The differences of pelvic lymph node metastasis between squamous cell carcinoma and adenocarcinoma in early-stage cervical cancer patients undergoing radical surgery and adjuvant radiotherapy: a large cohort study

Abstract

Background:

The differences in lymph node metastasis (LNM) between patients with early-stage squamous cell carcinoma (SCC) and adenocarcinoma (ADC) cervical cancer remained to be clarified.

Objectives:

To compare the differences of LNM between early-stage SCC and ADC cervical cancer patients receiving radical surgery and adjuvant radiotherapy.

Designs:

A retrospective large cohort study.

Methods:

The pelvic LNM rate was estimated and compared. Univariate and multivariate logistic regression analyses were applied to identify the risk factors for pelvic LNM. The cumulative survival rates were estimated and compared with Kaplan–Meier methods and log-rank test, respectively. The propensity score matching (PSM) was utilized for adjustment of baseline characteristics.

Results:

A total of 577 cervical cancer patients were included in the analysis. Pelvic LNM could be observed in 22.7% (51/225) of ADC and 25.9% (91/352) of SCC patients (p = 0.39). Lympho-vascular space involvement (LVSI) was the only risk factor for pelvic LNM in SCC patients while LVSI and parametrial involvement (PI) were risk factors for ADC patients. No significant survival differences were observed between SCC patients with LNM and those without (All p > 0.05). However, ADC patients without pelvic LNM appeared superior to those with LNM in 5-year overall survival whether before (70.7% vs 91.9%; p < 0.001) or after (78.7% vs 92.4%; p = 0.024) PSM. Moreover, consolidate chemotherapy after radiation improved the 5-year disease-free survival (DFS) for SCC patients with pelvic LNM (74.9% vs 96.8%; p = 0.019) while not for ADC patients (68.9% vs 64.1%; p = 0.8).

Conclusion:

No significant difference in pelvic LNM rate was observed between ADC and SCC patients. The presence of LNM seemed to further impair the oncological outcomes for ADC while not for SCC patients. Consolidate chemotherapy appeared to improve the DFS for SCC while not for ADC patients.

Keywords

cervical cancer consolidate chemotherapy early stage lymph node metastasis radical surgery

Introduction

Globally, cervical cancer (CC) ranked as the fourth most prevalent malignancy among women in 2022, with approximately 661,021 new diagnoses and 348,189 attributable deaths.¹ For patients with early-stage CC, the recommended treatment involves radical hysterectomy with pelvic lymphadenectomy, with adjuvant radiotherapy considered based on postoperative pathological findings.^2–6 The introduction of the International Federation of Gynecology and Obstetrics (FIGO) stage IIIC1, defined by the presence of pelvic lymph node metastasis (LNM), resulted in approximately 18%—40% of early-stage CC patients (stage I–II in the 2009 FIGO staging system) being classified into a more advanced stage.^7–10

Previous research has shown that most women with early-stage CC experience favorable outcomes; however, those with LNM face significantly higher risks of relapse and mortality.^11,12 Indeed, LNM is a critical determinant of poor survival among CC patients. Nonetheless, studies evaluating the prognostic significance of LNM in early-stage CC patients often group cases with exclusive pelvic LNM together with those exhibiting para-aortic involvement (either alone or in combination), thus overlooking the established detrimental impact of para-aortic LNM on survival.^13–18 Furthermore, as a significant majority of patients in previous studies were diagnosed with squamous cell carcinoma (SCC), the applicability of their findings to adenocarcinoma (ADC) cases is limited. Thus, the prognostic significance of pelvic LNM in early-stage CC patients undergoing primary radical surgery remains controversial.

Moreover, despite numerous studies exploring risk factors associated with LNM, conclusive evidence remains lacking.^19–23 Although histologic subtype has been identified as an independent risk factor for LNM,¹⁹ distinct risk factors for LNM in SCC and ADC patients have yet to be delineated. Therefore, a study that separately investigates the risk factors for LNM in early-stage SCC and ADC patients is necessary. In the current study, we aim to compare the risk factors and prognostic implications of LNM between SCC and ADC patients undergoing primary radical surgery and postoperative radiotherapy.

