Low-Volume Metastases in Apparent Early-Stage Endometrial Cancer: Prevalence, Clinical Significance, and Future Perspectives.
Diletta Fumagalli, Luigi A De Vitis, Giuseppe Caruso, Tommaso Occhiali, Emilia Palmieri, Benedetto E Guillot, Giulia Pappalettera, Carrie L Langstraat, Gretchen E Glaser, Evelyn A Reynolds, Robert Fruscio, Fabio Landoni, Andrea Mariani, Tommaso Grassi
Author Information
Diletta Fumagalli: Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Mayo Clinic, Rochester, MN 55905, USA. ORCID
Luigi A De Vitis: Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Mayo Clinic, Rochester, MN 55905, USA.
Giuseppe Caruso: Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Mayo Clinic, Rochester, MN 55905, USA. ORCID
Tommaso Occhiali: Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Mayo Clinic, Rochester, MN 55905, USA.
Emilia Palmieri: Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Mayo Clinic, Rochester, MN 55905, USA. ORCID
Benedetto E Guillot: Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Mayo Clinic, Rochester, MN 55905, USA.
Giulia Pappalettera: Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Mayo Clinic, Rochester, MN 55905, USA.
Carrie L Langstraat: Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Mayo Clinic, Rochester, MN 55905, USA.
Gretchen E Glaser: Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Mayo Clinic, Rochester, MN 55905, USA.
Evelyn A Reynolds: Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Mayo Clinic, Rochester, MN 55905, USA.
Robert Fruscio: Department of Medicine and Surgery, University of Milan-Bicocca, 20126 Milan, Italy. ORCID
Fabio Landoni: Department of Medicine and Surgery, University of Milan-Bicocca, 20126 Milan, Italy. ORCID
Andrea Mariani: Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Mayo Clinic, Rochester, MN 55905, USA.
Tommaso Grassi: Department of Medicine and Surgery, University of Milan-Bicocca, 20126 Milan, Italy. ORCID
Endometrial cancer (EC) is the most diagnosed gynecologic malignancy, and its incidence and mortality are increasing. The prognosis is highly dependent on the disease spread. Surgical staging includes retroperitoneal evaluation to detect potential lymph node metastases. In recent years, systematic lymphadenectomy has been replaced by sentinel lymph node (SLN) biopsy and ultrastaging, allowing for the detection of macrometastases, micrometastases, and isolated tumor cells (ITCs). Micrometastases and ITCs have been grouped as low-volume metastases (LVM). The reported prevalence of LVM in studies enrolling more than one thousand patients with apparent early-stage EC ranges from 1.9% to 10.2%. Different rates of LVM are observed when patients are stratified according to disease characteristics and their risk of recurrence. Patients with EC at low risk for recurrence have low rates of LVM, while intermediate- and high-risk patients have a higher likelihood of being diagnosed with nodal metastases, including LVM. Macro- and micrometastases increase the risk of recurrence and cause upstaging, while the clinical significance of ITCs is still uncertain. A recent meta-analysis found that patients with LVM have a higher relative risk of recurrence [1.34 (95% CI: 1.07-1.67)], regardless of adjuvant treatment. In a retrospective study on patients with low-risk EC and no adjuvant treatment, those with ITCs had worse recurrence-free survival compared to node-negative patients (85.1%; CI 95% 73.8-98.2 versus 90.2%; CI 95% 84.9-95.8). However, a difference was no longer observed after the exclusion of cases with lymphovascular space invasion. There is no consensus on adjuvant treatment in ITC patients at otherwise low risk, and their recurrence rate is low. Multi-institutional, prospective studies are warranted to evaluate the clinical significance of ITCs in low-risk patients. Further stratification of patients, considering histopathological and molecular features of the disease, may clarify the role of LVM and especially ITCs in specific contexts.
