Tailoring Endometrial Cancer Treatment Based on Molecular Pathology: Current Status and Possible Impacts on Systemic and Local Treatment
Abstract
:1. Introduction
2. Molecular Assessment—From Bokhman’s to TCGA and Beyond
Type | POLE (Ultramutated) | MSI (Hypermutated)/MMRd | Copy-Number Low (Endometrioid)/p53wt | Copy-Number High (Serous-like)/p53abn |
---|---|---|---|---|
Prevalence | 7% | 28% | 39% | 26% |
Mutation frequency | Very high (>100 mutations/Mb) | High (10–100 mutations/Mb) | Low (<10 mutations/Mb) | Low (<10 mutations/Mb) |
Commonly mutated genes | POLE (100%) DMD (100%) CSMD1 (100%) FAT4 (100%) PTEN (94%) | PTEN (88%) PIK3CA (54%) PIK3R1 (42%) RPL22 (37%) ARID1A (37%) | PTEN (77%) PIK3CA (53%) CTNNB1 (52%) ARID1A (42%) PIK3R1 (33%) | TP53 (92%) PIK3CA (47%) FBXW7 (22%) PPP2R1A (22%) PTEN (10%) |
Copy number aberrations | Very low | Low | Low | High |
MSI/MLH1 methylation | Mixed High and Low MSI, stable | High MSI (MLH1, PMS2, MSH2, and/or MSH6 deficiency) | MSI stable | MSI stable |
Histological subtype | Endometrioid | Mostly endometrioid | Endometrioid | Serous, 25% high-grade endometrioid and mixed G3 |
Grade | G1-G3 | G1-G3 | G1-G2 | G3 |
Other features | Ambiguous histomorphology Dense immune infiltrates | Display tumor infiltrate lymphocytes | CTNNB mutations are associated with poor prognosis Subgroup with amplification of chromosome arm 1p has poor prognosis | Similar to high-grade serous ovarian cancer L1CAM expression associated with poor prognosis |
Prognosis | Good | Moderate | Moderate | Poor |
Diagnostic test | Sanger/NGS Tumor mutation burden | MMR-IHC (MLH1, MSH2, MSH6, PMS2) MSI assay Tumor mutation burden | p53-IHC NGS Somatic copy-number aberrations |
3. Biomarkers and Therapeutic Targets
4. Current and Future Impact on Surgery
5. Current and Future Impact in the Adjuvant Systemic Therapy
6. Current and Future Impact on Radiotherapy
7. Current and Future Impact on the Systemic Treatment of the Advanced Disease
8. Conclusions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
CDK4/6 | Cyclin-dependent kinases 4 and 6 |
CT | Chemotherapy |
CTRT | Concurrent chemoradiotherapy |
DSS | Disease-specific survival |
EC | Endometrial cancer |
ER | Estrogen receptor |
ESGO | European Society of Gynecological Oncology |
ESMO | European Society for Medical Oncology |
ESP | European Society of Pathology |
ESTRO | European Society for Radiotherapy and Oncology |
FDA | Food and Drug Administration |
FIGO | International Federation of Gynecology and Obstetrics |
FST | Fertility-sparing treatment |
HER2 | Human epidermal growth factor receptor |
HRD | Homologous recombination deficiency |
ICI | Immune checkpoint inhibitors |
IHC | Immunohistochemistry |
L1CAM | L1-cell adhesion molecule |
LPS | Laparoscopic |
LPT | Laparotomic |
LSVI | Lymphovascular space invasion |
MMR | Mismatch repair |
MMRd | Mismatch repair deficiency |
NSMP | Nonspecific molecular subtype |
ORR | Objective response rate |
OS | Overall survival |
PARP | Poly-ADP ribose polymerase |
PFS | Progression free survival |
PR | Progesterone receptor |
ProMise | Proactive Molecular Risk Classifier for Endometrial Cancer |
QALY | Quality-adjusted life-year |
RFS | Relapse-free survival |
RT | Radiotherapy |
TCGA | The Cancer Genome Atlas |
TH/BSO | Bilateral Slapingo-oophorectomy |
TMT | Tumor molecular testing |
References
- Ferlay, J.E.M.; Lam, F.; Laversanne, M.; Colombet, M.; Mery, L.; Piñeros, M.; Znaor, A.; Soerjomataram, I.; Bray, F. Global Cancer Observatory: Cancer Today. 2024. Available online: https://gco.iarc.who.int/today (accessed on 15 April 2024).
- Vicky, M.; MacKay, H.; Ray-Coquard, I.; Levine, D.A.; Westin, S.N.; Daisuke, A.; Ana, O. Endometrial cancer. Nat. Rev. Dis. Primers 2021, 7, 88. [Google Scholar]
- Raglan, O.; Kalliala, I.; Markozannes, G.; Cividini, S.; Gunter, M.J.; Nautiyal, J.; Gabra, H.; Paraskevaidis, E.; Martin-Hirsch, P.; Tsilidis, K.K.; et al. Risk factors for endometrial cancer: An umbrella review of the literature. Int. J. Cancer 2019, 145, 1719–1730. [Google Scholar] [CrossRef] [PubMed]
- Society, A.C. 5-Year Relative Survival Rates for Endometrial Cancer. Available online: https://www.cancer.org/cancer/types/endometrial-cancer/detection-diagnosisstaging/survival-rates.html (accessed on 15 April 2024).
