Real-World Data Assessing the Impact of Lymphovascular Space Invasion on the Diagnostic Performance of Sentinel Lymph Node Mapping in Endometrial Cancer
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Patient Cohort and Clinicopathological Data
2.2. Surgical Procedure
2.3. Outcomes
2.4. Statistical Analysis
3. Results
3.1. General Characteristics of the Whole Study Cohort
3.2. Clinicopathological Characteristics of Tumors with Lymphovascular Space Invasion
3.3. Performance of ICG SLN Mapping
3.4. Oncological Outcome
4. Discussion
4.1. Summary of the Main Results
4.2. Results in the Context of the Published Literature
4.3. Strengths and Weaknesses
4.4. Implications for Practice and Future Research
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Correction Statement
References
- Colombo, N.; Creutzberg, C.; Amant, F.; Bosse, T.; González-Martín, A.; Ledermann, J.; Marth, C.; Nout, R.; Querleu, D.; Mirza, M.R.; et al. ESMO-ESGO-ESTRO consensus conference on endometrial cancer: Diagnosis, treatment and follow-up. Ann. Oncol. 2016, 27, 16–41. [Google Scholar] [CrossRef]
- Siegel, R.L.; Miller, K.D.; Fuchs, H.E.; Jemal, A. Cancer Statistics. CA Cancer J. Clin. 2021, 71, 7–33. [Google Scholar] [CrossRef]
- Panici, P.B.; Basile, S.; Maneschi, F.; Lissoni, A.A.; Signorelli, M.; Scambia, G.; Angioli, R.; Tateo, S.; Mangili, G.; Katsaros, D.; et al. Systematic pelvic lymphadenectomy vs no lymphadenectomy in early-stage endometrial carcinoma: Randomized clinical trial. JNCI J. Natl. Cancer Inst. 2008, 100, 1707–1716. [Google Scholar] [CrossRef]
- ASTEC Study Group; Kitchener, H.; Swart, A.M.C.; Qian, Q.; Amos, C.; Parmar, M.K.B. Efficacy of systematic pelvic lymphadenectomy in endometrial cancer (MRC ASTEC trial): A randomised study. Lancet 2009, 373, 125–136. [Google Scholar] [CrossRef]
- Geppert, B.; Lönnerfors, C.; Bollino, M.; Persson, J. Sentinel lymph node biopsy in endometrial cancer—Feasibility, safety and lymphatic complications. Gynecol. Oncol. 2018, 148, 491–498. [Google Scholar] [CrossRef]
- Zikan, M.; Fischerova, D.; Pinkavova, I.; Slama, J.; Weinberger, V.; Dusek, L.; Cibula, D. A prospective study examining the incidence of asymptomatic and symptomatic lymphoceles following lymphadenectomy in patients with gynecological cancer. Gynecol. Oncol. 2015, 137, 291–298. [Google Scholar] [CrossRef]
- Imboden, S.; Mereu, L.; Siegenthaler, F.; Pellegrini, A.; Papadia, A.; Tateo, S.; Mueller, M.D. Oncological safety and perioperative morbidity in low-risk endometrial cancer with sentinel lymph-node dissection. Eur. J. Surg. Oncol. EJSO 2019, 45, 1638–1643. [Google Scholar] [CrossRef]
- Papadia, A.; Imboden, S.; Siegenthaler, F.; Gasparri, M.L.; Mohr, S.; Lanz, S.; Mueller, M.D. Laparoscopic Indocyanine Green Sentinel Lymph Node Mapping in Endometrial Cancer. Ann. Surg. Oncol. 2016, 23, 2206–2211. [Google Scholar] [CrossRef]
