Uterine cancer is the most common malignancy of the female genital tract accounting for 6% of all female cancers with an overall survival 84%.
A malignant epithelial tumor that forms in the inner lining, or endometrium, of the uterus.
It is the most frequent gynecological cancer in developed countries, with increasing incidents among the elderly.
Fourth-sixth most common cancer among women overall.
Prevalence is increasing.
There is an approximately a 1% per year increase among postmenopausal women.
Incidence and associated mortality are rising.
The increased prevalence is due, in part, to declining rate of hysterectomy for a benign causes.
Since obesity is one of the most important risk factors, and the rates of obesity have been going up, the rates of endometrial cancer have also increased.
Obesity may contribute to EC through insulin resistance and abnormalities of insulin growth factor 1 signaling, resulting in increase cell proliferation, chronic low-grade, inflammation, alterations in adipokine physiology, and cellular and vascular perturbations that promote oncogenesis.
The most common gynecologic cancer in the US.
In 2020 approximately 417, 000 cases were diagnosed worldwide.
In 2021 there were an estimated 66,570 new cases and 12,940 deaths: making it the fourth most common cancer in women and the fifth most common cause of cancer death in the US.
Approximately 10% of patients die of endometrial cancer.
Early stage disease is associated with an excellent prognosis, however, patients with advanced or recurrent disease, have poor survival outcomes, with a five-year overall survival rate of 20 to 25%.
Most patients with endometrial carcinoma have localize disease, with a five-year relative survival rate of almost 95%, while patients627 with this disease have a five-year relative survival of approximately 18.5%.
About 75% of endometrial cancer are diagnosed at a localized stage, and for these patients treatments use surgery, chemotherapy and/or radiotherapy: however 20% of the women relapse mainly in the first five years.
Approximately 10 to 15% of patients present with advanced stage disease, and five-year survival among patients with distant metastasis has been reported to be 17%.
After recurrence of endometrial cancer, response to systemic therapy is often limited, and prognosis is poor.
Five years survival rates in patients with advanced stage III and IV endometrial cancer are 60% and 25%, respectively.
Affects 1 in 37 women.
Occurs mainly in postmenopausal women and 90% of patients were older than 50 years of age.
Almost half of patients have a body mass index higher than 30 kilograms per meter squared.
Five year, age adjusted survival has not improved recently and it is about 83%.
Racial disparities: estimated five-year relative survival in 2018 was 84% for white women and 62% for Black women.
Because of the high prevalence of fibroids and non-endometrioid histology types among black women, in comparison with white women, transvaginal ultrasound screening guidelines for postmenopausal bleeding have worse performance for black women contributing to racial inequality in endometrial cancer outcomes.
Postmenopausal bleeding is an early sign and allows 75% of patients can be diagnosed at an early stage.
Approximately 90% of women diagnosed with endometrial cancer report postmenopausal bleeding before the cancer is diagnosed.
See staging: endometrial_cancer_staging
Stage IA Tumor limited to the endometrium
Stage IB Invasion <50% of the myometrium
Stage IC Invasion ≥50% myometrium
Stage IIA Endocervical glandular involvement only
Stage IIB Cervical stromal invasion
Stage IIIA Tumor invading serosa of corpus uteri and/or adnexa and/ or positive cytology
Stage IIIB Vaginal metastases
Stage IIIC Metastases to pelvic and/or paraaortic lymph nodes
Stage IVA Tumor invasion of the bladder and/or bowel mucosa
Stage IVB Distant metastases, including intraabdominal metastases and or metastases to inguinal nodes
The disease is frequently symptomatic at an early stage and is therefore often diagnosed as stage I disease.
More than 70% are diagnosed as stage I.
And estimated 63,230 new cases were diagnosed in 2018.
Estimated 46,470 women were diagnosed with uterine cancer in 2011 and it was anticipated it 8120 of those women died of the disease.
In 2004 accounted for 3% of female cancer deaths.
Increasing trend in new cases and estimated deaths.
The fifth most common cancer in women with approximately 4.8% of cancers.
Cumulative risk of 1% of developing the disease by 75 years.
