Trial Title:
Study and Transformation of Tumor Molecular Features Screening Model of Endometrial Carcinoma Surgical Approach
NCT ID:
NCT05894915
Condition:
Endometrial Carcinoma
Tumor Molecular Features Screening Model
Conditions: Official terms:
Carcinoma
Endometrial Neoplasms
Study type:
Interventional
Study phase:
N/A
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
Single (Participant)
Intervention:
Intervention type:
Procedure
Intervention name:
open surgery
Description:
Open surgery is a traditional surgery method.
Arm group label:
open surgery group
Intervention type:
Procedure
Intervention name:
laparoscopic surgery
Description:
Laparoscopic surgery is a newly developed minimally invasive method.
Arm group label:
laparoscopic surgery group
Summary:
At present, endometrial carcinoma is one of the three most common malignant tumors in
gynecology, and the incidence has been increasing year by year, causing a large health
and economic burden to the society. Therefore, researchers regard the hierarchical
management and precise diagnosis and treatment of endometrial carcinoma as an important
direction for future research. In 2013, the American Cancer Genome Atlas Research Network
proposed a molecular typing of endometrial carcinoma. In recent years, international
scholars have conducted relevant research on the molecular characteristics of a large
number of endometrial carcinomas and immunity, targeted therapy and postoperative
adjuvant chemoradiotherapy. However, the molecular characteristics of endometrial
carcinoma and the choice of surgical route are still in a relatively lacking state. The
previous research of the investigators' group was the first to propose the concept of
selecting surgical routes for endometrial carcinoma based on molecular characteristics.
Then, on this basis, the investigators' research group plans to carry out a prospective
randomized controlled study to further analyze the impact of surgical routes on the
short-term safety and long-term prognosis of endometrial carcinoma patients with
different molecular characteristics, and transform it into a clinical decision-making
technical index system for endometrial carcinoma surgical selection based on molecular
characteristics and further promote and apply. The results of this study will make up for
the shortcomings in the relevant fields of endometrial carcinoma research in the world to
some extent, and become an important aspect of the decision-making system of clinical
comprehensive precision diagnosis and treatment of endometrial carcinoma patients.
Detailed description:
1. Research purpose and significance Endometrial carcinoma is one of the three most
common malignant tumors in gynecological diseases. At present, its emergence has
caused a relatively serious health economic burden worldwide, according to
statistics, the number of new cases of endometrial carcinoma in the world exceeded
400,000 in 2020. In China, the incidence of endometrial carcinoma is second only to
cervical cancer and ranks second among female reproductive tract malignancies. In
recent years, public health problems such hypertension, diabetes mellitus and poor
lifestyle have become increasingly serious, which has led to an increase in the
incidence of endometrial carcinoma and a younger age of onset.
The prognosis of patients with endometrial carcinoma is closely related to their
clinicopathological features, such as stage, grade, and pathological subtype.
Stratified individualized diagnosis and treatment of endometrial carcinoma patients
is an important direction that international scholars have been constantly
exploring. In 1983, Bohkman proposed the dichotomous classification systemof
endometrial carcinoma, which is based on the pathological characteristics to divide
endometrial carcinoma into two types, type I carcinoma into two types, of which type
I cancer mainly refers to endometrioid adenocarcinoma, type II carcinoma includes
serous carcinoma, clear cell carcinoma and other special types. However, further
evidence suggests that this approach is still limited in guiding patients'
management and outcome. In 2013, American scholars used he Cancer Genome Atlas data
to further propose the molecular typing of endometrial carcinoma, which divided
endometrial carcinoma into four categories: POLE (ultramutated)，microsatellite
instability (MSI)hypermutated, Copy-number low(CNL) and Copy-number high(CNH). Among
them, POLE (ultramutated)type has the best prognosis, CNH type has the worst
prognosis, and the other two types are in the middle. Effective individualized
diagnosis and treatment according to the clinicopathological and molecular
characteristics of patients is a hot issue that international scholars are concerned
about and is of great significance. At present, there are clinical trials related to
postoperative adjuvant therapy based on molecular characteristics, and a large
number of studies on targeted therapy and immunotherapy support the clinical
application of related drugs，so far, research on molecular characteristics and
endometrial carcinoma surgery is still in a state of scarcity.