Materials and methods

Study population

We conducted a retrospective review of patients diagnosed with early-stage CC between 2013 and 2022, who were treated with radical hysterectomy plus pelvic lymphadenectomy followed by adjuvant radiotherapy at our institution. The study protocol received ethical approval from the Institutional Review Board (IRB) of Peking Union Medical College Hospital (PUMCH; IRB number: K-6420), and written informed consent was obtained from all participants. Patients were excluded from the analysis if any of the following criteria were met: (1) diagnosis of 2009 FIGO stage III/IV disease; (2) receipt of any form of neoadjuvant treatment prior to surgery; (3) failure to undergo radical hysterectomy or bilateral pelvic lymphadenectomy; (4) lack of postoperative radiotherapy; (5) presence of retroperitoneal LNM; (6) diagnosis of a histologic type of CC other than SCC or ADC; (7) occurrence of 30-day postoperative mortality due to surgical complications; or (8) patients younger than 18 years or those with incomplete follow-up data. Notably, the detailed patient selection algorithm is illustrated in Figure 1.

Figure 1.

The detailed flowchart depicting the selection process of the included patients.

Treatment and follow-up

The initial treatment for all enrolled patients consisted of radical hysterectomy and pelvic lymphadenectomy, performed either via an open or laparoscopic approach. All patients received adjuvant radiotherapy, delivered using either intensity-modulated radiotherapy (IMRT) or volumetric-modulated arc therapy (VMAT). The clinical target volume (CTV) encompassed the upper 3–4 cm of the vaginal cuff, parametrial space, and adjacent nodal basins, including the common iliac, external/internal iliac, obturator, and presacral regions, in accordance with National Comprehensive Cancer Network (NCCN) guidelines.²⁴ The administration of concurrent weekly chemotherapy, brachytherapy (BRT) with a dose prescription of 10 Gy in two fractions, or consolidation chemotherapy following radiotherapy was guided by clinical assessment and patient preference. Notably, TP (paclitaxel and cisplatin) was uniformly prescribed for patients who planned to receive consolidation chemotherapy.

Patients were followed according to a standardized protocol, with clinical evaluations conducted 3 months post-treatment, then every 3 months for the first 2 years, every 6 months through year 5, and annually thereafter.²⁴

Cohort definition

All the included patients received radical hysterectomy and bilateral pelvic lymphadenectomy. Patients were divided into SCC and ADC groups according to pathological types. Furthermore, patients in different histologic groups would be separately classified into with-LNM and without-LNM subgroups based on the presence and absence of LNM, respectively. In addition, the patients’ data regarding age, tumor size, pretreatment SCC concentration for SCC patients, pretreatment CA125 concentration and human papilloma virus (HPV) genotyping for ADC patients, surgical approach (open or laparoscopic), the number of lymph node dissection (LND), Lympho-vascular space involvement (LVSI; no or yes), depth of myometrial invasion (DOI; <1/2 or ⩾1/2), uterus involvement (UI; no or yes), vaginal involvement (VI; no or yes), positive surgical margin (no or yes), concurrent chemotherapy (no or yes) and consolidate chemotherapy (no or yes) were systemically collected. FIGO staging data were not further collected, since existing information was considered sufficient, while avoiding stage-related confounding in logistic regression analysis.

Statistical analysis

Continuous and categorical variables were compared using Student’s t-tests and χ² tests, respectively. Survival outcomes were evaluated through Kaplan–Meier analysis, with between-group differences assessed via log-rank testing. The primary endpoint was overall survival (OS), measured from the date of initial diagnosis to death from any cause. The secondary endpoint was disease-free survival (DFS), defined as the time from treatment completion to the first documented recurrence or death from any cause.

The rate of pelvic LNM was estimated and compared between SCC and ADC groups. Besides, the clinical and pathological differences between patients with pelvic LNM and those without in each group were listed and compared. Univariate and multivariate logistic analyses were performed to identify the independent risk factors associated with pelvic LNM in SCC and ADC cohort, respectively.

The 5-year OS and DFS were compared between SCC patients with and without pelvic LNM, both before and after PSM. A corresponding comparative analysis was separately performed within the ADC patient cohort. We additionally assessed the impact of consolidation chemotherapy on patients with pelvic LNM in both SCC and ADC cohorts, respectively.