14th cancer in terms of mortality with 76,000 deaths worldwide and the cumulative risk of death by age 75 years of 0.2%.
Increasing incidence, in part, due to the growing epidemic of obesity.
High BMI accounts for nearly half of cases in Nort America.
Endometrial cancer, of all malignancies, most associated with obesity.
Obesity, accounts for approximately 60% of cases of endometrial cancer.
Prognosis is worse for patients with severe obesity.
Greater grade and depth of myometrial invasion, advanced stage, lymph node involvement, tumor size, lymphovascular space invasion, and lower, uterine, segment invasion are adverse prognostic findings.
Highest incidence is estimated in the US and Canada and Northern and Western
Europe ranging from 15.6 to 19/100 thousand.
About 3% of cases occur in women who have an autosomal dominant hereditary predisposition, the Lynch syndrome.
Thought to be a cancer of the post menopausal., yet 14% of cases are diagnose in premenopausal women with 5% younger than 40.
Over the last 20 years the number of annual deaths has doubled, and higher stage and poor histological cell types over time may partially explain this increased deaths associated with endometrial cancer.
Increased incidence related to increased prevalence of obesity and metabolic syndrome, polycystic ovary syndrome, plus aging.
Main risk factor is exposure to endogenous and exogenous estrogens in association with obesity, diabetes, early age at menarche, nulliparity, high fat diet, Lynch syndrome, late onset menopause, age greater than 55 years, and use of tamoxifen.
Tamoxifen, which has anti-estrogen effects in the breast and pro estrogenic effects in the uterus, approximately doubles the risk of both endometrioid and non-endometrioid types of endometrial cancer, with up to four times the risk when tamoxifen is used for more than five years.
Lifetime risk 2.6% for women living in developed nations.
Nearly twice as common as ovarian cancer and four times as many cases of cervix cancer.
Risk factors include unopposed estrogens, advancing age, diabetes, obesity and nulliparity.
Unopposed estrogen replacement therapy and tamoxifen are the most common sources of exogenous estrogen.
Oral contraceptives reduce the incidence of endometrial cancer.
Use of oral contraceptives confers long-term protection against endometrial malignancies, as does parity.
Oral contraceptives reduce the risk of endometrial cancer by 30-40%, and their longer use is associated with increased protection, which can persist for decades after cessation.
Almost 67% of patients with adenocarcinoma of the endometrium are diagnosed with disease confined to the uterus at diagnosis.
Regional and distant disease comprise approximately 21% and 8% of cases, respectively.
Inactivation of the PTEN tumor suppressor gene is most common genetic defect in endometrial cancers and is present in up to 83% of endometroid tumors.
PIK3CA mutations seen in 36% of endometrial cancers, and is most frequent in tumors with PTEN mutations.
Hormone receptor positive endometrial cancer counts for 65% of endometrial cancers, and mainly belongs to the endometrioid histologic subtype and frequently harbors nutations in PTEN
Endogenous sources of estrogen are related to obesity, cirrhosis, anovulation, and issued in producing tumors.
The levonorgestrel releasing intrauterine system may be protective against endometrial Ca.
Two histologic groups-type I related to increased estrogenous state and type II a more virulent type with early metastases and worse prognosis.
The majority of patients diagnosed with early stage disease have a good prognosis after surgery alone.
The mortality rate for uterine cancer has increased more rapidly than the incidence rate, and may be due to an increased rate of advanced staged cancers, high risk, histologies, and patients being diagnosed at an age of 65 years or greater.
Information suggests survival has increased in patients who are younger, have early stage, disease, and have low-grade disease.
Two sub types of endometrial cancer are considered:type I accounting for 70% of cases are mediated primarily by the sequelae of obesity and are associated with excess endometrial cell proliferation.
Type I endometrial cancers are frequently afflicted with hyperestrogenism, hyperlipidemia, diabetes, and anovulatory uterine bleeding.
All of these above conditions are associated with the metabolic syndrome identified as an independent risk factor for the development of endometrial cancer.
Type 1 tumors are predominantly well differentiated to moderately differentiated endometrioid tumors, at least 90% expressed in moderate to high levels of the estrogen receptor.
