ﺑﺎﺯﮔﺸﺖ ﺑﻪ ﺻﻔﺤﻪ ﻗﺒﻠﯽ
خرید پکیج
تعداد آیتم قابل مشاهده باقیمانده : 3 مورد
نسخه الکترونیک
medimedia.ir

Overview of approach to endometrial cancer survivors

Overview of approach to endometrial cancer survivors
Literature review current through: Jan 2024.
This topic last updated: Nov 23, 2022.

INTRODUCTION — Endometrial cancer is the most common of the gynecologic cancers. Over 3 percent of females born in the United States will be diagnosed with uterine cancer during their lifetime, based on 2016 to 2018 data [1]. Among solid tumors, uterine cancer is one of the only tumors in the United States that has increased in both incidence and death rates. Uterine cancer incidence rates increased by 0.7 percent per year from 1999 to 2015, likely due to patients living longer and the increasing rates of obesity in the United States [2]. Uterine cancer death rates increased by 21 percent from 1999 to 2016, approximately 1.1 percent per year on average, with larger increases among non-Hispanic/Pacific Islander, Hispanic, and Black patients compared with White patients. During this time, Black patients were approximately twice as likely to die from uterine cancer as were patients in other racial/ethnic groups.

Fortunately, most patients with endometrial cancer will survive their initial diagnosis, making this the largest group of survivors who had a gynecologic malignancy [3]. In the United States there were an estimated 813,861 survivors with a history of uterine cancer in 2019 [1]. Endometrial cancer is second only to breast cancer as the most common cancer in female cancer survivors [3]. Unfortunately, there is a lack of clear evidence for what constitutes best practices in caring for patients with a history of endometrial cancer. Recommendations for post-treatment surveillance after primary therapy of endometrial cancer will be reviewed here.

For purposes of this discussion, we will address survivorship as it pertains to patients who have completed initial treatment for endometrial cancer and who are without evidence of disease.

The treatment of patients with endometrial cancer is discussed separately.

(See "Overview of resectable endometrial carcinoma".)

(See "Endometrial carcinoma: Epidemiology, risk factors, and prevention".)

(See "Endometrial carcinoma: Staging and surgical treatment".)

OVERVIEW OF TREATMENT — An overview of the treatment of endometrial cancer is presented elsewhere. (See "Overview of resectable endometrial carcinoma".)

FOLLOW-UP POST-TREATMENT — Post-treatment surveillance is aimed at the early detection of recurrent disease. For patients with endometrial carcinoma, surveillance consists mainly of monitoring for symptoms and physical examinations. Routine use of serum cancer antigen (CA) 125 and imaging varies across institutions; however, the benefit of surveillance to detect asymptomatic disease is controversial. In our practice we do not use serum CA 125 or imaging studies unless clinically indicated [4].

There is no high-quality evidence that any specific post-treatment surveillance strategy is associated with improved outcomes. In the absence of data, we agree with the consensus-based guidelines from the United States National Comprehensive Cancer Network (NCCN) and the Society of Gynecologic Oncology (SGO), which include the following [4]:

Review of symptoms and physical examination including speculum and bimanual pelvic exam every three to six months for two years, then every six months or annually. The frequency of examinations depends upon the risk of persistent or recurrent disease. In a randomized trial, vaginal cytology, laboratory, or imaging investigations did not improve survival relative to physical examination only, even in high-risk patients [5].

Genetic counseling for patients with a family history suggestive of Lynch syndrome (hereditary nonpolyposis colon cancer) or the finding of microsatellite instability on tumor screening. (See "Lynch syndrome (hereditary nonpolyposis colorectal cancer): Clinical manifestations and diagnosis", section on 'Diagnostic approach'.)

We do not perform vaginal cytology in endometrial cancer survivors; this is consistent with the SGO "choosing wisely" guidelines, which recommend against routine vaginal cytology in endometrial cancer surveillance [6]. Data suggest vaginal smears are ineffective in the detection of recurrences compared with physical examination alone [4,7,8]. For example, in a retrospective study of patients with endometrial carcinoma (n = 433), all of whom had undergone hysterectomy, 13 percent (n = 55) had at least one abnormal result, representing three percent of all pap tests performed [7]. Abnormal vaginal cytology had a sensitivity of 40 percent and a specificity of 88 percent for detecting a vaginal recurrence.

When planning the posttreatment surveillance strategy, care should be taken to limit the number of CT scans, given concerns about radiation exposure and the risk for second malignancies. Routine use of chest radiography in an asymptomatic survivor is also not supported by evidence. However, imaging studies such as chest radiography, CT, magnetic resonance imaging should be performed for patients who are symptomatic or have abnormal findings on physical examination [4]. A 2013 meta-analysis of 11 studies (10 of which were retrospective) supports the use of positron emission tomography (PET) as another modality for the evaluation of a suspected recurrence, particularly when performed with a CT scan [9]. In this analysis, PET had a sensitivity and specificity of 95 and 93 percent, respectively. However, the use of PET for routine screening has not been well studied, and the high cost of this test limits its use in this setting. (See "Radiation-related risks of imaging".)

PATTERN OF RECURRENCE — The majority of endometrial carcinoma recurrences occur within three years after treatment (68 to 100 percent) [10-13]. Sites of recurrence are fairly evenly distributed between vaginal/pelvic and distant (abdominal or lung) metastases. The risk of local, but not distant, recurrence is lower in patients who have received radiation therapy. The most common sites of recurrent disease are the vaginal vault, pelvis, abdomen, and lungs [14].

Approximately 70 percent of endometrial carcinoma recurrences are associated with symptoms, based upon a systematic review of 16 observational studies [10]. It is important to note that no survival difference was found between patients with asymptomatic versus symptomatic recurrences. Signs or symptoms suggestive of recurrence include: vaginal bleeding, abdominal or pelvic pain, persistent cough, or unexplained weight loss.