All statistical analyses were performed using SPSS version 24.0 (IBM Corp, Armonk, NY, USA) and R statistical software (version 3.6.1; R Foundation for Statistical Computing, Vienna, Austria). A two-tailed p-value < 0.05 was considered statistically significant. The reporting of this study conformed to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement²⁵ (Table S1).

Results

Patients characteristics

A total of 352 SCC patients were included, with 261 (74.1%) and 91 (25.9%) patients were found to be diagnosed with and without pelvic LNM, respectively. Similarly, 77.3% (174/225) and 22.7% (51/225) of ADC patients were allocated to without-LNM and with-LNM group. The incidence of pelvic LNM was not significantly different between ADC and SCC patients (22.7% vs 25.9%; p = 0.39). The median LND count was comparable between the two groups (ADC: 26, IQR: 19–36; SCC: 25, IQR: 19–32), reflecting a comprehensive surgical lymphadenectomy. In SCC group, patients with older age, larger tumor size, higher pretreatment SCC concentration, and the presence of LVSI or parametrial involvement (PI) were inclined to generate pelvic LNM (All p < 0.05; Table 1). However, ADC patients with HPV independent (HPVI) status demonstrated a higher propensity for developing LNM than those with HPV associated (HPVA) status (51.0% vs 24.1%; p = 0.001; Table 1). Besides, the presence of UI, VI, and ⩾1/2 DOI was found to be related to pelvic LNM in ADC patients while not in SCC patients (Table 1).

Table 1.

Comparison of clinical and pathological characteristics between patients with and without pelvic LNM in SCC and ADC patients, respectively.

Variable	SCC			ADC
Variable	Without LNM (N = 261)	With LNM (N = 91)	p-Value	Without LNM (N = 174)	With LNM (N = 51)	p-Value
Age	46.28 ± 9.03	43.16 ± 9.01	0.005	45.23 ± 9.88	47.55 ± 10.48	0.147
HPV genotyping, n (%)						0.001
HPVA				121 (69.54)	22 (43.14)
HPVI				42 (24.14)	26 (50.98)
Unknown				11 (6.32)	3 (5.88)
Tumor size (cm)	2.99 ± 1.45	3.50 ± 1.85	0.011	2.49 ± 1.19	2.96 ± 1.30	0.017
Pretreatment SCC (µg/L)	2.66 ± 3.64	4.74 ± 5.61	0.004
Pretreatment CA125 (U/mL)				31.06 ± 52.48	52.23 ± 91.75	0.037
Surgical approach, n (%)			0.401			<0.001
Open	72 (27.59)	21 (23.08)		51 (29.31)	28 (54.90)
Laparoscopic	189 (72.41)	70 (76.92)		123 (70.69)	23 (45.10)
LND	26.19 ± 10.26	26.09 ± 11.00	0.938	26.16 ± 10.27	26.96 ± 10.60	0.625
LVSI, n (%)			<0.001			<0.001
No	136 (52.11)	23 (25.27)		122 (70.11)	18 (35.29)
Yes	125 (47.89)	68 (74.73)		52 (29.89)	33 (64.71)
DOI, n (%)			0.100			0.014
<1/2	85 (32.57)	21 (23.33)		74 (42.53)	12 (23.53)
⩾1/2	176 (67.43)	69 (76.67)		100 (57.47)	39 (76.47)
UI, n (%)			0.078			<0.001
No	217 (83.14)	68 (74.73)		131 (75.29)	26 (50.98)
Yes	44 (16.86)	23 (25.27)		43 (24.71)	25 (49.02)
VI, n (%)			0.129			0.012
No	236 (90.42)	77 (84.62)		161 (92.53)	41 (80.39)
Yes	25 (9.58)	14 (15.38)		13 (7.47)	10 (19.61)
PI, n (%)			<0.001			<0.001
No	253 (96.93)	79 (86.81)		172 (98.85)	41 (80.39)
Yes	8 (3.07)	12 (13.19)		2 (1.15)	10 (19.61)
Positive margin, n (%)			0.116			0.140
No	251 (96.17)	83 (91.21)		172 (98.85)	48 (94.12)
Yes	10 (3.83)	8 (8.79)		2 (1.15)	3 (5.88)

ADC, Adenocarcinoma of cervix; DOI, Depth of invasion; HPV, Human papillomavirus; HPVA, HPV associated; HPVI, HPV independent; LND, Lymph node dissection; LNM, Lymph node metastasis; LVSI, Lymphovascular invasion; PI, Parametrial invasion.; SCC, Squamous cell carcinoma; UI, Uterus involvement; VI, Vaginal involvement. The p values in bold indicated p < 0.05, which was statistically significant.