Type II endometrial cancers are not associated with hyperestrogenemia or endometrial hyperplasia, and often arise in non-obese women, and are not associate with metabolic or endocrine disorders.
Type II tumors are poorly differentiated, most commonly serous, clear-cell, or carcinomasarcoma types.
Type II tumors are clinically aggressive and are associated with a higher stage of initial presentation and a higher risk of recurrence.
Endometrial intraepithelial neoplasia is associated with type I cancers, and endometrial intraepithelial carcinoma is associated with type II cancers.
Most endometrial cancers are epithelial derived and arise in the endometrium.
Type I accounts for approximately 90% of endometrial cancers and is associated with the administration of estrogens and with obesity associated a result of the peripheral conversion of androstenedione to estrone in peripheral adipose tissue by 5-alpha reductase.
Type I lesions are classically associated with the prolonged administration of estrogens and are usually preceded by atypical endometrial hyperplasia.
Type I lesions are often confined to uterus, are associated with lower grade histology, and confer a more favorable prognosis.
Type II typically occurs in women over the age of 70 years and have papillary, serous or clear cell histology.
Type II sporadic cancers are associated with aging, unique genetic and molecular changes that produce a more aggressive cancer.
Type II cancers are described as non endometrioid, high grade, aneuploid, TPmutated, hormone receptive negative, associated with a higher risk of metastases and a poor prognosis.
Type II cancers account for less than 10% of endometrial cancers.
High-grade serous and clear cell stage I tumors have a worse prognosis.
Type II lesions typically have an atrophic endometrium, not associated with estrogen administration, and have a propensity for early metastatic disease resulting in the poor prognosis.
Type II usually metastatic at the time of diagnosis and spread like ovarian cancers.
Type I lesions, endometrioid histology, are associated with a backdrop of endometrial hyperplasia, while type II lesions of serous carcinoma and clear cell carcinoma are associated with endometrial atrophy.
20% of type I endometrial cancers relapse, whereas 50% of type II endometrial cancers do.
Patients with serous and clear cell type lesions present with more advanced disease and are. 5-10 years older than women with endometrioid cancer.
In Type I endometrial cancer the PIK3CA pathway is the most frequently altered, with mutations in more than 90% of lesions.
In Type I endometrial cancer KRAS mutations are common at about 20% of tumors, and 12% harbor FGFR2 mutation.
95% of endometrial cancers are caused by sporadic somatic mutations, but in about 5% genetic mutations cause endometrial cancer.
Genetic mutation caused endometrial cancer occurs 10 to 20 years before sporadic cancer.
In a series of greater than 2600 patients with clinically early-stage disease 78% had endometroid, 11% had serious and 1.6% had clear cell tumor types (Walker JL et al.).
While endometrioid histology is the most common form of endometrial cancer, comprising 75 to 80% of cases, serous and clear cell cases make up about 10% and 4%, respectively.
These latter types or more likely to present at an advanced stage and to have a worse prognosis at any given stage then grade 1 or II endometrioid tumors of similar stage.
70% of serous carcinomas will have already spread outside the uterus at the time of presentation and intraperitoneal disease is frequently present.
Histomorphologic assessment of endometrial cancer has poor reproducibility, especially among high-grade lesions: mixed histology is not infrequent.
Uterine papillary serous carcinoma comprises 5%-10% of newly diagnosed endometrial cancers.
Papillary serous carcinoma of the endometrium high risk of recurrence and accounts for 39% of deaths from endometrial cancers.
Papillary serous carcinoma of the uterus classified as type II endometrial cancer, more commonly seen in older, thinner women, and associated with hormonal risk factors.
Uterine papillary serous carcinoma incidence significantly higher in African-American women, and in women who have had breast cancer.
Uterine sarcomas are uncommon and account for approximately 3% of all uterine cancers.
About 20-30% of patients have microsatellite instability high disease.
Black women have a 55% greater mortality at 5 years.
Black women have a higher incidence of endometrial cancer.
Stage for stage patients with Type II cancers have a worse prognosis than patients with type I cancers.
