The impact of different surgical methods on the survival rate of patients with uterine sarcoma

doi:10.21203/rs.3.rs-4715202/v1

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The impact of different surgical methods on the survival rate of patients with uterine sarcoma

https://doi.org/10.21203/rs.3.rs-4715202/v1

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Objective: This article plans to retrospectively analyze patients with uterine sarcoma in our hospital to determine whether expanding the surgical resection range can improve patient prognosis, increase survival rate, and prolong survival.

Methods: A retrospective analysis was conducted on 153 patients with uterine sarcoma who underwent surgical treatment in our hospital, and factors affecting their prognosis were determined through survival analysis.

Results: The Kaplan Meier survival analysis revealed that pathological grading, staging, and surgical approach were the main factors significantly affecting the 5-year survival rate of patients (p<0.05), and postoperative radiotherapy can improve the overall 5-year survival rate. Multivariate COX regression survival analysis: postoperative adjuvant radiotherapy: HR=1.277, p=0.485，95%CI= 0.643- 2.536 . Staging: HR=0.647, p=0.176，95%CI= 0.344-1.216.Surgical methods: HR=2.249, p=0.007，95%CI=1.252- 4.038.Pathological grading: HR=0.503, p=0.026 95%CI= 0.275-0.923.

Conclusion: The use of extensive hysterectomy with double adnexectomy compared to simple hysterectomy with double adnexectomy can significantly improve the overall 5-year survival rate of patients, and is an independent prognostic factor for this type of patient. Postoperative radiotherapy may prolong patient survival and improve 5-year survival rate.

Uterine sarcoma

radiotherapy

chemotherapy

prognostic factor

survival rate

Uterine sarcoma is a malignant tumor originating from the mesenchymal tissues of the uterus, such as the endometrial stroma, uterine muscle layer, and connective tissue. It exhibits invasiveness and poor prognosis, accounting for approximately 1-3% of malignant tumors of the female reproductive tract and 3-7% of all malignant uterine tumors ^[1]. Due to its low incidence rate, there is currently a lack of prospective studies validating treatment methods, with existing literature primarily focused on retrospective analyses. For uterine sarcoma, surgery is the most important treatment method. Currently, the scope of surgical resection is mostly simple uterine and double adnexectomy, and there is no consensus on using extensive uterine and double adnexectomy. This article plans to retrospectively analyze patients with uterine sarcoma in our hospital to determine whether expanding the scope of surgical resection can improve patient prognosis, increase survival rate, and prolong survival.

1.1 Case Profile:

A total of 153 patients who underwent surgical treatment at our institution from June 2009 to March 2019 were selected for this study. The patients' ages ranged from 15 to 74 years, with a median age of 51.41 ± 9.99 years.

Pathological Types: Among the cases, there were 82 cases of leiomyosarcoma, 25 cases of carcinosarcoma, 14 cases of stromal sarcoma, 4 cases of rhabdomyosarcoma, 12 cases of undifferentiated sarcoma, 9 cases of adenocarcinoma, and 7 cases with unspecified pathological types.

Staging: There were 96 cases in stage I, 18 cases in stage II, 16 cases in stage III, and 23 cases in stage IV. The staging of carcinosarcoma followed the 2018 FIGO staging criteria for endometrial cancer, while the staging of other sarcomas followed the 2009 AJCC staging criteria.

Surgical Procedures: The surgical procedures included subtotal hysterectomy with bilateral adnexectomy in 6 cases, total hysterectomy in 21 cases, total hysterectomy with bilateral adnexectomy in 67 cases, total hysterectomy with bilateral adnexectomy and omentectomy in 12 cases, total hysterectomy with bilateral adnexectomy and pelvic lymph node dissection in 18 cases, total hysterectomy with bilateral adnexectomy and omentectomy with pelvic lymph node clearance in 19 cases, and total hysterectomy with bilateral adnexectomy and omentectomy with combined resection of other organs in 10 cases.

Radiation Therapy: Thirty patients underwent postoperative radiation therapy (doses ranging from 40 to 50 Gy over 20-25 sessions), including pelvic external beam radiation therapy in 18 cases and intensity-modulated radiation therapy in 12 cases (targeting lymphatic drainage areas and vaginal remnants). One hundred and twenty-three patients did not undergo radiation therapy.

