The evidence supporting this protocol is provided by a phase III multicentre randomised trial (GOG 92).rr This study included 277 women who had radical hysterectomy and pelvic lymph node dissection for Stage IB cervical cancer, were N0 and either:
- lymphovascular space invasion (LVSI) and deep 1/3 stromal invasion, OR
- LVSI, middle 1/3 stromal invasion, and tumour 2 cm3, OR
- LVSI, superficial 1/3 stromal invasion and tumour 5 cm3, OR
- no LVSI, middle or deep 1/3 stromal invasion, and tumour 4 cm3.
Between March 1988 and September 1995, patients were randomised to receive adjuvant radiation therapy (RT) alone (46 Gy/23 fractions–50.4 Gy/28 fractions, within 4-6 weeks of surgery, n = 137) or observation (n = 140). The primary endpoint was recurrence-free interval, and secondary endpoints were progression free survival (PFS), overall survival (OS), and toxicities. After a median follow-up of 10 years, there was a significant reduction in risk of recurrence (HR = 0.54; 90%CI = 0.35-0.81; p = 0.007), and progression/death (HR = 0.58; 90%CI = 0.40-0.85; p = 0.009) with adjuvant RT. When stratified by histology, those with adenocarcinoma or adeno-squamous in the observation group had higher failure rate (44%) compared to those who had adjuvant RT (8.8%), i.e. those with adenocarcinoma/adeno-squamous histology benefited the most from adjuvant RT (compared to those with squamous cell histology).
A Cochrane review meta-analysis identified two RCTs (n = 397 women) included data from GOG 92 and an earlier Phase II study published in 1982.r It compared adjuvant treatment (RT) versus no further treatment (NFT). Women who had adjuvant RT had a significantly lower risk of disease progression at five years (RR = 0.6, 95% CI:0.4-0.9), but no significant difference in survival at 5 years (RR = 0.84; 95%CI = 0.3-2.36).
||No. of patients (experimental/control)
|Recurrence free survival
Sedlis et al.1999r and Rotman et al. 2006r
Adjuvant RT arm
n = 137
n = 140
HR = 0.54
(90%CI = 0.35-0.81)
p = 0.007
|Stage IB, N0 and ≥ 2 intermediate risk features (i.e. deep stromal invasion, LVSI, or tumour size ≥ 4 cm)
|Progression free survival
HR = 0.58
(90%CI = 0.40-0.85)
p = 0.009
HR = 0.70
(90%CI = 0.46-1.05)
p = 0.07 (not significant)
Treatment technique - intensity modulated radiation therapy (IMRT) vs 3D-conformal radiation therapy (3D-CRT)
There is evidence from the RTOG 1203 study suggesting lower acute toxicity with IMRT compared to 3D-CRT treatment techniques.r Between 2012 and 2015, 278 women with cervical or endometrial cancer were randomised to receive post-operative pelvic radiation with standard four-field 3D-CRT (n = 149) or IMRT (n = 129). The primary endpoint was change in acute GI toxicity from baseline to 5 weeks measured using the EPIC bowel domain; the secondary endpoints were change in GU toxicity from baseline to 5 weeks measured using the EPIC urinary domain; toxicity measured using PRO-CTCAE, and QOL measured using FACT-Cx. At week 5 of radiation therapy, patients in the 3D-CRT arms experienced larger mean decline in EPIC bowel domain score compared to those in the IMRT arm (-23.6 vs. -18.6, p = 0.048). Evaluation of late toxicity is ongoing.
Intermediate risk patients
The current standard of care for patients with intermediate risk disease is adjuvant radiation therapy alone, however some retrospective studies have shown a potential benefit in PFS and OS with the addition of concurrent chemotherapy. The GOG 0263 trial is currently investigating the role of concurrent chemotherapy in this cohort and is expected to be completed at the end of 2020.r