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CA: a Cancer Journal For Clinicians Jul 2019Endometrial cancer is the most common gynecologic cancer in the United States, and its incidence is rising. Although there have been significant recent advances in our... (Review)
Review
Endometrial cancer is the most common gynecologic cancer in the United States, and its incidence is rising. Although there have been significant recent advances in our understanding of endometrial cancer biology, many aspects of treatment remain mired in controversy, including the role of surgical lymph node assessment and the selection of patients for adjuvant radiation or chemotherapy. For the subset of women with microsatellite-instable, metastatic disease, anti- programmed cell death protein 1 immunotherapy (pembrolizumab) is now approved by the US Food and Drug Administration, and numerous trials are attempting to build on this early success.
Topics: Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Chemotherapy, Adjuvant; Cytoreduction Surgical Procedures; Endometrial Neoplasms; Female; Genetic Predisposition to Disease; Humans; Hysterectomy; Lymph Node Excision; Neoplasm Metastasis; Neoplasm Recurrence, Local; Prognosis; Radiotherapy, Adjuvant; Risk Factors; Sentinel Lymph Node
PubMed: 31074865
DOI: 10.3322/caac.21561 -
International Journal of Gynecological... Jan 2020Recent advances in molecular studies, especially genome-wide analyses, have revealed the landscape of genomic alterations present in endometrial carcinomas, and have... (Review)
Review
Recent advances in molecular studies, especially genome-wide analyses, have revealed the landscape of genomic alterations present in endometrial carcinomas, and have provided valuable insight into the pathogenesis of this disease. The current challenges are in developing a molecular-morphologic classification system to enhance traditional pathologic diagnosis and in determining the optimal approach to using this new information to guide clinical management. Molecular assays may be particularly beneficial in allowing the earlier detection of endometrial cancer or precursor lesions and in guiding personalized treatment approaches. In this review, we describe the current molecular landscape of endometrial cancers, efforts underway to incorporate molecular alterations into the current classification systems, and the development of diagnostic tools for the early detection of endometrial cancer. Finally, we present opportunities for using these data to tailor therapeutic strategies. A comprehensive understanding of the molecular alterations responsible for the origination, relapse, and resistance patterns of this disease will ultimately improve outcomes for patients with endometrial cancer.
Topics: Early Detection of Cancer; Endometrial Neoplasms; Female; Genes, Neoplasm; Humans; Molecular Targeted Therapy; Mutation
PubMed: 30741844
DOI: 10.1097/PGP.0000000000000585 -
International Journal of Gynecological... Jan 2019This review of challenging diagnostic issues concerning high-grade endometrial carcinomas is derived from the authors' review of the literature followed by discussions... (Review)
Review
This review of challenging diagnostic issues concerning high-grade endometrial carcinomas is derived from the authors' review of the literature followed by discussions at the Endometrial Cancer Workshop sponsored by the International Society of Gynecological Pathologists in 2016. Recommendations presented are evidence-based, insofar as this is possible, given that the levels of evidence are weak or moderate due to small sample sizes and nonuniform diagnostic criteria used in many studies. High-grade endometrioid carcinomas include FIGO grade 3 endometrioid carcinomas, serous carcinomas, clear cell carcinomas, undifferentiated carcinomas, and carcinosarcomas. FIGO grade 3 endometrioid carcinoma is diagnosed when an endometrioid carcinoma exhibits >50% solid architecture (excluding squamous areas), or when an architecturally FIGO grade 2 endometrioid carcinoma exhibits marked cytologic atypia, provided that a glandular variant of serous carcinoma has been excluded. The most useful immunohistochemical studies to make the distinction between these 2 histotypes are p53, p16, DNA mismatch repair proteins, PTEN, and ARID1A. Endometrial clear cell carcinomas must display prototypical architectural and cytologic features for diagnosis. Immunohistochemical stains, including, Napsin A and p504s can be used as ancillary diagnostic tools; p53 expression is aberrant in a minority of clear cell carcinomas. Of note, clear cells are found in all types of high-grade endometrial carcinomas, leading to a tendency to overdiagnose clear cell carcinoma. Undifferentiated carcinoma (which when associated with a component of low-grade endometrioid carcinoma is termed "dedifferentiated carcinoma") is composed of sheets of monotonous, typically dyscohesive cells, which can have a rhabdoid appearance; they often exhibit limited expression of cytokeratins and epithelial membrane antigen, are usually negative for PAX8 and hormone receptors, lack membranous e-cadherin and commonly demonstrate loss of expression of DNA mismatch repair proteins and SWI-SNF chromatin remodeling proteins. Carcinosarcomas must show unequivocal morphologic evidence of malignant epithelial and mesenchymal differentiation.