- Bokhman, J.V. Two pathogenetic types of endometrial carcinoma. Gynecol. Oncol. 1983, 15, 10–17. [Google Scholar] [CrossRef] [PubMed]
- WHO. Classification of Tumours Editorial Board, 5th ed.; Female Genital Tumours; IARC: Lyon, France, 2020; Volume 4. [Google Scholar]
- Oaknin, A.; Bosse, T.; Creutzberg, C.; Giornelli, G.; Harter, P.; Joly, F.; Lorusso, D.; Marth, C.; Makker, V.; Mirza, M.; et al. Endometrial cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann. Oncol. 2022, 33, 860–877. [Google Scholar] [CrossRef] [PubMed]
- Wilczynski, M.; Danielska, J.; Wilczynski, J. An update of the classical Bokhman’s dualistic model of endometrial cancer. Prz. Menopauzalny 2016, 15, 63–68. [Google Scholar] [CrossRef] [PubMed]
- Weinstein, J.N.; Collisson, E.A.; Mills, G.B.; Shaw, K.R.; Ozenberger, B.A.; Ellrott, K.; Shmulevich, I.; Sander, C.; Stuart, J.M. The Cancer Genome Atlas Pan-Cancer analysis project. Nat. Genet. 2013, 45, 1113–1120. [Google Scholar] [CrossRef] [PubMed]
- Morice, P.; Leary, A.; Creutzberg, C.; Abu-Rustum, N.; Darai, E. Endometrial cancer. Lancet 2016, 387, 1094–1108. [Google Scholar] [CrossRef] [PubMed]
- Charo, L.M.; Plaxe, S.C. Recent advances in endometrial cancer: A review of key clinical trials from 2015 to 2019. F1000Res 2019, 8, 849. [Google Scholar] [CrossRef] [PubMed]
- Marnitz, S.; Walter, T.; Schömig-Markiefka, B.; Engler, T.; Kommoss, S.; Brucker, S.Y. A Modern Approach to Endometrial Carcinoma: Will Molecular Classification Improve Precision Medicine in the Future? Cancers 2020, 12, 2577. [Google Scholar] [CrossRef]
- McCluggage, W.G.; Bosse, T.; Gilks, C.B.; Howitt, B.E.; McAlpine, J.N.; Nucci, M.R.; Rabban, J.T.; Singh, N.; Talia, K.L.; Parra-Herran, C. FIGO 2023 endometrial cancer staging: Too much, too soon? Int. J. Gynecol. Cancer 2023, 34, 138–143. [Google Scholar] [CrossRef]
- Rulten, S.L.; Grose, R.P.; Gatz, S.A.; Jones, J.L.; Cameron, A.J.M. The Future of Precision Oncology. Int. J. Mol. Sci. 2023, 24, 12613. [Google Scholar] [CrossRef] [PubMed]
- Meric-Bernstam, F.; Makker, V.; Oaknin, A.; Oh, D.Y.; Banerjee, S.; González-Martín, A.; Jung, K.H.; Ługowska, I.; Manso, L.; Manzano, A.; et al. Efficacy and Safety of Trastuzumab Deruxtecan in Patients with HER2-Expressing Solid Tumors: Primary Results from the DESTINY-PanTumor02 Phase II Trial. J. Clin. Oncol. 2024, 42, 47–58. [Google Scholar] [CrossRef] [PubMed]
- Mirza, M.R.; Chase, D.M.; Slomovitz, B.M.; Christensen, R.D.; Novák, Z.; Black, D.; Gilbert, L.; Sharma, S.; Valabrega, G.; Landrum, L.M.; et al. Dostarlimab for Primary Advanced or Recurrent Endometrial Cancer. N. Engl. J. Med. 2023, 388, 2145–2158. [Google Scholar] [CrossRef] [PubMed]
- Vergote, I.; Pérez-Fidalgo, J.A.; Hamilton, E.P.; Valabrega, G.; Van Gorp, T.; Sehouli, J.; Cibula, D.; Levy, T.; Welch, S.; Richardson, D.L.; et al. Oral Selinexor as Maintenance Therapy after First-Line Chemotherapy for Advanced or Recurrent Endometrial Cancer. J. Clin. Oncol. 2023, 41, 5400–5410. [Google Scholar] [CrossRef] [PubMed]
- Westin, S.N.; Moore, K.; Chon, H.S.; Lee, J.-Y.; Pepin, J.T.; Sundborg, M.; Shai, A.; de la Garza, J.; Nishio, S.; Gold, M.A.; et al. Durvalumab plus Carboplatin/Paclitaxel Followed by Maintenance Durvalumab with or without Olaparib as First-Line Treatment for Advanced Endometrial Cancer: The Phase III DUO-E Trial. J. Clin. Oncol. 2024, 42, 283–299. [Google Scholar] [CrossRef]
- Kurman, R.J.; International Agency for Research on Cancer; World Health Organization. WHO Classification of Tumours of Female Reproductive Organs, 4th ed.; World Health Organization Classification of Tumours; International Agency for Research on Cancer: Lyon, France, 2014; 307p. [Google Scholar]
- Paudice, M.; Biatta, C.M.; Scaglione, G.; Parodi, A.; Mammoliti, S.; Moioli, M.; Centurioni, M.G.; Barra, F.; Ferrero, S.; De Cian, F.; et al. Histopathological and Immunohistochemical Prognostic Factors in High-Grade Non-Endometrioid Carcinomas of the Endometrium (HG-NECs): Is It Possible to Identify Subgroups at Increased Risk? Diagnostics 2023, 13, 2171. [Google Scholar] [CrossRef] [PubMed]
- Le Gallo, M.; Bell, D.W. The emerging genomic landscape of endometrial cancer. Clin. Chem. 2014, 60, 98–110. [Google Scholar] [CrossRef]
