Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT05894915 |
| Other study ID # |
2022PHB105-002 |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
June 1, 2023 |
| Est. completion date |
December 31, 2025 |
Study information
| Verified date |
May 2023 |
| Source |
Peking University People's Hospital |
| Contact |
Wang zhiqi |
| Phone |
8615611808362 |
| Email |
wangzqnet[@]sina.com |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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.
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.
