Efficacy of SLNB in Early Endometrial Adenocarcinoma in China: A Retrospective Cohort Study Using Propensity Score Matching

doi:10.21203/rs.3.rs-4832100/v1

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Efficacy of SLNB in Early Endometrial Adenocarcinoma in China: A Retrospective Cohort Study Using Propensity Score Matching

https://doi.org/10.21203/rs.3.rs-4832100/v1

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Background

Endometrial cancer significantly impacts women’s reproductive health and quality of life, with lymph node metastasis serving as a crucial prognostic factor. Given the low metastasis rate, not all early-stage patients require lymph node dissection. The NCCN upgraded Sentinel Lymph Node Biopsy (SLNB) technology to Class 2A evidence. However, the applicability of SLNB for Chinese patients remains uncertain. This study evaluates the efficacy and safety of SLNB in a Chinese population.

Methods

We conducted a retrospective cohort study at Guangdong Provincial Hospital of Chinese Medicine, involving 164 patients with early endometrial adenocarcinoma who underwent laparoscopic total hysterectomy with bilateral salpingo-oophorectomy from August 2019 to December 2022. Patients were divided into two groups based on the surgical approach: SLNB (N = 33) or systematic lymph node dissection (SLND, N = 33). The primary outcomes assessed were postoperative disease progression-free survival and complication incidence at one month. Secondary outcomes included surgery duration, blood loss, length of hospital stay, and total costs.

Result

Throughout the follow-up period, there were no recurrences case reported in either group. The complication rates were 6% for SLNB and 21% for SLND. In comparison to SLND, SLNB significantly reduced surgery duration (156.4 minutes vs. 267.18 minutes; p < 0.001), blood loss (33.90 ml vs. 98.18 ml; p < 0.01), length of hospital stay (13.48 days vs. 16.76 days; p < 0.01), and total costs (RMB47,203.88 vs. RMB57,969.58; p < 0.01).

Conclusion

SLNB is a less invasive and cost-effective alternative to SLND, offering comparable safety and efficacy for the management of early-stage endometrial cancer in Chinese patients.

Endometrial Cancer

Laparoscopic Surgery

Sentinel Lymph Node Biopsy

Postoperative Complications

Chinese patients

Endometrial cancer(EC) is the sixth most common cancer in women¹, the incidence has ubiquitously increased worldwide², Surgery is the primary treatment for women with EC, Total hysterectomy with bilateral salpingo- oophorectomy (BSO) is standard of care and can be performed by an open or a minimally invasive approach³, Lymph node metastasis is an important indicator for evaluating the prognosis of patients with endometrial cancer and guiding postoperative treatment. However, not all early-stage endometrial cancer patients without high-risk factors require lymph node dissection, as the metastasis rate is only 4% ⁴. Furthermore, traditional lymph node dissection may prolong surgery time, increase surgical risks, and result in postoperative complications⁵ use of NCCN's sentinel lymph node (SLN) mapping algorithm for the surgical staging of endometrial cancer has gained significant acceptance and is now commonly applied in many practices.

However, whether SLNB should be recommended in Chinese patients is still lack of supporting evidence from real-world data. Guangdong Provincial Hospital of Traditional Chinese Medicine has been utilizing SLNB technology for treating early-stage endometrial cancer patients since 2019, and a comprehensive clinical dataset has been established. This study aims to evaluate the efficacy and safety of SLNB in early endometrial adenocarcinoma patients who underwent laparoscopic total hysterectomy with bilateral salpingo-oophorectomy by comparing with systematic lymph node dissection (SLND) .

Study Design

A Retrospective Cohort Study Using Propensity Score Matching. The reporting of this study was followed The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement (ref: https://www.equator-network.org/reporting-guidelines/strobe/), the checklist can be found in the supplementary file. This study was approved by the Institutional Review Board of Guangdong Provincial Hospital of Chinese Medicine (Ethics Committee of Guangdong Provincial Hospital of Chinese Medicine ZE2024-144-01).

Patients

The study included 165 patients diagnosed with endometrial adenocarcinoma who were admitted for surgical treatment at the Guangdong Provincial Hospital of Chinese Medicine from August 2019 to December 2022.

Inclusion and exclusion criteria:

The inclusion criteria: Patients must have a preoperative diagnosis of endometrioid adenocarcinoma, with imaging showing lesions within the inner half of the myometrium (stage IA) without pelvic lymph node metastasis. They should have undergone laparoscopic total hysterectomy with bilateral salpingo-oophorectomy, along with either sentinel lymph node dissection or systematic lymph node dissection (with or without para-aortic lymph node dissection). Follow-up of at least 12 months with complete data is required.