- Murali, R.; Soslow, R.A.; Weigelt, B. Classification of endometrial carcinoma: More than two types. Lancet Oncol. 2014, 15, e268–e278. [Google Scholar] [CrossRef] [PubMed]
- Levine, D.A.; The Cancer Genome Atlas Research Network. Integrated genomic characterization of endometrial carcinoma. Nature 2013, 497, 67–73. [Google Scholar] [CrossRef]
- Liaw, D.; Marsh, D.J.; Li, J.; Dahia, P.L.M.; Wang, S.I.; Zheng, Z.; Bose, S.; Call, K.M.; Tsou, H.C.; Peacoke, M.; et al. Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome. Nat. Genet. 1997, 16, 64–67. [Google Scholar] [CrossRef]
- van den Heerik, A.; Horeweg, N.; de Boer, S.M.; Bosse, T.; Creutzberg, C.L. Adjuvant therapy for endometrial cancer in the era of molecular classification: Radiotherapy, chemoradiation and novel targets for therapy. Int. J. Gynecol. Cancer 2021, 31, 594–604. [Google Scholar] [CrossRef]
- Bosse, T.; Nout, R.A.; McAlpine, J.N.; McConechy, M.K.; Britton, H.; Hussein, Y.R.; Gonzalez, C.; Ganesan, R.; Steele, J.C.; Harrison, B.T.; et al. Molecular Classification of Grade 3 Endometrioid Endometrial Cancers Identifies Distinct Prognostic Subgroups. Am. J. Surg. Pathol. 2018, 42, 561–568. [Google Scholar] [CrossRef]
- O’Hara, A.J.; Bell, D.W. The genomics and genetics of endometrial cancer. Adv. Genom. Genet. 2012, 2012, 33–47. [Google Scholar]
- Aubrey, B.J.; Strasser, A.; Kelly, G.L. Tumor-Suppressor Functions of the TP53 Pathway. Cold Spring Harb. Perspect. Med. 2016, 6, a026062. [Google Scholar] [CrossRef]
- Santoro, A.; Angelico, G.; Travaglino, A.; Inzani, F.; Arciuolo, D.; Valente, M.; D’alessandris, N.; Scaglione, G.; Fiorentino, V.; Raffone, A.; et al. New Pathological and Clinical Insights in Endometrial Cancer in View of the Updated ESGO/ESTRO/ESP Guidelines. Cancers 2021, 13, 2623. [Google Scholar] [CrossRef]
- Orellana, T.J.; Kim, H.; Beriwal, S.; Taylor, S.E.; Smith, K.J.; Lesnock, J.L. Cost-effectiveness analysis of tumor molecular testing in stage III endometrial cancer. Gynecol. Oncol. 2023, 173, 81–87. [Google Scholar] [CrossRef]
- McConechy, M.K.; Ding, J.; Cheang, M.C.; Wiegand, K.C.; Senz, J.; A Tone, A.; Yang, W.; Prentice, L.M.; Tse, K.; Zeng, T.; et al. Use of mutation profiles to refine the classification of endometrial carcinomas. J. Pathol. 2012, 228, 20–30. [Google Scholar] [CrossRef]
- McAlpine, J.; Leon-Castillo, A.; Bosse, T. The rise of a novel classification system for endometrial carcinoma; integration of molecular subclasses. J. Pathol. 2018, 244, 538–549. [Google Scholar] [CrossRef]
- Alexa, M.; Hasenburg, A.; Battista, M.J. The TCGA Molecular Classification of Endometrial Cancer and Its Possible Impact on Adjuvant Treatment Decisions. Cancers 2021, 13, 1478. [Google Scholar] [CrossRef]
- Talhouk, A.; McConechy, M.K.; Leung, S.; Li-Chang, H.H.; Kwon, J.S.; Melnyk, N.; Yang, W.; Senz, J.; Boyd, N.; Karnezis, A.N.; et al. A clinically applicable molecular-based classification for endometrial cancers. Br. J. Cancer 2015, 113, 299–310. [Google Scholar] [CrossRef]
- Cosgrove, C.M.; Tritchler, D.L.; Cohn, D.E.; Mutch, D.G.; Rush, C.M.; Lankes, H.A.; Creasman, W.T.; Miller, D.S.; Ramirez, N.C.; Geller, M.A.; et al. An NRG Oncology/GOG study of molecular classification for risk prediction in endometrioid endometrial cancer. Gynecol. Oncol. 2018, 148, 174–180. [Google Scholar] [CrossRef] [PubMed]
- Talhouk, A.; McConechy, M.K.; Leung, S.; Yang, W.; Lum, A.; Senz, J.; Boyd, N.; Pike, J.; Anglesio, M.; Kwon, J.S.; et al. Confirmation of ProMisE: A simple, genomics-based clinical classifier for endometrial cancer. Cancer 2017, 123, 802–813. [Google Scholar] [CrossRef] [PubMed]
- Stelloo, E.; Bosse, T.; Nout, R.A.; Mackay, H.J.; Church, D.N.; Nijman, H.W.; Leary, A.; Edmondson, R.J.; Powell, M.E.; Crosbie, E.J.; et al. Refining prognosis and identifying targetable pathways for high-risk endometrial cancer; a TransPORTEC initiative. Mod. Pathol. 2015, 28, 836–844. [Google Scholar] [CrossRef] [PubMed]
- Stelloo, E.; Nout, R.A.; Osse, E.M.; Jürgenliemk-Schulz, I.J.; Jobsen, J.J.; Lutgens, L.C.; van der Steen-Banasik, E.M.; Nijman, H.W.; Putter, H.; Bosse, T.; et al. Improved Risk Assessment by Integrating Molecular and Clinicopathological Factors in Early-stage Endometrial Cancer-Combined Analysis of the PORTEC Cohorts. Clin. Cancer Res. 2016, 22, 4215–4224. [Google Scholar] [CrossRef] [PubMed]
