Prognostic Value of Peritoneal Cytology in Stage I Serous and Clear Cell Carcinoma of the Endometrium

doi:10.21203/rs.3.rs-1943664/v1

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Prognostic Value of Peritoneal Cytology in Stage I Serous and Clear Cell Carcinoma of the Endometrium

https://doi.org/10.21203/rs.3.rs-1943664/v1

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OBJECTIVE: To investigate the relation of malignant peritoneal cytology and survival outcomes in patients who underwent primary staging surgery for stage I uterine serous (USC) or clear cell carcinoma (UCCC).

METHODS: In this retrospective analysis, patients with stage I USC or UCCC who underwent staging surgery between 2010 - 2020 from the Peking Union Medical College Hospital were identified and reviewed.

RESULTS: A total of 101 patients were included and 11 patients had malignant cytology (10.9%). None of the covariates were associated with an increased likelihood of malignant peritoneal cytology. The median follow-up time was 44 months (range 6-120). A total of 11 (10.9%) patients developed recurrence: 6 (54.4%) in the malignant cytology group and 5 (5.6%) in the comparative group. Patients with malignant cytology had a higher likelihood of peritoneal recurrence and shorter time to relapse (13 vs 38 months, p=0.022), as compared to patients with negative cytology. In univariate analysis, malignant cytology and serous histology had worse progression free survival (PFS) and overall survival (OS) (all, p < 0.05). Advanced age (>60 years old), higher stage (IB), and no omentectomy were additionally associated with inferior OS (all, p < 0.05). In sensitive analysis, the detrimental effects of malignant cytology on survival were more prominent in patients over 60 years old, those with serous histology, stage IB disease, and those who received hysteroscopy as a diagnostic test.

CONCLUSION: Stage I USC or UCCC patients with malignant peritoneal cytology had higher recurrence and inferior survival.

Malignant peritoneal cytology was associated with inferior PFS and OS in stage I USC and UCCC.
Patients with malignant cytology had a higher peritoneal recurrence and shorter time to relapse.
Diagnostic hysteroscopy was associated with worse survival in patients with malignant cytology.

Endometrial cancer (EC) is the most common gynecologic malignancy in developed countries.¹ Endometrial malignancies have been divided into two subtypes based on clinicopathologic features.² Type I tumors have endometrioid histology, comprising approximately 80% of EC and are generally diagnosed in early stages with favorable prognosis. On the contrary, Type II ECs, including serous, clear cell, undifferentiated and high-grade endometrioid carcinoma, etc., are associated with poorer prognosis compared to Type I ECs.² Since the malignant behavior of these two types of EC are varied, management of each are different in clinical practice. In type II ECs, the prognostic factors in patients with stage I disease are even more important because post-operative adjuvant therapy in patients with certain risk factors may significantly reduce the rate of tumor relapse leading to better survival outcomes.^{3 4}

The prognostic value of malignant peritoneal cytology is controversial. Previous studies have not been able to identify a significant association between cytology and prognosis in early stage and low-risk EC.^{5 6} The 2009 revision of cancer staging system by the International Federation of Gynecology and Obstetrics (FIGO) has excluded malignant peritoneal cytology as a criteria for staging in ECs, and is not considered a factor for post-operative treatments.⁷ The incidence of malignant peritoneal cytology is reported higher in type II EC cancer, but studies specifically evaluating malignant peritoneal cytology in stage I non-endometrioid endometrial cancer are limited.^{8 9} Since the pathophysiologic features of type II EC are different from endometrioid type, evaluating the prognostic value of factors such as peritoneal cytology would be substantial.

The primary objective of this study was to evaluate the prognostic value of malignant peritoneal cytology in patients with stage I uterine serous cancer (USC) and clear cell cancer (UCCC).

The Institutional Review Board of Peking Union Medical College Hospital approved this retrospective study. We reviewed the clinical records of patients with stage I serous or clear cell EC who underwent peritoneal cytology examination at staging surgery between 2010–2020.

