Molecular Markers in the Treatment of Endometrial Cancer 2

Endometrial cancer (EC) is the most common pelvic gynaecological disease in the
western world. Low-risk patients with localized disease face good prognosis and
can often be treated with surgery alone. Current risk classification in EC is
based on the International Federation of Gynecology and Obstetrics FIGO stage,
tumor subtype and histological grade. Yet, 20% of those tumors with estimated
low-risk will recur and up to 50% of those with high-risk do not. Standard
treatment of EC is based on preoperative risk stratification, and consists of
hysterectomy and bilateral salpingo-oophorectomy for low-risk (grade 1 or 2)
EC, and additional lymphadenectomy for high-risk (grade 3) EC. Based on data of
the MoMaTEC1 series, it was demonstrated that additional immunohistochemical
analysis of estrogen receptor (ER) and progesterone receptor (PR)
preoperatively, improved the currently used risk stratification both with
respect to lymph node metastasis and poor prognosis. The percentage of lymph
node metastasis was shown to increase from 8% in patients with preoperatively
low-grade histology and positive expression of hormone receptors, to 15.4% in
patients with low-grade histology and loss of either ER/PR, compared to 23% for
patients with loss of either ER/PR regardless of histology. Implementing
hormone receptor status to improve risk stratification for selecting high-risk
patients likely to benefit from lymphadenectomy seems justified.

Primary objectives:
MoMaTEC2 aims to test the applicability of already identified and promising
molecular biomarkers ER and PR, to improve risk stratification and
individualisation of treatment for patients with EC.

Secondary objectives:
To perform a phase 4 implementation trial for optimized stratification of
surgical treatment, specifically the performance of (para-aortic and pelvic)
lymphadenectomy guided by expression of ER and PR. In this way, to improve
identification of those at risk for lymph node metastasis and poor outcome.
Moreover, to give a foundation for a more homogenous practice of preoperative
risk stratification and surgical treatment of endometrial cancer among
different centers in Europe.
To investigate the impact of peri-operative morbidity by determination of
quality of life with structured and validated endometrial cancer-specific
questionnaires.
To collect additional tissues for identification and validation of novel
prognostic markers.

Prospective multicenter interventional study

Low-risk patients will undergo a hormone-receptor guided lymphadenectomy, in
addition to standard hysterectomy and salpingo-oophorectomy. This will be
performed according to the local protocols, which means a pelvic and lower
para-aortic (up to to arteria mesenterica inferior) lymphadenectomy.

Possible discomforts and risks:
1.Due to the lymphadenectomy procedure, approximately 7% of patients may get
lymphedema or lymphocele in varying degree and discomfort. Assuming an increase
of 11.3% in lymphadenectomies, an additional 1% of patients will experience
these side-effects.
2.Patients will fill out a number of quality of life questionnaires
preoperatively and during follow up and provide some specific information
related to prior medication and obesity related factors. These questionnaires
will take approximately 30 minutes to fill out.
3.Due to the increased detection of lymph node metastasis, there will be an
increased need for systemic therapy. With an expected prevalence of 15.4% lymph
node metastasis in this group, an additional 1.7% will be recommended to
receive systemetic therapy, with subsequently possible side-effects, but with
an increased disease specific survival.
4.The collection of tissue for the biobank consists of collecting two blood
samples, urine, an additional endometrial biopsy, and frozen tumor tissue, and
will be performed intra-operative, when the patient is under general
anesthesia. In this way, no extra burden on the patients is expected.

Possible advantages:
1.We expect a decrease in false negative low-risk stratification for patients
resulting in more correct stratification of high-risk patients to the high-risk
group with appropriate clinical management for this population.
2. Due to a better risk stratification and resulting treatment consequences one
hopes to note an increase of 5-year life expectancy and a reduction in
(systemic) recurrence rate in the population.
3.Through systematic appraisal of their quality of life, focusing on
endometrial cancer related issues, patients may hopefully take up symptoms more
easily with their treating physician