Asymptomatic recurrences were detected by the following modalities [10]:

Physical examination (5 to 33 percent)

Abdominal ultrasound (4 to 13 percent)

Abdominal/pelvic computed tomography (CT) (5 to 21 percent)

Chest radiography (0 to 14 percent)

Cancer antigen 125 in selected patients (15 percent)

Vaginal vault cytology (0 to 4 percent)

Any visible lesion identified on pelvic exam should be biopsied because isolated vaginal recurrences are most often curable [15,16]. This was illustrated in the Post-Operative Radiation Therapy for Endometrial Cancer (PORTEC) trial in which 39 of 174 patients experienced an isolated vaginal relapse [16]. Of these, 31 of 35 (89 percent) who underwent treatment with curative intent had a complete response.

A more in-depth review of the clinical presentation, work-up, and treatment for patients with recurrent or metastatic endometrial cancer are discussed separately. (See "Management of locoregional recurrence of endometrial cancer", section on 'Clinical presentation'.)

SPECIFIC ISSUES — There is a paucity of data to inform the general survivorship experience of the endometrial cancer survivor and therefore, general management guidelines for cancer survivors should also apply to this population. What follows are specific issues addressed in the literature that relate to this population. More general information on cancer survivorship is discussed elsewhere. (See "Overview of cancer survivorship care for primary care and oncology providers".)

Chemotherapy- and immunotherapy-related toxicities — The agents used to treat endometrial cancer include carboplatin, paclitaxel, and doxorubicin. Although most patients do well with treatment, all three of these agents are associated with lingering toxicities which may persist after treatment has ended, including neurotoxicity and fatigue. Based on the results of the Gynecologic Oncology Group (GOG) 209 trial, carboplatin and paclitaxel are most commonly used in the adjuvant or first-line treatment setting [17]; doxorubicin is most often prescribed in the setting of recurrent disease. The results of GOG 209 are discussed separately. (See "Adjuvant treatment of high-risk endometrial cancers", section on 'Choice of chemotherapy regimen' and "Initial treatment of metastatic endometrial cancer", section on 'Rationale for multiagent chemotherapy'.)

Neuropathy – Neurologic complications of anticancer therapy may result from direct toxic effects on the nervous system or indirectly from drug-induced metabolic derangements or cerebrovascular disorders. While peripheral neuropathy and/or central nervous toxicity is uncommon with carboplatin, paclitaxel can induce a serious (grade 3/4) motor neuropathy affecting the proximal muscles in up to 14 percent of patients [18]. The management of peripheral neuropathy is discussed separately. (See "Prevention and treatment of chemotherapy-induced peripheral neuropathy", section on 'Symptomatic treatment'.)

Fatigue – Chemotherapy is directly related to the development of cancer-related fatigue, whether as a primary side effect or by interaction with other side effects, including premature menopause, exacerbation of a pre-existing mental health condition, or heart-failure related to doxorubicin. The evaluation and treatment of cancer-related fatigue is discussed separately. (See "Cancer-related fatigue: Prevalence, screening, and clinical assessment" and "Cancer-related fatigue: Treatment".)

Pembrolizumab has been approved by the US Food and Drug Administration (FDA) for microsatellite-instable solid tumors [19]. Additionally, the combination of pembrolizumab and lenvatinib received accelerated FDA approval in September 2019 for all patients with advanced endometrial cancer who have disease progression following prior systemic therapy [20]. It is anticipated that more patients with endometrial cancer will be treated with pembrolizumab as second-line therapy.

Pembrolizumab as a single agent is relatively well tolerated. Patients with endometrial cancer are able to stay on treatment for months and tolerate this well [21].

By contrast, the combination of pembrolizumab and lenvatinib, approved for mismatch repair-deficient tumors, has a high toxicity profile, with 96 percent of patients experiencing adverse events in the pivotal clinical trial [22]. Active management of treatment-related toxicity is critical to patients successfully staying on therapy. Notably, in the randomized trial of pembrolizumab/lenvatinib versus clinician's choice chemotherapy, there were no significant differences observed in health-related quality of life (QOL) scores between treatment groups [23]. (See "Initial treatment of metastatic endometrial cancer", section on 'Initial therapy'.)

Obesity — Approximately 70 to 90 percent of patients with estrogen-dependent endometrial cancer (also known as Type I endometrial cancer) are obese [24-26]. Despite this, patients with endometrial cancer appear not to understand that there is relationship between obesity and their cancer diagnosis. In one survey, only 42 percent were aware that obesity was a risk factor for endometrial cancer [27]. Weight group (obese versus nonobese) was not associated with an increased awareness of this risk. The impact of weight and physical activity on outcomes of survivors of endometrial cancer is discussed elsewhere. (See "The roles of diet, physical activity, and body weight in cancer survivors".)

Sexual dysfunction — Sexual dysfunction in endometrial cancer survivors is complex and multifactorial. Sexual dysfunction may be related to the surgical procedure itself or may be related to adjuvant radiation therapy (RT) or chemotherapy.

The impact on sexual function related to surgery alone was demonstrated in a study that examined 72 patients with early stage endometrial cancer (none of whom underwent postoperative treatment) [28]. While the studied cohort reported an overall good QOL, 89 percent reported sexual dysfunction. In the multivariate analysis, diabetes was a significant contributor to poor sexual function.

Studies regarding sexual function of patients who have been treated with RT are variable. When reported, late adverse effects of vaginal brachytherapy (VBT) include vaginal dryness with painful intercourse and tightening and/or shortening of the vagina [29-32]. However, data from one randomized trial that evaluated pelvic RT versus VBT found no difference in sexual function between patients who had received radiation and those who had not [33].

