Organ preservation in cervix cancer

From 1970 to 1994, 642 patients with carcinomas of intact uterine cervix were treated with radiotherapy alone Univariate and multivariate analysis was carried out of predictive factors for: 1) pelvic control and survival rates; 2) complications using French-Italian Syllabus, combined with an evaluation of the impact of customized treatment planning policy (CTP) on G3-G4. According to Figo substaging 30% of patients were stage I, 42% stage II and 28% stage III/IV. Diameter of cervical disease was 3-5 cm in 38% of cases and > 5 cm in 15%. Nodal involvement from lymphangiogram was 21%. The distribution of sequelae and complications was: G1 23%, G2 18%, G3 6%, G4 2.5%. The distribution of G3-G4 per organ was: genitalia 6% (no G4), rectum 4%, colon 1.5%, bladder 1.2%, soft tissues 1%, small bowel 0.5%. Stage (RR ranging from 1.5 for stage IIb to 5 for stage III/IV), tumor size (RR = 1.5), nodal involvement (RR = 2) were significant predictive factors for survival and pelvic control rates (p < 0.0001). In univariate analysis the main factors influencing the risk of G3-G4 complications were: Figo substaging, external radiation dose over 40 Gy (ED), parametrium boost (PB), use of brachytherapy vaginal cylinders applicator (CA), high HWT and mean rectal dose rate for rectal complications. In multivariate analysis, CA remained the only predictive factor for G3-G4 bladder events (odds ratio OR = 10.8) while the increase of mean dose rate (OR = 1.1), use of CA (OR = 4.2) and ED > 40 Gy (OR = 4.4) were predictive of severe rectal sequelae. Prevention of complications based upon individual changes of treatment planning according to dosimetry parameters led to a sharp decrease in severe complications with time. No G4 occurred after 1983. G3 rates dropped from 5% before 1978 to 0% after 1983 in stage I, from 10% to 6% in stage II and from 23% to 12% in stages III/IV. Meanwhile 5-year LC rates remained stable in early stages, about 91% in stage I and 85% in stage II, conversely they fell from 75% to 55% in stages III/IV, thus raising the problem of underdosage and/or more reliable staging with time. It is concluded that radiotherapy prescriptions based upon tumor diameter per stage and delivered using CTP led to an eradication of lethal complications and provided significant decrease of G3 in all cases while maintaining high cure rates in early stages. Dose reduction should be considered with caution in stages III/IV.