Type I endometrial cancers invade local tissues before metastasizing via lymphatics and vascular systems.
Type I patients present with irregular or postmenopausal bleeding, allowing for early diagnosis.
Standard treatment consists of hysterectomy, bilateral salpingo-oophorectomy, pelvic lymph node dissection followed by adjuvant therapy on the basis of final histology.
In early-stage endometrial cancer type I, surgery alone, with or without adjuvant radiotherapy, is curative with a 96% five-year survival rate with such disease.
In type I cancer long-term survival is related to surgical stage and women with the regional or distant metastatic disease have a poorer prognosis, five year survivals of 68 and 17%, respectively.
Uterine papillary serous carcinoma, type II endometrial cancer, spreads to peritoneal surfaces and the depth of the lesion’s invasion is not a reliable indicator of metastases or the potential of metastases.
Many cases of uterine papillary serous carcinoma present as polyp like structures with no apparent invasion of the endometrium.
Uterine papillary serous carcinoma may be found in extrauterine tissues in 40% of cases in whom no myometrial invasion is present.
The recurrence rate in stage I uterine papillary serous carcinoma is much higher than for endometroid cancers, and the recurrence is also more likely to be distant than local.
Any degree of involvement of an endometrial cancer with a papillary serous component should be treated as a uterine papillary serous carcinoma.
Uterine papillary serous carcinoma surgical treatment is more aggressive than for endometroid carcinomas, with TAH/BSO, removal of the omentum, an evaluation of peritoneal surfaces, and debulking, similar to management of ovarian cancer.
Uterine papillary serous carcinoma recurrence rate not indicated by size, extent or depth of invasion.
Uterine papillary serous carcinoma ha a greater likelihood of recurring distally than locally.
Patients with uterine serous carcinoma have a poor prognosis for a five year overall survival of 46-53%, largely due to early metastatic spread.
Up to 55% of patients with uterine serous carcinoma confined to the inner one half of the myometrium will have extrauterine metastases compared to only 17% with high-grade endometrioid carcinoma.
Among patients with year in serious carcinoma, even without you doing invasion 37% may have extrauterine disease.
Uterine sarcomas represent 3-5% of all uterine cancers.
Chemotherapy part of treatment for uterine papillary serous carcinoma in all stages except IA.
For stage IA radiation to the pelvis, including vaginal brachytherapy is indicated for uterine papillary serous carcinoma following TAH/BSO.
Vaginal cuff brachytherapy plus chemotherapy as treatment in patients with early-stage endometrial carcinoma showed higher acute toxicity and did not demonstrate superiority over pelvic radiation therapy, according to results from a phase 3 trial GOG-0249.
The primary objective was to determine if vaginal cuff brachytherapy and chemotherapy increases recurrence-free survival (RFS) compared with pelvic RT,
Vaginal brachytherapy plus chemotherapy did not show superiority over pelvic RT in terms of 60-month relapse free survival, or overall survival.
For stage IB,IC uterine papillary serous carcinoma radiation to the abdomen/pelvis is indicated with or without vaginal brachytherapy.
Combination of radiation and paclitaxel for uterine papillary serous carcinoma now considered appropriate care for all stages of disease.
Serous tumors associated with positive stains for p53 gene and tend not to express estrogen and progesterone receptors.
Estrogen receptor testing is recommended in the setting of stage III, IV, or recurrent endometrial carcinoma.
HER2 overexpression is presentin 16% of GYN carcinosarcomas.
Serous endometrial carcinoma resembles ovarian papillary serous carcinoma and psammoma bodies may be detected.
Prognosis for serous endometrial cancer is poor with an estimated 18-27% five year overall survival.
Serous endometrial cancer may metastasize in the absence of any myometrial invasion.
Clear cell carcinoma of the endometrium is a high grade subtype that often can spread to extra uterine sites without deep muscle invasion.
Atypical hyperplasia associated with a 29 fold greater chance of the development of endometrial carcinoma.
Higher body mass index associated with increased risk.
Estimated 68% of women with endometrial carcinoma are obese.
