The upper two-thirds of the uterus above the level of the internal cervical os is called the corpus. The fallopian tubes enter at the upper lateral corners of a pear-shaped body. The portion of the muscular organ that is above a line joining the tubo-uterine orifices is often referred to as the fundus. The major lymphatic trunks are the utero-ovarian (infundibulopelvic), parametrial, and presacral, which drain into the hypogastric, external iliac, common iliac, presacral, and para-aortic nodes. Although a direct route of lymphatic spread from the corpus uteri to the para-aortic nodes through the infundibulopelvic ligament has been suggested from anatomical and sentinel lymph node studies, direct metastases to the para-aortic lymph nodes are uncommon. The vagina and lungs are the common metastatic sites. The FIGO Committee on Gynecologic Oncology, following its meeting in 1988, recommended that endometrial cancer be surgically staged. There should be histologic verification of grading and extent of the tumor. All tumors are to be microscopically verified. Endometrioid carcinoma: adenocarcinoma; adenoacanthoma (adenocarcinoma with squamous metaplasia); and adenosquamous carcinoma (mixed adenocarcinoma and squamous cell carcinoma). Mucinous adenocarcinoma. Serous adenocarcinoma. Clear cell adenocarcinoma. Undifferentiated carcinoma. Mixed carcinoma (carcinoma composed of more than one type, with at least 10% of each component). Type 1 (grade 1 and 2 endometrioid carcinoma) may arise from complex atypical hyperplasia and is linked to unopposed estrogenic stimulation. Type 2 includes grade 3 endometrioid tumors as well as tumors of non-endometrioid histology and develops from atrophic endometrium. GX: Grade cannot be assessed. G1: Well differentiated. G2: Moderately differentiated. G3: Poorly or undifferentiated. G1: less than 5% of a nonsquamous or nonmorular solid growth pattern. G2: 6%–50% of a nonsquamous or nonmorular solid growth pattern. G3: greater than 50% of a nonsquamous or nonmorular solid growth pattern. Notable nuclear atypia (pleomorphism and prominent nucleoli), inappropriate for the architectural grade, raises the grade of a grade 1 or grade 2 tumor by 1. In serous and clear cell adenocarcinomas, nuclear grading takes precedent. Most authors consider serous and clear cell carcinomas high grade by definition. Adenocarcinomas with squamous differentiation are graded according to the nuclear grade of the glandular component. The current FIGO staging classification for cancer of the corpus uteri is given in Table 1. Comparison of the stage groupings with the TNM classification is given in Table 2. NX: Regional lymph nodes cannot be assessed. N0: No regional lymph node metastasis. N1: Regional lymph node metastasis to pelvic lymph nodes. N2: Regional lymph node metastasis to para-aortic lymph nodes, with or without positive pelvic lymph nodes. MX: Distant metastasis cannot be assessed. M0: No distant metastasis. M1: Distant metastasis (includes metastasis to inguinal lymph nodes or intraperitoneal disease). Corpus cancer is surgically staged, therefore procedures previously used for determination of stage are no longer applicable (e.g. the findings of fractional curettage to differentiate between Stage I and Stage II). There may be a small number of patients with corpus cancer who will be treated primarily with radiation therapy. In these cases, the clinical staging adopted by FIGO in 1971 would still apply, but designation of that staging system should be noted. Ideally, distance from tumor to serosa should be measured. The presence of lymphovascular space invasion (LVSI) should also be reported in the pathological report of the hysterectomy specimen. A LVSI-positive status has a significantly worse prognosis, especially if extensive LVSI is found [1]. The distinction by LVSI status could be more relevant than the distinction between Stages IA and IB for predicting survival in Stage I endometrial cancer [2]. As a minimum, any enlarged or suspicious lymph nodes should be removed in all patients. For high-risk patients (grade 3, deep myometrial invasion, cervical extension, serous or clear cell histology), complete pelvic lymphadenectomy and resection of any enlarged para-aortic nodes is recommended. Worldwide, endometrial cancer is the sixth most common malignant disorder with approximately 290 000 new cases annually. The incidence is higher in high-income countries (5.5%) compared with low-income countries (4.2%), although specific mortality is higher in the latter. The cumulative risk