Exclusion Criteria: Patients with simultaneous pelvic and abdominal malignant tumors; a history of uterine, tubal, or ovarian resection for other conditions; a history of pelvic lymph node dissection for other reasons; a history of pelvic radiotherapy; incomplete medical records.

Surgical Procedures

SLNB group

Administer 25mg of indocyanine green (ICG) powder dissolved in 20mL of sterile water. Inject 1–2 mL of the diluted ICG at 3 and 9 o’clock positions on the cervix, then wait for 15–20 minutes before surgery begins. After abdominal lavage, collect the lavage fluid. Perform electrocautery to ligate the distal ends of both fallopian tubes, open the lateral peritoneum, and examine the pelvic and para-aortic lymph nodes under laparoscopic fluorescence mode. Identify green-stained lymphatic vessels and nodes; those showing first-stage staining are considered sentinel lymph nodes (SLNs). A successful SLN mapping is achieved if at least one clearly visible green-stained lymph node is detected in each pelvic side. Remove the stained lymph nodes for histopathological evaluation, followed by total hysterectomy with bilateral salpingo-oophorectomy.

Based on the NCCN guidelines, if sentinel lymph node mapping fails or shows any suspicious or enlarged lymph nodes, concurrent ipsilateral lymph node dissection is recommended, followed by total hysterectomy with bilateral salpingo-oophorectomy. The removed lymph nodes undergo histopathological examination using pathologic staging techniques. Initially, routine hematoxylin and eosin (H&E) staining is performed. If metastasis is detected, further analysis is unnecessary. If no metastasis is found, consecutive tissue sections are prepared at 50-micron intervals, with two slices taken from each level, approximately 5 microns thick. These sections are subjected to standard H&E staining and immunohistochemical staining for cytokeratin AE1:AE3. If the sentinel lymph node is positive, a hysterectomy with bilateral salpingo-oophorectomy, pelvic lymphadenectomy, and para-aortic lymph node dissection is performed.

SLND Group

Perform laparoscopic total hysterectomy with bilateral salpingo-oophorectomy and pelvic lymph node dissection. In cases of deep myometrial invasion of the uterus, para-aortic lymph node dissection would be conducted, reaching the level of the left renal vein.

Observation indicators.

Primary observation indicators

postoperative disease progression-free survival rate, incidence of complications within 1 month after surgery

Secondary observation indicators

duration of surgery, intraoperative blood loss; length of hospital stay, total hospital costs.

Collected data

Age, body-mass index (BMI), preoperative history of hypertension and diabetes, pelvic surgery history, method of preoperative pathology acquisition, radiological assessment of pelvic and abdominal conditions preoperatively, surgical approach, surgery duration, intraoperative blood loss, postoperative pathological staging, need for additional postoperative treatment, total hospital stay duration, postoperative hospital stay duration, total hospitalization cost, postoperative complications within the first month, postoperative follow-up data.

Follow-up methods.

Follow-up was conducted through outpatient re-examination and by phone. Patients were followed up every 3–6 months for the first year post-surgery and annually thereafter. The follow-up encompassed general condition, occurrence of both short-term and long-term complications after surgery, as well as the long-term treatment outcomes. Abdominal ultrasound or MRI/CT scans were performed as needed. Follow-up endpoints are defined as patient relapse, death, or loss to follow-up, with follow-up scheduled until December 2023.

Statistical Analysis

To mitigate selection bias, 1:1 propensity score-matching was performed using logistic regression models. The following 7 clinically relevant covariates that may affect surgical or oncologic outcomes were included: age, BMI, history of diabetes, hypertension, history of pelvic surgery, method of preoperative pathology acquisition, and preoperative tumor differentiation - were included. Covariate balance is evaluated by analyzing the standardized mean difference (SMD), with an absolute value of mean difference less than 0.2 indicating successful matching.Categorical variables were presented as frequencies and percentages, and continuous variables as mean ± standard deviation or median (interquartile range). Chi-square test, Fisher’s exact test, or Mann‒Whitney U test were used for categorical variables comparison, while Student’s t test was used for continuous variables. Logistic regression analysis identified independent risk factors for complications. Statistical analyses were conducted using SPSS v.26.0 for Windows and R. All reported P values are two-sided, with values below 0.05 considered statistically significant.

Clinicopathologic Characteristics

Figure 1 shows the flow chart of patient selection, with 40 patients laparoscopic total hysterectomy with bilateral salpingo-oophorectomy and Sentinel Lymph Node Biopsy, and 95 patients undergoing laparoscopic total hysterectomy with bilateral salpingo-oophorectomy and the systematic lymph node dissection ,All these patients met the aforementioned inclusion and exclusion criteria. After 1:1 propensity score-matching, 33 patients in the SLNB group and 33patients in the SLND group were included in the post-matching cohort.

