The Role of Micrometastasis and Isolated Tumor Cells (ITCs) in Endometrial and Cervical Cancer. A Multicenter Study.

Endometrial Neoplasms

Endometrial Neoplasms — a type of gynecological cancer.

Does small volume metastatic lymph node disease affect long-term prognosis in early cervical cancer?

As sentinel lymph node biopsy is evolving to an accepted standard of care, clinicians are being faced with more frequent cases of small volume nodal metastatic disease. The objective of this study is to describe the management and to measure the effect on recurrence rates of nodal micrometastasis and isolated tumor cells in patients with early stage cervical cancer at two high-volume centers. We conducted a review of prospectively collected patients with surgically treated cervical cancer who were found to have micrometastasis or isolated tumor cells on ultrastaging of the sentinel lymph node. Our practice is to follow patients for ≥5 years post-operatively either at our center or another cancer center closer to home. Nineteen patients with small volume nodal disease were identified between 2006 and 2018. Median follow-up was 62 months. Ten (53%) had nodal micrometastatic disease, while nine (47%) had isolated tumor cells detected in the sentinel lymph node. Seven patients (37%) underwent completion pelvic lymphadenectomy and four of them also had para-aortic lymphadenectomy; there were no positive non-sentinel lymph nodes. The majority (74%) received adjuvant treatment, mostly driven by tumor factors. We observed two recurrences. Recurrence-free survival was comparable with historical cohorts of node negative patients, and adjuvant treatment did not seem to impact the recurrence rate (p=0.5). Given the uncertainties around the prognostic significance of small volume nodal disease in cervical cancer, a large proportion of patients receive adjuvant treatment. We found no positive non-sentinel lymph nodes, suggesting that pelvic lymphadenectomy or para-aortic lymphadenectomy may not be of benefit in patients diagnosed with small volume nodal metastases. Recurrence-free survival in this group did not seem to be affected. However, given the small numbers of patients and lack of level 1 evidence, decisions should be individualized in accordance with patient preferences and tumor factors.

Oncologic impact of micrometastases or isolated tumor cells in sentinel lymph nodes of patients with endometrial cancer: a meta-analysis

There is a gap in knowledge regarding the impact of micrometastases (MIC) and isolated tumor cells (ITCs) found in the sentinel lymph nodes of patients with endometrial cancer. Here, we present a meta-analysis of the published literature on the rate of MIC and ITCs after lymphatic mapping and determine trends in postoperative management. Literature search of Medline and PubMed was done using the terms: micrometastases, isolated tumor cells, endometrial cancer, and sentinel lymph node. Inclusion criteria were: English-language manuscripts, retrospectives, or prospective studies published between January 1999 and June 2019. We removed manuscripts on sentinel node mapping that did not specify information on micrometastases or isolated tumor cells, non-English-language articles, no data about oncologic outcomes, and articles limited to ten cases or less. A total of 45 manuscripts were reviewed, and 8 studies met inclusion criteria. We found that the total number of patients with MIC/ITCs was 286 (187 and 99, respectively). The 72% of patients detected with MIC/ITCs in sentinel nodes received adjuvant therapies. The MIC/ITCs group has a higher relative risk of recurrence of 1.34 (1.07, 1.67) than the negative group, even if the adjuvant therapy was given. We noted that there is an increased relative risk of recurrence in patients with low-volume metastases, even after receiving adjuvant therapy. Whether adjuvant therapy is indicated remains a topic of debate because there are other uterine factors implicated in the prognosis. Multi-institutional tumor registries may help shed light on this important question.

Retrospective detection of isolated tumor cells by immunohistochemistry in sentinel lymph node biopsy performed for endometrial carcinoma: is there clinical significance?

Several studies have reported optimizing ultrastaging protocols using immunohistochemistry for sentinel lymph node (SLN) biopsy in endometrial carcinoma; however, the clinical significance of isolated tumor cells (ITCs) detected by ultrastaging is unknown. This study aimed to: (1) determine the frequency of retrospective ITC detection in patients with endometrial carcinoma and reported negative SLNs determined by hematoxylin and eosin (H&E) examination only; and (2) determine the clinicopathological features and outcomes of patients with endometrial carcinoma and previously undetected ITCs. 474 SLNs from 155 patients with endometrial carcinoma and reported negative SLNs were subjected to an immunohistochemistry protocol which included staining slides with cytokeratin at 1, 10, 20, and 50 µm levels, to examine for ITCs. Clinicopathological data of patients with ITCs detected by this method were analyzed to determine patient outcomes. Using immunohistochemistry, ITCs were detected in 5.7% (27/474) of SLNs and 13.5% (21/155) of patients with previously reported negative SLNs. In this patient cohort, 95.2% (20/21) had endometrioid histology, with the remaining case being carcinosarcoma. 38.1% (8/21) received adjuvant therapy (either brachytherapy alone (4/8) or chemotherapy and radiation (4/8)) based on other parameters, while 61.9% (13/21) had no adjuvant therapy. Of the patients who did not receive adjuvant therapy, all had endometrioid histology and 84.6% (11/13) were International Federation of Gynecology and Obstetrics (FIGO) stage IA. No patients (0/13) recurred after a median follow-up of 31.5 (range 2-84.4) months. In this study, 38.1% of patients with previously undetected ITCs had adjuvant treatment based on other high risk factors; as such, reporting ITCs would not have altered patient management for those who received adjuvant chemotherapy. To date, no patients with previously undetected ITCs without adjuvant treatment had a recurrence, suggesting that ITC detection may not be clinically relevant.

Natalia Rodriguez Gomez-Hidalgo