of endometrial cancer up to the age of 75 years has been estimated as 1.6% for high-income regions and 0.7% for low-income countries [3]. This difference has been associated with an epidemic of obesity and physical inactivity, two important risk factors, in high-income countries. Moreover, endometrial cancer patients with obesity also tend to have a poorer outcome [4]. On the other hand, physical activity and long-term use of continuous combined estrogen–progestin therapy is associated with a reduced risk of endometrial cancer [4,5]. Obesity is associated with earlier age at diagnosis, and with endometrioid-type endometrial cancers. Similar associations were not observed with nonendometrioid cancers, consistent with different pathways of tumorigenesis [6]. In North America and Europe, endometrial cancer is the most frequent cancer of the female genital tract and the fourth most common site after breast, lung, and colorectal cancer [3]. The incidence is rising as life expectancy increases. Furthermore, an estimated 23 700 European women died of endometrial cancer in 2012, which is the eighth most common cause of death from cancer in women [7]. Importantly, the corrected corpus uteri cancer mortality rates showed a decrease in most European Union member states among women born before 1940 [8]. In North America, it is the seventh most frequent cause of death, with approximately 55 000 new cases and 10 000 estimated new deaths each year [3]. The increase in endometrial cancer incidence rates after 2002 may be related to the widespread decrease in estrogen plus progestin menopausal hormone therapy use, which has been reported to lower endometrial cancer risk in overweight and obese women [9]. However, the main reasons underlying the increase in endometrial cancer incidence in high-income countries remain the increasing prevalence of obesity in postmenopausal as well as the increased life expectancy. Endometrioid adenocarcinoma progresses through a premalignant phase of intraepithelial endometrial neoplasia in a large proportion of cases [10]. Other forms such as serous and clear cell carcinoma arise as a result of a sequence of genetic mutations. In serous endometrial cancer, the mutant p53 plays a pivotal role [11]. Endometrial cancer research has gained some momentum in recent years and now provides better information for clinical practice. Its early presentation following postmenopausal bleeding results in a generally good prognosis, but it should be treated using evidence-based protocols, and where appropriate, by expert multidisciplinary teams. The role of population screening for endometrial cancer remains low [12], although certain high-risk groups such as those with Lynch type 2 syndrome can undergo endometrial surveillance by biopsy, or transvaginal ultrasonography if post menopausal. Transvaginal ultrasound is reasonably sensitive and specific but screening of asymptomatic women has in general been recommended only for those with Lynch syndrome [13]. Following presentation, ultrasound is an effective first test with a high negative predictive value when the endometrial thickness is less than 5 mm. In one of the largest studies undertaken, there was a negative predictive value of 96% among 1168 women in whom the results of transvaginal ultrasound were correlated with an endometrial biopsy obtained by curettage [14]. When a biopsy is required, this can be obtained usually as an office procedure using a number of disposable instruments developed for this purpose. In certain cases, hysteroscopy may be helpful, and with flexible instruments can also be done without recourse to general anesthesia. However, the biological role of cells that are transtubally flushed during hysteroscopy remains uncertain. If cervical stenosis or patient tolerance does not permit an office procedure, hysteroscopy and curettage under anesthesia may be necessary. Individuals whose pelvic examination is unsatisfactory may also be evaluated with transvaginal or abdominal ultrasound to rule out concomitant adnexal pathology. Following a histopathologic diagnosis of endometrial adenocarcinoma, the local extent of the tumor, and evidence of metastatic disease should be determined. In addition, the perioperative risk should be assessed. As a minimum, the pathology report from endometrial sampling should indicate the tumor type and grade of the lesion. A chest X-ray, full biochemistry (renal and liver function tests), and blood count are routine. A serum CA125 may be of value in advanced disease for follow-up. Evaluation