- Stewart, A.P. Genetic testing strategies in newly diagnosed endometrial cancer patients aimed at reducing morbidity or mortality from lynch syndrome in the index case or her relatives. PLoS Curr. 2013, 5. [Google Scholar] [CrossRef] [PubMed]
- Enneli, D. The importance of molecular classification of endometrial carcinomas in clinical practice: How to apply it and difficulties in application. J. Turk. Ger. Gynecol. Assoc. 2023, 24, 197–205. [Google Scholar] [CrossRef] [PubMed]
- Califf, R.M. Biomarker definitions and their applications. Exp. Biol. Med. 2018, 243, 213–221. [Google Scholar] [CrossRef]
- Hutt, S.; Tailor, A.; Ellis, P.; Michael, A.; Butler-Manuel, S.; Chatterjee, J. The role of biomarkers in endometrial cancer and hyperplasia: A literature review. Acta Oncol. 2019, 58, 342–352. [Google Scholar] [CrossRef]
- Kreizman-Shefer, H.; Pricop, J.; Goldman, S.; Elmalah, I.; Shalev, E. Distribution of estrogen and progesterone receptors isoforms in endometrial cancer. Diagn. Pathol. 2014, 9, 77. [Google Scholar] [CrossRef]
- Wagner, V.M.; Backes, F.J. Do Not Forget about Hormonal Therapy for Recurrent Endometrial Cancer: A Review of Options, Updates, and New Combinations. Cancers 2023, 15, 1799. [Google Scholar] [CrossRef]
- Carlson, M.J.; Thiel, K.W.; Leslie, K.K. Past, present, and future of hormonal therapy in recurrent endometrial cancer. Int. J. Womens Health 2014, 6, 429–435. [Google Scholar] [PubMed]
- Mirza, M.R.; Bjørge, L.; Marmé, F.; Christensen, R.D.; Gil-Martin, M.; Auranen, A.; Ataseven, B.; Rubio, M.J.; Salutari, V.; Lund, B.; et al. A randomised double-blind placebo-controlled phase II trial of palbociclib combined with letrozole (L) in patients (pts) with oestrogen receptor-positive (ER+) advanced/recurrent endometrial cancer (EC): NSGO-PALEO/ENGOT-EN3 trial. Ann. Oncol. 2020, 31, S1160. [Google Scholar] [CrossRef]
- Konstantinopoulos, P.A.; Lee, E.K.; Xiong, N.; Krasner, C.; Campos, S.; Kolin, D.L.; Liu, J.F.; Horowitz, N.; Wright, A.A.; Bouberhan, S.; et al. A Phase II, Two-Stage Study of Letrozole and Abemaciclib in Estrogen Receptor-Positive Recurrent Endometrial Cancer. J. Clin. Oncol. 2023, 41, 599–608. [Google Scholar] [CrossRef] [PubMed]
- Karpel, H.; Slomovitz, B.; Coleman, R.L.; Pothuri, B. Biomarker-driven therapy in endometrial cancer. Int. J. Gynecol. Cancer 2023, 33, 343–350. [Google Scholar] [CrossRef] [PubMed]
- Slomovitz, B.M.; Filiaci, V.L.; Walker, J.L.; Taub, M.C.; Finkelstein, K.A.; Moroney, J.W.; Fleury, A.C.; Muller, C.Y.; Holman, L.L.; Copeland, L.J.; et al. A randomized phase II trial of everolimus and letrozole or hormonal therapy in women with advanced, persistent or recurrent endometrial carcinoma: A GOG Foundation study. Gynecol. Oncol. 2022, 164, 481–491. [Google Scholar] [CrossRef] [PubMed]
- Jain, E.; Prasad, S.; Dhar, A.; Kini, L.; Sharma, S.; Dewan, A. The utility of evaluating mismatch repair proteins in endometrial carcinoma: An experience from a tertiary referral centre in North India. Pathologica 2021, 113, 115–120. [Google Scholar] [CrossRef]
- Urick, M.E.; Bell, D.W. Clinical actionability of molecular targets in endometrial cancer. Nat. Rev. Cancer 2019, 19, 510–521. [Google Scholar] [CrossRef]
- Diver, E.J.; Foster, R.; Rueda, B.R.; Growdon, W.B. The Therapeutic Challenge of Targeting HER2 in Endometrial Cancer. Oncologist 2015, 20, 1058–1068. [Google Scholar] [CrossRef] [PubMed]
- Fader, A.N.; Roque, D.M.; Siegel, E.; Buza, N.; Hui, P.; Abdelghany, O.; Chambers, S.K.; Secord, A.A.; Havrilesky, L.; O’Malley, D.M.; et al. Randomized Phase II Trial of Carboplatin-Paclitaxel versus Carboplatin-Paclitaxel-Trastuzumab in Uterine Serous Carcinomas That Overexpress Human Epidermal Growth Factor Receptor 2/neu. J. Clin. Oncol. 2018, 36, 2044–2051. [Google Scholar] [CrossRef]
- ASCO. Trastuzumab Deruxtecan Effectively Treats HER2-Expressing Cancers Regardless of Tumor Location. 2023. Available online: https://society.asco.org/about-asco/press-center/news-releases/trastuzumab-deruxtecan-effectively-treats-her2-expressing (accessed on 12 April 2024).