Risk factors for pelvic LNM

The univariate analysis revealed that age, tumor size, pretreatment SCC concentration, LVSI, and PI were associated with pelvic LNM in SCC patients. In the multivariate model, only LVSI was independently associated with LNM (OR = 3.64, 95% CI: 1.79–7.40; p < 0.001; Table 2).

Table 2.

Univariate and multivariate logistic regression analyses on risk factors for pelvic LNM in SCC patients.

Variable	Univariate analysis			Multivariate analysis
	OR	95% CI	p Value	OR	95% CI	p Value
Age	0.96	(0.94–0.99)	0.005
Tumor size	1.22	(1.04–1.43)	0.013
Pretreatment SCC	1.11	(1.04–1.18)	0.002
Surgical approach
Open	ref
Laparoscopic	1.27	(0.73 ~ 2.22)	0.402
LND	1.00	(0.98 ~ 1.02)	0.937
LVSI
No	ref			ref
Yes	3.22	(1.89–5.47)	<0.001	3.64	(1.79–7.40)	<0.001
DOI
<1/2	ref
⩾1/2	1.59	(0.91–2.76)	0.102
UI
No	ref
Yes	1.67	(0.94–2.96)	0.080
VI
No	ref
Yes	1.72	(0.85–3.47)	0.132
PI
No	ref
Yes	4.80	(1.90–12.17)	<0.001
Positive margin
No	ref
Yes	2.42	(0.92–6.33)	0.072

CI, confidence interval; DOI, depth of invasion; LND, lymph node dissection; LNM, lymph node metastasis; LVSI, lymphovascular invasion; OR, odds ratio; PI, parametrial invasion; SCC, squamous cell carcinoma; UI, uterus involvement; VI, vaginal involvement. The p values in bold indicated p < 0.05, which was statistically significant.

In ADC patients, eight factors including tumor size, HPV genotyping, surgical approach, LVSI, DOI, VI, UI, and PI were identified as significant from univariate analysis. However, only two factors including LVSI (OR = 3.22, 95% CI: 1.56–6.64; p = 0.002) and PI (OR = 7.18, 95% CI: 1.25–41.33; p = 0.027) were served as the independent risk factors for generating pelvic LNM in multivariate logistic regression analysis (Table 3). Collectively, LVSI markedly facilitated pelvic LNM in both histological types, whereas PI additionally impacted the risk of LNM specifically in ADC patients.

Table 3.

Univariate and multivariate logistic regression analysis on risk factors for pelvic LNM in ADC patients.

Variable	Univariate analysis			Multivariate analysis
	OR	95% CI	p value	OR	95% CI	p value
Age	1.02	(0.99–1.05)	0.148
Tumor size	1.34	(1.05–1.71)	0.020
Pretreatment CA125	1.00	(1.00–1.01)	0.060
HPV genotyping
HPVA	ref
HPVI	3.40	(1.75–6.64)	<0.001
Unknown	1.50	(0.39–5.82)	0.558
Surgical approach
Open	ref
Laparoscopic	0.34	(0.18–0.65)	<0.001
LND	1.01	(0.98–1.04)	0.624
LVSI
No	ref			ref
Yes	4.30	(2.22–8.32)	<0.001	3.22	(1.56–6.64)	0.002
DOI
<1/2	ref
⩾1/2	2.41	(1.18–4.91)	0.016
UI
No	ref
Yes	2.93	(1.53–5.60)	0.001
VI
No	ref
Yes	3.02	(1.24–7.38)	0.015
PI
No	ref			ref
Yes	20.98	(4.43–99.41)	<0.001	7.18	(1.25–41.33)	0.027
Positive margin
No	ref
Yes	2.42	(0.92–6.33)	0.072

ADC, adenocarcinoma of cervix; CI, confidence interval; DOI, depth of invasion; HPV, human papillomavirus; HPVA, HPV associated; HPVI, HPV independent; LND, lymph node dissection; LNM, lymph node metastasis; LVSI, lymphovascular invasion; OR, odds ratio; PI, parametrial invasion.; UI, uterus involvement; VI, vaginal involvement.