The following information were extracted from the medical records: age at time of cancer diagnosis, year of diagnosis, initial diagnostic method in biopsy (Dilation and Curettage, D&C, versus hysteroscopy), histology subtypes (serous, clear cell), cancer stage (IA versus IB), tumor size (≤ 2cm, 2.1-4cm, >4cm), lymph vascular space invasion (LVSI), depth of invasion (submucous, ≤ 1/2 myometrium, > 1/2 myometrium) and peritoneal cytology results (malignant versus negative). The grade was not specially reviewed because USC and UCCC were regard as high grade endometrial cancer.

Surgical data reviewed included the procedure type (minimally invasive versus open surgery), performance of pelvic lymphadenectomy (LND) (yes versus no), appendectomy (yes versus no) and omentectomy (yes versus no). Post-operative treatments were documented as either chemotherapy, radio therapy (vaginal brachytherapy, external beam radio therapy [EBRT]) or both. The cytology status from surgical staging was reviewed and confirmed by two pathologists independently. The presence of malignant cells in the peritoneal cytology was defined as positive.

After treatment completion, patients were followed every 3–6 months for the first 2 years, 6–12 months for 3–5 years, then annually thereafter. Recurrence was confirmed by either imaging or surgical resection. The pattern of recurrence was documented as peritoneal (vaginal cuff, pelvis, or abdomen), lymph node metastasis (retroperitoneal, or above para-aortic nodes), hematogenous (liver, lung, bone, or brain) and multiple. Progression free survival (PFS) was defined as the time (months) from initial diagnosis to disease recurrence. Overall survival (OS) was defined as the time (months) from diagnosis to death from all causes. Data on patients with no evidence of disease recurrence or death were censored at the date of last follow-up.

Statistics

Mann-Whitney U-test was used to analyze continuous variables as appropriate. Frequency distributions were compared using Chi-square and Fisher's exact test for categorical variables. Baseline clinicopathological characteristics were compared between the malignant and negative peritoneal cytology groups. Survival outcomes (PFS and OS) were estimated using the Kaplan-Meier method and log rank test. Univariate and multivariate Cox proportional hazard ratio (HR) analyses were performed to identify independent prognostic factors. The clinicopathological factors included in the univariate analyses were primarily selected from the commonly known prognostic factors by reviewing previous studies that investigated the prognostic factors in EC, including age, initial surgery type, stage, mitotic counts, adjuvant chemotherapy. Possible prognostic factors were assessed using univariate analyses. Multivariate Cox models included factors associated with a statistically significant increased risk for recurrence or death in the univariate analysis. Stratified sensitivity analyses were performed to assess the association of peritoneal cytology results and survival outcomes by age (≤ 60 versus > 60 years), histology (serous, clear cell), cancer stage (IA versus IB), diagnostic methods (D&C versus hysteroscopy), and post-operative chemotherapy (yes versus no). In all cases, a p value < 0.05 was considered statistically significant. SPSS ver. 23.0 (IBM, Armonk, NY, USA) and Prism 6.0c software (GraphPad, San Diego, CA, USA) were used for statistical analyses.

From January 2010 to December 2020, 101 patients with stage I serous or clear cell EC who underwent EC staging surgery in the Gynecologic department of Peking Union Medical College Hospital were identified and included in the study.

The mean age of the patients was 61.6 (SD 10, range 31–81) years. The average pre-surgical tumor maximum diameter on imaging examination was 2.7 (SD 1.76, range 0.4-9) cm. A total of 11 patients had malignant peritoneal cytology (10.9%). There were 55 patients with serous carcinoma histology and 46 patients with clear cell carcinoma included in this study. More than one half patients had earlier stage disease (IA 77 patients, IB 24 patients). Lymph-vascular space invasion (LVSI) was found in 10 patients (9.9%). The initial diagnostic procedure was either dilation and curettage (D&C) (n = 51, 50.5%) or hysteroscopy (n = 50, 49.5%). There were 63 patients (62.4%) who underwent open surgery and 38 patients underwent laparoscopic surgery (37.6%). Omentectomy was performed in 86 (85.1%) patients and appendectomy in 36 (35.6%) patients. Lymphadenectomy was omitted in 7 patients due to advanced age or other severe comorbidities. Table 1 summarizes patient demographics and tumor characteristics allocated by cytology result. None of these factors (age, histology type, tumor size, depth of invasion, LVSI, initial diagnostic surgery type, route of staging surgery, performance of omentectomy and lymphadenectomy) were associated with malignant peritoneal cytology.

