Chang 2000.

Study characteristics
Methods	RCT conducted in China. Unclear whether this was a single or multicentre trial.
Participants	120 eligible women with FIGO Stage IB (bulky) to IIA (bulky) cervical cancer. No difference in baseline characteristics between arms. Histopathological type Squamous cell cancer: 91% of women in the NACT + RH arm and 88% in the radiotherapy arm. Adenocarcinoma: 4% of women in the NACT + RH arm and 8% in the radiotherapy arm. Adenosquamous carcinoma: 4% of women in the NACT + RH arm and 4% in the radiotherapy arm. Age Median age 46 years in the NACT + RH group and 47 years in radiotherapy group. Performance status 0: 85% in the NACT + RH arm and 83% in the radiotherapy arm. 1: 15% in the NACT + RH arm and 15% in the radiotherapy arm. 2: 0% in the NACT + RH arm and 2% in the radiotherapy arm. FIGO Stage FIGO Stage IB bulky: 53% of women in the NACT + RH arm and 50% in the radiotherapy arm. FIGO Stage IIA bulky: 47% of women in the NACT + RH arm and 50% in the radiotherapy arm. Mean tumour size Mean tumour size was 5.0 (SD 0.8) cm in the NACT + RH arm and 4.9 (SD 0.7) cm in the radiotherapy arm. Mean tumour size was > 6 cm in 10% in the NACT + RH arm and 10% in the radiotherapy arm. Tumour type Endophytic: 51% in the NACT + RH arm and 54% in the radiotherapy arm. Exophytic: 49% in the NACT + RH arm and 46% in the radiotherapy arm. Tumour grade Grade I: 3% in the NACT + RH arm and 6% in the radiotherapy arm. Grade II: 40% in the NACT + RH arm and 27% in the radiotherapy arm. Grade III: 44% in the NACT + RH arm and 40% in the radiotherapy arm. Undifferentiated grade: 9% in the NACT + RH arm and 6% in the radiotherapy arm. Unspecified grade: 4% in the NACT + RH arm and 21% in the radiotherapy arm.
Interventions	NACT + RH (68 participants) NACT was cisplatin and vincristine, followed by bleomycin. 2–4 weeks after the completion of NACT, women underwent a type III radical abdominal hysterectomy and pelvic lymphadenectomy. The adnexae were usually left in women aged < 40 years if they were grossly normal in appearance. Radiotherapy (52 participants) Radiotherapy usually included external irradiation + high‐dose rate brachytherapy. Women received 40–44 Gy of whole pelvic irradiation; the para‐aortic lymph nodes were not routinely included in the treatment field. Parametria received up to 50 Gy. Daily fraction was 1.8–2 Gy, 5 fractions per week. If bulky tumour persisted after 44 Gy of irradiation, external‐beam doses to the lower pelvis were increased to 50–54 Gy without central block, followed by brachytherapy, or to 70 Gy without brachytherapy. 7 women received external irradiation alone. Brachytherapy 3 different dose ranges for brachytherapy during this period. Before April 1992, brachytherapy given as 3 fractions with 2‐week intervals between each fraction; dose to 'point A' was 6.5–7.2 Gy/fraction. Of the women in the radiotherapy arm, 1 received this method. Between July 1992 and September 1993, 5 women were transferred to another hospital for brachytherapy because the remote control after‐loading system of the main hospital was out of order. Women received a total of 4 fractions of high‐dose brachytherapy by 2 applicator insertions; on each insertion, 2 fractions of 7–7.5 Gy to 'point A' were given during the same day with an interval of 4–6 hours. The median cumulative dose to 'point A' was 72 Gy. After August 1993, brachytherapy performed in the main hospital and given in 6 fractions at 2 fractions per week; the dose to 'point A' was 4.3 Gy/fraction. The median cumulative dose to 'point A' in this treatment protocol was 70 Gy. 37 women received this method. Response to radiotherapy was evaluated by a radiation oncologist and a gynaecological oncologist weekly during treatment. Postoperative radiotherapy given using techniques similar to those described above, the dose to the whole pelvis was 44–45 Gy, and that to the true pelvis was 50–54 Gy. After external irradiation, intravaginal brachytherapy was given in 2–3 fractions with a total dose of 4–6 Gy/0.5 cm below vaginal mucosa.
Outcomes	OS DFS Response Toxicity
Notes	Women with enlarged para‐aortic lymph nodes on image study were ineligible unless results of cytological or histological studies were negative. Type III radical hysterectomies were performed. Median duration of follow‐up was 39 months. Median DFS for the radiotherapy arm was 68 months, but median for the NACT + RH arm could not be calculated as more than half of women did not experience a relapse. There was no difference in DFS between arms (P = 0.8). 2‐year survival rate was 81% (95% CI 71% to 91%) in the NACT + RH arm and 84% (95% CI 72% to 95%) in the radiotherapy arm, and the estimated 5‐year survival rates were 70% (95% CI 56% to 83%) in the NACT + RH arm and 62% (95% CI 43% to 80%) in the radiotherapy arm. DFS and OS of the women who underwent NACT + RH did not differ from those of women treated with radiotherapy alone. Women in the NACT + RH arm had a higher incidence of receiving adjuvant therapy, with either radiotherapy or chemotherapy, after the scheduled treatment than those in the radiotherapy arm, who received RH as the adjuvant therapy. Of the 68 women in the NACT + RH arm, 62 underwent RH and 19 of those had adjuvant radiotherapy, 6 had adjuvant chemotherapy and 2 had chemoradiotherapy. The NACT + RH group had higher incidence of local (21%) vs distant (9%) relapse, whereas the radiotherapy had equal incidence of local vs distant relapse (12%). Higher incidences of relapse over the vagina and over the lung were noted in the NACT + RH arm, whereas the radiotherapy arm showed a higher rate of para‐aortic node relapse. Incidence of acute toxicity, mainly mild‐to‐moderate gastrointestinal and haematological toxicity and urinary retention, was higher in the NACT + RH arm than in the radiotherapy arm. Incidence of cystitis (due to radiation), proctitis (due to radiation) and lymphoedema was higher in the radiotherapy arm.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not reported.
Allocation concealment (selection bias)	Low risk	Quote: "Randomisation was conducted by the Biostatistics Consulting Center of Chang Gung Memorial Hospital".
Blinding of participants and personnel (performance bias) All outcomes	High risk	Impossible to blind participants and clinicians to these interventions.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Authors stated that to allocate more women to the presumably favourable treatment arm, they allocated 60% of the women to the NACT + RH arm and 40% to the radiotherapy arm. This could potentially have introduced bias when clinicians assessed subjective outcomes such as classification of response and toxicity.
Incomplete outcome data (attrition bias) All outcomes	Low risk	120/120 eligible women were analysed for primary survival outcomes using appropriate statistical techniques.
Selective reporting (reporting bias)	Low risk	All pertinent outcomes appeared to have been reported by the trial authors.
Other bias	Unclear risk	Insufficient information to assess whether an additional risk of bias existed.