Relative risk of death for morbidly obese women with endometrial cancer is 6.25 compared to women with normal weight.
Accounts for the largest number of new cases of gynecologic cancer cases, but has the best overall 5-year survival rate.
Annual mortality: incidence ratio has more than doubled in the past decade.
80% of women present with disease confined to the uterus.
20% of women present with regional spread or distant metastases.
Endometrial cancer staging according to the International Federation of Gynecology and Obstetrics (FIGO) staging system. indicates that the majority of patients are diagnosed at an early stage: 72% stage I, 12% stage II, 13% stage III and 3% stage IV.
Women with Stage I-II endometrial cancer confined to the uterus, comprising approximately 80% of all newly diagnosed cases, have 5 year survival prognosis from 80-90%.
Women with node positive or pathological Stage IIIC disease representing 6% of newly diagnosed cases, have significantly higher risks of recurrence and mortality.
Patients with Stage IIIC endometrial cancer include women with metastases to pelvic lymph nodes
N1 or IIIC1 or to the paraaortic lymph nodes N2 or Stage IIIC1 or to the paraaortic lymph nodes N2 or a Stage IIIC2with or without pelvic nodal mvolement.
In patients with Stage IIIC adjuvant therapy is often used after surgery to reduce risks of recurrence.
PORTEC-3 study randomly assigned patients with high-risk EC to pelvic radiotherapy alone, or adjuvant chemotherapy during and after radiotherapy: 5 year failure free survival favored the chemoradiotherapy group with a 7% difference.
Chemotherapy plus radiation was not associated with longer relapse free survival than chemotherapy alone in patients with stage III or IVA endometrial carcinoma (Matei, D).
In the above study patients with stage III disease had the greatest benefit from chemoradiotherapy, with ore than an 11% absolute improvement in failure free survival, but anoverall survival rate improvement in overall survival.
SEER data suggests 5 year survival for stage I disease is 95% (2008).
Women with stage I disease with intermediate and high-risk features deep muscle Invasion and grade 3 disease have a 5 year overall survival rate of 80-90%
Confined to the uterus after surgical staging has a cure rate of 85%.
For tumors confined to the fundal portion of the uterus, the recommended surgical procedure includes removal of the uterus and bilateral tubes and ovaries with lymph node and abdominal assessment.
Minimally invasive surgery is the preferred approach when technically feasible.
Regimens combining taxane and platinum are feasible alternatives to doxorubicin plus cisplatin in adjuvant chemotherapy for patients with endometrial cancer.
Carboplatin plus paclitaxel (TC) should be the first-line standard treatment for advanced endometrial cancer.
The combination proved to be noninferior to paclitaxel-doxorubicin-cisplatin (TAP) in terms of response, progression-free survival, and overall survival, and with lower toxicity.
Overall survival was a median of 37 months for TC and 41 months for TAP, and there were more adverse events of grade 3 or higher with TAP.
The efficacy of taxane plus platinum regimens has been demonstrated for advanced or recurrent endometrial cancer.
A total of 788 patients with endometrial cancer at high-risk stage I or II or stage III or IV that did not extend beyond the abdominal cavity and had ?2 cm residual tumor.
After a median of 7 years follow-up there was reported no statistical difference of in PFS (doxorubicin plus cisplatin, docetaxel plus cisplatin, paclitaxel plus carboplatin,or OS between the 3 study arms.
At 5 years, the PFS rates were 73.3% for the doxorubicin plus cisplatin arm, 79.0% for the docetaxel plus cisplatin arm, and 73.9% for the paclitaxel plus carboplatin arm; 5-year OS rates were 82.7%, 88.1%, and 86.1%, respectively.
Risk factors for recurrence after primary surgical treatment include: deep myometrial invasion, cervical stromal invasion, lymphovascular invasion, tumor histology, extrauterine progression, and distant metastases.
For patients with risk factors, postoperative adjuvant therapy is indicated to reduce the risk of recurrence.
In patients with early disease, postoperative radiation therapy reduces local recurrence, but not survival.
In patients with advanced disease postoperative systemic chemotherapy has a survival benefit compared with the radiotherapy.