- US Food & Drug Administration. FDA Grants Accelerated Approval to Fam-Trastuzumab Deruxtecan-Nxki for Unresectable or Metastatic HER2-Positive Solid Tumors. 2024. Available online: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-fam-trastuzumab-deruxtecan-nxki-unresectable-or-metastatic-her2 (accessed on 12 April 2024).
- Makker, V.; Perez-Fidalgo, J.A.; Bergamini, A.; Spitz, D.L.; Van Gorp, T.; Sehouli, J.; Klat, J.; Perri, T.; Oza, A.M.; Hogdall, E.V.; et al. Randomized phase III study of maintenance selinexor versus placebo in endometrial cancer (ENGOT-EN5/GOG-3055/SIENDO): Impact of subgroup analysis and molecular classification. J. Clin. Oncol. 2022, 40 (Suppl. S16), 5511. [Google Scholar] [CrossRef]
- Karaszewski, K.; Jędrzejczak, W.W. Selinexor and Other Selective Inhibitors of Nuclear Export (SINEs)—A Novel Approach to Target Hematologic Malignancies and Solid Tumors. Drugs Drug Candidates 2023, 2, 459–476. [Google Scholar] [CrossRef]
- Corr, B.; Cosgrove, C.; Spinosa, D.; Guntupalli, S. Endometrial cancer: Molecular classification and future treatments. BMJ Med. 2022, 1, e000152. [Google Scholar] [CrossRef]
- ASCO. Dostarlimab-Based Combinations in Advanced Endometrial Cancer. 2024. Available online: https://ascopost.com/news/march-2024/dostarlimab-based-combinations-in-advanced-endometrial-cancer/ (accessed on 29 May 2024).
- Peters, I.; Marchetti, C.; Scambia, G.; Fagotti, A. New windows of surgical opportunity for gynecological cancers in the era of targeted therapies. Int. J. Gynecol. Cancer 2024, 34, 352–362. [Google Scholar] [CrossRef] [PubMed]
- Asami, Y.; Kato, M.K.; Hiranuma, K.; Matsuda, M.; Shimada, Y.; Ishikawa, M.; Koyama, T.; Komatsu, M.; Hamamoto, R.; Nagashima, M.; et al. Utility of molecular subtypes and genetic alterations for evaluating clinical outcomes in 1029 patients with endometrial cancer. Br. J. Cancer 2023, 128, 1582–1591. [Google Scholar] [CrossRef]
- American College of Obstetricians and Gynecologists. ACOG Practice Bulletin: Clinical Management Guidelines for Obstetrician-Gynecologists Number 76, October 2006: Postpartum hemorrhage. Obs. Gynecol. 2006, 108, 1039–1047. [Google Scholar]
- Koskas, M.; Bendifallah, S.; Luton, D.; Daraï, E.; Rouzier, R. Safety of uterine and/or ovarian preservation in young women with grade 1 intramucous endometrial adenocarcinoma: A comparison of survival according to the extent of surgery. Fertil. Steril. 2012, 98, 1229–1235. [Google Scholar] [CrossRef] [PubMed]
- Mourits, M.J.; Bijen, C.B.; Arts, H.J.; ter Brugge, H.G.; van der Sijde, R.; Paulsen, L.; Wijma, J.; Bongers, M.Y.; Post, W.J.; van der Zee, A.G.; et al. Safety of laparoscopy versus laparotomy in early-stage endometrial cancer: A randomised trial. Lancet Oncol. 2010, 11, 763–771. [Google Scholar] [CrossRef] [PubMed]
- Walker, J.L.; Piedmonte, M.R.; Spirtos, N.M.; Eisenkop, S.M.; Schlaerth, J.B.; Mannel, R.S.; Spiegel, G.; Barakat, R.; Pearl, M.L.; Sharma, S.K. Laparoscopy compared with laparotomy for comprehensive surgical staging of uterine cancer: Gynecologic Oncology Group Study LAP2. J. Clin. Oncol. 2009, 27, 5331–5336. [Google Scholar] [CrossRef] [PubMed]
- Coronado, P.J.; Herraiz, M.A.; Magrina, J.F.; Fasero, M.; Vidart, J.A. Comparison of perioperative outcomes and cost of robotic-assisted laparoscopy, laparoscopy and laparotomy for endometrial cancer. Eur. J. Obs. Gynecol. Reprod. Biol. 2012, 165, 289–294. [Google Scholar] [CrossRef]
- Frederick, P.J.; Straughn, J.M., Jr. The role of comprehensive surgical staging in patients with endometrial cancer. Cancer Control 2009, 16, 23–29. [Google Scholar] [CrossRef]
- Benedetti Panici, P.; 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. J. Natl. Cancer Inst. 2008, 100, 1707–1716. [Google Scholar] [CrossRef] [PubMed]