for metastasis is indicated particularly in patients with abnormal liver function tests, and clinical findings such as parametrial or vaginal tumor extension. In high-risk patients, imaging of the abdomen and lymph nodes may help determine the surgical approach. In certain situations, cystoscopy and/or proctoscopy/barium enema may be helpful if direct extension to the bladder or rectum is suspected. Tumor grade 3 (poorly differentiated). More than 50% of myometrial invasion. Lymphovascular space invasion. Non-endometrioid histology (serous, clear cell, undifferentiated, small cell, anaplastic, etc.). Cervical stromal involvement. The most accurate means of assessing both depth of myometrial invasion and cervical involvement is MRI scanning and intraoperative frozen section [15–17]. CT and MRI are equivalent in terms of evaluating nodal metastases, but neither is good enough to replace surgical lymph node assessment, which provides histological confirmation [18,19]. The role of PET-CT and PET-MRI is currently being investigated. Nonsurgical staging for endometrial cancer, where extrauterine disease exists, is inherently inaccurate, particularly in respect to small nodal involvement, intraperitoneal implants, and adnexal metastasis. In 1988, the FIGO Cancer Committee changed the official FIGO staging from clinical to surgical for endometrial cancer. Since that recommendation, considerable debate has ensued as to what constitutes an internationally acceptable approach. A generally recommended protocol would be that the abdomen should be opened with a vertical midline abdominal incision and peritoneal washings taken immediately from the pelvis and abdomen, followed by careful exploration of the intra-abdominal contents. The omentum, liver, peritoneal cul-de-sac, and adnexal surfaces should be examined and palpated for any possible metastases, followed by careful palpation for suspicious or enlarged nodes in the aortic and pelvic areas. The standard surgical procedure should be an extrafascial total hysterectomy with bilateral salpingo-oophorectomy. Adnexal removal is recommended even if the tubes and ovaries appear normal, as they may contain micrometastases. Vaginal cuff removal is not necessary, nor is there any benefit from excising parametrial tissue in the usual case. Where obvious cervical stromal involvement is demonstrated preoperatively, a modified radical hysterectomy has been historically performed. However, there is consensus (ESMO-ESGO-ESTRO) that simple hysterectomy with free-margins together with pelvic lymphadenectomy can be sufficient. There has also been considerable debate on the safety of endoscopic surgery for the treatment of endometrial cancer. Recent studies have demonstrated that laparoscopic removal of the uterus and adnexae (in experienced hands) appears to be safe. Whereas there is no difference in terms of major complications between abdominal hysterectomy and laparoscopically assisted vaginal hysterectomy (LAVH) or total laparoscopic hysterectomy (TLH), the laparoscopic approach is associated with a significantly decreased risk of major surgical adverse event, a shorter hospital stay, less pain, and quicker resumption of daily activities [20–22]. Since the oncological safety of the laparoscopic approach has now been demonstrated in several randomized studies [23,24], hysterectomy and bilateral salpingo-oophorectomy should be performed with laparoscopy in those patients with no contraindications to laparoscopy (e.g. large-volume uterus). This approach can be accompanied by a laparoscopic lymphadenectomy, if surgical staging is to be undertaken. Robotic surgery for the surgical management of the morbidly obese patient is an option only in experienced hands. In such cases, the surgical management using robotics has been reported to be safe and have less perioperative complications compared with open surgery [25]. Retrospective studies have suggested equivalent oncologic outcomes compared with traditional laparoscopic surgery [26,27]. Although mandated through the staging system, lymphadenectomy of the pelvic and para-aortic areas remains controversial. Selective node sampling is of dubious value as a routine and complete lymphadenectomy should be reserved for cases with high-risk features. Many individuals with endometrial cancer are obese or elderly, with other medical problems, and clinical judgment is required to determine if additional surgery is warranted. Any deeply invasive tumor or radiological suggestion of positive nodes is an indication for retroperitoneal