Chemotherapy: Ninety patients received postoperative chemotherapy, among whom 63 did not undergo systemic chemotherapy. The main chemotherapy drugs included ifosfamide, doxorubicin, dacarbazine, docetaxel, cisplatin, and carboplatin.

1.2 Follow-up:

All patients were followed up via telephone based on the contact information provided. The follow-up period extended until March 2024. Nine patients were lost to follow-up, resulting in an overall loss rate of 5.88%.

1.3 Statistical Methods:

The collected data were statistically analyzed using SPSS version 25.0. Patients were grouped based on staging, receipt of radiation therapy, chemotherapy, pathological grading, and surgical approach. Correlation analysis was conducted between the data and the overall survival rate at 60 months. Survival analysis was performed using the Kaplan-Meier method. The Log-Rank test was utilized to compare the 5-year overall survival rates, with a significance level set at p < 0.05. After univariate analysis, multivariate Cox proportional hazards regression analysis was conducted to identify independent factors influencing patient prognosis, with a significance level set at p < 0.05.

2.1 Univariate Survival Analysis by Staging:

Patients classified as stage III-IV (Group 1, n=39) were compared with those in stages I-II (Group 2, n=114). The results revealed a significant decrease in the 5-year survival rate among stage III-IV patients, with a statistically significant difference (p < 0.05).

Table 1 Analysis of survival at 1, 3, and 5 years in different stages

OS（ years）	n	stage	95%CI	survival rate	Chi square	P
5	39	Ⅲ-Ⅳ	34.58-47.74	46.2%	5.426	0.020
5	114	Ⅰ-Ⅱ	44.81-52.07	66.7%	5.426	0.020
3	39	Ⅲ-Ⅳ	24.98-31.94	64.1%	2.798	0.094
3	114	Ⅰ-Ⅱ	29.17-32.86	78.1%	2.798	0.094
1	39	Ⅲ-Ⅳ	10.79-11.97	89.7%	0.167	0.683
1	114	Ⅰ-Ⅱ	11.21-11.76	86.8%	0.167	0.683

2.2Univariate Survival Analysis by Pathological Grade:

Patients were categorized into two groups based on pathological grade: high-grade tumors (Group 1, n=69) and low-grade tumors (Group 2, n=84). There was no statistically significant difference in the 1-year survival rate between the two groups (p > 0.05). However, significant differences were observed in the 3rd and 5th-year survival rates (p < 0.05).

Table2 Pathological grade univariate survival analysis

OS （ years）	n	Pathological degree	95%CI	survival rate	Chi square	P
5	69	2-3	34.58-47.74	46.4%	10.860	0.001
5	84	1	44.81-52.07	73.8%	10.860	0.001
3	69	2-3	25.85-31.08	65.2%	7.377	0.020
3	84	1	29.90-33.96	82.1%	7.377	0.020
1	69	2-3	10.98-11.81	88.4%	0.046	0.829
1	84	1	11.20-11.82	86.9%	0.046	0.829

2.3 Univariate Survival Analysis by Surgical Approach:

2.31 Univariate Surgical Survival Analysis of 114 Patients in Stages I-II:

All patients underwent hysterectomy, and 114 patients in stages I-II were grouped according to different surgical methods. The first group consisted of simple hysterectomy with or without double appendectomy, while the second group consisted of extensive hysterectomy. Through analysis, we found that extensive hysterectomy significantly improved the overall survival rate of patients at this stage at 3 and 5 years (p<0.05).Figure 1 shows the 5-year survival curves of two groups of patients, indicating a significant difference between the two.

Table3 Single factor survival analysis results of different surgical methods in stage I-II patients

OS （ years）	n	group	95%CI	survival rate	Chi square	P
1	73	1	10.94-11.72	83.6%	1.903	0.168
1	41	2	11.46-12.06	92.7%	1.903	0.168
3	73	1	27.09-32.12	71.2%	5.219	0.022
3	41	2	31.21-35.86	90.2%	5.219	0.022
5	73	1	40.23-49.84	57.5%	7.160	0.007
5	41	2	49.65-59.45	82.9%	7.160	0.007

2.32 Univariate Surgical Survival Analysis of 39 Patients in Stages III-IV:

The first group (16 cases) consisted of simple hysterectomy with or without double adnexectomy, while the second group (23 cases) underwent extensive hysterectomy. The results showed that the survival rate of Group 1 was higher than that of Group 2, but the difference was not statistically significant (p>0.05).