Topics: Biomarkers, Tumor; Carcinoma, Endometrioid; Endometrial Neoplasms; Female; Humans; Immunohistochemistry; Neoplasm Grading; Practice Guidelines as Topic; Societies, Medical
PubMed: 30550483
DOI: 10.1097/PGP.0000000000000491 -
Acta Bio-medica : Atenei Parmensis Dec 2019Endometrial Cancer (EC) is the commonest gynecological cancer and its incidence is increasing. The diagnosis of endometrial carcinoma in young women of childbearing age... (Review)
Review
Endometrial Cancer (EC) is the commonest gynecological cancer and its incidence is increasing. The diagnosis of endometrial carcinoma in young women of childbearing age is rare. Indeed, only 4% of patients with endometrial carcinoma are <40 years of age. It's typically diagnosed in postmenopausal women. The standard approach for the management of endometrial cancer in young women of childbearing age is hysterectomy and bilateral salpingo-oophorectomy with or without lymphadenectomy but is not ideal for women interested in future fertility. We reviewed the published literature to clarify in fertile women who have not yet fulfilled their desire for motherhood, what are the strategies, the risks of a conservative treatment of early stage of Endometrial Cancer and what are the obstetric outcomes in this patients. Recently, several studies have reported encouraging results on fertility-sparing management of EC with high dose of progestins in selected women associated or not with hysteroscopic resection.
Topics: Aftercare; Conservative Treatment; Endometrial Neoplasms; Female; Humans; Neoplasm Staging
PubMed: 31910163
DOI: 10.23750/abm.v90i4.7800 -
Current Oncology (Toronto, Ont.) Jan 2022Endometrial carcinoma (EC) is traditionally treated with surgery and adjuvant treatment depending on clinicopathological risk factors. The genomic analysis of EC in 2013... (Review)
Review
Endometrial carcinoma (EC) is traditionally treated with surgery and adjuvant treatment depending on clinicopathological risk factors. The genomic analysis of EC in 2013 and subsequent studies using immunohistochemistry have led to the current EC molecular classification into: polymerase epsilon mutated (POLEmut), p53 abnormal (p53abn), mismatch repair deficient (MMRd), and no specific molecular profile (NSMP). The four groups have prognostic value and represent a promising tool for clinical decision-making regarding adjuvant treatment. Molecular classification was integrated into the recent European Society of Gynecologic Oncology (ESGO) management guidelines. POLEmut EC has favorable outcomes and retrospective studies found that omitting adjuvant treatment is safe in this group; two prospective clinical trials, PORTEC-4 and TAPER, are ongoing to assess this. p53 abn is associated with increased recurrence, decreased survival, and benefitted from chemotherapy in the PORTEC-3 subgroup molecular analysis. The clinical trials PORTEC-4a and CANSTAMP will prospectively assess this. MMRd and NSMP groups have intermediate prognosis and will likely continue to rely closely on clinicopathological features for adjuvant treatment decisions. In addition, the molecular classification has led to exploring novel treatments such as checkpoint inhibitors. Overall, the molecular perspective on EC and associated clinical trials will likely refine EC risk stratification to optimize care and avoid overtreatment.
Topics: Biomarkers, Tumor; Endometrial Neoplasms; Female; Genomics; Humans; Mutation; Prospective Studies; Retrospective Studies
PubMed: 35200562
DOI: 10.3390/curroncol29020063 -
The New England Journal of Medicine Jun 2019Stage III or IVA endometrial cancer carries a significant risk of systemic and locoregional recurrence. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Stage III or IVA endometrial cancer carries a significant risk of systemic and locoregional recurrence.
METHODS
In this randomized phase 3 trial, we tested whether 6 months of platinum-based chemotherapy plus radiation therapy (chemoradiotherapy) is associated with longer relapse-free survival (primary end point) than six cycles of combination chemotherapy alone in patients with stage III or IVA endometrial carcinoma. Secondary end points included overall survival, acute and chronic toxic effects, and quality of life.
RESULTS
Of the 813 patients enrolled, 736 were eligible and were included in the analysis of relapse-free survival; of those patients, 707 received the randomly assigned intervention (346 received chemoradiotherapy and 361 received chemotherapy only). The median follow-up period was 47 months. At 60 months, the Kaplan-Meier estimate of the percentage of patients alive and relapse-free was 59% (95% confidence interval [CI], 53 to 65) in the chemoradiotherapy group and 58% (95% CI, 53 to 64) in the chemotherapy-only group (hazard ratio, 0.90; 90% CI, 0.74 to 1.10). Chemoradiotherapy was associated with a lower 5-year incidence of vaginal recurrence (2% vs. 7%; hazard ratio, 0.36; 95% CI, 0.16 to 0.82) and pelvic and paraaortic lymph-node recurrence (11% vs. 20%; hazard ratio, 0.43; 95% CI, 0.28 to 0.66) than chemotherapy alone, but distant recurrence was more common in association with chemoradiotherapy (27% vs. 21%; hazard ratio, 1.36; 95% CI, 1.00 to 1.86). Grade 3, 4, or 5 adverse events were reported in 202 patients (58%) in the chemoradiotherapy group and 227 patients (63%) in the chemotherapy-only group.