Clinicians should be aware that sexual function will be impacted by endometrial cancer and/or its treatment. Unfortunately, most experts agree that there are significant barriers to effective communication about sexual health [34]. Despite these barriers, the majority of patients would prefer to discuss issues of sexual dysfunction but may be unwilling to initiate the discussion. Although the best time to discuss sexual health is likely prior to treatment, the time of diagnosis and discussion of cancer treatment can be stressful and introducing a discussion about treatment related sexual issues is difficult. Nevertheless, incorporating a sexual history into the routine review of systems may help to normalize sexual health as an appropriate area to discuss between patients and their clinicians. After treatment, questions about sexual health should be a routine part of surveillance. If a problem is identified, open-ended questions should be asked in order to avoid any misconceptions about the patient's sexual preferences. Resources should be made available for those patients who wish to pursue treatment for sexual dysfunction [35].

Nonendocrine and endocrine therapies are available to address sexual health concerns. These include polycarbophilic moisturizers (eg, Replens), vaginal pH-balanced gels (eg, RepHresh), and local estrogen therapies, which can be administered as gels or as a vaginal tablet. Beyond these remedies, referral to a local resource in sexual function after cancer, or an oncology sexual health clinic, if available, may be helpful. A more comprehensive discussion on the treatment of sexual dysfunction is beyond the scope of this topic, but several comprehensive reviews are available. [35-37]. The administration of local estrogen therapy is discussed below. (See 'Menopausal symptoms' below.)

Beyond pharmacologic therapies, vaginal dilators may be useful for patients who experience pain with vaginal penetration, which may be common among patients treated with vaginal or pelvic RT. In our experience, most patients find the use of dilators distressing and significant reassurance and counseling is required to achieve compliance.

Menopausal symptoms — The majority of endometrial carcinomas are diagnosed in postmenopausal patients, but 25 percent occur in premenopausal patients [38,39]. The surgical management of endometrial cancer renders patients post-menopausal with the associated array of symptoms and side-effects. Patients treated for endometrial cancer may experience new or ongoing menopausal symptoms (eg, vasomotor symptoms, vaginal atrophy). There are multiple treatments available for menopausal symptoms, which are discussed separately. (See "Treatment of menopausal symptoms with hormone therapy" and "Menopausal hot flashes", section on 'Management'.)

Of available treatments, studies suggest that progestins are safe and effective for use in endometrial cancer survivors [40]. In addition, nonhormonal options are also safe, including selective serotonin reuptake inhibitors and serotonin/norepinephrine reuptake inhibitors, antiepileptics (gabapentin and pregabalin), and clonidine [41,42]. Other interventions include yoga, hypnosis, relaxation-training/paced respiration, acupuncture, mindfulness-based stress reduction (MBSR), and cognitive behavioral therapy (CBT) [43]. While much of the research evaluating the role of nonhormonally based therapies has been conducted in breast cancer survivors, extrapolation of the data to endometrial cancer survivors is entirely reasonable.

Approach to younger patients — Although younger patients (age ≤40) comprise less than seven percent of those diagnosed with endometrial cancer, surgical treatment (which includes oophorectomy) will induce premature menopause. As in patients who undergo an elective oophorectomy, this may be associated with long-term serious health consequences, such as cardiovascular disease and osteoporosis. Very young patients without a family history of cancer may consider retaining ovaries at the time of endometrial cancer surgery [44]. (See "Elective oophorectomy or ovarian conservation at the time of hysterectomy", section on 'Long-term health risks'.)

Therefore, treatment of menopausal symptoms should take in to account patient and disease-related factors:

For patients with low-risk disease, estrogen-replacement therapy should be administered as first line therapy which may decrease the risks of long-term health consequences [45].

Although there is a theoretical risk that exogenous estrogen may stimulate growth of dormant cancer cells [46,47] the limited data in patients with low-risk disease suggest that endocrine therapy does not increase the risk of recurrence [48-51]. For example, in GOG trial 137, over 1200 endometrial cancer survivors (95 percent with stage I disease and 90 percent with endometrioid type adenocarcinomas) were randomly assigned to treatment with oral estrogen or a placebo preparation [52]. With an average follow-up of three years, there was no difference in the rate of recurrence among those on estrogen replacement therapy (ERT) compared with placebo (recurrence rate 2.3 versus 1.9 percent, respectively; risk ratio 1.27, 90% CI 0.92-1.77). However, the data are limited due to multiple factors including:

The small number of absolute events in both the ERT and control groups (14 versus 12 recurrences, respectively; 5 versus 4 deaths due to endometrial cancer)

Poor compliance in the group assigned to ERT (41 percent stayed on treatment throughout the course of the study)

Poor accrual, which resulted in early study termination

Given the wide confidence interval and the small absolute increase in risk associated with ERT (0.4 percent), we consider ERT a reasonable approach to the treatment of menopausal symptoms in this population.

For patients with intermediate-risk or high-risk disease, we prefer nonhormonal interventions for menopausal symptoms. However, if symptoms are not controlled, vaginal rather than systemic estrogen therapy should be prescribed with dosing individualized according to the severity of symptoms and the risk of recurrence. Our practice is consistent with guidelines issued by the American College of Obstetricians and Gynecologists [53] and The National Comprehensive Cancer Network [54]. Unfortunately, there are no prospective data to inform the safety of estrogen therapy in these patients.

In general, an opposing progestin is not necessary for endometrial protection following hysterectomy. Progestins are used to treat endometrial carcinoma in patients who desire fertility preservation. It is not known whether the addition of a progestin would decrease the risk of recurrence of endometrial cancer in patients treated with ET.

