Due to the increasing amount of published data suggesting that endometrial carcinoma is a heterogenic entity with possible different treatment sequences and post-treatment follow-up, the Polish Society of Gynecological Oncology (PSGO) has developed new guidelines to summarize the evidence for diagnosis.
1. Endometrial Biopsy
The biopsy of the endometrium (abrasion, aspiration biopsy and hysteroscopic biopsy) is recommended for
- (1)
-
Women with postmenopausal bleeding whose endometrial thickness is > 3 mm
[1] (strength of evidence IIIA) (grade of recommendation 2A);
- (2)
-
Women with adult granulosa cell tumour undergoing fertility-sparing treatment (with preservation of the uterus)
[2] (strength of evidence IVA) (grade of recommendation 2B);
- (3)
-
Women with bleeding during tamoxifen treatment lasting up to 5 years
[3] (strength of evidence IVA) (grade of recommendation 2B).
There are no data regarding the safety of such an approach for patients using tamoxifen for up to 10 years. Tamoxifen therapy beyond 5 years significantly increases the risk of endometrial cancer (HR-1.74)
[4] (strength of evidence IIA). Caution is recommended in this group of women (transvaginal ultrasound evaluation of the uterus every 6 months) (expert opinion) (strength of evidence V) (grade of recommendation 2B).
Regardless of the duration of tamoxifen use, special attention should be paid to menopausal women who can be asymptomatic due to stenosis of the cervical canal (grade of recommendation 1).
The endometrial thickness cut-off at which biopsy in asymptomatic women in the general population (pre- and postmenopausal) and in those with increased risk of endometrial cancer (PCOS, obesity, no childbirths or late menopause) *, which would have acceptable sensitivity and specificity, has not been established. Thus, an individual approach is recommended (expert opinion) (strength of evidence V) (grade of recommendation 2B). * Note: The management of endometrial hyperplasia (a precancerous condition) is a separate subject not covered by this recommendation.
The sensitivity of endometrial biopsy (cumulative value for abrasion and aspiration biopsy) is 89% and the false-negative rate is 10%
[5] (strength of evidence IVA)
[6] (strength of evidence IIIA).
The sensitivity of an adequate aspiration biopsy is significantly higher: 91% for premenopausal and 99.6% for postmenopausal women
[7] (strength of evidence IIIA). However, obtaining tissue material adequate for the histopathological assessment using this method concerns 85% of samples
[6] (strength of evidence IIIA).
For the reasons mentioned above, there is no preferred method of endometrial biopsy (grade of recommendation 2A).
2. Histopathological Report of Endometrial Biopsy
The report should specify the histological type, and for endometroid carcinoma, its differentiation grade assessed in two categories: low-grade (G1/G2) and high-grade (G3)
[8][9][10][11][12][13] (strength of evidence V) (grade of recommendation 2B).
The existing scientific evidence indicates
- (1)
-
The advantage of the new molecular classification over the former based solely on the type of endometrial cancer and grading in making therapeutic decisions at the beginning of treatment
[14][15][16] (strength of evidence IIIE, IIIA and IIA);
- (2)
-
A significantly higher concordance between pre- and postoperative results for the new molecular classification based on the ProMisE classifier and/or sequencing compared to previously considered features (type and grading)
[17][18][19][20][21][22] (strength of evidence IIIB, IIIB, IIID, IIID, IIID, IIIB),
- (3)
-
High sensitivity and specificity of the ProMisE classifier
[23][24] (strength of evidence IIID and IIIC), which is potentially realisable in most pathomorphology units. It is recommended that molecular classification be defined (at least a basic variant of ProMisE) at the initial diagnosis of endometrial cancer (biopsy), and if this is impossible, it should be performed at the latest before the decision on adjuvant treatment (grade of recommendation 2A).
CAUTION: Every woman with endometrial cancer for whom fertility-sparing treatment is being considered must obligatorily be subject to molecular classification (at least a basic variant of ProMisE). A similar requirement applies to high-risk patients with comorbidities who do not qualify for surgical treatment (grade of recommendation 2A).
A detailed description of the ProMisE classifier and comprehensive endometrial carcinoma diagnosis algorithm NGS+IHC is included in one paper
[25].
The centres where the diagnostic minimum (ProMisE molecular classification) cannot be performed may, in the transitional period, use existing criteria: type and grading (does not apply to the decision on fertility-sparing treatment and management of nonoperable cases) (grade of recommendation 3).
3. Final Postoperative Pathological Report (Examination of the Uterus)
The report should include a verified histological type, and for endometroid carcinoma, verified grading assessed in two categories: low-grade (G1/G2) and high-grade (G3)
[8][9][10][11][12][13] (strength of evidence V) (grade of recommendation 2B).
If molecular classification was not performed at the time of the biopsy, it must be performed for the final report (at least a basic variant of ProMisE) (grade of recommendation 2B).
LVSI invasion is a very important predictive factor indicating individual risk of recurrence and a decisive factor in the choice of adjuvant therapy
[26] (strength of evidence IIC).
The semiquantitative LVSI assessment system, which distinguishes focal and substantial * LVSI depending on the number of vessels involved, confirmed the high agreement of the results
[18] (strength of evidence IIC).
* Substantial LVSI signifies the involvement of more than five lymphovascular spaces (LVSI) and does not include LVSI within the tumour and in the immediate vicinity of the tumour margin
[27] (strength of evidence IA).
The presence of substantial LVSI
[27][28][29] (strength of evidence IB, IIIA and IIIE) is both predictive and prognostic and, therefore, the final histopathological result in the case of LVSI invasion should indicate if it is focal or substantial (grade of recommendation 1).
A detailed description of all clinically necessary elements of the histopathological report is included in
File S2.
4. Imaging Prior to Treatment Decision
The best method of assessing the local advancement of endometrial cancer (the depth of the myometrial invasion and infiltration of the cervical stroma—pT2) is magnetic resonance imaging (MRI) with contrast
[30][31] (strength of evidence V and IIIA). Expert ultrasound has a diagnostic value comparable to MRI in the assessment of myometrial infiltration but is significantly worse in the assessment of the T2 feature
[30] (strength of evidence V). Computed tomography (CT) is only useful in assessing the spread of cancer beyond the pelvis. Radiological assessment of the pelvis by CT is inferior to MRI and expert ultrasound
[31] (strength of evidence IIID).
Therefore, before deciding on the sequence of endometrial cancer treatment, clinical and radiological staging should be performed based on gynaecological examination, pelvic MRI and CT of the abdomen and the chest (grade of recommendation 2B).
In justified cases, expert ultrasound can replace magnetic resonance imaging in the assessment of changes in the pelvis (grade of recommendation 2B).
FIGO staging for endometrial carcinoma is shown in
Table 1 [32].
Table 1. FIGO staging for endometrial carcinoma.