There is no significant difference of survival among patients receiving doxorubicin plus cisplatin, docetaxel plus cisplatin, or paclitaxel plus carboplatin as postoperative adjuvant chemotherapy for endometrial cancer.
Generally favorable outcomes related to the early symptoms of postmenopausal vaginal bleeding and irregular vaginal bleeding in pre and per menopausal women.
Office endometrial biopsy or dilatation and curettage have approximately 100% sensitivity in the diagnosis.
With grade 1 or 2 cancer with greatest surface dimension equal or less than 2 cm, myometrial invasion equal to or less than 50%, and no surgical evidence of macroscopic disease can be optimally treated with hysterectomy alone.
Overall incidence of 25 per 100,000 increases to more than 85 per 100,000 in women over 60 years of age.
Median age at diagnosis 61 years.
Rarely diagnosed before the age of 25 years.
Incidence is 1.2-24 per 100,000 women aged 25-49 years.
Lifetime incidence rate about 22 per 100,000.
Recent analysis suggests the incidence of uterine malignancies higher than the 1 in 10,000 women in the general population or 1in 1000 undergoing surgery for fibroids.
Incidence of sarcoma in patients with presumed fibroids is 0.2-0.7%.
Prevalence of unsuspected sarcoma in women undergoing surgery for fibroids is approximately 1 in 352, to as low as 1 in 7,450.
Lifetime risk 3%, but in women with hereditary nonpolyposis colorectal cancer (HNPCC) the lifetime risk is up to 40%-60%.
Defect in DNA mismatch repair system affecting approximately 20% of tumors occurring predominantly in type I class endometrial cancer.
The most common extracolonic tumor in HNPCC.
Most cases are sporadic and develop in postmenopausal women, but approximately 2-5% are associated with hereditary gene alteration of the non-polyposis colorectal cancer syndrome.
Transvaginal ultrasound has a sensitivity of 92% and specificity of 81% for diagnosis of endometrial disease.
A disease of postmenopausal women but 30% occur prior to menopause and 5% prior to age 40.
Induced by Tamoxifen associated with a worse prognosis due to less favorable histology and higher stage.
Patients with pre-op level of CA125 <20 U/ml have less than a 3% risk of extrauterine disease.
When confined to the uterus the primary risk factors for recurrent disease are tumor histology, tumor grade, depth of myometrial invasion, lymphovascular space involvement and patient age.
African-American women have a higher percentage of more aggressive cancers.
The standard of surgical therapy is total extrafascial hysterectomy, bilateral salpingo-oophorectomy and selective sampling of the pelvic and para-aortic lymph nodes (some patients have low risk disease and do not need lymph node staging), biopsy of suspicious areas and peritoneal cytology analysis: In the future laparoscopic assisted vaginal hysterectomy and pelvic and para-aortic lymphadenectomy will become the surgical procedure of choice.
Guidelines delineate treatment for disease limited to the uterus, for suspected of gross cervical involvement, and for suspected extra uterine disease.
Most patients have stage I disease presentation and surgery with the without adjuvant therapy is recommended for medically operable patients.
Lymph node dissection identifies patients requiring adjuvant treatment with radiation therapy and/or systemic therapy.
Total lymphadenectomy carries a 23% risk of lymphedema of the lower extremities.
Sentinel lymph nodes excision has value in evaluating the extent of surgery that is required, and has been incorporated into lymph node mapping, along with standard, minimally invasive removal of the uterus, fallopian tubes, and ovaries.
In sentinel lymph node mapping, dyes anre injected into the cervix, which travels to the sentinel nodes and is useful to identify lymph nodes that are high risk for metastasis.
Surgery is the primary treatment for uterine cancer except when there is a desire to preserve fertility, when operative risk is high, and when the disease is unresectable.
The goal of surgical treatment is to remove all disease with at least a 1 cm margin and to stage of the tumor.
Endometrial cancers potentially spread by: direct invasion, lymphatic invasion, hematogenous spread, and intraperitoneal dissemination.
Preoperative PET /CT scan is standard practice.