Lymphedema — Because sentinel lymph node dissection (SLND) has largely replaced full lymphadenectomy in the management of endometrial cancer, especially in the United States [55,56], lymphedema has become uncommon in endometrial cancer survivors. In one study, the frequency of lymphedema in patients who underwent SLND and those who underwent full lymphadenectomy was 1.3 and 18.1 percent, respectively [57]. Notably, lower-extremity lymphedema (LEL) is not always well reported or systematically prospectively studied. In a retrospective study including almost 600 patients who underwent primary surgical management for endometrial carcinoma, patients who underwent SLND compared with lymphadenectomy had lower rates of self-reported LEL (27 versus 41 percent, odds ratio 1.85, 95% CI 1.25-2.74) [58]. In a randomized trial comparing no lymph node dissection with systematic lymphadenectomy, the frequency was 2 and 35 percent, respectively [59].

Increased body mass index and use of adjuvant external-beam RT (EBRT) are also both associated with an increased prevalence of LEL [58]. Adjuvant chemotherapy was also associated with LEL in at least one study [60]; the mechanism by which this occurs is unclear and more studies are needed.

While lymphedema most often manifests as lower-extremity edema, it may also present as lower-extremity heaviness, discomfort, or pain. Education, support, and referral to a physical therapist with expertise in treating LEL can improve QOL [61-64]. However, treatment success is contingent on patients being identified and referred appropriately [63,64].

Radiation-related gastrointestinal toxicity — Adjuvant whole pelvic RT, particularly after extensive surgical staging, can be expected to increase morbidity as it can result in chronic alterations in both bladder and bowel function. Radiation effects can be classified as acute, occurring during or shortly after completion of treatment, or chronic, usually defined as beginning 3 to 12 months following completion of treatment and lasting a lifetime. Severe problems are fortunately rare, occurring in 4 to 10 percent of patients over a 5 to 10 year period following treatment completion, and include transfusion dependent rectal bleeding, fistula formation, bowel obstruction, and secondary malignancies [65]. Chronic GI symptoms are far more common, and include diarrhea, abdominal and rectal pain, bloating, flatulence, and fecal incontinence [65].

There are limited data specific to the effect of pelvic radiation on overall QOL for endometrial cancer patients. Many studies combine patients with cervical and endometrial cancer, a combination that may not be logical given the very different patient populations and radiation techniques utilized. One study from Britain confirmed a rate of 47 percent of patients with cervical and endometrial cancer with symptoms of chronic radiation enteritis. Despite their symptoms, however, many patients stated that their overall QOL was good, even though 42 percent had to rush to the toilet and 32 percent suffered fecal incontinence, suggesting a tendency to understate these symptoms. Most patients had to carefully watch their diet, wear pads to keep clean, and frequently had to change their underclothes. About a third of patients felt depressed, anxious, or experienced fatigue due to bowel problems. Limited data on effects on QOL suggest that patients treated with RT have a lower QOL compared with matched healthy controls [66-68]. It has also been demonstrated that oncologists frequently underestimate the radiation-related long-term morbidities in cancer survivors compared with the patients' actual experience [69]. This may be secondary to patient factors, as the patient may not report symptoms for a variety of reasons [65].

EBRT results in increases in diarrhea scores and bowel symptoms [33,70,71]. The PORTEC study, which randomized patients with endometrial cancer to receive either whole-pelvic EBRT or VBT, considered QOL with respect to gastrointestinal symptoms [33]. Patients treated with EBRT reported a 21 percent increase in mean diarrhea scores. After EBRT, 15.4 percent and 7.3 percent of patients reported quite a bit or very much diarrhea. While these scores decreased over time, they still remained at significantly higher levels than patients who received VBT with additional follow-up. In addition, patients treated with EBRT reported an 8 percent increase in fecal leakage 6 months after RT. Patients treated with EBRT reported a significantly higher need to remain close to a toilet, which resulted in a higher level of limitation of daily activities because of a bowel problem. As a result, social functioning after EBRT was significantly lower than after VBT.

While patients may have significant acute gastrointestinal problems during and immediately after radiation treatment, these issues do not seem to impact overall QOL and also seem to improve over time [72]. However, compared with patients treated with surgery alone, those treated with adjuvant RT report continued chronic persistent bowel problems months to years after completing RT that do not improve with time [67,72]. Interestingly, even though patients believed they were significantly impacted by the RT, they felt overall better having successfully completed the treatment protocol, perhaps due to the perceived benefit of reducing recurrence risk [72]. Patients having EBRT report higher gastrointestinal symptom burden than patients who receive only brachytherapy. In one study 16 percent of patients who received EBRT had quite a bit or very much diarrhea compared with 5 percent of patients who received brachytherapy only. GI and diarrhea symptoms were highest among patients who received EBRT [73].

The best solution to the problem of GI toxicity following radiation may be avoiding radiation treatment, especially in light of randomized studies that show the lack of a survival benefit for many patients who have traditionally received whole pelvic RT [71]. Despite this, we acknowledge the tendency to prescribe adjuvant RT continues to be a common practice [74]. When RT is required, new radiation planning techniques can be utilized to minimize bowel toxicity. These include the use of intensity modulated RT, which spares the GI tract and results in decrease in GI toxicity with equivalent treatment effect [75,76]. (See "Radiation therapy techniques in cancer treatment", section on 'Intensity-modulated radiation therapy'.)

Health providers need to be more proactive in identifying and treating patients with chronic bowel symptoms, as they are often reluctant to mention symptoms due to embarrassment or reluctance to complain. Most patients will not admit to fecal leakage or chronic diarrhea due to embarrassment as well as fear of judgment from their physician. There is a need for clinicians who are adequately trained to help patients manage chronic GI problems, which ideally consists of a multidisciplinary model, including nutritionists and gastroenterologists. Techniques to prevent excessive bowel toxicity during treatment, such as new radiation techniques or bowel protection modalities as well as early intervention to prevent late radiation toxicities can be helpful prior to the development of symptoms.

The publication of the results of GOG 258 will likely shift recommendations for patients with advanced disease away from radiation and toward chemotherapy as adjuvant therapy [77]; this study demonstrated that chemotherapy plus radiation was not associated with longer relapse-free survival than chemotherapy alone in patients with stage III or IVa endometrial cancer.