- ASTEC Study Group; Kitchener, H.; Swart, A.M.; Qian, Q.; Amos, C.; Parmar, M.K. Efficacy of systematic pelvic lymphadenectomy in endometrial cancer (MRC ASTEC trial): A randomised study. Lancet 2009, 373, 125–136. [Google Scholar] [PubMed]
- Dellino, M.; Cerbone, M.; Laganà, A.S.; Vitagliano, A.; Vimercati, A.; Marinaccio, M.; Baldini, G.M.; Malvasi, A.; Cicinelli, E.; Damiani, G.R.; et al. Upgrading Treatment and Molecular Diagnosis in Endometrial Cancer-Driving New Tools for Endometrial Preservation? Int. J. Mol. Sci. 2023, 24, 9780. [Google Scholar] [CrossRef] [PubMed]
- Dowdy, S.C.; Borah, B.; Bakkum-Gamez, J.; Weaver, A.; McGree, M.; Haas, L.; Keeney, G.; Mariani, A.; Podratz, K. Prospective assessment of survival, morbidity, and cost associated with lymphadenectomy in low-risk endometrial cancer. Gynecol. Oncol. 2012, 127, 5–10. [Google Scholar] [CrossRef] [PubMed]
- Zhai, L.; Zhang, X.; Cui, M.; Wang, J. Sentinel Lymph Node Mapping in Endometrial Cancer: A Comprehensive Review. Front. Oncol. 2021, 11, 701758. [Google Scholar] [CrossRef] [PubMed]
- Bogani, G.; Raspagliesi, F.; Maggiore, U.L.R.; Mariani, A. Current landscape and future perspective of sentinel node mapping in endometrial cancer. J. Gynecol. Oncol. 2018, 29, e94. [Google Scholar] [CrossRef] [PubMed]
- Pados, G.; Zouzoulas, D.; Tsolakidis, D. Recent management of endometrial cancer: A narrative review of the literature. Front. Med. 2023, 10, 1244634. [Google Scholar] [CrossRef] [PubMed]
- Manning-Geist, B.L.; Rios-Doria, E.; Liu, Y.L.; Ellenson, L.H.; Zhou, Q.C.; Iasonos, A.; Leitao, M.M.; Abu-Rustum, N.R.; Weigelt, B.; Mueller, J.J. Molecular and pathologic data to guide selection of patients with endometrioid endometrial cancer for ovarian preservation. Int. J. Gynecol. Cancer 2024, 34, 697–704. [Google Scholar] [CrossRef] [PubMed]
- Bani, M.A.; Maulard, A.; Morice, P.; Chargari, C.; Genestie, C. Integration of the Molecular Classification of Endometrial Carcinoma to Select Patients for Fertility Sparing Strategies. Anticancer Res. 2024, 44, 445–452. [Google Scholar] [CrossRef]
- Kasius, J.C.; Trozzi, R.; Pijnenborg, J.; Baert, T.; Laenen, A.; Van Rompuy, A.-S.; Zapardiel, I.; Vizzielli, G.; Knez, J.; Fanfani, F.; et al. Improving Endometrial cancer assessment by combining the new techniqUe of GENomic profiling with surgical Extra uterIne disEase assessment (EUGENIE). Int. J. Gynecol. Cancer 2023, 33, 823–826. [Google Scholar] [CrossRef]
- Nero, C.; Ciccarone, F.; Pietragalla, A.; Duranti, S.; Daniele, G.; Scambia, G.; Lorusso, D. Adjuvant Treatment Recommendations in Early-Stage Endometrial Cancer: What Changes with the Introduction of The Integrated Molecular-Based Risk Assessment. Front. Oncol. 2021, 11, 612450. [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]
- Leon-Castillo, A.; De Boer, S.M.; Powell, M.E.; Mileshkin, L.R.; Mackay, H.J.; Leary, A.; Nijman, H.W.; Singh, N.; Pollock, P.M.; Bessette, P.; et al. Molecular Classification of the PORTEC-3 Trial for High-Risk Endometrial Cancer: Impact on Prognosis and Benefit from Adjuvant Therapy. J. Clin. Oncol. 2020, 38, 3388–3397. [Google Scholar] [CrossRef] [PubMed]
- Jamieson, A.; Huvila, J.; Leung, S.; Chiu, D.; Thompson, E.F.; Lum, A.; Kinloch, M.; Helpman, L.; Salvador, S.; Vicus, D.; et al. Molecular subtype stratified outcomes according to adjuvant therapy in endometrial cancer. Gynecol. Oncol. 2023, 170, 282–289. [Google Scholar] [CrossRef] [PubMed]
- McMeekin, D.S.; Tritchler, D.L.; Cohn, D.E.; Mutch, D.G.; Lankes, H.A.; Geller, M.A.; Powell, M.A.; Backes, F.J.; Landrum, L.M.; Zaino, R.; et al. Clinicopathologic Significance of Mismatch Repair Defects in Endometrial Cancer: An NRG Oncology/Gynecologic Oncology Group Study. J. Clin. Oncol. 2016, 34, 3062–3068. [Google Scholar] [CrossRef]
