Efficacy
The incidence of endometrial cancer is growing and is the second most commonly diagnosed gynaecological malignancy worldwide.r
The standard of care for endometrial cancer in high-intermediate-risk disease is surgery followed by adjuvant radiation therapy (RT). In high-risk disease the addition of concurrent adjuvant chemotherapy is appropriate.rr A small percentage (<5% to up to 10%) of patients are deemed inoperable due to medical co-morbidities.rr Primary RT with curative intent is reserved for patients in this setting. Local control can be achieved by a combination of external beam radiation therapy (EBRT) and intra-cavitary high dose rate (HDR) brachytherapy or HDR brachytherapy alone. Pelvic external beam RT treats areas at risk for locoregional spread and with the aim of cytoreduction of bulkier tumours prior to brachytherapy treatment.
A search of the literature did not find strong (level 1) evidence to support the use of definitive RT in the treatment of inoperable endometrial cancer. For patients with extrauterine spread (stage II or III) or bulky stage 1 disease a combination of external beam radiation therapy to the whole pelvis and brachytherapy is recommended.r Early-stage disease can be treated with brachytherapy alone and is covered in ID 3747: Gynaecological endometrium definitive HDR brachytherapy alone or boost.
There are several retrospective and observational studies describing the use of definitive EBRT and brachytherapy for inoperable endometrial cancer. A selection of the most recent and pertinent studies is outlined in the above evidence table. Dose fractionations are highly variable and often patient specific but in the majority of cases the EBRT doses ranges from 45 Gy in 25 fractions to 50.4Gy in 28 fractions with some studies utilising higher doses (up to 59 Gy) for gross nodal disease with sequential or simultaneous integrated boost techniques.
There is large variability in the outcome measures reported in this cohort largely due to the heterogeneity of patients included. Local control rates ranged between 81-100% at 2-4 years for stages I-III. Cause specific survival (CSS) and overall survival (OS) at 5 years ranged similarly from 71%- 93%.rrrrrrr As expected, outcomes for high-risk histological subtypes, where reported as worse than low risk disease.
For patients unable to undergo brachytherapy there is limited evidence to guide management. Evidence for high dose EBRT is lacking. Consideration can be given to a stereotactic body RT (SBRT) boost in lieu of brachytherapy in select cases. Kemmerer et al. reported comparable outcomes to EBRT + brachytherapy using a SBRT boost technique sequentially to conventional EBRT.r This approach can be considered on a case-by-case basis with input from a specialist multidisciplinary team (MDT).
There is no level 1 evidence to guide the use of systemic therapy in the medically inoperable setting, with the above studies employing various uses and sequencing of chemotherapy. Extrapolating from the cervical cancer literature and given the inferior outcomes of these patients, especially in the high-risk histological subgroups, consideration should be given for radiosensitising chemotherapy given concurrently with definitive RT, if tolerated by the patient, as there may be a potential benefit.r However, the same medical reasons that preclude surgery in these patients may also preclude systemic therapy.
Study |
No. of patients |
Outcomes |
Local control (LC) |
Cause specific survival (CSS) |
Overall survival (OS) |
Huang et al. 2023r |
50 |
96% at 2 years. |
83% at 2 years. |
75% at 2 years. |
Shen et al. 2022r |
55 |
82% at 2 years [low-risk endometrial carcinoma (LREC)].
80% at 2 years [high-risk endometrial carcinoma (HREC)]. |
100% at 2 years for both LREC and HREC. |
92% at 2 years (LREC).
80% at 2 years (HREC).
|
Mutyala et al 2021r |
31 |
83.1% at 2 years. |
n/a |
77.4% at 2 years. |
Yaney et al. 2021r |
51 |
100% at 1 and 2 years with brachytherapy (BT) alone.
93% at 1 year and 89% at 2 years with external beam radiation therapy (EBRT) and BT.
|
n/a |
88% at 1 year and 72% at 2 years with BT alone.
94% at 1 year and 84% at 2 years with EBRT and BT.
|
Espenel et al 2020r |
27 |
81% at 3 years. |
n/a |
63% at 5 years. |
Gannavarapu et al 2020r |
29 |
93% at 2 years. |
100% at 2 years for both HREC and LREC. |
73% at 2 years (HREC).
77% at 2 years (LREC).
|
Arians et al. 2020r |
13 |
76.2% at 2 years.
56.4% at 5 years.
|
n/a |
Estimated OS: 76.9% at 2 years.
69.2% at 5 years.
|
Jordan et al 2017r |
15 |
93.4% at 4 years. |
73% at 4 years. |
n/a |
Acharya et al. 2016r |
43 |
91.7% at 2 years. |
n/a |
65% at 2 years. |
Inciura et al. 2010r |
29 |
83% at 5 years. |
73.5 % at 5 years.
67.9% at 10 years.
|
48.3% at 5 years.
20.7% at 10 years.
|
Wegener et al. 2010r |
26 |
100% at 1 year.
92% at 2 years.
|
93% at 1 year.
73% at 2 years.
|
89% at 1 year.
28% at 2 years.
|
Coon et al 2008r |
49
|
94% at 5 years.
|
93% at 3 years.
87% at 5 years.
|
83% at 3 years.
42% at 5 years.
|
Niazi et al 2005r |
38
|
84% at 57.7 months (median follow up).
|
78% at 15 years for all stages.
90% at 15 years for Stage I.
42% at 15 years for Stage II.
91% at 15 years for Grade 1.
67% at 15 years for Grade II and III combined.
|
n/a |