For patients who present with gastrointestinal toxicities related to prior treatment, the management is similar to other patients and is discussed separately. (See "Overview of gastrointestinal toxicity of radiation therapy".)

Other radiation-related toxicities — While GI side effects, lymphedema, and sexual side effects are the most significant resulting from pelvic RT, pelvic radiation may also result in side effects for other pelvic organs. With long term follow-up, patients treated with pelvic radiation also report symptoms related to the urinary tract, the pelvic bones, and the lower abdomen, when compared with a control group [78]. In one large study, urinary symptoms included difficulty feeling a full bladder or feeling when the bladder is empty [78]. Patients also reported pelvic bone pain and lower abdominal discomfort.

COORDINATION OF CARE — Practice patterns vary according to whether follow-up is provided by an oncologist or another clinician [10]. In our practice, an oncologist follows patients for three to five years, after which they may transition back to a general gynecologist or primary care physician. Patients may also choose to alternate follow-up visits with their gynecologist and the gynecologic oncologist to limit travel time and cost where appropriate. (See "Overview of cancer survivorship care for primary care and oncology providers", section on 'Coordination of care'.)

Regardless of who is seeing the patient, surveillance should consist of yearly pelvic exams with visual examination of the vaginal mucosa and vaginal cuff via speculum examination and digital recto-vaginal exam. Symptoms such as vaginal bleeding or post-coital bleeding, pelvic pressure or change in bowel or bladder habits should be carefully investigated to rule out recurrent disease. (See 'Follow-up post-treatment' above.)

Most endometrial cancer patients (particularly those with type I disease) also have other medical problems, including hypertension, metabolic syndrome, diabetes and obesity. In one series of patients with type I endometrial cancer, 90 percent of participants were at high-risk for development of cardiovascular disease [79]. It is therefore important to address these other medical issues in addition to monitoring for disease recurrence.

All patients with endometrial cancer may be at increased risk for colon cancer (hereditary nonpolyposis colorectal cancer [HNPCC] or Lynch syndrome), and microsatellite-instability testing should be performed on the patient's endometrial cancer tissue as a screening test [80]. Our practice is to test all specimens using either immunohistochemistry to identify loss of mismatch repair (MMR) proteins or polymerase chain reaction to identify the microsatellite instability that attends dysfunctional MMR [81]. In one population based study of over 3000 endometrial cancer patients, age standardized rates of breast and colorectal cancers were 0.5 and 0.7 percent respectively, compared with 0.5 percent (p = 0.76) and 0.2 percent (p <0.001) in the general population [82]. (See "Lynch syndrome (hereditary nonpolyposis colorectal cancer): Clinical manifestations and diagnosis" and "Lynch syndrome (hereditary nonpolyposis colorectal cancer): Cancer screening and management".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Uterine cancer".)

SUMMARY AND RECOMMENDATIONS

Endometrial cancer is the most common of the gynecologic cancers. Fortunately, most patients will survive their initial diagnosis, making this the largest group of survivors who had a gynecologic malignancy. (See 'Introduction' above.)

Unlike the majority of other solid tumors, endometrial cancer incidence and death rates have been increasing; the mortality from uterine cancer is almost double in Black patients compared with White patients. The overall trends in incidence and death may be due to patients living longer, increasing rates of obesity (in the United States), and increase in higher-risk histologies. (See 'Introduction' above.)

Posttreatment surveillance is aimed at the early detection of recurrent disease. For patients with endometrial carcinoma, surveillance consists mainly of monitoring for symptoms and physical examinations. We do not perform vaginal cytology in endometrial cancer survivors because the data suggest they are not useful in early detection of recurrent disease. (See 'Follow-up post-treatment' above.)

The majority of recurrences of endometrial carcinoma occur within three years after treatment and are fairly evenly distributed between vaginal/pelvic and distant (abdominal or lung) metastases. The most common sites of recurrent disease are the vaginal vault, pelvis, abdomen, and lungs. (See 'Pattern of recurrence' above.)

The chemotherapy agents used to treat endometrial cancer include carboplatin, paclitaxel, and doxorubicin. Although most patients do well with treatment, all three of these agents are associated with lingering toxicities that may persist after treatment has ended. These include neuropathy, risk of cardiotoxicity, fatigue, and postchemotherapy cognitive impairment. Pembrolizumab is also approved by the US Food and Drug Administration for microsatellite-instable solid tumors or in combination with lenvatinib in all endometrial cancers, and is associated with certain immune-related toxicities. (See 'Chemotherapy- and immunotherapy-related toxicities' above and "Toxicities associated with immune checkpoint inhibitors".)

The combination of pembrolizumab and lenvatinib has a high rate of toxicity, with the most common toxicities of hypertension, diarrhea, and fatigue. (See 'Chemotherapy- and immunotherapy-related toxicities' above.)

Obesity is perhaps the most important risk factor for the development of endometrial cancer. In addition, obesity may be associated with poorer outcomes after treatment. Therefore, we encourage endometrial cancer survivors to adopt lifestyle modifications, including increased physical activity, regular exercise routines, and overall be less sedentary. (See 'Obesity' above.)

Sexual dysfunction in endometrial cancer survivors is complex and multifactorial. Sexual dysfunction may be related to the surgical procedure itself or may be related to adjuvant radiation therapy (RT) or chemotherapy. Sexual symptoms are important to address in these patients because treatments are available if symptoms are present. (See 'Sexual dysfunction' above.)

Our approach to patients with endometrial cancer who have menopausal symptoms takes into account the risk-status of their disease (see 'Menopausal symptoms' above):

For patients with low-risk disease, we suggest estrogen-replacement therapy rather than a nonhormonal treatment (Grade 2B).