- Leon-Castillo, A.; Horeweg, N.; Peters, E.E.; Rutten, T.; ter Haar, N.; Smit, V.T.; Kroon, C.D.; Boennelycke, M.; Hogdall, E.; Hogdall, C.; et al. Prognostic relevance of the molecular classification in high-grade endometrial cancer for patients staged by lymphadenectomy and without adjuvant treatment. Gynecol. Oncol. 2022, 164, 577–586. [Google Scholar] [CrossRef] [PubMed]
- McAlpine, J.N.; Chiu, D.S.; Nout, R.A.; Church, D.N.; Schmidt, P.; Lam, S.; Leung, S.; Bellone, S.; Wong, A.; Brucker, S.Y.; et al. Evaluation of treatment effects in patients with endometrial cancer and POLE mutations: An individual patient data meta-analysis. Cancer 2021, 127, 2409–2422. [Google Scholar] [CrossRef]
- Consortium, R.R. Refining adjuvant treatment in endometrial cancer based on molecular features: The RAINBO clinical trial program. Int. J. Gynecol. Cancer 2022, 33, 109–117. [Google Scholar] [CrossRef]
- Keys, H.M.; Roberts, J.A.; Brunetto, V.L.; Zaino, R.J.; Spirtos, N.M.; Bloss, J.D.; Pearlman, A.; Maiman, M.A.; Bell, J.G. A phase III trial of surgery with or without adjunctive external pelvic radiation therapy in intermediate risk endometrial adenocarcinoma: A Gynecologic Oncology Group study. Gynecol. Oncol. 2004, 92, 744–751. [Google Scholar] [CrossRef]
- Creutzberg, C.L.; Nout, R.A.; Lybeert, M.L.; Wárlám-Rodenhuis, C.C.; Jobsen, J.J.; Mens, J.-W.M.; Lutgens, L.C.; Pras, E.; van de Poll-Franse, L.V.; van Putten, W.L. Fifteen-year radiotherapy outcomes of the randomized PORTEC-1 trial for endometrial carcinoma. Int. J. Radiat. Oncol. Biol. Phys. 2011, 81, e631–e638. [Google Scholar] [CrossRef]
- Creutzberg, C.L.; van Putten, W.L.; Koper, P.C.; Lybeert, M.L.; Jobsen, J.J.; Wárlám-Rodenhuis, C.C.; De Winter, K.A.; Lutgens, L.C.; van den Bergh, A.C.; van de Steen-Banasik, E.; et al. Surgery and postoperative radiotherapy versus surgery alone for patients with stage-1 endometrial carcinoma: Multicentre randomised trial. PORTEC Study Group. Post Operative Radiation Therapy in Endometrial Carcinoma. Lancet 2000, 355, 1404–1411. [Google Scholar] [CrossRef]
- Nout, R.A.; Smit, V.T.; Putter, H.; Jürgenliemk-Schulz, I.M.; Jobsen, J.J.; Lutgens, L.C.; van der Steen-Banasik, E.; Mens, J.; Slot, A.; Kroese, M.S.; et al. Vaginal brachytherapy versus pelvic external beam radiotherapy for patients with endometrial cancer of high-intermediate risk (PORTEC-2): An open-label, non-inferiority, randomised trial. Lancet 2010, 375, 816–823. [Google Scholar] [CrossRef]
- Wortman, B.G.; Creutzberg, C.L.; Putter, H.; Jürgenliemk-Schulz, I.M.; Jobsen, J.J.; Lutgens, L.C.H.W.; van der Steen-Banasik, E.M.; Mens, J.W.M.; Slot, A.; Stenfert Kroese, M.C.; et al. Ten-year results of the PORTEC-2 trial for high-intermediate risk endometrial carcinoma: Improving patient selection for adjuvant therapy. Br. J. Cancer 2018, 119, 1067–1074. [Google Scholar] [CrossRef]
- Randall, M.E.; Filiaci, V.; McMeekin, D.S.; Von Gruenigen, V.; Huang, H.; Yashar, C.M.; Mannel, R.S.; Kim, J.W.; Salani, R.; DiSilvestro, P.A.; et al. Phase III Trial: Adjuvant Pelvic Radiation Therapy versus Vaginal Brachytherapy plus Paclitaxel/Carboplatin in High-Intermediate and High-Risk Early Stage Endometrial Cancer. J. Clin. Oncol. 2019, 37, 1810–1818. [Google Scholar] [CrossRef] [PubMed]
- de Boer, S.M.; Powell, M.E.; Mileshkin, L.; Katsaros, D.; Bessette, P.; Haie-Meder, C.; Ottevanger, P.B.; Ledermann, J.A.; Khaw, P.; D’Amico, R.; et al. Adjuvant chemoradiotherapy versus radiotherapy alone in women with high-risk endometrial cancer (PORTEC-3): Patterns of recurrence and post-hoc survival analysis of a randomised phase 3 trial. Lancet Oncol. 2019, 20, 1273–1285. [Google Scholar] [CrossRef] [PubMed]
- Matei, D.; Filiaci, V.; Randall, M.E.; Mutch, D.; Steinhoff, M.M.; DiSilvestro, P.A.; Moxley, K.M.; Kim, Y.M.; Powell, M.A.; O’Malley, D.M.; et al. Adjuvant Chemotherapy plus Radiation for Locally Advanced Endometrial Cancer. N. Engl. J. Med. 2019, 380, 2317–2326. [Google Scholar] [CrossRef] [PubMed]