CONCLUSIONS
Chemotherapy plus radiation was not associated with longer relapse-free survival than chemotherapy alone in patients with stage III or IVA endometrial carcinoma. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT00942357.).
Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy, Adjuvant; Chemotherapy, Adjuvant; Disease-Free Survival; Endometrial Neoplasms; Female; Humans; Kaplan-Meier Estimate; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Neoplasm, Residual; Prognosis; Quality of Life; Recurrence; Statistics, Nonparametric; Treatment Outcome
PubMed: 31189035
DOI: 10.1056/NEJMoa1813181 -
International Journal of Gynecological... Jan 2019In this review, we sought to address 2 important issues in the diagnosis of endometrial carcinoma: how to grade endometrial endometrioid carcinomas and how to... (Review)
Review
Endometrial Carcinoma Diagnosis: Use of FIGO Grading and Genomic Subcategories in Clinical Practice: Recommendations of the International Society of Gynecological Pathologists.
In this review, we sought to address 2 important issues in the diagnosis of endometrial carcinoma: how to grade endometrial endometrioid carcinomas and how to incorporate the 4 genomic subcategories of endometrial carcinoma, as identified through The Cancer Genome Atlas, into clinical practice. The current International Federation of Gynecology and Obstetrics grading scheme provides prognostic information that can be used to guide the extent of surgery and use of adjuvant chemotherapy or radiation therapy. We recommend moving toward a binary scheme to grade endometrial endometrioid carcinomas by considering International Federation of Gynecology and Obstetrics defined grades 1 and 2 tumors as "low grade" and grade 3 tumors as "high grade." The current evidence base does not support the use of a 3-tiered grading system, although this is considered standard by International Federation of Gynecology and Obstetrics, the American College of Obstetricians and Gynecologists, and the College of American Pathologists. As for the 4 genomic subtypes of endometrial carcinoma (copy number low/p53 wild-type, copy number high/p53 abnormal, polymerase E mutant, and mismatch repair deficient), which only recently have been identified, there is accumulating evidence showing these categories can be reproducibly diagnosed and accurately assessed based on biopsy/curettage specimens as well as hysterectomy specimens. Furthermore, this subclassification system can be adapted for current clinical practice and is of prognostic significance independent of conventional variables used for risk assessment in patients with endometrial carcinoma (eg, stage). It is too soon to recommend the routine use of genomic classification in this setting; however, with further evidence, this system may become the basis for the subclassification of all endometrial carcinomas, supplanting (partially or completely) histotype, and grade. These recommendations were developed from the International Society of Gynecological Pathologists Endometrial Carcinoma project.
Topics: Carcinoma, Endometrioid; Endometrial Neoplasms; Female; Genomics; Gynecology; Humans; Neoplasm Grading; Neoplasm Staging; Pathologists; Practice Guidelines as Topic; Prognosis; Societies, Medical
PubMed: 30550484
DOI: 10.1097/PGP.0000000000000518 -
International Journal of Radiation... Nov 2011To evaluate the very long-term results of the randomized Post Operative Radiation Therapy in Endometrial Carcinoma (PORTEC)-1 trial for patients with Stage I endometrial... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
To evaluate the very long-term results of the randomized Post Operative Radiation Therapy in Endometrial Carcinoma (PORTEC)-1 trial for patients with Stage I endometrial carcinoma (EC), focusing on the role of prognostic factors for treatment selection and the long-term risk of second cancers.
PATIENTS AND METHODS
The PORTEC trial (1990-1997) included 714 patients with Stage IC Grade 1-2 or Stage IB Grade 2-3 EC. After surgery, patients were randomly allocated to external-beam pelvic radiotherapy (EBRT) or no additional treatment (NAT). Analysis was by intention to treat.
RESULTS
426 patients were alive at the date of analysis. The median follow-up time was 13.3 years. The 15-year actuarial locoregional recurrence (LRR) rates were 6% for EBRT vs. 15.5% for NAT (p < 0.0001). The 15-year overall survival was 52% vs. 60% (p = 0.14), and the failure-free survival was 50% vs. 54% (p = 0.94). For patients with high-intermediate risk criteria, the 15-year overall survival was 41% vs. 48% (p = 0.51), and the 15-year EC-related death was 14% vs. 13%. Most LRR in the NAT group were vaginal recurrences (11.0% of 15.5%). The 15-year rates of distant metastases were 9% vs. 7% (p = 0.25). Second primary cancers had been diagnosed over 15 years in 19% of all patients, 22% vs. 16% for EBRT vs. NAT (p = 0.10), with observed vs. expected ratios of 1.6 (EBRT) and 1.2 (NAT) compared with a matched population (p = NS). Multivariate analysis confirmed the prognostic significance of Grade 3 for LRR (hazard ratio [HR] 3.4, p = 0.0003) and for EC death (HR 7.3, p < 0.0001), of age >60 (HR 3.9, p = 0.002 for LRR and 2.7, p = 0.01 for EC death) and myometrial invasion >50% (HR 1.9, p = 0.03 and HR 1.9, p = 0.02).