In 2018, American scholars published a prospective and retrospective study on
laparoscopic surgery for the treatment of early cervical carcinoma. The results
suggest that the risk of recurrence and death in the minimally invasive surgery
group is much higher than in the open surgery group, and the reasons are likely to
include uterine lifting cup, the effects of laparoscopic CO2 pneumoperitoneum, or
surgeon experience. It led the investigators to wonder whether similar factors would
also have an impact on the safety of eminimally invasive surgery in endometrial
carcinoma. Furthermore, regarding the choice of the endometrial carcinoma surgical
route, although large-scale clinical trials have demonstrated that the prognosis of
patients after minimally invasive surgery and open surgery is similar, the current
study did not include patient molecular characteristics. According to the
clinicopathological and molecular characteristics of patients, the formulation of
personalized surgical strategies suitable for different groups of people is an
important clinical problem that needs to be solved urgently.
This project is based on theresults of previous retrospective studies of this
research group, so as to carry out prospective randomized controlled studies,
further evaluate the impact of surgical approaches on the prognosis of patients with
endometrial cancer with different molecular characteristics, establish a clinical
application model based on molecular characteristics to guide the selection of
surgical routes, and transform it into a clinical decision-making technical index
system for endometrial cancer surgical selection based on molecular characteristics
for further promotion and application.
2. The research status at home and abroad After TCGA endometrial carcinoma molecular
typing was proposed in 2013, many international research teams further simplified
it, which greatly promoted the clinical promotion and application of molecular
typing. The existing endometrial carcinoma typing system includes the PromisE
classification proposed by Canadian scholars, TranPORTEC typing proposed by Dutch
scholars. Based on this, the researchers carried out further work on molecular
characteristics to guide patients with postoperative adjuvant therapy. Recently,
Dutch scholars have further analyzed the effects of different molecular
characteristics on the efficacy of adjuvant chemoradiotherapy in high-risk
endometrial carcinoma patients based on PORTEC3 research data ，and are designing a
prospective randomized controlled trial (i.e., PORTEC-4a study) based on TransPORTEC
classification guidance for postoperative adjuvant radiotherapy in patients with
high-risk endometrial carcinoma. Recently, Korean scholars published an analysis on
the efficacy of PromisE typing and fertility preserving treatment of endometrial
cancer. The above studies show that patients with different molecular
characteristics respond differently to different therapeutic measures, so further
establishing individualized diagnosis and treatment strategies for patients with
different subtypes is an important direction for future research.
Surgery is the most important part of the endometrial carcinoma complex. Moreover,
the application of minimally invasive techniques significantly reduced the incidence
of perioperative complications, reduced intraoperative blood loss, and shortened the
average length of hospital stay，but the long-term safety of this technique is still
an important issue worthy of further investigation. Although clinical trials have
confirmed that the long-term prognosis of minimally invasive surgery for early
endometrial carcinoma is similar to that of open surgery，none of the above studies
included the molecular characteristics of patients. In recent years, more and more
research evidence has shown the importance of molecular characteristics in the
prognosis and stratified management of endometrial carcinoma patients, so it is
necessary to further evaluate and analyze the prognosis of endometrial carcinoma
patients with different molecular characteristics after minimally invasive surgery.