In the Laparoscopic Surgery or Standard Surgery in Treating Patients With Endometrial Cancer or Cancer of the Uterus (LAP2)_trial laparoscopic surgery was associated with fewer hospital days, fewer perioperative complications, reduced blood loss, improved body image, increased surgical time, 26% conversion rate to laparotomy and identification metastatic disease was 17% in both groups.
In the above study LAP2, recurrence rates in 3 years were 11.39 percent in the laparoscopic group and 10.24% in the open surgery group.
In the LAP2 trial open and laproscopic approaches have equivalent overall survival.
The recommendation of the Society of Gynecologic Oncology and the American College of Obstetricians and Gynecologists at this time (2009) is primary surgery including hysterectomy, bilateral salpinogo-oophorectomy, pelvic and para-aortic lymphadenectomy and peritoneal washings.
Reasons for more complete surgical staining include: often the grade of the tumor on endometrial sampling is often incomplete compared to the hysterectomy specimen, determining the depth of tumor invasion is unreliable by gross inspection or by frozen section evaluation, pelvic lymph node sampling is a poor substitute for identifying lymph node metastases compared to lymphadenectomy, and the para-aortic lymph nodes may be involved in the absence of pelvic nodal disease.
Lymphadenectomy is generally not performed if uterine tumors are less than 2 cm in size, grade 1 or 2, and invade less than 50% of the myometrium.
The greatest risk for majority of patients with disease confined to the uterus is to fail loco-regionally and adjuvant treatment is directed to reduce this possibility.
For patients with advanced local disease or spread to areas beyond the uterus there is a high risk for distant metastases and systemic therapy must be considered.
Patients with surgical stage IA, grades 1 and 2 are at low risk for recurrence and no postoperative adjuvant therapy is administered.
Adjuvant radiation therapy has not been shown to improve overall survival in early stage patients.
Postoperative pelvic radiation may decrease locoregional recurrence and meta-analyses suggests it may reduce risks of death in patients with high risk stage I disease including stage IC and stage I grade 3.
Pelvic Radiation Therapy for Early Endometrial Cancer
The benefit of pelvic radiation in endometrial cancer of the intermediate-risk subgroup is controversial.
Trials comparing adjuvant whole-pelvic radiation therapy to either vaginal brachytherapy or observation, there is a consistent lack of an overall survival benefit, despite improvements in pelvic control.
The Postoperative Radiation Therapy in Endometrial Carcinoma (PORTEC) trial showed survival and vaginal recurrence rates were the same regardless for adjuvant whole pelvic radiation or vaginal brachytherapy.
In the above study there was a modest increase in pelvic recurrences outside the vaginal cuff in exchange for a much lower morbidity with vaginal brachytherapy compared to whole pelvic radiation treatment, suggesting vaginal brachytherapy as the most appropriate choice for high-intermediate-risk subgroup.
It is appropriate to reserve pelvic radiation for those with deep invasion plus other risk factors, where the higher morbidity associated with radiation is an acceptable price to pay for superior pelvic control.
Patients with stage IB are at low risk for recurrence and surgery alone is adequate treatment.
A rare subset of patients with stage IA, grade 3 disease are at low risk for lymph node metastases and postsurgical options include brachytherapy.
Randomized studies comparing the outcome of total abdominal hysterectomy with or without lymphadenectomy: there is no evidence that links that lymphadenectomy provides benefit over no lymphadenectomy in women with early endometrial cancer (Malzoni M et al.).
A randomized trial involving 283 patients with stage I endometroid adenocarcinoma or complex atypical hyperplasia randomized to total abdominal hysterectomy and bilateral salpingo-oophorectomy versus total laparoscopic hysterectomy and bilateral salpingo-oophorectomy: no evidence of benefit for total laparoscopic hysterectomy and bilateral salpingo-oophorectomy over total abdominal hysterectomy history in terms of complications, but the latter was beneficial in terms of hospital stay, less pain, less blood loss, and quicker resumption of daily activities (Moutits MJE).
Number of completed pregnancies have an inverse correlation to endometrial cancer.
Oral progestins yield a response rate ranging from 15-25%.