Survival outcomes

Intriguingly, pelvic LNM didn’t confer inferior prognosis for SCC patients, with no significant differences observed in terms of a 5-year OS (91.9%, 95% CI: 90.2–93.6 vs 88.3%, 95% CI: 84.6–92.0; p = 0.3; Figure 2(a)) and 5-year DFS (87.7%, 95% CI: 85.5–89.9 vs 84.9%, 95% CI: 81.1–88; p = 0.3; Figure 2(b)) for those without and with pelvic LNM before PSM. Consistently, comparable 5-year OS (91.1%, 95% CI: 88.7–93.4 vs 90.6%, 95% CI: 86.2–95.0; p > 0.9; Figure 2(c)) and 5-year DFS (90.4%, 95% CI: 87.6–93.2 vs 89.0%, 95% CI: 84.3–93.7; p = 0.7; Figure 2(d)) were observed among SCC patients with and without pelvic LNM after the baseline characteristics were balanced. However, ADC patients with pelvic LNM had worse 5-year OS than those without LNM whether before (70.7%, 95% CI: 63.8–77.6 vs 91.9%, 95% CI: 90.2–93.6; p < 0.001; Figure 2(e)) or after (78.7%, 95% CI: 71.5–85.9 vs 92.4%, 95% CI: 88.8–96.0; p = 0.024; Figure 2(g)) PSM. Also, ADC patients without pelvic LNM outperformed those with pelvic LNM in 5-year DFS before (82.9%, 95% CI: 79.8–86.0 vs 54.9%, 95% CI: 47.1–62.7; p < 0.001; Figure 2(f)) and after (89.8%, 95% CI: 86.2–93.4 vs 56.3%, 95% CI: 47.4–65.2; p = 0.002; Figure 2(h)) PSM. Of note, the differences between with-LNM and without-LNM before and after PSM in SCC and ADC patients are displayed in Tables S1 and S2, respectively.

Figure 2.

The comparison of OS (a) and DFS (b) between SCC patients with LNM and without LNM before PSM. The comparison of OS (c) and DFS (d) between SCC patients with LNM and without LNM after PSM. The comparison of OS (e) and DFS (f) between cervical ADC patients with LNM and without LNM before PSM. The comparison of OS (g) and DFS (h) between ADC patients with LNM and without LNM after PSM.

Given that adjuvant concurrent chemoradiotherapy (CCRT) was recommended by NCCN guidelines for CC patients with LNM,²⁴ we further evaluated the value of consolidate chemotherapy in this population.²⁴ It showed that consolidate chemotherapy conferred a significant DFS advantage (with chemo: 96.8%, 95% CI: 93.7–99.9 vs without chemo: 74.9%, 95% CI: 68.5–81.3; p = 0.019; Figure S1b) for SCC patients with pelvic LNM metastasis while this advantage couldn’t be converted to OS benefits (with chemo: 96.8%, 95% CI: 93.7–99.9 vs without chemo: 84.4%, 95% CI: 78.9–89.9; p = 0.11; Figure S1a). However, consolidate chemotherapy failed to provide extra survival benefits for ADC patients with pelvic LNM whether in 5-year OS (with chemo: 72.5%, 95% CI: 60.9–84.1 vs without chemo: 75.8%, 95% CI: 65.0–86.6; p > 0.9; Figure S1c) or DFS (with chemo: 64.1%, 95% CI: 51.4–76.8 vs without chemo: 68.9%, 95% CI: 57.2–80.6; p = 0.8; Figure S1d).