Table 1 presents the general clinical data of the two groups of patients before and after matching. Prior to matching, the mean absolute differences in age, history of pelvic surgery, and pathological differentiation exceeded 0.2. After matching, the mean absolute differences of the matched covariates were less than 0.2, indicating successful matching as shown in Table 1.

Primary Outcome Indicators

Follow-up and recurrence situations.

There was no significant difference of the duration for the postoperative follow-up periods (P > 0.05) and no recurrence was reported in both groups.table2

Postoperative complications within one month after surgery

There were 2 complications in the SLNB group (6%). One case was postoperative infection, and the other was deep vein thrombosis in the lower limb. In the SLND group, a total of 7 patients had postoperative complications (21%), including 1 case of lymphocele with infection, 2 cases of lower limb deep vein thrombosis, and 4 cases of postoperative pelvic and abdominal cavity infections. SLNB groups showed a lower complication rates than SLND group, but there was no statistically difference (p=0.15) (Table 3).

Secondary Outcome Indicators

Duration of surgery (minutes, median， IQR): SLNB group 156.40 (122, 176), SLND group 267.18 (200, 310); Intraoperative blood loss (milliliters, median , IOR): SLNB group 33.90 (20, 50), SLND group 98.18 (50, 100); Total hospitalization days (days, median, IOR): SLNB group 13.48 (11, 15.5), SLND 16.76 (14, 19); Postoperative average hospitalization days (days, median, IOR):SLNB group 6.70 (5.5, 7), SLND group 8.67 (7, 10); In terms of total hospitalization expenses (RMB, median, IOR)： SLNB group 47203.88 (40004.23, 52373.29), SLND group 57969.58 (53001.19, 63693.57). The results show significant differences between the two groups in all variables (see Table 4).

Sentinel lymph node biopsy detection results

The SLNB detection rate was 94% (32/33) for preoperative lymph nodes, with one case showing no uptake on imaging; intraoperative frozen section pathology suggested changes following diagnostic curettage, revealing no cancer in residual endometrial tissue and no further systematic lymphadenectomy was performed.One patient had a positive SLNB (inguinal 1/1 and right internal iliac lymph node 1/5) but no cancer was found in the excised tissue, leading to a systematic lymphadenectomy. For one patient with a >4cm uterine lesion, a pelvic lymphadenectomy plus an aortic lymph node dissection was done. Bilateral detection was achieved in 65% (22/33) of cases, with a total of 190 sentinel lymph nodes identified among the 32 endometrial cancer patients. The distribution was as follows: external iliac region - 124 (65%), internal iliac region - 14 (7%), inguinal region - 40 (22%), aortic region - 5 (3%), and inguinal canal - 2 (1%). Five nodes were found in the presacral area (3%) (Table 5).

Surgical pathology

Table 6 shows there was no statistical difference in postoperative pathological staging. Each group had 1 case with pelvic lymph node metastasis indicated by surgical pathology, with the sentinel group being positive for para-aortic sentinel lymph node. There was a statistically significant difference in tumor size and postoperative pathological differentiation between the two groups, but it did not affect the postoperative adjuvant treatment decision for patients. There was no statistical difference in the need for postoperative adjuvant treatment between the two groups (Table 6).

This is a study using real-world clinical data to evaluate the effectiveness and safety of SLNB and SLND conducted in China. A propensity score matching method was used to further ensure the baseline level of patients. Research data show that the total detection rate of sentinel lymph nodes is 94%, which is basically consistent with the overall detection rate of research at 93.4%⁶, There is no statistical difference in postoperative pathological staging between the two groups. This indicates that SLNB is effective.

We found that no recurrence was reported in both group during over 30 months follow-up period. The SLNB group showed a lower rate of complications, demonstrated advantages in reducing surgical duration, intraoperative blood loss, length of hospital stay, and total hospital costs. These findings suggest that SLNB is a safe option.

In conclusion, our data support that SLNB is a safe and feasible alternative to SLND for early-stage endometrial adenocarcinoma patients in China, to a certain extent revealing that the use of this technology benefits the Chinese population with early-stage endometrial adenocarcinoma.

Regarding the occurrence of postoperative complications, other studies have reported that SLND increases the risk of postoperative complications by three times within 30 days after surgery⁷. However, the results of this study suggest that although the incidence of postoperative complications in the SLNB group is lower than that in the SLND group, the difference between the two groups is not statistically significant, which may be related to the strict selection of early endometrial adenocarcinoma cases in this study and the small number of cases.