CONCLUSIONS
The 15-year outcomes of PORTEC-1 confirm the relevance of HIR criteria for treatment selection, and a trend for long-term risk of second cancers. EBRT should be avoided in patients with low- and intermediate-risk EC.
Topics: Adult; Aged; Aged, 80 and over; Analysis of Variance; Breast Neoplasms; Disease-Free Survival; Endometrial Neoplasms; Female; Humans; Middle Aged; Neoplasm Grading; Neoplasm Recurrence, Local; Neoplasms, Second Primary; Prognosis; Risk; Treatment Outcome; Vaginal Neoplasms
PubMed: 21640520
DOI: 10.1016/j.ijrobp.2011.04.013 -
International Journal of Gynaecology... Oct 2021Endometrial cancer is the most common gynecological malignancy in high- and middle-income countries. Although the overall prognosis is relatively good, high-grade...
Endometrial cancer is the most common gynecological malignancy in high- and middle-income countries. Although the overall prognosis is relatively good, high-grade endometrial cancers have a tendency to recur. Recurrence needs to be prevented since the prognosis for recurrent endometrial cancer is dismal. Treatment tailored to tumor biology is the optimal strategy to balance treatment efficacy against toxicity. Since The Cancer Genome Atlas defined four molecular subgroups of endometrial cancers, the molecular factors are increasingly used to define prognosis and treatment. Standard treatment consists of hysterectomy and bilateral salpingo-oophorectomy. Lymphadenectomy (and increasingly sentinel node biopsy) enables identification of lymph node-positive patients who need adjuvant treatment, including radiotherapy and chemotherapy. Adjuvant therapy is used for Stage I-II patients with high-risk factors and Stage III patients; chemotherapy is especially used in non-endometrioid cancers and those in the copy-number high molecular group characterized by TP53 mutation. In advanced disease, a combination of surgery to no residual disease and chemotherapy with or without radiotherapy results in the best outcome. Surgery for recurrent disease is only advocated in patients with a good performance status with a relatively long disease-free interval.
Topics: Chemotherapy, Adjuvant; Endometrial Neoplasms; Female; Humans; Hysterectomy; Lymph Node Excision; Neoplasm Recurrence, Local; Neoplasm Staging; Radiotherapy, Adjuvant; Retrospective Studies; Uterus
PubMed: 34669196
DOI: 10.1002/ijgo.13866 -
Journal of the National Comprehensive... Feb 2018Endometrial cancers are the most common gynecologic malignancies. The staging of endometrial cancer has evolved from a clinical-based system to a comprehensive... (Review)
Review
Endometrial cancers are the most common gynecologic malignancies. The staging of endometrial cancer has evolved from a clinical-based system to a comprehensive surgical-pathologic approach that allows for better risk stratification and treatment planning. Over the past few years, use of NCCN's sentinel lymph node (SLN) mapping algorithm for the surgical staging of endometrial cancer has gained significant acceptance and is now commonly applied in many practices. However, pathologic evaluation of prognostic factors is beset by challenges, including the reproducibility of histologic classification and FIGO's grading, as well as the questionable clinical significance of low-volume tumor in SLNs. With the revelation of major genomic classes of endometrial cancer comes the potential for improved, reproducible, and prognostically relevant classification schemes, which integrate traditional pathologic parameters with genomic findings, to aid in treatment decisions. Pathologic identification of new variants of endometrial cancer, such as undifferentiated carcinoma, continues to advance the phenotypic spectrum of these tumors, spurring genomic and functional studies to further characterize their mechanistic underpinnings and potentially reveal new avenues for treatment. In the era of precision medicine, pathologic assessment of biomarkers (eg, mismatch repair proteins) and recognition of phenotypes that are amenable to specific targeted therapies (such as -mutated tumors) have become integral to the management of women with endometrial carcinoma.
Topics: Animals; Disease Management; Endometrial Neoplasms; Female; Genetic Association Studies; Genetic Predisposition to Disease; Genomics; Humans; Neoplasm Staging; Prognosis; Sentinel Lymph Node Biopsy
PubMed: 29439179
DOI: 10.6004/jnccn.2017.7066