For patients with intermediate-risk or high-risk disease, we suggest a nonestrogenic treatment rather than estrogen replacement therapy (Grade 2C). However, estrogen may be indicated if symptoms are not controlled.

Because sentinel node dissection has largely replaced full lymphadenectomy in the management of endometrial cancer, lymphedema has become uncommon in endometrial cancer survivors. If it occurs, education, support, and referral to a physical therapist with expertise in treating lower-extremity lymphedema can improve quality of life. (See 'Lymphedema' above.)

Health providers need to be more proactive in identifying and treating patients with chronic bowel symptoms related to RT, as they are often reluctant to mention symptoms due to embarrassment or reluctance to complain. Most patients will not admit to fecal leakage or chronic diarrhea due to embarrassment as well as fear of judgment from their physician. (See 'Radiation-related gastrointestinal toxicity' above.)

  1. National Cancer Institute Surveillance, Epidemiology, and End Results Program. Cancer Stat Facts: Endometrial Cancer. https://seer.cancer.gov/statfacts/html/corp.html (Accessed on September 05, 2021).
  2. Henley SJ, Miller JW, Dowling NF, et al. Uterine Cancer Incidence and Mortality - United States, 1999-2016. MMWR Morb Mortal Wkly Rep 2018; 67:1333.
  3. United States Centers for Disease Control and Prevention. United States Cancer Statistics: Data visualizations. https://gis.cdc.gov/Cancer/USCS/#/Prevalence/ (Accessed on September 05, 2021).
  4. Salani R, Khanna N, Frimer M, et al. An update on post-treatment surveillance and diagnosis of recurrence in women with gynecologic malignancies: Society of Gynecologic Oncology (SGO) recommendations. Gynecol Oncol 2017; 146:3.
  5. Zola P, Ciccone G, Piovano E, et al. Effectiveness of Intensive Versus Minimalist Follow-Up Regimen on Survival in Patients With Endometrial Cancer (TOTEM Study): A Randomized, Pragmatic, Parallel Group, Multicenter Trial. J Clin Oncol 2022; 40:3817.
  6. Rimel BJ, Burke WM, Higgins RV, et al. Improving quality and decreasing cost in gynecologic oncology care. Society of gynecologic oncology recommendations for clinical practice. Gynecol Oncol 2015; 137:280.
  7. Novetsky AP, Kuroki LM, Massad LS, et al. The utility and management of vaginal cytology after treatment for endometrial cancer. Obstet Gynecol 2013; 121:129.
  8. Bristow RE, Purinton SC, Santillan A, et al. Cost-effectiveness of routine vaginal cytology for endometrial cancer surveillance. Gynecol Oncol 2006; 103:709.
  9. Kadkhodayan S, Shahriari S, Treglia G, et al. Accuracy of 18-F-FDG PET imaging in the follow up of endometrial cancer patients: systematic review and meta-analysis of the literature. Gynecol Oncol 2013; 128:397.
  10. Fung-Kee-Fung M, Dodge J, Elit L, et al. Follow-up after primary therapy for endometrial cancer: a systematic review. Gynecol Oncol 2006; 101:520.
  11. Ben Arie A, Lavie O, Gdalevich M, et al. Temporal pattern of recurrence of stage I endometrial cancer in relation to histological risk factors. Eur J Surg Oncol 2012; 38:166.
  12. Tjalma WA, van Dam PA, Makar AP, Cruickshank DJ. The clinical value and the cost-effectiveness of follow-up in endometrial cancer patients. Int J Gynecol Cancer 2004; 14:931.
  13. Sartori E, Pasinetti B, Chiudinelli F, et al. Surveillance procedures for patients treated for endometrial cancer: a review of the literature. Int J Gynecol Cancer 2010; 20:985.
  14. Menczer J. Endometrial carcinoma. Is routine intensive periodic follow-up of value? Eur J Gynaecol Oncol 2000; 21:461.
  15. Otsuka I, Uno M, Wakabayashi A, et al. Predictive factors for prolonged survival in recurrent endometrial carcinoma: Implications for follow-up protocol. Gynecol Oncol 2010; 119:506.
  16. Creutzberg CL, van Putten WL, Koper PC, et al. Survival after relapse in patients with endometrial cancer: results from a randomized trial. Gynecol Oncol 2003; 89:201.
  17. Miller DS, Filiaci VL, Mannel RS, 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.
  18. Lee JJ, Swain SM. Peripheral neuropathy induced by microtubule-stabilizing agents. J Clin Oncol 2006; 24:1633.
  19. Ott PA, Bang YJ, Berton-Rigaud D, et al. Safety and Antitumor Activity of Pembrolizumab in Advanced Programmed Death Ligand 1-Positive Endometrial Cancer: Results From the KEYNOTE-028 Study. J Clin Oncol 2017; 35:2535.
  20. United States Food and Drug Administration press release. Simultaneous review decisions for pembrolizumab plus lenvatinib in Australia, Canada and US https://www.fda.gov/drugs/resources-information-approved-drugs/simultaneous-review-decisions-pembrolizumab-plus-lenvatinib-australia-canada-and-us (Accessed on October 07, 2019).
  21. Marabelle A, Le DT, Ascierto PA, et al. Efficacy of Pembrolizumab in Patients With Noncolorectal High Microsatellite Instability/Mismatch Repair-Deficient Cancer: Results From the Phase II KEYNOTE-158 Study. J Clin Oncol 2020; 38:1.
  22. Makker V, Taylor MH, Aghajanian C, et al. Lenvatinib Plus Pembrolizumab in Patients With Advanced Endometrial Cancer. J Clin Oncol 2020; 38:2981.