Table 1

Patient demographics, tumor characteristics and treatment approaches.
	Total (n = 101)	Malignant cytology (n = 11)	Negative cytology (n = 90)	p value
Age at diagnosis (years) ± SD	61.6 ± 10.0	65.5 ± 9.8	61.1 ± 9.8	0.18¹
BMI ± SD	25.0 ± 4.2	24.5 ± 2.6	25.1 ± 4.4	0.67¹
Maximum tumor diameter on image ± SD	2.7 ± 1.8	2.4 ± 1.5	2.8 ± 1.8	0.56¹
Histology type, n (%) Serous Clear cell	55 (54.5) 46 (45.5)	8 (72.7) 3 (27.3)	47 (52.2) 43 (47.8)	0.34²
Stage, n (%) IA IB	77 (76.2) 24 (23.8)	7 (63.6) 4 (36.4)	70 (77.8) 20 (22.2)	0.29²
Pathologic tumor size, n (%) ≤ 1cm 1.1-2cm > 2cm	23 (22.8) 25 (24.8) 53 (52.5)	2 (18.2) 4 (36.4) 5 (45.5)	21 (23.3) 21 (23.3) 48 (53.3	0.64³
DOI, n (%) Submucous < 1/2 myometrium ≥ 1/2 myometrium	30 (29.7) 47 (46.5) 24 (23.8)	3 (27.2) 4 (36.4) 4 (36.4)	27 (30.0) 43 (47.8) 20 (22.2)	0.39³
LVSI, n (%) No Yes	91 (90.1) 10 (9.9)	10 (90.9) 1 (9.1)	81 (90.0) 9 (10.0)	1.00²
Diagnostic surgery, n (%) D&C Hysteroscopy	51 (50.5) 50 (49.5)	6 (54.5) 5 (45.5)	45 (50.0) 45 (50.0)	1.00²
Surgery route, n (%) Open MIS	63 (62.4) 38 (37.6)	6 (54.5) 5 (45.5)	57 (63.3) 33 (36.7)	0.74²
Omentectomy, n (%) No Yes	15 (14.9) 86 (85.1)	1 (9.1) 10 (90.9)	14 (15.6) 76 (84.4)	1.00²
Appendectomy, n (%) No Yes	65 (64.4) 36 (35.6)	8 (72.7) 3 (27.3)	57 (63.3) 33 (36.7)	0.74²
Lymphadenectomy, n (%) No Yes	7 (6.9) 94 (93.1)	1 (9.1) 10 (90.9)	6 (6.7) 84 (93.3)	0.56²
Postop therapy, n (%) Chemotherapy Radiation therapy	65 (64.4) 13 (12.9)	8 (72.7) 2 (18.2)	57 (63.3) 11 (12.2)	0.74² 0.49²
¹ Wilcoxon rank sum p-value; ² Fisher Exact p-value; ³ Chi-Square p-value; DOI, depth of invasion; LVSI, lymph-vascular space invasion; D&C, Dilation and Curettage; MIS, minimally invasive surgery;

The post-operative managements included chemotherapy and radiotherapy. There were 53 patients (52.4%) who received chemotherapy alone. Radiation therapy after adjuvant chemotherapy was performed in 12 patients (11.9%). Only one patient received EBRT and brachytherapy without chemotherapy due to impaired kidney function. The radiation therapy included EBRT in 2 patients (1.98%), 8 vaginal brachytherapy (7.92%), 3 both EBRT and brachytherapy (2.97%). There were no differences of preference in adjuvant treatments of chemotherapy (p = 0.74) or radiation therapy (p = 0.49) between cytology positive and negative group.