- Bogani, G.; Murgia, F.; Ditto, A.; Raspagliesi, F. Sentinel node mapping vs. lymphadenectomy in endometrial cancer: A systematic review and meta-analysis. Gynecol. Oncol. 2019, 153, 676–683. [Google Scholar] [CrossRef]
- Rossi, E.C.; Kowalski, L.D.; Scalici, J.; Cantrell, L.; Schuler, K.; Hanna, R.K.; Method, M.; Ade, M.; Ivanova, A.; Boggess, J.F. A comparison of sentinel lymph node biopsy to lymphadenectomy for endometrial cancer staging (FIRES trial): A multicentre, prospective, cohort study. Lancet Oncol. 2017, 18, 384–392. [Google Scholar] [CrossRef]
- Accorsi, G.S.; Paiva, L.L.; Schmidt, R.; Vieira, M.; Reis, R.; Andrade, C. Sentinel Lymph Node Mapping vs Systematic Lymphadenectomy for Endometrial Cancer: Surgical Morbidity and Lymphatic Complications. J. Minim. Invasive Gynecol. 2019, 27, 938–945. [Google Scholar] [CrossRef] [PubMed]
- Kahn, R.; Leitao, M. Mapping the landscape of sentinel lymph nodes in endometrial cancer: Let us continue in the right direction. Int. J. Gynecol. Cancer 2023, 33, 860–861. [Google Scholar] [CrossRef] [PubMed]
- Concin, N.; Matias-Guiu, X.; Vergote, I.; Cibula, D.; Mirza, M.R.; Marnitz, S.; Ledermann, J.; Bosse, T.; Chargari, C.; Fagotti, A.; et al. ESGO/ESTRO/ESP guidelines for the management of patients with endometrial carcinoma. Int. J. Gynecol. Cancer 2021, 31, 12–39. [Google Scholar] [CrossRef] [PubMed]
- dos Reis, R.; Burzawa, J.K.; Tsunoda, A.T.; Hosaka, M.; Frumovitz, M.; Westin, S.N.; Munsell, M.F.; Ramirez, P.T. Lymphovascular Space Invasion Portends Poor Prognosis in Low-Risk Endometrial Cancer. Int. J. Gynecol. Cancer 2015, 25, 1292–1299. [Google Scholar] [CrossRef] [PubMed]
- Bosse, T.; Peters, E.E.; Creutzberg, C.L.; Jürgenliemk-Schulz, I.M.; Jobsen, J.J.; Mens, J.W.M.; Lutgens, L.C.; van der Steen-Banasik, E.M.; Smit, V.T.; Nout, R.A. Substantial lymph-vascular space invasion (LVSI) is a significant risk factor for recurrence in endometrial cancer—A pooled analysis of PORTEC 1 and 2 trials. Eur. J. Cancer 2015, 51, 1742–1750. [Google Scholar] [CrossRef] [PubMed]
- Siegenthaler, F.; Epstein, E.; A Büchi, C.; Gmür, A.; Saner, F.A.C.M.; Rau, T.T.; Carlson, J.W.; Mueller, M.D.; Imboden, S. Prognostic value of lymphovascular space invasion according to the molecular subgroups in endometrial cancer. Int. J. Gynecol. Cancer 2023, 33, 1702–1707. [Google Scholar] [CrossRef] [PubMed]
- Jorge, S.; Hou, J.Y.; Tergas, A.I.; Burke, W.M.; Huang, Y.; Hu, J.C.; Ananth, C.V.; Neugut, A.I.; Hershman, D.L.; Wright, J.D. Magnitude of risk for nodal metastasis associated with lymphvascular space invasion for endometrial cancer. Gynecol. Oncol. 2016, 140, 387–393. [Google Scholar] [CrossRef]
- Raffone, A.; Fanfani, F.; Raimondo, D.; Rovero, G.; Renzulli, F.; Travaglino, A.; De Laurentiis, U.; Santoro, A.; Zannoni, G.F.; Casadio, P.; et al. Predictive factors of sentinel lymph node failed mapping in endometrial carcinoma patients: A systematic review and meta-analysis. Int. J. Gynecol. Cancer 2023, 33, 853–859. [Google Scholar] [CrossRef]