- Berek, J.S.; Matias-Guiu, X.; Creutzberg, C.; Fotopoulou, C.; Gaffney, D.; Kehoe, S.; Lindemann, K.; Mutch, D.; Concin, N. FIGO staging of endometrial cancer: 2023. Int. J. Gynaecol. Obs. 2023, 162, 383–394. [Google Scholar] [CrossRef] [PubMed]
- Horeweg, N.; Nout, R.A.; Jürgenliemk-Schulz, I.M.; Lutgens, L.C.H.W.; Jobsen, J.J.; Haverkort, M.A.D.; Mens, J.W.M.; Slot, A.; Wortman, B.G.; de Boer, S.M.; et al. Molecular Classification Predicts Response to Radiotherapy in the Randomized PORTEC-1 and PORTEC-2 Trials for Early-Stage Endometrioid Endometrial Cancer. J. Clin. Oncol. 2023, 41, 4369–4380. [Google Scholar] [CrossRef] [PubMed]
- Harkenrider, M.M.; Abu-Rustum, N.; Albuquerque, K.; Bradfield, L.; Bradley, K.; Dolinar, E.; Doll, C.M.; Elshaikh, M.; Frick, M.A.; Gehrig, P.A.; et al. Radiation Therapy for Endometrial Cancer: An American Society for Radiation Oncology Clinical Practice Guideline. Pract. Radiat. Oncol. 2023, 13, 41–65. [Google Scholar] [CrossRef]
- Miller, D.S.; Filiaci, V.L.; Mannel, R.S.; Cohn, D.E.; Matsumoto, T.; Tewari, K.S.; DiSilvestro, P.; Pearl, M.L.; Argenta, P.A.; Powell, M.A.; et al. Carboplatin and Paclitaxel for Advanced Endometrial Cancer: Final Overall Survival and Adverse Event Analysis of a Phase III Trial (NRG Oncology/GOG0209). J. Clin. Oncol. 2020, 38, 3841–3850. [Google Scholar] [CrossRef]
- Mirza, M.R.; Sharma, S.; Herrstedt, J.; Shahin, M.S.; Cibula, D.; Fleming, E.; Raspagliesi, F.; Buscema, J.; Hanker, L.C.; Coleman, R.L.; et al. 740MO Dostarlimab + chemotherapy for the treatment of primary advanced or recurrent endometrial cancer (pA/rEC): Analysis of progression free survival (PFS) and overall survival (OS) outcomes by molecular classification in the ENGOT-EN6-NSGO/GOG-3031/RUBY trial. Ann. Oncol. 2023, 34, S507. [Google Scholar]
- Eskander, R.N.; Sill, M.W.; Beffa, L.; Moore, R.G.; Hope, J.M.; Musa, F.B.; Mannel, R.; Shahin, M.S.; Cantuaria, G.H.; Girda, E.; et al. Pembrolizumab plus Chemotherapy in Advanced Endometrial Cancer. N. Engl. J. Med. 2023, 388, 2159–2170. [Google Scholar] [CrossRef] [PubMed]
- Colombo, N.; Harano, K.; Hudson, E.; Galli, F.; Antill, Y.; Choi, C.; Rabaglio, M.; Marmé, F.; Petru, E.; Lai, C.-H.; et al. LBA40 Phase III double-blind randomized placebo controlled trial of atezolizumab in combination with carboplatin and paclitaxel in women with advanced/recurrent endometrial carcinoma. Ann. Oncol. 2023, 34, S1281–S1282. [Google Scholar] [CrossRef]
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Ribeiro-Santos, P.; Martins Vieira, C.; Viana Veloso, G.G.; Vieira Giannecchini, G.; Parenza Arenhardt, M.; Müller Gomes, L.; Zanuncio, P.; Silva Brandão, F.; Nogueira-Rodrigues, A. Tailoring Endometrial Cancer Treatment Based on Molecular Pathology: Current Status and Possible Impacts on Systemic and Local Treatment. Int. J. Mol. Sci. 2024, 25, 7742. https://doi.org/10.3390/ijms25147742
Ribeiro-Santos P, Martins Vieira C, Viana Veloso GG, Vieira Giannecchini G, Parenza Arenhardt M, Müller Gomes L, Zanuncio P, Silva Brandão F, Nogueira-Rodrigues A. Tailoring Endometrial Cancer Treatment Based on Molecular Pathology: Current Status and Possible Impacts on Systemic and Local Treatment. International Journal of Molecular Sciences. 2024; 25(14):7742. https://doi.org/10.3390/ijms25147742
Chicago/Turabian StyleRibeiro-Santos, Pedro, Carolina Martins Vieira, Gilson Gabriel Viana Veloso, Giovanna Vieira Giannecchini, Martina Parenza Arenhardt, Larissa Müller Gomes, Pedro Zanuncio, Flávio Silva Brandão, and Angélica Nogueira-Rodrigues. 2024. "Tailoring Endometrial Cancer Treatment Based on Molecular Pathology: Current Status and Possible Impacts on Systemic and Local Treatment" International Journal of Molecular Sciences 25, no. 14: 7742. https://doi.org/10.3390/ijms25147742