Characterizing isolated tumor cells in regional lymph nodes of early endometrial cancer

Matsuo, Koji; Khetan, Varun; Brunette, Laurie L.; Jooya, Neda; Klar, Maximilian; Wright, Jason D.; Roman, Lynda D.

doi:10.1016/j.ygyno.2022.02.015

Cited by 6 publications

(15 citation statements)

References 19 publications

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“…These data, together with other studies, suggest that ITCs are likely a harbinger for early tumor spread and metastasis. 9,16,17 Among the tumor factors associated with ITCs, the risk was greatest when LVSI was observed.…”

Section: Discussionmentioning

confidence: 99%

“…20 Specimens from patients who receive SLN biopsy typically undergo ultrastaging, which is more likely to identify ITCs. 9,16,21 Based on these trends, we anticipate that detection of ITCs will be increasingly frequent in the future. Decreased rates of ITCs in Black compared with White individuals may possibly be due to the decreased utilization of SLN biopsy.…”

Section: Discussionmentioning

confidence: 99%

“…[5][6][7][8][9] In clinical practice in the United States, despite the lack of clear consensus and recommendations, health care practitioners frequently offer adjuvant therapy for patients with ITCs identified in the regional lymph nodes. 9 This trend in the use of adjuvant therapy includes patients with tumors with an otherwise low risk of recurrence for whom prognosis is generally favorable and adjuvant therapy has historically not been indicated. 4,9,10 Several investigators have previously suggested that ITCs are not prognostic and adjuvant therapy based on the presence of ITCs alone may not improve survival.…”

Section: Introductionmentioning

confidence: 99%

“…9 This trend in the use of adjuvant therapy includes patients with tumors with an otherwise low risk of recurrence for whom prognosis is generally favorable and adjuvant therapy has historically not been indicated. 4,9,10 Several investigators have previously suggested that ITCs are not prognostic and adjuvant therapy based on the presence of ITCs alone may not improve survival. 5,7,11 Thus, the objective of the current study was to assess clinico-pathological characteristics and oncologic outcomes associated with ITCs in patients with endometrial cancer in a large, nationwide population.…”

Section: Introductionmentioning

confidence: 99%

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Lymph Node Isolated Tumor Cells in Patients With Endometrial Cancer

Matsuo,

Chen,

Neuman

et al. 2024

JAMA Netw Open

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ImportanceIsolated tumor cells (ITCs) are the histopathological finding of small clusters of cancer cells no greater than 0.2 mm in diameter in the regional lymph nodes. For endometrial cancer, the prognostic significance of ITCs is uncertain.ObjectiveTo assess clinico-pathological characteristics and oncologic outcomes associated with ITCs in endometrial cancer.Design, Setting, and ParticipantsThis retrospective cohort study using the National Cancer Database included patients with endometrial cancer who had primary hysterectomy and nodal evaluation from 2018 to 2020. Patients with microscopic and macroscopic nodal metastases and distant metastases were excluded. Data were analyzed from June to September 2023.ExposureRegional nodal status with ITCs (N0[i+] classification) or no nodal metastasis (N0 classification).Main Outcomes and Measures(1) Clinical and tumor characteristics associated with ITCs, assessed with multivariable binary logistic regression model, and (2) overall survival (OS) associated with ITCs, evaluated by nonproportional hazard analysis with restricted mean survival time at 36 months.ResultsA total of 56 527 patients were included, with a median (IQR) age of 64 (57-70) years. The majority had T1a lesion (37 836 [66.9%]) and grade 1 or 2 endometrioid tumors (40 589 [71.8%]). ITCs were seen in 1462 cases (2.6%). In a multivariable analysis, ITCs were associated with higher T classification, larger tumor size, lymphovascular space invasion (LVSI), and malignant peritoneal cytology. Of those tumor factors, LVSI had the largest association with ITCs (7.9% vs 1.4%; adjusted odds ratio [aOR], 4.37; 95% CI, 3.87-4.93), followed by T1b classification (5.3% vs 1.3%; aOR, 2.62; 95% CI, 2.30-2.99). At the cohort level, 24-month OS rates were 94.3% (95% CI, 92.4%-95.7%) for the ITC group and 96.1% (95% CI, 95.9%-96.3%) for the node-negative group, and the between-group difference in expected mean OS time at 36 months was 0.35 (SE, 0.19) months, but it was not statistically significant (P = .06). There was a statistically significant difference in OS when the low-risk group (stage IA, grade 1-2 endometrioid tumors with no LVSI) was assessed per nodal status and adjuvant therapy use (P &lt; .001): (1) among the cases treated with surgical therapy alone, 24-month OS rates were 95.9% (95% CI, 89.5%-98.5%) for the ITC group and 98.8% (95% CI, 98.6%-99.0%) for the node-negative group, and the between-group mean OS time difference at 36 months was 0.61 (SE, 0.43) months (P = .16); and (2) among the cases with ITCs, adjuvant therapy (radiotherapy alone, systemic chemotherapy alone, or both) was associated with improved survival compared with no adjuvant therapy (24-month OS rates, 100% vs 95.9%; between-group mean OS time difference at 36 months, 0.95 [SE, 0.43] months; P = .03).Conclusions and RelevanceIn this cohort study of patients with surgically staged endometrial cancer, the results of exploratory analysis suggested that presence of ITCs in the regional lymph node may be associated with OS in the low-risk group. While adjuvant therapy was associated with improved OS in the low-risk group with ITCs, careful interpretation is necessary given the favorable outcomes regardless of adjuvant therapy use. This hypothesis-generating observation in patients with low-risk endometrial cancer warrants further investigation, especially with prospective setting.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Lymph Node Isolated Tumor Cells in Patients With Endometrial Cancer

Matsuo,

Chen,

Neuman

et al. 2024

JAMA Netw Open

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“…The finding of ITC and its management is slightly more ambiguous. The incidence of ITC ranged from 2% to 36% [ 74 , 75 , 76 ], and was associated with deep myometrial invasion and tumor size [ 75 ]. A survey amongst gynecologic oncologists in Society of Gynecologic Oncology (SGO) in 2017 found that 21% would treat ITC as node positive disease [ 77 ].…”

Section: Management Of Sln- and Non-sln Metastasismentioning

confidence: 99%

Applications and Safety of Sentinel Lymph Node Biopsy in Endometrial Cancer

Chiu

Kwok

Wang

et al. 2022

JCM

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Lymph node status is important in predicting the prognosis and guiding adjuvant treatment in endometrial cancer. However, previous studies showed that systematic lymphadenectomy conferred no therapeutic values in clinically early-stage endometrial cancer but might lead to substantial morbidity and impact on the quality of life of the patients. The sentinel lymph node is the first lymph node that tumor cells drain to, and sentinel lymph node biopsy has emerged as an acceptable alternative to full lymphadenectomy in both low-risk and high-risk endometrial cancer. Evidence has demonstrated a high detection rate, sensitivity and negative predictive value of sentinel lymph node biopsy. It can also reduce surgical morbidity and improve the detection of lymph node metastases compared with systematic lymphadenectomy. This review summarizes the current techniques of sentinel lymph node mapping, the applications and oncological outcomes of sentinel lymph node biopsy in low-risk and high-risk endometrial cancer, and the management of isolated tumor cells in sentinel lymph nodes. We also illustrate a revised sentinel lymph node biopsy algorithm and advocate to repeat the tracer injection and explore the presacral and paraaortic areas if sentinel lymph nodes are not found in the hemipelvis.

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