Discussion

Summary of main results

The incidence of pelvic LNM was similar between SCC (25.9%) and ADC (22.7%) patients following radical surgery and lymphadenectomy, with no statistically significant difference observed. Multivariate logistic regression analysis identified distinct risk profiles for pelvic LNM between the two subtypes, indicating that lymphovascular space involvement (LVSI) was the sole independent predictor in SCC patients, while both LVSI and perioperative infarction (PI) were significantly associated with LNM in ADC patients. Furthermore, pelvic LNM did not result in a significant reduction in survival for SCC patients compared to their counterparts without LNM. In contrast, ADC patients without pelvic LNM had better survival outcomes than those with pelvic LNM, both in terms of OS and DFS. Moreover, the therapeutic benefit of consolidation chemotherapy in early-stage CC patients with pelvic LNM was assessed among those receiving adjuvant CCRT after radical surgery. This evaluation revealed that the 5-year DFS for SCC patients with pelvic LNM was further improved by the addition of consolidation chemotherapy, while no additional benefits were observed for ADC patients with pelvic LNM.

Results in the context of published literature

Despite slight numerical differences, the rates of pelvic LNM post-radical hysterectomy were comparable between SCC patients (25.9%) and ADC patients (22.7%; p = 0.39), indicating that histologic subtype did not appear to be a major determinant of nodal metastasis according to the current study. Previous research has identified histologic subtype as an independent risk factor for LNM.^19,23 However, methodological differences may account for this discrepancy. For instance, Deng et al. included patients with para-aortic LNM,¹⁹ which conflated the risk factors for pelvic and para-aortic metastasis. Moreover, the inclusion of non-squamous subtypes, such as adenosquamous carcinoma, in these studies may limit the applicability of their findings to pure ADC populations.^19,23 Additionally, the lymphadenectomy procedure for ADC patients did not necessitate special modifications and could adhere to the same surgical guidelines established for SCC, given the absence of a significant difference in pelvic LNM rates between ADC and SCC.

LVSI was identified as the sole risk factor for the development of pelvic LNM in SCC patients in the current study. This finding contrasts with previous reports that associated LNM with multiple factors, including DOI, tumor size, PI, and pretreatment SCC concentration.^23,26–28 However, these prior studies were limited by either the restrictive inclusion of specific-stage patients or the pooling of all histological subtypes, which may restrict the generalizability of their findings. Few existing studies exclusively focused on SCC patients when assessing risk factors for LNM. Shang et al. revealed that LVSI, DOI, and PI were significantly associated with pelvic LNM in SCC patients, including a total of 266 early-stage cervical cancer patients undergoing radical surgery in their study.²⁹ However, the proportion of patients with positive PI was notably low in both Shang’s study (4.5%) and our cohort (5.7%), potentially undermining the credibility of these findings. For the pre-treatment assessment of LNM in SCC patients, one study reported that both serum SCC antigen levels and computed tomography evaluation held potential clinical value.³⁰ A previous study demonstrated that LVSI and tumor size were risk factors for developing pelvic LNM in ADC patients, while patients with PI were not incorporated into the analysis, which partially explains the discrepancy in risk factor identification between our findings and prior research.³¹ However, the generalizability of this finding might be limited by the small subset of ADC patients with PI (5.3%) included in our study, underscoring the need for validation in larger cohorts. As defined in historical literature, “small-pelvis radiotherapy” referred to pelvic radiotherapy in which the clinical target volume did not encompass the common iliac lymph node region. While previous studies have confirmed its safety and efficacy for postoperative patients with only intermediate-risk factors,^32–33 we recommended exercising greater caution when considering it for patients with LVSI or PI, due to their higher risk of pelvic LNM.