Table 4 Single factor survival analysis results of different surgical methods in stage Ⅲ-Ⅳpatients

OS （ years）	n	group	95%CI	survival rate	Chi square	P
1	16	1	10.22-12.28	87.5%	0.144	0.704
1	23	2	10.78-12.18	91.3%	0.144	0.704
3	16	1	20.77-32.23	56.3%	0.791	0.374
3	23	2	25.58-34.07	66.9%	0.791	0.374
5	16	1	25.57-45.72	31.3%	2.784	0.095
5	23	2	36.67-53.32	56.5%	2.784	0.095

2.4 Univariate Analysis of Postoperative Adjuvant Therapy:

All patients who did not receive adjuvant radiotherapy after surgery were in Group 1 (123 cases), while those who received radiotherapy were in Group 2 (30 cases). Radiation therapy can improve overall survival rate, but there was no statistically significant difference between the two groups (total survival rates at 1, 3, and 5 years) (p>0.05).

Table 5 Results of Univariate Analysis of Radiotherapy or Chemotherapy

OS （ years）	n	group	95%CI	survival rate	Chi square	P
1	123	1	11.02-11.65	85.4%	2.803	0.094
1	30	2	11.90-12.03	96.7%	2.803	0.094
3	123	1	27.75-31.02	72.4%	1.712	0.191
3	30	2	30.63-35.70	83.3%	1.712	0.191
5	123	1	41.87-49.36	60.2%	0.841	0.359
5	30	2	45.06-56.27	66.7%	0.841	0.359

2.5 Multivariate Analysis Results:

Multivariate analysis of 5-year overall survival rate was conducted based on factors such as extensive hysterectomy, staging and grouping, pathological grading, and whether postoperative adjuvant radiation therapy was performed. HR=1.277, p=0.485，95%CI= 0.643- 2.536.Staging: HR=0.647, p=0.176，95%CI= 0.344-1.216。 Surgical method: HR=2.249, p=0.007，95%CI= 1.252- 4.038.Pathological grading: HR=0.503, p=0.026 95%CI= 0.275-0.923.

The treatment of uterine sarcoma still lacks precise consensus due to its low incidence rate and the absence of prospective studies ^[2-3]. This study aimed to summarize and analyze the medical records of our institution to identify prognostic factors affecting this disease and provide recommendations for treatment strategies, thereby offering a basis for standardized treatment approaches.

Our study found that staging and pathological grade were the most important prognostic factors for uterine sarcoma, a conclusion consistent with similar findings in other literature ^[4-5]. Pathological grade reflects the malignancy of the tumor, indicating its invasiveness and to some extent its metastatic potential, directly affecting patient prognosis. Staging, on the other hand, assesses the tumor's developmental status at the time of surgical intervention, guiding treatment principles. Given these results, accurate description of pathological grade and staging post-surgery is crucial for assessing patient prognosis. In multivariate analysis, we found that pathological grade of the tumor independently influenced patient prognosis more than staging. Therefore, the malignant potential of uterine sarcoma warrants attention, particularly for intermediate and high-grade tumors, where systemic treatments such as chemotherapy, immunotherapy, and targeted therapy may be beneficial.

