METHODS
Three hundred and ninety patients who were treated with the indication of endometrial cancer in our
clinic were evaluated with the approval of the ethics committee. The data of 114 patients who were
evaluated retrospectively between 2014-2018.
RESULTS
In patients with a median age of 58 (35-89) years, histological distribution of pathologies revealed the
presence of cases of the 107 endometrioid adenocarcinoma (93%), two serous (1.7%), two clear cells
(1.7%), one mucinous (0.8%) carcinomas and two (1.7%) carcinosarcoma. High risk was detected in 14
(12.28%), high to intermediate risk in nine (7%), intermediate risk in 35 (30.7%), and low-risk in 56 p
(49%) patients. Recurrence developed in five (4%) patients whose survival was found to be statistically
significantly lower than those without recurrence (logrank: 41.74 p=0.0001). Five -year survival rate was
95% and the mean (±SD) survival time was 78.46±1.27 months.
CONCLUSION
In the treatment of Stage 1 endometrial cancer, the survival rates achieved in our disease-recurrence
group was statistically significantly lower than those who did not develop recurrences (logrank: 41.74
p=0.0001).
Keywords: Brachytherapy; endometrial cancer; radiotherapy; risk factors
European Society for Radiotherapy and Oncology
(ESTRO) evaluates risk factors in low, intermediate, low-intermediate and high risk groups due to their effects
on disease-free survival and survival (Table
Ongoing molecular studies give an idea about the
prognosis, although they have not yet taken their place
in the treatment of endometrial cancer. Hypermethylation
of PTEN, KRAS, CTNNB1 and PIK3CA and MLH1
promoters have been associated with type 1 cancers. The
presence of P53 mutation in severe carcinomas often
suggests a poor prognosis, and the L1 adhesion protein
L1CAM is a determinant for distant metastasis. In patients
with a POLE mutation, a very good prognosis is
reported and adjuvant therapy is not recommended.[
In 75% of the cases, the tumor is inside the uterus
at the time of diagnosis, and it spreads directly to the
cervix or pelvic and then to the paraaortic lymph
nodes. While pelvic lymph node metastasis is seen at
a rate of 10% in the early stage, this rate increases by
up to 20% as myometrial invasion increases and tumor
differentiates.[
When radiotherapy is not applied to the patient
in the high risk group in the postoperative period, it
can be seen that locoregional recurrence occurred in
the vaginal stump in 75% of the cases. PORTEC1 and
GOG99 studies, which showed the effect of radiotherapy
in local control, pioneered further studies.[
This study aims to evaluate the treatment outcomes
according to the risk groups of patients with Stage 1 endometrial
cancer and to examine the effects of the risks
associated with the disease in the control of the disease.
In this study, statistical analyzes were performed with the NCSS (Number Cruncher Statistical System) 2007 Statistical Software (Utah, USA) package program. Overall (OS) and disease-free (DFS) survival rates of the study group were calculated and the descriptive statistical methods (mean, standard deviation, frequency and percentage distributions) were used in the evaluation of the data. The results were evaluated at the significance level of p<0.05.
As shown in Table
Ir-192 after loading brachytherapy system was used in patients undergoing brachytherapy. One of two radiotherapy sessions per week, and 550-700 cGy were applied on the vaginal surface for 3-5 times.
In patients undergoing pelvic radiotherapy, organs at risk were better protected with the use of intensive modulated radiotherapy (IMRT) technique and 46-50 Gy was applied. In the high-risk group, after external radiotherapy, 600 cGy was applied once a week, as were three applications on the vaginal surface.
Patients in the low-risk group were solely followed
up, if there were no additional risk factors, and patients
in the high-risk group were treated with external and
intracavitary brachytherapy (Table
According to grade, there was no statistically significant
difference between the survival times of the
groups (LogRank: 0.26 p=0.877) (Table
In the group with myometrial invasion less than
50%, 2-, 3-, and 5 year-survival rates were 0.978, 0.978,
and 0.978, respectively, while overall mean survival
time was 75.95±1.11months. In the group with myometrial
invasion more than 50%, 2-, 3-, and 5 yearsurvival
rates were 0.971, 0.900, and 0.900, respectively,
while overall mean survival time was 62.67±2.38
months, without any statistically significant difference
between the survival times of the groups (LogRank:
2.19 p=0.138). Overall disease free survival and survival
of all patients at 2-,3-,5 years is shown in Table
The number of LVSI data is not sufficient to make the same assessment. Because three of five patients who developed recurrence did not have invasion and in two patients presence of invasion (if any) was not reported.