The median follow-up time was 44 months (range 6-120). A total of 11 (10.9%) patients developed recurrence: 6 (54.4%) in the malignant cytology group and 5 (5.6%) in the negative cytology group. In the malignant cytology group, there was 1 patient with recurrence at the vaginal cuff, 2 patients with pelvic recurrence, 2 patients with multiple tumor implantation in abdomen and 1 patient with lung metastasis. In the negative cytology group, there was 1 patient with retrorectal space recurrence, two patients with pelvic and para-aortic lymph node recurrence, and 2 patients with lung metastases. Patients with malignant cytology had a higher peritoneal recurrence (5/6, 83.3%) versus patients with negative cytology (1/5, 20%) (p = 0.036). The time to relapse was shorter in the malignant cytology group (median 13, range 3–41 months), as compared to patients with negative cytology (median 38, range 15–95 months) (p = 0.022). (Table 2)

Table 2

Recurrence data
	Malignant cytology (n = 11)	Negative cytology (n = 90)	p value
Total n (%)	6 (54.5)	5 (5.6)	< 0.001¹
Peritoneal (%) Vaginal cuff Pelvis Abdomen	1 (16.7) 2 (33.3) 2 (33.3)	1 (20)	0.036¹
Lymph node (%)		2 (40)
Hematogenous^* (%)	1 (16.7)	2 (40)
Months to relapse median (range)	13 (3–41)	38 (15–95)	0.022²
¹ Chi-Square p-value; ² Fisher Exact p-value;
* All the hematogenous metastasis were recurrence in lung.

The demographic features between the cytology positive and negative groups were not significantly difference, thus the survival outcomes were compared between women with malignant and negative peritoneal cytology. Patients with malignant cytology had inferior PFS and OS, as compared to those who had negative cytology. The 5-year PFS and OS were 39.8% and 60.6% for the malignant cytology group, and 94.2% and 97.8% for the negative cytology group, respectively. Malignant peritoneal cytology was associated with nearly a 12-fold increased risk of recurrence (HR 12.6, 95% CI 1.54–103, p < 0.001) and a 9-fold increased risk of all-cause mortality (HR 9.66, 95% CI 1.21–112, p < 0.001). (Fig. 1)

Univariate analysis of other potential prognostic factors for survival outcomes were performed. On PFS analysis, histology type of USC (HR 4.56, p = 0.031) was a poor prognostic factor. Advanced age (HR 6.95, p = 0.030), higher stage (HR 12.5, p = 0.009), and no omentectomy at surgery (HR 7.96, p = 0.015) were associated with decreased OS. Significant variables from univariate analysis were included in multivariate analysis. On multivariate analysis, only malignant cytology had statistical significance in predicting unfavorable PFS. When analyzing OS, malignant cytology, higher stage and no omentectomy were found to be poor prognosticators. (Table 3)

