In a study of 60 pairs of irradiated and nonirradiated women matched for age, lesion size, number, and location of positive nodes after radical hysterectomy, no significant difference was found in projected 5-year survival rates (72% for surgery alone, 64% for surgery plus radiation) (125). The proportion of recurrences confined to the pelvis was 67% in patients treated with surgery only and 27% in patients treated with postoperative radiation (p = 0.03). In a Cox regression analysis of 320 women who underwent radical hysterectomy, for the 72 who received postoperative radiation, there was a significant decrease in pelvic recurrence but no survival benefit (95). A multi-institutional retrospective study was performed on 185 women with positive pelvic nodes after radical hysterectomy, including 103 who received postoperative radiotherapy (97). Multivariate analysis disclosed that radiotherapy was not an independent predictor of survival, whereas age, lesion diameter, and number of positive nodes did inﬂuence survival. These authors concluded that additional treatment is needed to improve survival rates. Because survival is limited by distant recurrence, the addition of chemotherapy to postoperative radiotherapy was proposed. A 75% disease-free survival rate was reported at 3 years in 40 high-risk patients given cisplatin, vinblastine, and bleomycin after radical hysterectomy, and a 46% disease-free survival rate was found in 79 comparable patients who refused treatment (126). Only 4 (11.8%) of 34 patients with positive pelvic nodes had recurrences, whereas disease recurred in 8 (33%) of 24 untreated patients with positive nodes. An 82% rate of disease-free survival was reported at 2 years among 32 patients who were treated postoperatively with radiation therapy plus cisplatin and bleomycin (127).
The location of lymph node metastases apparently is relevant to postirradiation recurrence rates. When common iliac lymph nodes are involved, the survival rate drops to 20%. As the number of positive pelvic nodes increases, the percentage of positive common iliac and low paraaortic nodes increases (i.e., 0.6% when pelvic lymph nodes are negative, 6.3% with one positive pelvic node, 21.4% with two or three positive nodes, and 73.3% with four or more positive nodes). This information was used to recommend extended-field radiotherapy to patients with positive pelvic lymph nodes in an attempt to treat undetected extrapelvic nodal disease (107). A 3-year disease-free survival rate of 85% occurred in patients with positive pelvic nodes, and a survival rate of 51% occurred in patients with positive common iliac nodes; these rates are better than the survival rates of 50% and 23%, respectively, for historical control groups receiving radiotherapy to the pelvis alone.
The GOG reported the results of a randomized controlled trial on patients with cervical cancer treated by radical hysterectomy and found to have at least two of the following risk factors: capillary lymphatic space invasion, more than one-third stromal invasion, and large tumor burden (101). A total of 277 patients were entered into the study, with 140 patients randomized to no further therapy and 137 patients randomized to adjuvant pelvic radiotherapy.
Patients with these risk factors who were treated postoperatively with radiation therapy had a statistically significant (47%) decrease in recurrent disease. After extensive follow-up, there is no statistically significant difference in mortality rates (128). The morbidity with combination therapy was acceptable, with a low rate of enteric and urinary complications. A second GOG study of patients with high-risk cervical cancer randomized patients to concurrent chemoradiation therapy or radiation therapy alone, as discussed below (100).