TUMOR SIZE, IRRADIATION DOSE, AND LONG-TERM OUTCOME OF CARCINOMA OF UTERINE CERVIX

Purpose: To assess the impact of tumor size and extent, and dose of ir radiation on pelvic tumor control, incidence of distant metastases, an d disease-free survival in carcinoma of the uterine cervix. Methods an d Materials: Records were reviewed of 1499 patients (Stages IA-IVA) tr eated with definitive irradiation (combination of external beam plus t wo intracavitary insertions to deliver doses of 65-95 Gy to point A, d epending on stage and tumor volume). Follow-up was obtained in 98% of patients (median 11 years, minimum 3 years, maximum 30 years). The rel ationship between outcome and tumor size was analyzed in each stage. P elvic tumor control wats correlated with total doses to point A and to the lateral pelvic wall. Results: The 10-year actuarial pelvic failur e rate in Stage IB was 5% for tumors <2 cm, 15% for 2.1-5 cm, and 35% for tumors >5 cm (p = 0.01); in Stage IIA, the rates were 0%, 28%, and 25%, respectively (p = 0.12). Stage IIB unilateral or bilateral nonbu lky tumors <5 cm had a 23% pelvic failure rate compared with 34% for u nilateral or bilateral bulky tumors >5 cm (p = 0.13). In Stage IIB, pe lvic failures were 18% with medial parametrial involvement only, compa red with 28% when tumor extended into the lateral parametrium (p = 0.0 5). In Stage III, unilateral parametrial involvement was associated wi th a 32% pelvic failure rate versus 50% for bilateral extension (p < 0 .01). Ten-year disease-free survival rates were 90% for IB tumors <2 c m, 76% for 2.1-4 cm, 61% for 4.1-5 cm, and 47% for >5 cm (p = 0.01); i n Stage IIA, the rates were 93%, 63%, 39%, and 59%, respectively (p le ss than or equal to 0.01). Patients with Stage HB medial parametrial i nvolvement had better 10-year disease-free survival (67%) than those w ith lateral parametrial extension (56%) (p = 0.02). Stage III patients with unilateral tumor extension had a 48% 10-year disease-free surviv al rate compared with 32% for bilateral parametrial involvement (p les s than or equal to 0.01). The presence of endometrial extension or tum or only in the endometrial curettings had no significant impact on pel vic failure. However, in patients with Stage IB disease, the incidence of distant metastases was 31% with positive curettings, 15% with nega tive curettings, and 22% with admixture (p less than or equal to 0.01) . In Stage IIA, the corresponding values were 51%, 33%, and 18% (p = 0 .05). The 10-year disease-free survival rates in Stage IB were 67% wit h positive curettings, 81% for negative curettings, and 77% for admixt ure (p = 0.02); in Stage IIA, the rates were 45%, 66%, and 67%, respec tively (p = 0.14). Because this is not a prospective Phase II dose-esc alation study, the correlation of doses of irradiation with pelvic tum or control in the various stages and tumor size groups is not consiste nt. Nevertheless, with Stage IB and HA tumors <2 cm in diameter, the p elvic failure rate was under 10% with doses of 70-80 Gy to point A, wh ereas for larger lesions even doses of 85-90 Gy resulted in 25% to 37% pelvic failure rates. In Stage IIB with doses of 70 Gy to point A, th e pelvic failure rate was at,out 50% compared with about 20% in nonbul ky and 30% in bulky tumors with doses >80 Gy. In Stage III unilateral lesions, the pelvic failure rate was about 50% with less than or equal to 70 Gy to point A versus 35% with higher doses, and in bilateral or bulky tumors it was 60% with doses <70 Gy and 50% with higher doses. Conclusions: Clinical stage and size of tumor are critical factors in prognosis, therapy efficacy, and evaluation of results in carcinoma of the uterine cervix. The doses to point A suggest that for lesions <2 cm, doses of 75 Gy result in less than or equal to 10% pelvic failures , whereas in more extensive lesions, even with doses of 85 Gy, the pel vic failure rate is about 30%; and in Stage IIB-III tumors, doses of 8 5 Gy result in 35-50% pelvic failures. Refinements in brachytherapy te chniques and/or use of agents to selectively sensitize the tumors to i rradiation will be necessary to improve the present results in invasiv e carcinoma of the uterine cervix. (C) 1998 Elsevier Science Inc.