Table 3

Univariate and multivariate analysis of potential prognostic risk factors in patients with stage I USC and UCCC.
	5-year PFS					5-year OS
	Univariate			Multivariate		Univariate			Multivariate
Variable	%	HR (95%CI)	p	HR	p	%	HR (95%CI)	p	HR	p
Cytology Malignant Negative	39.8 94.2	12.6 (1.54–103)	< 0.001 Ref	20.9	< 0.001	60.6 97.8	9.66 (1.21–112)	< 0.001 Ref	56.2	0.001
Age > 60 ≤ 60	81.5 97.1	3.75 (1.15–12.3)	0.064 Ref	2.00	0.459	88.8 100	6.95 (1.88–25.7)	0.030 Ref	6.64	0.173
Histology USC UCCC	83.2 93.3	4.56 (1.40–14.9)	0.031 Ref	0.20	0.096	91.0 95.8	2.52 (0.68–9.39)	0.166 Ref	0.19	0.162
Stage IA IB	89.0 84.8	0.51 (0.10–2.55)	0.303 Ref			98.4 74.8	0.08 (0.01–0.52)	0.009 Ref	10.2	0.021
Size ≤ 2cm > 2cm	86.2 89.5	0.534 (0.16–1.74)	0.306 Ref			97.4 89.8	0.500 (0.13–1.87)	0.303 Ref
DOI < 1/2 ≥ 1/2	89.1 83.5	0.492 (0.10–2.51)	0.280 Ref			96.0 81.9	0.360 (0.58–2.21)	0.128 Ref
LVSI No Yes	87.0 88.8	0.983 (0.12–7.79)	0.987 Ref			94.0 87.5	0.673 (0.58–7.74)	0.704 Ref
Diagnostic surgery D&C Hysteroscopy	89.8 86.1	0.574 (0.17–1.91)	0.347 Ref			97.6 87.6	0.309 (0.08–1.19)	0.072 Ref
Surgery route Open MIS	89.6 85.2	0.648 (0.17–2.45)	0.467 Ref			98.1 82.0	0.354 (0.07–1.71)	0.090 Ref
Omentectomy No Yes	61.1 92.1	2.814 (0.29–27.2)	0.159 Ref			46.1 95.9	7.96 (0.50–127)	0.015 Ref	0.02	0.003
Appendectomy No Yes	85.4 92.5	2.121 (0.75–6.97)	0.247 Ref			90.9 96.7	1.253 (0.34–4.63)	0.726 Ref
Lymphadenectomy No Yes	80.0 88.5	3.500 (0.10–127)	0.198 Ref			NA 96.2		NA Ref
Chemotherapy No Yes	81.8 91.0	1.225 (0.34–4.35)	0.745 Ref			90.7 94.5	2.506 (0.62-10.0)	0.151 Ref
Radiation therapy No Yes	87.2 92.8	1.369 (0.22–8.41)	0.762 Ref			93.6 92.8	0.993 (0.12–7.99)	0.995 Ref
D&C, dilation and curettage; Ref, reference;

In sensitivity analyses, malignant cytology was associated with decreased PFS in patients over 60 years old (HR 19.05), who had serous histology (HR 24.12), stage IB (HR 2063) and chemotherapy after surgery (HR 10.78). Malignant cytology was associated with inferior OS in patients who had serous histology (HR 20.26) and post-operative chemotherapy (HR 23.77). The difference in PFS and OS between the patients with or without malignant peritoneal cytology was most significant for patients in the stage IB subgroup. (Fig. 2) Diagnostic hysteroscopy seems more hazardous in patients with malignant cytology than D&C on Fig. 2, thus a subgroup analysis on hysteroscopy was performed. In patients with malignant cytology, hysteroscopy was associated with inferior PFS (HR 5.48, 95% CI 1.47–33.4, p = 0.03) and OS (HR 6.32, 95% CI 0.96–51.5, p = 0.05), as compared to D&C. In the negative cytology cases, there were no survival differences in PFS (p = 0.88) or OS (p = 0.20) between patients who received diagnostic hysteroscopy or D&C.

In this study, we found that malignant peritoneal cytology was independently associated with inferior PFS and OS in patients with stage I USC and UCCC. Malignant peritoneal cytology was seen in 10.9% of stage I USC and UCCC patients. Patients with malignant peritoneal cytology had more peritoneal recurrence and shorter time to relapse.

The incidence of malignant peritoneal cytology in stage I EC has been reported from 5.3–10.5% in prior studies, and it is higher in non-endometrioid EC.^10–12 A retrospective observational study using the Surveillance, Epidemiology and End Results (SEER) database reported a 9.2% incidence of malignant peritoneal cytology in non-endometrioid EC and 10.7% in USC/UCCC.¹¹ We found a similar incidence of 10.9% in USC/UCCC.

