%) (p < 0.0001). Outcome was also compared for four time periods during which different treatment policies were in place for patients with Stage IIIB disease. The highest DSS (51%) and lowest actuarial complication rate (17%) were achieved during the most recent period (1981–1993) when modest doses of EBRT were combined with relatively intensive ICRT (p < 0.01 for both comparisons).

Conclusion: Aggressive use of ICRT, carefully balanced with pelvic EBRT, is necessary to achieve the best ratio between tumor control and complications for patients with FIGO Stage IIIB carcinoma of the cervix. In our experience, the highest DSS rates and the lowest complication rates were achieved with a combination of 40–45 Gy of EBRT combined with ICRT.

Introduction

Definitive radiation therapy is widely accepted as the treatment of choice for patients with FIGO Stage IIIB carcinoma of the cervix. Investigators have reported survival rates of between 30% and 50% for patients treated with radiation therapy alone 1, 2, 3, 4, 5. However, while Stage IIIB carcinomas metastasize to extrapelvic sites more often than do earlier stage tumors, pelvic recurrence continues to be a major cause of morbidity and mortality in treated patients. Clinicians continue to disagree about the relative importance of external beam irradiation (EBRT), which can be used to treat all of the pelvic tissues, and intracavitary radiation therapy (ICRT), which gives a very high dose of radiation to the central tumor, but delivers a lower dose to disease near the pelvic wall. Some clinicians have tried to increase the dose of radiation to the paracervical tissues and pelvic wall, usually at the expense of some decrease in the central dose, by substituting interstitial brachytherapy for the more traditional ICRT. Investigators have also tried a number of experimental treatments designed to enhance the response of tumors to radiation therapy: neutrons, hyperbaric oxygen, radiation sensitizers, and concurrent or neoadjuvant chemotherapy delivered intravenously or intraarterially. None of these approaches has yet been proven to improve results over treatment with radiation alone, although the role of concurrent chemoradiation is being actively studied.

At The University of Texas M. D. Anderson Cancer Center, the approach to treating Stage III disease has evolved significantly over the past several decades. Concern that ICRT may not adequately address tumor fixed to the pelvic wall led to the use of progressively higher doses of EBRT to the central pelvis after a high-energy (25 MV) betatron beam became available in the late 1950s. This trend was gradually reversed in the 1980s and 1990s, when greater emphasis was placed on the intracavitary component of treatment for these advanced lesions.

This retrospective review of the experience at M. D. Anderson Cancer Center was performed to explore the influence of changes in treatment policy on the results of radiation therapy and to refine our understanding of the influence of tumor characteristics on the outcome of patients with FIGO Stage IIIB disease.