Surgery stands as the cornerstone of treatment for uterine sarcoma, with the primary approach being total hysterectomy with bilateral salpingo-oophorectomy. However, the necessity of extensive hysterectomy remains debated ^[6]. Our study included cases that underwent surgical treatment, revealing a significant extension in the 5-year overall survival (OS) for patients undergoing extensive hysterectomy with or without omentectomy and pelvic lymph node dissection compared to those undergoing only hysterectomy with bilateral salpingo-oophorectomy, with statistically significant differences. Moreover, multivariate analysis confirmed this surgical approach as an independent factor influencing 5-year OS, alongside staging, pathological grade, and radiotherapy. An essential question arises: what contributes to the improved overall survival rate – is it the extensive hysterectomy, omentectomy, lymph node dissection, or a combination of different surgical approaches? There is skepticism regarding lymph node dissection as an independent prognostic factor because all cases in our study that underwent lymph node dissection also underwent extensive hysterectomy. Other researchers have found that lymph node positivity is not an independent prognostic factor in similar retrospective analyses ^[7]. In retrospective analyses of adenocarcinoma, some researchers have even found that lymph node dissection does not benefit survival rates ^[8]. It is suggested that the improvement in survival rates may be attributed to extensive hysterectomy and/or omentectomy. Ensuring an adequate resection range is crucial to prevent tumor residue, as achieving complete tumor resection has been reported as an independent factor influencing patient overall survival ^[9]. The omentum is often the most commonly affected local site in uterine sarcoma, and merely removing the uterus and bilateral adnexa may result in tumor recurrence in the residual omentum ^[10]. In conclusion, based on the comprehensive analysis, extensive hysterectomy with bilateral salpingo-oophorectomy and omentectomy appears to contribute to the enhancement of patients' 5-year overall survival rates.

The role of adjuvant radiotherapy and chemotherapy in postoperative treatment for uterine sarcoma remains contentious and lacks consensus. In our study, we observed a marginal increase in the 5-year overall survival rate for patients receiving adjuvant radiotherapy postoperatively, but the difference was not statistically significant. No survival rate elevation was found for patients receiving chemotherapy. Some researchers have reported through retrospective analyses that chemotherapy does not improve overall survival rates or prolong survival in leiomyosarcoma patients ^[11]. However, there are differing viewpoints regarding postoperative adjuvant radiotherapy. Some scholars have suggested that adjuvant radiotherapy after uterine sarcoma surgery can prevent recurrence, effectively control tumor locally, and contribute to increased overall survival rates and prolonged survival periods ^[12-13]. Synchronous radiotherapy and chemotherapy appear to yield better results, compared to either radiotherapy or chemotherapy alone, by enhancing the overall survival rate of uterine sarcoma and reducing local recurrence ^[14-15]. Combining the results of these studies with our retrospective analysis, it is believed that radiotherapy plays a definite role in controlling local recurrence and prolonging the survival period of some patients. Although many retrospective analyses did not show statistically significant differences, the efficacy of radiotherapy is noteworthy, and it is recommended for patients postoperatively. Consequently, we included postoperative radiotherapy as a factor in the multivariate survival analysis. Regarding chemotherapy, due to the diverse chemotherapy regimens used in our retrospective analysis and its lack of standardization, only univariate survival analysis was conducted, indicating lower survival rates for patients receiving adjuvant chemotherapy, and further investigation is needed to determine its efficacy.

In summary, staging, pathological grade, and surgical approach are crucial factors influencing patient prognosis. When compared with simple hysterectomy with bilateral salpingo-oophorectomy, extensive surgical procedures involving total hysterectomy, bilateral salpingo-oophorectomy, and omentectomy significantly improves the 5-year overall survival rate of patients. Postoperative radiotherapy or synchronous radiotherapy and chemotherapy can reduce local recurrence, potentially prolonging patient survival and improving the 5-year survival rate, while the efficacy of adjuvant chemotherapy after surgery appears to be uncertain.

Ethics approval

This retrospective analysis was reviewed by the Ethics Committee of Shanxi Cancer Hospital in April 2024 and approved for the study. During the study, the Ethics Committee continued to review all materials and acknowledged that they met ethical requirements.The ethical review criteria for this study are based on the Helsinki Declaration.

Patient participation declaration consent form

All patients shall fill in the treatment informed consent form when they are admitted to the hospital. On the premise of not revealing the patient's name, ID number, hospitalization number and other private information, the information about medical treatment, laboratory report, prognosis and other information can be used for scientific research. And this retrospective analysis was reviewed by the hospital ethics committee.

Consent for publication

The articles published in the study do not involve the personal privacy of patients, such as name, ID number, hospitalization number and other information, and each patient agrees to publish other relevant information as a research project when admitted to the hospital.

Availability of data and materials

All the data in the article comes from the medical record room of Shanxi Cancer Hospital. Currently, the hospital has not established a database that can be accessed through public networks. However, employees of our hospital can access relevant medical record information through application.

Funding

The article lacks financial support and only collected and analyzed medical records, which were jointly completed by two authors.