Further analysis revealed that two groups of postoperative complications were concentrated in surgical site infections (9%, 6/66). Surgical site infection (SSI) is one of the common postoperative complications after hysterectomy for endometrial cancer (EC), involving infections related to the subcutaneous tissues, incision skin, fascia, and muscle layers within 30 days postoperatively. Studies from abroad have shown that significant risk factors associated with surgical site infections include laparotomy, diabetes, and surgical staging⁸. A domestic study⁹ indicated that the incidence of surgical site infections in endometrial cancer patients was 14.47%, and was associated with FIGO staging, surgical type, drainage time, and postoperative blood sugar. Based on literature review and clinical considerations, this study included diabetes, previous history of pelvic surgery, surgical type, duration of surgery, intraoperative blood loss, drainage status, FIGO staging, etc., in a binary logistic regression analysis, which did not suggest these as risk factors. However, from a real clinical perspective, enlarging the surgical incision, increased blood loss, and longer surgical duration may increase the risk of postoperative infections, which needs further confirmation through large sample studies. Large sample studies can also provide evidence for effective risk assessment of surgical site infections and rational prevention strategies for surgical site infections.

Domestic and foreign studies^10,11have shown that the incidence of lymphocele and lymphedema after systematic lymphadenectomy is high. Another study¹² observed that the incidence of lymphocele in cases of systematic lymphadenectomy for endometrial malignant tumors under laparoscopy was 14.4%, but the data from this study suggested that the incidence of lymphatic reflux obstruction was 1.5% (1/66). This discrepancy may be due to the fact that the complications observed in the study occurred within 30 days after surgery, and there were no specific evaluations of lymphatic reflux obstruction in patients within 30 days after surgery. Further prospective studies are needed to understand the timing and location of postoperative lymphatic reflux obstruction occurrence in order to provide a basis for effective prevention and management.

Limitations

The limitations of this study are its retrospective study design, which inherently tends to introduce bias, as well as the study being conducted in a single institution with a small sample size and possibly inadequate data collection. This lack of more comprehensive data on potential risk factors such as dietary habits, genetic risks, etc., potentially limits the generalizability of the results.

Most of the cases included in this article are early-stage endometrial cancer patients, who have a relatively good prognosis and a lower risk of short-term recurrence, requiring longer follow-up to further assess the long-term benefits and advantages of sentinel lymph node biopsy.

SLNB has shown benefits in the treatment of early-stage endometrial adenocarcinoma. There were no cases of recurrence in both groups during the follow-up period, and there was no statistically significant difference in postoperative complications. Compared to systematic lymphadenectomy, sentinel lymph node dissection can significantly reduce surgery time, decrease intraoperative blood loss, shorten patient hospital stay, and lower total hospital costs. Local studies in China have demonstrated that the application of SLNB in early-stage endometrial adenocarcinoma patients is safe and effective.

Authors Contribution

Jing Xiao developed the concept of this study. Yanmei Sun and Lingjuan Hu led the study. Lingjuan Hu, Xudong Hu, Xiujun Zhu and Huanmei Lin verified the underlying data. Lingjuan Hu, Jingyuan Luo and Xiaofeng Chen wrote the original draft. All authors contributed to the review and editing. All authors had access to all data in the study and the corresponding author had final responsibility for the decision to submit for publication.

Conflict of interests

All authors declare no conflicts of interest.

Fundings

This study was supported by the Zhaoyang Talent Special Project from Guangdong Provincial Hospital of Chinese Medicine (ZY2022YL15).

Research Project of the Guangdong Provincial Administration of Traditional Chinese Medicine (Project Number: 20211170): Acupuncture and Cupping Therapy for the Treatment of Secondary Lower Limb Lymphedema Associated with Gynecologic Malignancies: A Randomized Controlled Clinical Study.