  23. Lorusso D, Colombo N, Herraez AC, et al. Health-related quality of life in advanced endometrial cancer patients treated with lenvatinib plus pembrolizumab or treatment of physician’s choice. J Clin Oncol 2021; 39S: ASCO #5570.
  24. von Gruenigen VE, Gil KM, Frasure HE, et al. The impact of obesity and age on quality of life in gynecologic surgery. Am J Obstet Gynecol 2005; 193:1369.
  25. Kaaks R, Lukanova A, Kurzer MS. Obesity, endogenous hormones, and endometrial cancer risk: a synthetic review. Cancer Epidemiol Biomarkers Prev 2002; 11:1531.
  26. Fader AN, Arriba LN, Frasure HE, von Gruenigen VE. Endometrial cancer and obesity: epidemiology, biomarkers, prevention and survivorship. Gynecol Oncol 2009; 114:121.
  27. Soliman PT, Bassett RL Jr, Wilson EB, et al. Limited public knowledge of obesity and endometrial cancer risk: what women know. Obstet Gynecol 2008; 112:835.
  28. Onujiogu N, Johnson T, Seo S, et al. Survivors of endometrial cancer: who is at risk for sexual dysfunction? Gynecol Oncol 2011; 123:356.
  29. Chadha M, Nanavati PJ, Liu P, et al. Patterns of failure in endometrial carcinoma stage IB grade 3 and IC patients treated with postoperative vaginal vault brachytherapy. Gynecol Oncol 1999; 75:103.
  30. Eltabbakh GH, Piver MS, Hempling RE, Shin KH. Excellent long-term survival and absence of vaginal recurrences in 332 patients with low-risk stage I endometrial adenocarcinoma treated with hysterectomy and vaginal brachytherapy without formal staging lymph node sampling: report of a prospective trial. Int J Radiat Oncol Biol Phys 1997; 38:373.
  31. Pearcey RG, Petereit DG. Post-operative high dose rate brachytherapy in patients with low to intermediate risk endometrial cancer. Radiother Oncol 2000; 56:17.
  32. Weiss E, Hirnle P, Arnold-Bofinger H, et al. Adjuvant vaginal high-dose-rate afterloading alone in endometrial carcinoma: patterns of relapse and side effects following low-dose therapy. Gynecol Oncol 1998; 71:72.
  33. Nout RA, Putter H, Jürgenliemk-Schulz IM, et al. Quality of life after pelvic radiotherapy or vaginal brachytherapy for endometrial cancer: first results of the randomized PORTEC-2 trial. J Clin Oncol 2009; 27:3547.
  34. White ID. The assessment and management of sexual difficulties after treatment of cervical and endometrial malignancies. Clin Oncol (R Coll Radiol) 2008; 20:488.
  35. Falk SJ, Dizon DS. Sexual dysfunction in women with cancer. Fertil Steril 2013; 100:916.
  36. DeSimone M, Spriggs E, Gass JS, et al. Sexual dysfunction in female cancer survivors. Am J Clin Oncol 2014; 37:101.
  37. Krychman ML, Pereira L, Carter J, Amsterdam A. Sexual oncology: sexual health issues in women with cancer. Oncology 2006; 71:18.
  38. Gallup DG, Stock RJ. Adenocarcinoma of the endometrium in women 40 years of age or younger. Obstet Gynecol 1984; 64:417.
  39. Whitaker GK, Lee RB, Benson WL. Carcinoma of the endometrium in young women. Mil Med 1986; 151:25.
  40. Hitchcock CL, Prior JC. Oral micronized progesterone for vasomotor symptoms--a placebo-controlled randomized trial in healthy postmenopausal women. Menopause 2012; 19:886.
  41. Loprinzi CL, Sloan J, Stearns V, et al. Newer antidepressants and gabapentin for hot flashes: an individual patient pooled analysis. J Clin Oncol 2009; 27:2831.
  42. Nelson HD, Vesco KK, Haney E, et al. Nonhormonal therapies for menopausal hot flashes: systematic review and meta-analysis. JAMA 2006; 295:2057.
  43. Hunter MS, Grunfeld EA, Mittal S, et al. Menopausal symptoms in women with breast cancer: prevalence and treatment preferences. Psychooncology 2004; 13:769.
  44. Lee TS, Lee JY, Kim JW, et al. Outcomes of ovarian preservation in a cohort of premenopausal women with early-stage endometrial cancer: a Korean Gynecologic Oncology Group study. Gynecol Oncol 2013; 131:289.
  45. SEER Cancer Stat Facts: Uterine Cancer. http://seer.cancer.gov/statfacts/html/corp.html (Accessed on December 14, 2011).
  46. Biglia N, Gadducci A, Ponzone R, et al. Hormone replacement therapy in cancer survivors. Maturitas 2004; 48:333.
  47. Ibeanu O, Modesitt SC, Ducie J, et al. Hormone replacement therapy in gynecologic cancer survivors: why not? Gynecol Oncol 2011; 122:447.
  48. Chapman JA, DiSaia PJ, Osann K, et al. Estrogen replacement in surgical stage I and II endometrial cancer survivors. Am J Obstet Gynecol 1996; 175:1195.
  49. Suriano KA, McHale M, McLaren CE, et al. Estrogen replacement therapy in endometrial cancer patients: a matched control study. Obstet Gynecol 2001; 97:555.
  50. Creasman WT, Henderson D, Hinshaw W, Clarke-Pearson DL. Estrogen replacement therapy in the patient treated for endometrial cancer. Obstet Gynecol 1986; 67:326.
  51. Lee RB, Burke TW, Park RC. Estrogen replacement therapy following treatment for stage I endometrial carcinoma. Gynecol Oncol 1990; 36:189.
  52. Barakat RR, Bundy BN, Spirtos NM, et al. Randomized double-blind trial of estrogen replacement therapy versus placebo in stage I or II endometrial cancer: a Gynecologic Oncology Group Study. J Clin Oncol 2006; 24:587.
  53. Committee on Gynecologic Practice. ACOG committee opinion. Hormone replacement therapy in women treated for endometrial cancer. Number 234, May 2000 (replaces number 126, August 1993). Int J Gynaecol Obstet 2001; 73:283.