None of the patients died in the <60 age group. In
the ?60 age group 2-, 3-, and 5- year survival rates
were 0.949, 0.919, and 0.877, with an overall mean
survival time was 59.68±2.35 months. Therefore, patients
over 60 are considered to be in the high risk
group (Fig.
Survival rates in patients with recurrence (+) were
statistically significantly higher than those without recurrence
(LogRank: 41.74 p=0.0001) (Fig.
In cancer surgery, lymphadenectomy is an integral
part of staging. However, its role in early endometrial cancer
is uncertain. Discussions about indications, anatomical
scope, and therapeutic value of lymphadenectomy
are still ongoing. In Panici and ASTEC studies, it has
been reported that pelvic lymphadenectomy does not
provide disease-free survival and survival advantage
in early stage endometrial cancer, whereas in the metanalysis
of nine studies by Kim et al. it was reported that
extended lymph dissection did not provide benefit, especially
in low-risk patients, and offered survival advantage
in intermediate and high-risk patients.[
Decision should be made at the time of diagnosis
according to histological type, the evaluation of myometrium
thickness by ultrasonography, tumor grade,
magnetic resonance imaging findings, and findings detected
during surgery. Colombo et al. indicated that the
number of lymph nodes to be removed in patients undergoing
lymphadenectomy affects prognosis as much
as risk factors.[
Pelvic and para-aortic lymph node dissections were
performed in 53.5% of our patients. It was found that
this application was not specific to a certain risk group
due to variability in approaches between clinics. Two
of the four patients with pelvic recurrence underwent
complete lymphatic dissection, and two underwent
TAH-BSO only.
In the GOG 99 study, the presence of lymphovascular
invasion, age 60 and older, myometrial invasion and
higher tumor grade were reported to be the factors that
worsen the prognosis, and in PORTEC 1 and 2 trials, it was concluded that the presence of grade 3 disease, and
lymphovascular invasion in the tumor was the most
important risk factor for recurrence.
Of the five patients with recurrent disease, three patients
had no lymphovascular invasion and the presence
of lymphovascular invasion (if any) was not reported
in two patients. Any statistically significant difference
was not observed between the survival times in groups
categorized according to tumor grades (Log Rank: 0.26
p=0.877). Any statistically significant difference was not
observed between groups with <50% and ?50% myometrial
invasion as for 5-year survival times (LogRank:
2.19 p=0.198). However, all patients with disease recurrence
were over 60 years of age and showed compliance
with the literature concerning risks.
The success of external radiotherapy in local control
after TAH-BSO in Stage 1 endometrial cancer was evaluated
in the twenty-centered PORTEC1 study. Success
in local control evaluated based on the results of 15 years
of follow-up was also associated with increasing side effects
over the years. However, this approach did not contribute
to survival.[
In the study in which the observation was randomized
with brachytherapy in the low-risk group,
brachytherapy contributed to local control, although
it did not show a statistically significant difference.
Brachytherapy could not contribute to survival in this
group.[
External pelvic radiotherapy was found to improve
survival in patients with deep myometrial invasion in
21,249 endometrial cancer patients evaluated in the
SEER database.
Besides, the addition of intracavitary radiotherapy
to external radiotherapy in the intermediate -risk
patient group has been reported to contribute to survival.[
In the PORTEC -2 randomized study, intermediate-
high-risk patients with Grade 1-2 tumors without
deep lymphovascular invasion but with deep myometrial
invasion were randomized to pelvic radiotherapy
or vaginal brachytherapy. Despite similar local diseasecontrol
rates, 5-year overall, and disease-free survival
rates were better in the brachytherapy arm.[
Clinical outcomes were evaluated retrospectively in
a single-center study. Although the number of patients
was sufficient, the data obtained were not conclusive
since the approach was not homogeneous in the risk
groups. In addition, since molecular studies were not
performed on our patients, our patient group could not
be evaluated in the light of this information. The evaluation
of patients with molecular studies in the subsequent
pathology reports is expected to guide different studies.
Acknowledgement: We would like to thank to Rana Konyalıoğlu for statistical evaluations.
Peer-review: Externally peer-reviewed.
Conflict of Interest: The authors declare that no conflict of interest.
Ethics Committee Approval: Ethics committee approval was received for this study as a retrospective study.
Financial Support: The authors received no financial supports.
Authorship contributions: Concept - B.D.Y.; Design - B.D.Y.; Materials - B.D.Y.,Ö.K.G.; Data collection and/or processing - Ö.K.G.; Data analysis and/or interpretation - B.D.Y.,Ö.K.G.; Literature search - B.D.Y.; Writing - B.D.Y.; Critical review - Ö.K.G.