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Table 1:Baseline characteristics of patients before and after matching
Characteristicse	All patients		SMD	Propensity-matched patients		SMD
Characteristicse	SLNB(N=40）	SLND(N=95）	SMD	SLNB(N=33)	SLND(N=33)	SMD
Age，x̅ ± s	50.93 ± 10.67	53.68± 7.05	0.31	53.58 ± 9.40	52.21± 6.85	0.17
BMI， x̅ ± s	25.77 ± 3.58	25.06 ± 3.82	0.2	25.89± 3.26	25.58± 4.20	0.06
Pelvic surgery history，n (%)			0.25			0.13
No	29 (72.5)	58 (61)		22(67)	20(61)
Yes	11 (27.5)	37(39)		11(33)	13(39)
History of hypertension , n (%)			0.05			0.13
No	30(75)	69 (73)		24(73)	22(67)
Yes	10(25)	26（27）		9(27)	11(33)
History of diabetes, n (%)			0.19			0.15
No	39 (97.5)	89 (94)		32(97)	31(94)
Yes	1 (2.5)	6（6）		1(3)	2(6)
Preoperative pathological acquisition method (using hysteroscopy, n %)			0.03			0.10
No	3 (7.5)	8（9）		3(9)	4(6)
Yes	37 (92.5)	87 (91)		30(91)	29(94)
Preoperative pathological differentiation, n (%)			0.23			0.10
Upper	31(77.5)	64(67)		24(76)	23(71)
Middle	9(22.5)	31(33)		9(24)	10(29)

Table 2 Comparison of postoperative recurrence between two groups
Observation Indicators	Group		p-value
Observation Indicators	SLNB(N=33)	SLND(N=33)	p-value
Postoperative follow-up duration (months), x̅ ± s	31.51± 10.44	36.30± 10.60	0.07
Postoperative recurrence, n（%）			1.00
No	33(100)	33（100）
Yes	0(0)	0(0)

Table 3 Comparison of postoperative complications in two groups.
Observation Indicators	Group		p-value
Observation Indicators	SLNB(N=33)	SLND(N=33)	p-value
Postoperative complications, n（%）			0.15
Yes	2（6）	7（21）
No	31（94）	26（79）
Postoperative infection, n（%）			0.20
Yes	1（3）	5（24）
No	32（97）	28（76）
Postoperative lymphatic reflux obstruction, n（%）			1.00
No	33 (100)	32(97）
Yes	0(0)	0(0)

Table 4: Comparison of surgical duration, intraoperative blood loss, length of hospital stay, and hospital costs in two groups.
Observation Indicators	Group		p-value
Observation Indicators	SLNB(N=33)	SLND(N=33)，	p-value
Surgical Duration (min),Median（Q1，Q3）	156.40（122,176）	267.18（200,310）	0.00
Intraoperative Blood Loss (ml), Median（Q1，Q3）	33.90（20,50）	98.18（50,100）	0.00
Total Hospitalization Duration (days), Median（Q1，Q3）	13.48（11,15.5）	16.76（14,19）	0.00
Postoperative Hospitalization Duration (days), Median（Q1，Q3）	6.70（5.5,7）	8.67（7,10）	0.00
Total Hospitalization Cost (RMB), Median（Q1，Q3）	47203.88（40004.23,52373.29）	57969.58（53001.19,63693.57）	0.00

Table 5 Sentinel lymph node detection status.
	N	%
Successful lymph node visualization and detection cases	32	94
Failed visualization cases	1	3
Successful visualization but undetected lymph node cases	1	3
Bilateral detection rate	22	65
Sentinel lymph node localization
Total	190
External iliac area	124	65
Obturator fossa area	40	21
Internal iliac area	14	7
Para-aortic area	5	3
Inguinal area	2	1
Presacral area	5	3

Table 6 Comparison of surgical pathology findings in the two matched groups.
Observation Indicators	Group		p-value
Observation Indicators	SLNB(N=33)	SLND(N=33)	p-value
FIGO stage, n（%）			0.08
IA	32(97)	26(94)）
IB	0(0)	5(15)
II	0(0)	1(3)
III	1(3)	1(3)
Tumor size, n（%）			0.04
＜2cm	21(74）	11(33)
≥2cm，≤4cm	7(11)	15(46)
08＞4cm	5(15)	7(21)
Grade, n（%）			0.00
G1	20(65)	7(21)
G2	12(32)	25(76)
G3	1(3)	1(3)
Adjunctive therapy, n（%）			0.19
Yes	3(9)	8(24)
No	30(91)	25(76)

FIGO: International Federation of Gynecology and Obstetrics

No competing interests reported.

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You are reading this latest preprint version

Efficacy of SLNB in Early Endometrial Adenocarcinoma in China: A Retrospective Cohort Study Using Propensity Score Matching

Status:

Version 1

Abstract

Background

Methods

Result

Conclusion

Figures

INTRODUCTION

METHODS

Study Design

Patients

Inclusion and exclusion criteria:

Surgical Procedures

Statistical Analysis

Results

Clinicopathologic Characteristics

Primary Outcome Indicators

Secondary Outcome Indicators

Sentinel lymph node biopsy detection results

Surgical pathology

Discussion

Limitations

Conclusion

Declarations

References

Tables

Additional Declarations

Status:

Version 1