  54. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. Uterine cancer. https://www.nccn.org/professionals/physician_gls/pdf/uterine.pdf (Accessed on May 05, 2020).
  55. Koh WJ, Abu-Rustum NR, Bean S, et al. Uterine Neoplasms, Version 1.2018, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 2018; 16:170.
  56. Bogani G, Raspagliesi F, Leone Roberti Maggiore U, Mariani A. Current landscape and future perspective of sentinel node mapping in endometrial cancer. J Gynecol Oncol 2018; 29:e94.
  57. 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.
  58. Leitao MM Jr, Zhou QC, Gomez-Hidalgo NR, et al. Patient-reported outcomes after surgery for endometrial carcinoma: Prevalence of lower-extremity lymphedema after sentinel lymph node mapping versus lymphadenectomy. Gynecol Oncol 2020; 156:147.
  59. Angioli R, Plotti F, Cafà EV, et al. Quality of life in patients with endometrial cancer treated with or without systematic lymphadenectomy. Eur J Obstet Gynecol Reprod Biol 2013; 170:539.
  60. Forsse D, Barbero ML, Werner HMJ, et al. Longitudinal effects of adjuvant chemotherapy and lymph node staging on patient-reported outcomes in endometrial cancer survivors: a prospective cohort study. Am J Obstet Gynecol 2022; 226:90.e1.
  61. Frid M, Strang P, Friedrichsen MJ, Johansson K. Lower limb lymphedema: experiences and perceptions of cancer patients in the late palliative stage. J Palliat Care 2006; 22:5.
  62. Kim SJ, Park YD. Effects of complex decongestive physiotherapy on the oedema and the quality of life of lower unilateral lymphoedema following treatment for gynecological cancer. Eur J Cancer Care (Engl) 2008; 17:463.
  63. Langbecker D, Hayes SC, Newman B, Janda M. Treatment for upper-limb and lower-limb lymphedema by professionals specializing in lymphedema care. Eur J Cancer Care (Engl) 2008; 17:557.
  64. Williams AF, Franks PJ, Moffatt CJ. Lymphoedema: estimating the size of the problem. Palliat Med 2005; 19:300.
  65. Andreyev HJ. Gastrointestinal problems after pelvic radiotherapy: the past, the present and the future. Clin Oncol (R Coll Radiol) 2007; 19:790.
  66. Klee M, Machin D. Health-related quality of life of patients with endometrial cancer who are disease-free following external irradiation. Acta Oncol 2001; 40:816.
  67. Bye A, Tropé C, Loge JH, et al. Health-related quality of life and occurrence of intestinal side effects after pelvic radiotherapy--evaluation of long-term effects of diagnosis and treatment. Acta Oncol 2000; 39:173.
  68. Li C, Samsioe G, Iosif C. Quality of life in endometrial cancer survivors. Maturitas 1999; 31:227.
  69. Vistad I, Cvancarova M, Fosså SD, Kristensen GB. Postradiotherapy morbidity in long-term survivors after locally advanced cervical cancer: how well do physicians' assessments agree with those of their patients? Int J Radiat Oncol Biol Phys 2008; 71:1335.
  70. Creutzberg CL, van Putten WL, Koper PC, 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.
  71. Keys HM, Roberts JA, Brunetto VL, et al. 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.
  72. Le T, Menard C, Samant R, et al. Longitudinal assessments of quality of life in endometrial cancer patients: effect of surgical approach and adjuvant radiotherapy. Int J Radiat Oncol Biol Phys 2009; 75:795.
  73. van de Poll-Franse LV, Pijnenborg JM, Boll D, et al. Health related quality of life and symptoms after pelvic lymphadenectomy or radiotherapy vs. no adjuvant regional treatment in early-stage endometrial carcinoma: a large population-based study. Gynecol Oncol 2012; 127:153.
  74. Ko EM, Funk MJ, Clark LH, Brewster WR. Did GOG99 and PORTEC1 change clinical practice in the United States? Gynecol Oncol 2013; 129:12.
  75. Poorvu PD, Sadow CA, Townamchai K, et al. Duodenal and other gastrointestinal toxicity in cervical and endometrial cancer treated with extended-field intensity modulated radiation therapy to paraaortic lymph nodes. Int J Radiat Oncol Biol Phys 2013; 85:1262.
  76. Shih KK, Hajj C, Kollmeier M, et al. Impact of postoperative intensity-modulated radiation therapy (IMRT) on the rate of bowel obstruction in gynecologic malignancy. Gynecol Oncol 2016; 143:18.
  77. Matei D, Filiaci V, Randall ME, et al. Adjuvant Chemotherapy plus Radiation for Locally Advanced Endometrial Cancer. N Engl J Med 2019; 380:2317.
  78. Lind H, Waldenström AC, Dunberger G, et al. Late symptoms in long-term gynaecological cancer survivors after radiation therapy: a population-based cohort study. Br J Cancer 2011; 105:737.
  79. von Gruenigen VE, Waggoner SE, Frasure HE, et al. Lifestyle challenges in endometrial cancer survivorship. Obstet Gynecol 2011; 117:93.
  80. Bruegl AS, Djordjevic B, Urbauer DL, et al. Utility of MLH1 methylation analysis in the clinical evaluation of Lynch Syndrome in women with endometrial cancer. Curr Pharm Des 2014; 20:1655.
  81. Mills AM, Longacre TA. Lynch Syndrome Screening in the Gynecologic Tract: Current State of the Art. Am J Surg Pathol 2016; 40:e35.
  82. Kwon JS, Elit L, Saskin R, et al. Secondary cancer prevention during follow-up for endometrial cancer. Obstet Gynecol 2009; 113:790.
Topic 17006 Version 29.0

References

آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