Adjuvant vaginal brachytherapy (VBT) is recommended by the ESGO-ESTRO-ESMO guidelines for patients with high-intermediate risk (HIR) endometrial cancer (stage I endometrioid, grade 1-2, ≥ 50% myometrial invasion, LVSI negative) to decrease the risk of vaginal recurrence. Another option for this cohort of patients is for surveillance only, with no adjuvant treatment.r The 2015 ASTRO-ASCO consensus guidelines recommend that adjuvant VBT alone is given for FIGO stage IA grade 3, and IB grade 1-2, and considered for FIGO grade 1-2 with high risk features (LVSI or > 60 years of age).r
To help identify those women at higher risk of recurrent disease, risk factors for HIR endometrial cancer have been previously defined in PORTEC-1 and GOG 99, and are discussed in the Gynaecological endometrium adjuvant EBRT protocol.rr
The randomised PORTEC-2 trial for FIGO 1988 stage I-IIA endometrial cancer patients with HIR factors confirmed external beam radiotherapy (EBRT) could safely be substituted by VBT, with less toxicity and better quality of life.r The trial included 427 women and had a median follow-up of 116 months. Patients were randomised to receive adjuvant VBT or EBRT. The 10-year vaginal recurrence rate was similar in the VBT group (3.4% vs 2.4%, p = 0.55). Ten-year pelvic recurrence was more often seen in the VBT group (6.3% vs 0.9%, p = 0.004), which most often occurred with distant metastases. The 10-year isolated pelvic recurrence was 2.5% vs 0.5% (p = 0.10). There was a non-significant difference in the rate of overall distant metastases (10.4% vs 8.9%, p = 0.45), and overall survival was similar in the VBT group (69.5% vs 67.6%, p = 0.72).
In the 10-year update of PORTEC-2, central pathology review and molecular analysis was performed on 416 patients with endometrial cancer.r L1CAM and p53-mutant expression and substantial LVSI were shown to be risk factors for pelvic recurrence and distant metastases, and EBRT was found to reduce pelvic recurrence in cases where these risk factors were found. There is likely to be an increasing role of molecular subtyping and risk stratification.
The 5-year quality of life review for PORTEC-2 demonstrated that patients tolerated VBT significantly better than EBRT, with better social functioning and lower symptoms scores for gastro-intestinal symptoms (p <0.001). Sexual functioning in both groups was lower, and sexual symptoms more frequent, in both treatment groups compared to the normal population.r
The GOG 99 trial group recommend adjuvant pelvic EBRT should be limited to patients with HIR disease.r The randomised control trial scheduled patients with intermediate risk endometrial cancer to receive either whole pelvic EBRT (50.4 Gy in 28 fractions) versus no adjuvant therapy. Patients were categorised into ‘high-intermediate’ or ‘low-intermediate’. High-intermediate included patients with:
- moderate to poorly differentiated tumour, LVSI positivity, and outer third myometrial invasion.
- age 50 years or greater, with any two risk factors listed above.
- age 70 years or above with any risk factor listed above.
The difference in the 2-year cumulative incidence of recurrence was particularly marked for the HIR disease group (26% no adjuvant therapy vs 6% pelvic EBRT). In patients with HIR disease, pelvic EBRT significantly reduced the number of pelvic and vaginal recurrences (18 patients that received no adjuvant therapy vs 3 patients that received pelvic EBRT). There was no significant difference seen in the estimated 4-year survival between the two treatment arms (86% vs 92%).
Post-operative VBT for low risk disease
There does not appear to be a benefit of post-operative VBT for low risk disease. Sorbe et al. 2009 reported on their randomised controlled trial of post-operative vaginal vault brachytherapy versus surgery alone for FIGO stage I low risk endometrial cancer (FIGO stage IA-IB, endometrioid histology, and FIGO grade 1-2).r The rate of loco-regional recurrence overall was low (2.6%) as was the rate of distant metastatic disease (1.4%). There was no significant difference in the rate of vaginal recurrence in the vaginal brachytherapy group (1.2%) vs the control group (3.1%) (p = 0.114), and survival was similar between the 2 groups.
The American Brachytherapy Society consensus guidelines discuss acceptable ranges for brachytherapy dose fractionation; noting dose is dependent on whether EBRT is given, the dose specification point, and the vaginal length to be treated.r For adjuvant brachytherapy alone, multiple dose fractionations exist. Suggested doses generally aim to deliver approximately 60 Gy low dose rate (LDR) equivalent to the vaginal surface. Suggested doses for high dose rate (HDR) range from 16.2 Gy x 2 with ovoids at vaginal surface, to 7 Gy in 3 fractions prescribed to 0.5 cm depth from the vaginal surface (the latter most commonly utilised in previous trials).
When utilised in combination with EBRT, a vault brachytherapy boost aims to deliver approximately 70 Gy LDR equivalent to the vaginal surface. Where 45 Gy EBRT is delivered, a brachytherapy boost of 18 Gy in 3 fractions is commonly delivered. Where 50.4 Gy EBRT is delivered, a brachytherapy boost of 12 Gy in 2 fractions is commonly delivered. The guidelines recommend consideration of higher brachytherapy doses in the setting of positive resection margins or recurrent disease.