- Emons, G.; Steiner, E. S3 guidelines on the diagnosis and treatment of carcinoma of the endometrium: Requirements for pathology. Pathologe 2018, 51, 996–999. [Google Scholar] [CrossRef]
- Smith, A.J.B.; Fader, A.N.; Tanner, E.J. Sentinel lymph node assessment in endometrial cancer: A systematic review and meta-analysis. Am. J. Obstet. Gynecol. 2017, 216, 459–476.e10. [Google Scholar] [CrossRef]
- Peters, E.E.; León-Castillo, A.; Smit, V.T.; Boennelycke, M.; Hogdall, E.; Hogdall, C.; Creutzberg, C.; Jürgenliemk-Schulz, I.M.; Jobsen, J.J.; Mens, J.W.M.; et al. Defining Substantial Lymphovascular Space Invasion in Endometrial Cancer. Int. J. Gynecol. Pathol. 2021, 41, 220–226. [Google Scholar] [CrossRef] [PubMed]
- Briët, J.M.; Hollema, H.; Reesink, N.; Aalders, J.G.; Mourits, M.J.; Hoor, K.A.T.; Pras, E.; Boezen, H.M.; van der Zee, A.G.; Nijman, H.W. Lymphvascular space involvement: An independent prognostic factor in endometrial cancer. Gynecol. Oncol. 2005, 96, 799–804. [Google Scholar] [CrossRef] [PubMed]
- Matanes, E.; Eisenberg, N.; Lau, S.; Salvador, S.; Ferenczy, A.; Pelmus, M.; Gotlieb, W.H.; Kogan, L. Absence of prognostic value of lymphovascular space invasion in patients with endometrial cancer and negative sentinel lymph nodes. Gynecol. Oncol. 2021, 162, 256–261. [Google Scholar] [CrossRef] [PubMed]
- Li, W.; Jiang, J.; Fu, Y.; Shen, Y.; Zhang, C.; Yao, S.; Xu, C.; Xia, M.; Lou, G.; Liu, J.; et al. Implications of Isolated Para-Aortic Lymph Node Metastasis in Endometrial Cancer: A Large-Scale, Multicenter, and Retrospective Study. Front. Med. 2021, 8, 754890. [Google Scholar] [CrossRef]
- McMeekin, D.; Lashbrook, D.; Gold, M.; Scribner, D.R.; Kamelle, S.; Tillmanns, T.D.; Mannel, R. Nodal distribution and its significance in FIGO stage IIIc endometrial cancer. Gynecol. Oncol. 2001, 82, 375–379. [Google Scholar] [CrossRef]
- Holloway, R.W.; Abu-Rustum, N.R.; Backes, F.J.; Boggess, J.F.; Gotlieb, W.H.; Lowery, W.J.; Rossi, E.C.; Tanner, E.J.; Wolsky, R.J. Sentinel lymph node mapping and staging in endometrial cancer: A Society of Gynecologic Oncology literature review with consensus recommendations. Gynecol. Oncol. 2017, 146, 405–415. [Google Scholar] [CrossRef]
- Kumar, S.; Podratz, K.C.; Bakkum-Gamez, J.N.; Dowdy, S.C.; Weaver, A.L.; McGree, M.E.; Cliby, W.A.; Keeney, G.L.; Thomas, G.; Mariani, A. Prospective assessment of the prevalence of pelvic, paraaortic and high paraaortic lymph node metastasis in endometrial cancer. Gynecol. Oncol. 2014, 132, 38–43. [Google Scholar] [CrossRef]
- Chang, S.-J.; Kong, T.W.; Kim, W.Y.; Yoo, S.-C.; Yoon, J.-H.; Chang, K.-H.; Ryu, H.-S. LLymph-vascular space invasion as a significant risk factor for isolated para-aortic lymph node metastasis in endometrial cancer: A study of 203 consecutive patients. Ann. Surg. Oncol. 2010, 18, 58–64. [Google Scholar] [CrossRef]