The most recognized theory for the mechanism of malignant peritoneal cytology is the retrograde spread of tumor cells via the fallopian tubes. A review of 4489 EC patients and their history of tubal ligation revealed that tubal ligation is inversely associated with stage III/IV disease.¹³ The risk reduction of peritoneal metastasis is much more significant in patients with serous histology than endometroid cancer (OR 0.28, 95% CI 0.11–0.68 versus OR 1.27, 95% CI 0.41–3.89).¹³ Non-endometrioid EC is more likely to have trans-tubal spread, which may explain the higher incidence of malignant peritoneal cytology in USC/UCCC than endometrioid tumors.

We compared the clinical features between malignant and negative peritoneal cytology group and none of the clinical and pathological factors were identified as independent risk factors for malignant cytology in stage I USC/UCCC. One study reported diagnosis at an older age (> 78 years old), serous histology and larger tumor size were associated with increased risks of malignant peritoneal cytology.¹¹ Other studies however have failed to find an association between clinical pathological factors and malignant peritoneal cytology.^{12 14} A meta-analysis demonstrated that hysteroscopy is associated with higher rate of positive peritoneal cytology when compared with no hysteroscopy, but this phenomenon is not identified in early stage EC.¹⁵ In our study, we did not find a relationship between hysteroscopy and positive peritoneal cytology. However, in patients with malignant peritoneal cytology subgroup, we found hysteroscopy was associate with inferior survival outcomes. Patients with malignant peritoneal cytology may have tumor cells more capable of migration and invasion. The intrauterine pressure during hysteroscopy can lead to tumor cell reflux and intra-abdominal dissemination. In our institution, we are more conserved to use hysteroscopy as a diagnostic method if in suspect EC.

In our study, we found a higher recurrence rate and shorter time to relapse in patients with malignant peritoneal cytology, as compared to those who have negative cytology. The recurrence patterns were different between the two groups. A retrospective study in low-risk EC including 478 patients reported an increased intra-abdominal recurrence in patients with positive peritoneal cytology.¹⁶ Our study also suggested that patients with malignant cytology were more likely to have peritoneal recurrence.

The strengths of this study include: a collection of patients from one, large academic medical institution. This reflects the standard surgical approaches and postoperative management of our practice; data were complete and well documented in all patients with consistent pathology review; the long follow-up period; and the balanced basic characteristics between groups.

Our study has certain limitations: first, inherent bias given the retrospective nature of the study; second, the limited number of patients with malignant peritoneal cytology resulted in a few underpowered analyses; and thirdly highly individualized postoperative treatment added heterogeneity to this study.

The prognostic importance of malignant peritoneal cytology in early EC is controversial.^{9 12 17} In the revised 2009 FIGO staging system, positive peritoneal cytology is no longer included in defining surgical staging.¹⁸ Several large retrospective studies using the SEER database¹⁰ and the National Cancer Database (NCDB)⁹ have reported that positive peritoneal cytology was significantly associated with decreased survival in early-stage EC. Historical arguments for omission of peritoneal cytology in staging of EC were predominantly focused on type I EC. Type II EC has a worse overall survival and higher recurrence rate, the rate of malignant peritoneal cytology is much higher than type I EC.¹¹ The recognition of peritoneal cytology as a tumor prognostic factor is necessary in early stage non-endometrioid EC.

The cytology as a prognostic indicator in type II EC is under evaluated.⁸ Our study demonstrated that malignant peritoneal cytology was associated with decreased PFS and OS in early stage USC/UCCC and the impact on survival is quite significant (37% decrease in 5-year OS). Multivariate analysis in our study also suggested that malignant peritoneal cytology was an independent risk factor for both PFS and OS. These findings are consistent with two previous reports focusing on non-endometrioid EC.^{11 14} Matsuo et al. reported that the mortality risk is nearly tripled (HR 2.59) with a 5-year survival rate decrease of 19.4% in stage I non-endometrioid EC patients with malignant peritoneal cytology.¹¹ Another case series study focusing on USC showed in patients with intermediate- and high-risk early stage USC, cytology status is significantly related with prognosis.¹⁴