10% of stage I and 17% of stage II patients experience recurrence.
It may develop after radiation for cervical cancer occurs with an average latency period of 14 years and is associated with a preponderance of high-risk histological subtypes and poor prognosis.
Obesity increases risk with tripling of risk for a 30 pound overweight female and five times risk for an individual 50 pounds overweight.
Morbidly obese women with endometrial cancer have a 6.25 times relative risk of death compared to women of normal weight.
Obese patients have the highest fatality rate among all cancers.
The average age diagnosis diagnosis is 63 years, but a sustained rise in cases among women under the age of 50 years is occurring.
Adjuvant radiation therapy in uterine confined and extrauterine disease decreases local recurrence rate but does not have a significant impact on overall survival.
Advanced stage disease 263 patients randomly assigned to doxorubicin and cisplatin vs. paclitaxel, doxorubicin and cisplatin: response rate 34% vs. 57%, respectively, median progression free survival 5.3 months vs 8.3 months, respectively, and median overall survival 12.3 months vs 153 months, respectively (Fleming GF et al).
Patients with advanced the recurrent disease respond to cytotoxic chemotherapy/and/or radiotherapy with the response rates of 12-42% in the recurrent setting and provide only a short benefit to progression free survival with a median of six months, and overall survival median of 12 months.
Bevacizumab in recurrent or persistent endometrial cancers associated with a 13.5% clinical response rate and 40.4% progression free survival at 6 months (Aghajanian C et al).
Bevacizumab postoperatively in addition to chemotherapy and pelvic intensity modulated radiotherapy-induced high survival rates in patients with high risk endometrial cancer: Overall survival at 2 years was 96.7% and 2 year disease-free survival was 79.1% (Viswanathan AN).
Erlotinib had a response rate of 12.5% in patients with metastatic disease (Oza MM et al).
The angiogenesis inhibitor cediranib demonstrated acceptable activity and a tolerable safety profile as a monotherapy for patients with recurrent or persistent endometrial cancer.
In the phase II study, known as NRG/GOG 229J, partial responses were observed in 12.5% of patients.
The 6-month progression free survival (PFS) rate was 33.3% and the median overall survival (OS) was 12.5 months.
A multi-tyrosine kinase inhibitor that blocks VEGF, PDGF, and PGF receptors.
Treatment consisted of cediranib at 30mg orally per day in a 28-day cycle.
The combination of cediranib and chemotherapy as a treatment for patients with advanced cervical cancer reduced the risk of progression by 39% compared with chemotherapy alone.
The combination of cediranib and olaparib demonstrated a near doubling in median PFS compared with olaparib alone in women with recurrent ovarian cancer.
The pivotal phase 3 KEYNOTE-775/Study 309 trial evaluating the use of pembrolizumab (Keytruda) plus lenvatinib (Lenvima) met its dual primary end points of overall and progression-free survival in patients with advanced endometrial cancer.
Phase3 KEYNOTE-775/Study 309 trial, the combination demonstrated statistically significant improvements in overall survival (OS), reducing the relative risk of death by 32%, hazard and progression-free survival, reducing the relative risk of disease progression or death by 40% vs chemotherapy with doxorubicin or paclitaxel.
Patients had advanced endometrial cancer following at least 1 prior platinum-based regimen.
Positive results were reported in the mismatch repair proficient (pMMR) subgroup and patients whose disease is microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR).
Using checkpoint inhibitors for patients progressing on or after first line chemotherapy is efficacious.
Pembrolizumab plus lenvatinib demonstrated a statistically significant and clinically meaningful improvement in OS, PFS, and response rate versus chemotherapy treatment of physician’s choice of doxorubicin or paclitaxel.
In patients with advanced the recurrent endometrial cancer, the addition of pembrolizumab to standard chemotherapy result in significantly longer progression free, survival than with chemotherapy alone (Eskander, RN).
((Dostarlimab)) is approved for the treatment of patients with recurrent or advanced endometrial cancer that has progressed on or following prior treatment with a platinum-containing chemotherapy and whose cancers are mismatch repair deficient.
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