- Legge, F.; Restaino, S.; Leone, L.; Carone, V.; Ronsini, C.; Di Fiore, G.L.M.; Pasciuto, T.; Pelligra, S.; Ciccarone, F.; Scambia, G.; et al. Clinical outcome of recurrent endometrial cancer: Analysis of post-relapse survival by pattern of recurrence and secondary treatment. Int. J. Gynecol. Cancer 2019, 30, 193–200. [Google Scholar] [CrossRef]
- Raffone, A.; Travaglino, A.; Raimondo, D.; Neola, D.; Maletta, M.; Santoro, A.; Insabato, L.; Casadio, P.; Fanfani, F.; Zannoni, G.F.; et al. Lymphovascular space invasion in endometrial carcinoma: A prognostic factor independent from molecular signature. Gynecol. Oncol. 2022, 165, 192–197. [Google Scholar] [CrossRef]
- Harris, K.L.; Maurer, K.A.; Jarboe, E.; Werner, T.L.; Gaffney, D. LVSI positive and NX in early endometrial cancer: Surgical restaging (and no further treatment if N0), or adjuvant ERT? Gynecol. Oncol. 2020, 156, 243–250. [Google Scholar] [CrossRef] [PubMed]
- Persson, J.; Geppert, B.; Lönnerfors, C.; Bollino, M.; Måsbäck, A. Description of a reproducible anatomically based surgical algorithm for detection of pelvic sentinel lymph nodes in endometrial cancer. Gynecol. Oncol. 2017, 147, 120–125. [Google Scholar] [CrossRef] [PubMed]
- Son, J.; Chambers, L.M.; Carr, C.; Michener, C.M.; Yao, M.; Beavis, A.; Yen, T.-T.; Stone, R.L.; Wethington, S.L.; Fader, A.N.; et al. Adjuvant treatment improves overall survival in women with high-intermediate risk early-stage endometrial cancer with lymphovascular space invasion. Int. J. Gynecol. Cancer 2020, 30, 1738–1747. [Google Scholar] [CrossRef] [PubMed]
Whole Study Cohort (n = 466) | |
---|---|
Mean age, years ± SD | 65.7 ± 11.3 |
Mean BMI, kg/m2 ± SD | 29.2 ± 7.5 |
Menopausal status, n (%) | |
| 55 (11.8) |
| 409 (87.8) |
| 2 (0.4) |
Surgical approach, n (%) | |
| 449 (96.4) |
| 2 (0.4) |
| 15 (3.2) |
FIGO stage, n (%) | |
| 353 (75.8) |
| 21 (4.5) |
| 87 (18.7) |
| 5 (1.1) |
Grading, n (%) | |
| 160 (34.3) |
| 165 (35.4) |
| 141 (30.3) |
Histological subtype, n (%) | |
| 379 (81.3) |
| 29 (6.2) |
| 11 (2.4) |
| 2 (0.4) |
| 21 (4.5) |
| 23 (4.9) |
| 1 (0.2) |
Lymphovascular space invasion, n (%) | |
| 101 (21.7) |
| 359 (77.0) |
| 6 (1.3) |
Blood vessel invasion, n (%) | |
| 45 (9.7) |
| 415 (89.1) |
| 6 (1.3) |
Lymph node metastasis, n (%) | |
| 69 (14.8) |
| 392 (84.1) |
| 5 (1.1) |
Adjuvant treatment, n (%) | |
| 219 (47.0) |
| 4 (0.9) |
| 121 (26.0) |
| 107 (23.0) |
| 14 (3.0) |
| 1 (0.2) |
LVSI Negative (n = 359) | LVSI Positive (n = 101) | p-Value a | |
---|---|---|---|
Mean age, years ± SD | 64.9 ± 11.2 | 69.3 ± 10.6 | <0.001 |
Advanced FIGO stage, n (%) | 31 (8.6) | 61 (60.4) | <0.001 |
High-grade tumors, n (%) | 90 (25.1) | 50 (49.5) | <0.001 |
Tumor size, mm ± SD | 27.1 ± 18.6 | 47.9 ± 24.5 | <0.001 |
Endometrioid histology, n (%) | 301 (83.8) | 71 (70.3) | 0.002 |