Authors contribution:

The first author (Qianni Yang)completed the collection of medical records and data statistics, while the corresponding author(xiaodong Han) completed the overall design of the project. Both authors checked the data in the article and made modifications to it.The two authors have no objection to the contribution and ranking of the article, and this is hereby declared.

Stoelinga B, Juffermans L, Dooper A, et al. ContrastEnhanced Ultrasound Imaging of Uterine Disorders: A Systematic Review [J]. Ultrason Imaging, 2021, 43(5): 239-252.
Nina L Eng , Shushan R Rana, Kevin L Hall,et al.The Effect of Adjuvant Pelvic Radiotherapy on Distant Metastasis for Uterine Carcinosarcoma.Am J Clin Oncol. 2021 Apr 1;44(4):169-173.
Eva Roser , Philipp Harter , Dario Zocholl ,et al.Treatment strategies in patients with gynecological sarcoma: Results of the prospective intergroup real-world registry for gynecological sarcoma in Germany (REGSA-NOGGO RU1)Int J Gynecol Cancer. 2023 Feb 6;33(2):223-230.
Yuan-Jie Li, Jun Lyu, Chen Li,et al.A novel nomogram for predicting cancer-specific survival in women with uterine sarcoma: a large population-based study.BMC Womens Health. 2022 May 14;22(1):175.
Ilker Kahramanoglu,Fuat Demirkiran, Hasan Turan, et al.Adjuvant Treatment Modalities, Prognostic Factors, and Outcome of the Uterine CarcinosarcomaJ Obstet Gynaecol Can. 2021 Jan;43(1):34-42.
Cigdem Kiliç 1, Dilek Yuksel 1, Caner Cakir 1,et al.Primary leiomyosarcoma of the uterine cervix: report of 4 cases, systematic review, and meta-analysis. Tumori. 2020 Oct;106(5):413-423.
Nilanchali Singh,Mohammed Al-Ruwaisan,Atul Batra,et al.Factors Affecting Overall Survival in Premenopausal Women With Uterine Leiomyosarcoma: A Retrospective Analysis With Long-Term Follow-Up.J Obstet Gynaecol Can. 2020 Dec;42(12):1483-1488.
Hanjie Hu, Zhewen Wei , Hong Zhao, et al.Epidemiology of adenosarcoma and the inverse probability of treatment weighting (IPTW) adjusted survival analysis of lymph node dissection in uterine adenosarcoma.Medicine (Baltimore). 2022 Sep 23;101(38):e30607.
Myriam Gracia , Yusuf Yildirim, Ronalds Macuks, et al.Impact of perioperative characteristics on the recurrence risk and survival of patients with uterine leiomyosarcoma.Int J Gynaecol Obstet. 2023
You Wu , Nan Li, Rong Zhang,et al. Primary low-grade extrauterine endometrial stromal sarcoma: analysis of 10 cases with a review of the literature.World J Surg Oncol. 2022 Jan 13;20(1):17.Dec;163(3):868-874.
Su Hyun Chae, Seung-Hyuk Shim, Misoo Chang,et al.Effect of adjuvant therapy on the risk of recurrence in early-stage leiomyosarcoma: A meta-analysis.Gynecol Oncol. 2019 Sep;154(3):638-650.
A Cordoba , J Prades, L Basson, et al.Adjuvant management of operated uterine sarcomas: A single institution experience.Cancer Radiother. 2019 Sep;23(5): 401-407.
Zhimin Hao, Sufen Yang.The role of postoperative radiotherapy in patients with uterine sarcomas: A PSM-IPTW analysis based on SEER database.Front Surg. 2022 Aug 9:9:985654.
Jennifer McEachron Yi-Ju Chen, Nancy Zhou, et al.Improved survival with combination chemotherapy and external beam radiation therapy in uterine carcinosarcoma.Int J Gynecol Cancer2022 Nov 7;32(11):1402-1409.
Chi-Yuan Chiang , Huei-Jean Huang, Wei-Yang Chang, et al.Adjuvant therapy and prognosis in uterine carcinosarcoma JFormos Med Assoc. 2021 Nov;120(11): 1977-1987.

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The impact of different surgical methods on the survival rate of patients with uterine sarcoma

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