The surgical staging for type II EC in National Comprehensive Cancer Network (NCCN) guidelines includes TH/BSO, peritoneal lavage for cytology, omental and peritoneal biopsies.¹⁹ We found omentectomy was related to superior OS, but not PFS. This unpaired outcome may be due to the frail physical status of the patients who did not receive omentectomy, such as advanced age or medical comorbidities. Physicians may omit omentectomy and lymphadenectomy to minimize the aggressive procedures.

Adjuvant treatment in USC/UCCC is highly individualized.¹⁹ Chemotherapy is recommended by NCCN and observation is only adopted in patients with stage IA disease who has no residual tumor in hysterectomy specimens.¹⁹ Chemotherapy is routinely used in our institution but may be omitted in patients with severe medical comorbidities or those who refuse additional treatment. We did not find significant therapeutic benefit of chemotherapy on PFS or OS in patients with stage I USC/UCCC. Adding vaginal brachytherapy is preferred but whole pelvic EBRT is no longer recommended.¹⁹ Clinical trials are warranted in making the adjuvant treatment strategies.

The result of our study showed that malignant peritoneal cytology was an independent prognostic factor for inferior survival outcomes in patients with stage IA USC/UCCC. Patients with malignant peritoneal cytology had more peritoneal recurrence and a shorter time to relapse. Diagnostic hysteroscopy was associated with worse prognosis in patients with malignant cytology.

Ethics approval and consent to participate:

The Institutional Review Board of Peking Union Medical College Hospital approved this retrospective study.

Consent for publication

All authors approved the submission and publication of this manuscript.

Availability of data and materials

Data and materials are available from the corresponding author on reasonable request.

Competing interests

All authors have no conflict of interest or potential financial disclosures.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Authors' contributions

Conception and design: Jie Yang, Jiaxin Yang

Provision of study material or patients: Jiaxin Yang, Dongyan Cao, Ming Wu, Yang Xiang

Data collection and interpretation: Jie Yang, Jiaxin Yang

Statistical analysis: Jie Yang

Manuscript preparation: Jie Yang, Jiaxin Yang

Accountable for all aspects of the work: All authors

Acknowledgements

We thank Dr. Richard Lee for assistance with the language editing and comments that greatly improved the manuscript.

Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA: a cancer journal for clinicians 2020;70(1):7–30. doi: 10.3322/caac.21590 [published Online First: 2020/01/09]
Morice P, Leary A, Creutzberg C, et al. Endometrial cancer. Lancet (London, England) 2016;387(10023):1094 − 108. doi: 10.1016/s0140-6736(15)00130-0 [published Online First: 2015/09/12]
Lee EK, Fader AN, Santin AD, et al. Uterine serous carcinoma: Molecular features, clinical management, and new and future therapies. Gynecologic oncology 2021;160(1):322 − 32. doi: 10.1016/j.ygyno.2020.10.017 [published Online First: 2020/11/09]
Tate K, Yoshida H, Ishikawa M, et al. Prognostic factors for patients with early-stage uterine serous carcinoma without adjuvant therapy. J Gynecol Oncol 2018;29(3):e34-e34. doi: 10.3802/jgo.2018.29.e34 [published Online First: 2018/02/19]
Fadare O, Mariappan MR, Hileeto D, et al. Upstaging based solely on positive peritoneal washing does not affect outcome in endometrial cancer. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 2005;18(5):673 − 80. doi: 10.1038/modpathol.3800342 [published Online First: 2004/12/04]
Scott SA, van der Zanden C, Cai E, et al. Prognostic significance of peritoneal cytology in low-intermediate risk endometrial cancer. Gynecologic oncology 2017;145(2):262 − 68. doi: 10.1016/j.ygyno.2017.03.011 [published Online First: 2017/04/01]
Pecorelli S. Revised FIGO staging for carcinoma of the vulva, cervix, and endometrium. International Journal of Gynecology & Obstetrics 2009;105(2):103-04. doi: https://doi.org/10.1016/j.ijgo.2009.02.012
Matsuo K, Yabuno A, Hom MS, et al. Significance of abnormal peritoneal cytology on survival of women with stage I-II endometrioid endometrial cancer. Gynecologic oncology 2018;149(2):301-09. doi: 10.1016/j.ygyno.2018.02.012 [published Online First: 2018/04/02]
Seagle BL, Alexander AL, Lantsman T, et al. Prognosis and treatment of positive peritoneal cytology in early endometrial cancer: matched cohort analyses from the National Cancer Database. American journal of obstetrics and gynecology 2018;218(3):329.e1-29.e15. doi: 10.1016/j.ajog.2017.11.601 [published Online First: 2017/12/11]
Garg G, Gao F, Wright JD, et al. Positive peritoneal cytology is an independent risk-factor in early stage endometrial cancer. Gynecologic oncology 2013;128(1):77–82. doi: https://doi.org/10.1016/j.ygyno.2012.09.026
Matsuo K, Nusbaum DJ, Matsuzaki S, et al. Malignant peritoneal cytology and increased mortality risk in stage I non-endometrioid endometrial cancer. Gynecologic oncology 2020;159(1):43–51. doi: 10.1016/j.ygyno.2020.07.010 [published Online First: 2020/07/22]
Takenaka M, Kamii M, Iida Y, et al. Re-thinking the prognostic significance of positive peritoneal cytology in endometrial cancer. Gynecologic oncology 2021;161(1):135 − 42. doi: 10.1016/j.ygyno.2021.01.007 [published Online First: 2021/02/09]
Felix AS, Brinton LA, McMeekin DS, et al. Relationships of Tubal Ligation to Endometrial Carcinoma Stage and Mortality in the NRG Oncology/ Gynecologic Oncology Group 210 Trial. Journal of the National Cancer Institute 2015;107(9) doi: 10.1093/jnci/djv158 [published Online First: 2015/06/20]
Corey L, Fucinari J, Elshaikh M, et al. Impact of positive cytology in uterine serous carcinoma: A reassessment. Gynecol Oncol Rep 2021;37:100830-30. doi: 10.1016/j.gore.2021.100830
Chang YN, Zhang Y, Wang YJ, et al. Effect of hysteroscopy on the peritoneal dissemination of endometrial cancer cells: a meta-analysis. Fertility and sterility 2011;96(4):957 − 61. doi: 10.1016/j.fertnstert.2011.07.1146 [published Online First: 2011/08/30]
Fujiwara S, Nishie R, Ueda S, et al. Prognostic significance of peritoneal cytology in low-risk endometrial cancer: comparison of laparoscopic surgery and laparotomy. International journal of clinical oncology 2021;26(4):777 − 83. doi: 10.1007/s10147-020-01854-z [published Online First: 2021/01/09]
Sutton GP. The significance of positive peritoneal cytology in endometrial cancer. Oncology (Williston Park, NY) 1990;4(6):21 − 6; discussion 30 − 2. [published Online First: 1990/06/01]
Creasman W. Revised FIGO staging for carcinoma of the endometrium. International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics 2009;105(2):109. doi: 10.1016/j.ijgo.2009.02.010 [published Online First: 2009/04/07]
Abu-Rustum NR, Yashar CM, Bradley K, et al. NCCN Guidelines® Insights: Uterine Neoplasms, Version 3.2021. Journal of the National Comprehensive Cancer Network : JNCCN 2021;19(8):888 − 95. doi: 10.6004/jnccn.2021.0038 [published Online First: 2021/08/21]

No competing interests reported.

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Prognostic Value of Peritoneal Cytology in Stage I Serous and Clear Cell Carcinoma of the Endometrium

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Abstract

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Introduction

Materials And Methods

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