Deep myometrial invasion (>50%), n (%) | 98 (27.3) | 72 (71.3) | <0.001 |
Lymph node metastasis, n (%) | 13 (3.6) | 56 (55.4) | <0.001 |
Adjuvant treatment, n (%) | 157 (43.7) | 90 (89.1) | <0.001 |
Whole Study Cohort (n = 466) | LVSI Negative (n = 359) | LVSI Positive (n = 101) | p-Value | |
---|---|---|---|---|
SLN mapping, n (%) | ||||
| 424 (91.0) | 325 (90.5) | 93 (92.1) | |
| 30 (6.4) | 24 (6.7) | 6 (5.9) | |
| 12 (2.6) | 10 (2.8) | 2 (2.0) | 0.868 |
Number of sentinel lymph nodes removed, mean ± SD | 3.9 ± 2.5 | 3.9 ± 2.5 | 4.0 ± 2.5 | 0.604 |
LN staging performed, n (%) | ||||
| 278 (59.7) | 240 (66.9) | 32 (31.7) | |
| 188 (40.3) | 119 (33.1) | 69 (68.3) | <0.001 |
SLN metastasis, n (%) | ||||
| 396 (85.0) | 340 (94.7) | 50 (49.5) | |
| 3 (0.6) | 2 (0.6) | 1 (1.0) | |
| 14 (3.0) | 2 (0.6) | 12 (11.9) | |
| 41 (8.8) | 5 (1.4) | 36 (35.6) | |
| 12 (2.6) | 10 (2.8) | 2 (2.0) | <0.001 |
Isolated para-aortic lymph node metastasis, n (%) | 14 (3.0) | 3 (0.8) | 11 (10.9) | <0.001 |
Clinicopathological Factor | p-Value | HR | 95% CI |
---|---|---|---|
Lymphovascular space invasion | 0.036 | ||
No (ref) | 1.0 | Reference | |
Yes | 3.480 | 1.073–11.289 | |
Grading | 0.415 | ||
Low grade (G1, G2) (ref) | 1.0 | Reference | |
High grade (G3) | 2.516 | 0.273–23.191 | |
Tumor stage | 0.026 | ||
Early stage (FIGO I and II) (ref) | 1.0 | Reference | |
Advanced stage (FIGO III and IV) | 6.926 | 1.262–38.002 |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Buechi, C.A.; Siegenthaler, F.; Sahli, L.; Papadia, A.; Saner, F.A.M.; Mohr, S.; Rau, T.T.; Solass, W.; Imboden, S.; Mueller, M.D. Real-World Data Assessing the Impact of Lymphovascular Space Invasion on the Diagnostic Performance of Sentinel Lymph Node Mapping in Endometrial Cancer. Cancers 2024, 16, 67. https://doi.org/10.3390/cancers16010067
Buechi CA, Siegenthaler F, Sahli L, Papadia A, Saner FAM, Mohr S, Rau TT, Solass W, Imboden S, Mueller MD. Real-World Data Assessing the Impact of Lymphovascular Space Invasion on the Diagnostic Performance of Sentinel Lymph Node Mapping in Endometrial Cancer. Cancers. 2024; 16(1):67. https://doi.org/10.3390/cancers16010067
Chicago/Turabian StyleBuechi, Carol A., Franziska Siegenthaler, Laura Sahli, Andrea Papadia, Flurina A. M. Saner, Stefan Mohr, Tilman T. Rau, Wiebke Solass, Sara Imboden, and Michael D. Mueller. 2024. "Real-World Data Assessing the Impact of Lymphovascular Space Invasion on the Diagnostic Performance of Sentinel Lymph Node Mapping in Endometrial Cancer" Cancers 16, no. 1: 67. https://doi.org/10.3390/cancers16010067
APA StyleBuechi, C. A., Siegenthaler, F., Sahli, L., Papadia, A., Saner, F. A. M., Mohr, S., Rau, T. T., Solass, W., Imboden, S., & Mueller, M. D. (2024). Real-World Data Assessing the Impact of Lymphovascular Space Invasion on the Diagnostic Performance of Sentinel Lymph Node Mapping in Endometrial Cancer. Cancers, 16(1), 67. https://doi.org/10.3390/cancers16010067