Since 2018, American scholars proposed that laparoscopic radical hysterectomy is
associated with poor prognosis in patients with early cervical cancer compared with
open surgery, research teams in various countries have carried out further research
and analysis on the relationship between surgical methods and the long-term
prognosis of cervical cancer patients, and most of the conclusions are consistent
with the results of American scholars. A recent meta-analysis pooled the results of
15 clinical studies and further confirmed the adverse effects of minimally invasive
surgery on the prognosis of cervical cancer patients. The above research has led us
to further think about this question, that is, the endometrial carcinoma
laparoscopic surgery also has the influence of pneumoperitoneum, uterine cup and
other factors, so is it also associated with a poorer prognosis?This issue needs to
be further examined and analyzed. Recently, on the basis of large-scale
retrospective analysis, scholars have put forward the view that the use of uterine
cups in laparoscopic surgery is related to the adverse prognosis of patients with
endometrial carcinoma, and the possible mechanism of uterine cups promoting
intraperitoneal spread has been further elaborated. Furthermore, a recent study by
Canadian scholars suggested that the disease-free survival of patients with
endometrial carcinoma after robotic-assisted laparoscopic surgery was significantly
shortened, and suggested that this situation is most likely related to the delay in
postoperative adjuvant radiotherapy caused by delayed healing of the vaginal cuff
after minimally invasive surgery. According to the above situation, more and more
evidences suggests that the investigators still need to conduct a more in-depth and
detailed analysis of the safety of laparoscopic surgery in the treatment of
endometrial carcinoma, and further analyze the prognostic impact of different
surgical methods based on molecular characteristics, which is of great significance
to the establishment of a precise individualized diagnosis and treatment system of
endometrial carcinoma in the future.
3. The preliminary research results directly related to this project support the
research team Based on the retrospective TCGA data, the research team analyzed the
effect of surgical pathway on the prognosis of endometrial carcinoma patients with
different molecular characteristics. According to preliminary studies, patients with
MSI endometrial carcinoma who underwent minimally invasive and had similar prognosis
after laparotomy, while patients with microsatellite stability endometrial carcinoma
who underwent minimally invasive surgery had significantly shorter recurrence-free
survival than those in the open surgery group. Therefore, the investigators believe
that MSI endometrial carcinoma has a higher mutational load and can promote
neoantigen expression, resulting in a stronger anti-tumor immune response in vivo,
which may balance the negative effects of laparoscopic surgery in promoting tumor
dissemination, but this feature is not present in microsatellite stability tumors.
Subsequently, the investigators further analyzed the relationship between other molecular
features and the prognosis of patients with endometrial carcinoma undergoing different
surgical procedures. According to the investigators' study, endometrial carcinoma
patients with POLE gene mutations, homologous recombinant repair pathway mutations, and
MUC16 gene mutations had a similar prognosis after minimally invasive surgery than the
open surgery group, while patients with TP53 gene mutations had significantly shorter
recurrence-free survival after minimally invasive surgery than those in the open surgery
group. Through the above results, the investigators preliminarily established an
Endometrial Carcinoma selection model based on molecular features. The above research
results have laid a solid foundation for the investigators' further prospective clinical
research and serve as strong support for this study.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Women aged 40-80 years.
- Preoperative hysteroscopic biopsy pathology is endometrial carcinoma, preoperative
imaging evaluation of tumor limited to uterine or extrauterine metastasis limited to
pelvic or para-aortic lymph nodes.
- No liver and kidney function abnormalities and bone marrow suppression before
surgery.
- ECOG score 0 points.
- Subjects voluntarily joined the study, signed an informed consent form, had good
compliance, and cooperated with follow-up.
- Molecular testing has confirmed that the participant does not have high mutational
burden characteristics (including POLE mutations, MSI-H, homologous recombinant
repair pathway mutations).
Exclusion Criteria:
- Preoperative adjuvant therapy.
- Have contraindications to chemoradiotherapy and cannot receive postoperative
adjuvant chemoradiotherapy.
- Previous history of other malignant tumors or other malignant tumors at the same
time.
- Laparoscopic surgery transferred to open surgery for special reasons.
- unable or unwilling to comply with the requirements of the study.
Gender:
Female
Gender based:
Yes
Minimum age:
40 Years
Maximum age:
80 Years
Healthy volunteers:
No
Start date:
June 1, 2023
Completion date:
December 31, 2025
Lead sponsor:
Agency:
Peking University People's Hospital
Agency class:
Other
Source:
Peking University People's Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05894915