Pelvic LNM has been widely recognized as a negative factor affecting survival outcomes in early-stage CC patients; accordingly, more intensive adjuvant treatment is recommended for those with LNM following radical surgery.^9–14,17,18 Regrettably, none of these studies has separately investigated the significance of pelvic LNM on oncological outcomes for SCC and ADC patients, resulting in ambiguity regarding the role of pelvic LNM in guiding postoperative treatment for early-stage CC patients after radical surgery. The current study found that pelvic LNM significantly deteriorates DFS and OS for early-stage ADC patients receiving primary surgery, which is consistent with previous research.^34–36 Specifically, ADC patients with multiple LNM derived minimal benefit from more intensive adjuvant treatment.³⁵ Similarly, consolidation chemotherapy did not provide additional survival benefits for ADC patients who underwent radical surgery and adjuvant CCRT in this study. Additionally, research from a tertiary cancer center in China demonstrated that early-stage CC patients with non-squamous histology do not benefit from consolidation chemotherapy,³⁷ indicating that sufficient adjuvant treatment for ADC patients with pelvic LNM should be prioritized; specifically, small-pelvis radiotherapy should be avoided for these patients, and full-course concurrent chemotherapy should be guaranteed. Furthermore, innovative therapeutic interventions, such as novel drugs apart from chemotherapy, for early-stage ADC patients with pelvic LNM are urgently needed. Interestingly, our study revealed that pelvic LNM status was not associated with prognostic outcomes in early-stage SCC patients after radical surgery, a finding that diverges from existing literature.^7,38 However, these earlier investigations combined all CC histologic types in their analyses, thereby limiting their applicability in providing tailored clinical recommendations. Finally, while consolidation chemotherapy appeared to offer additional benefits for SCC patients with pelvic LNM following completion of CCRT in our study, limited references can be drawn from previous research due to the combined analysis of SCC and ADC patients.^37–39

Strengths and weaknesses

A comprehensive comparison of pelvic LNM between early-stage SCC and ADC patients was conducted, potentially providing more specific and instructive recommendations for clinical practice. Additionally, SCC and ADC patients were separately investigated in the current study, aligning with the heterogeneity between these patient groups and resulting in the provision of more informative and referential insights than previous research. Moreover, the efficacy of consolidation chemotherapy for early-stage CC patients was assessed separately in SCC and ADC cohorts, advocating for novel therapeutic approaches for ADC patients with pelvic LNM. However, this study has several inherent limitations, the most significant being selection bias due to its retrospective design. Additionally, the limited number of patients with PI might reduce the statistical power to reliably establish PI as a risk factor for pelvic LNM in early-stage ADC patients, underscoring the need for validation in larger cohorts with sufficient PI-positive cases.

Implications for practice and future research

Early-stage ADC patients did not exhibit a higher prevalence of pelvic LNM compared to their counterparts diagnosed with SCC. Furthermore, the presence of pelvic LNM significantly jeopardizes the survival outcomes for ADC patients and could not be improved by the addition of consolidation chemotherapy after the completion of adjuvant CCRT. In contrast, pelvic LNM does not confer inferior survival for early-stage SCC patients undergoing primary surgery, and these patients may gain potential benefits from consolidation chemotherapy. In the future, more innovative treatment approaches should be explored for early-stage ADC patients with pelvic LNM, while identifying specific patients who might benefit from consolidation chemotherapy will require deeper investigation for early-stage SCC patients with pelvic LNM.

Conclusion

No significant difference in the rate of pelvic LNM was observed between patients with ADC and those with SCC. The presence of LNM appeared to further impair oncological outcomes for ADC patients, whereas it did not have the same effect on SCC patients. It appeared that consolidation chemotherapy improved DFS for SCC while not for ADC patients. While this study provided valuable insights, its single-center nature might affect the generalizability of these findings. Future research involving multiple centers would allow for larger sample sizes and more robust conclusions.

Supplemental Material

sj-docx-1-tam-10.1177_17588359261425694 – Supplemental material for The differences of pelvic lymph node metastasis between squamous cell carcinoma and adenocarcinoma in early-stage cervical cancer patients undergoing radical surgery and adjuvant radiotherapy: a large cohort study

Supplemental material, sj-docx-1-tam-10.1177_17588359261425694 for The differences of pelvic lymph node metastasis between squamous cell carcinoma and adenocarcinoma in early-stage cervical cancer patients undergoing radical surgery and adjuvant radiotherapy: a large cohort study by Zheng Miao, Xi-Lin Yang, Jia-Wei Zhu, Yun-Can Zhou, Hui Guan, Jun-Fang Yan, Peng Peng and Fu-Quan Zhang in Therapeutic Advances in Medical Oncology

Footnotes

Acknowledgements

None.

Declarations

ORCID iDs

Jun-Fang Yan

Fu-Quan Zhang

Supplemental material

Supplemental material for this article is available online.

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