lymph node evaluation, with removal of any enlarged or suspicious nodes. Documentation of positive nodes identifies a high-risk population and helps to tailor adjuvant treatment, since patients with Stage III disease appear to benefit from chemotherapy [28]. Indications for aortic node sampling would include suspicious aortic or common iliac nodes, grossly positive adnexae, grossly positive pelvic nodes, and high-grade tumors showing full thickness myometrial invasion. Patients with clear cell, papillary serous, or carcinosarcoma histologic subtypes are also candidates for aortic node sampling. Low-risk tumors will have positive nodes in less than 5% of cases (well differentiated and < 1/2 myometrial invasion) and do not require full surgical staging. These women can be safely operated on by a general gynecologist, but those at greater risk of extrauterine disease, who may require lymphadenectomy, should be referred to a gynecological oncologist since care provided by gynecologic oncologists has been associated with better survival in high-risk cancers [29]. Moreover, primary management by gynecologic oncologists has been suggested to result in an efficient use of health care resources and minimization of the potential morbidity associated with adjuvant radiation [30]. This triaging of women can be done most effectively by a thorough preoperative assessment, paying particular attention to the pathology and to radiological features. Triaging for lymphadenectomy is also possible during surgery. Intraoperative assessment mainly involves assessment of myometrial invasion [15,17,27]. Grading on frozen section is possible, though suboptimal compared with preoperative grading [17]. The effect of waiting time for surgical staging on survival outcome of endometrial cancer is controversial. A recent population-based study concluded that a longer waiting time for surgical staging was associated with worse survival outcomes in uterine cancer [31]. However, when focusing on type I endometrial cancer only, the waiting time for surgical staging was not associated with decreased survival outcome, presumably due to its excellent prognosis anyway [32]. Although required for accurate staging, a therapeutic benefit for lymphadenectomy is controversial. Historically, one case–control study suggested that it may be therapeutic [33] and another showed a good prognosis even in node-positive women [34]. Another retrospective study showed a survival benefit of complete lymphadenectomy for patients with grade 3 tumors [35]. In the UK, the MRC ASTEC trial, however, which randomized 1400 women undergoing surgery for presumed Stage I endometrial cancer to pelvic lymphadenectomy or no lymphadenectomy, showed no therapeutic benefit [36]. An Italian randomized trial of pelvic (and in 30% para-aortic) lymphadenectomy versus no lymphadenectomy in 540 women also did not show any difference in rates of relapse or survival [37]. Both studies have been criticized because of a limited effort with respect to the extent of dissection and lymph node evaluation, because of the high proportion of low-risk patients, and because no direct decision on adjuvant therapy based on lymphadenectomy was part of the protocols. Lymphadenectomy is primarily used for staging and should be considered in women with high-risk factors [38]. Although a direct survival benefit of lymphadenectomy has not been documented, the procedure identifies node-positive patients that may benefit from adjuvant treatment. An international trial of the role of lymphadenectomy to direct adjuvant therapy for high-risk endometrial cancer (STATEC) is planned. The ongoing ENGOT-EN2-DGCG/EORCT 55102 trial aims to answer this question by comparing survival in patients with Stage I grade 3 endometrioid endometrial cancer, Stage I and II type 2 endometrial cancer or Stage II endometrioid endometrial cancer and without metastatic node after randomization for adjuvant chemotherapy. In a retrospective study, para-aortic lymphadenectomy resulted in an improved outcome in intermediate and high-risk patients when compared with pelvic lymphadenectomy alone [39]. However, adjuvant therapy was not comparable in the two groups. In patients who underwent both pelvic and para-aortic lymphadenectomy, 77% received chemotherapy whereas this was given to only 45% of patients who underwent pelvic lymphadenectomy alone. This study suggests both pelvic and para-aortic lymphadenectomy are beneficial in comparison with patients who undergo pelvic lymphadenectomy alone, but it does not imply that extensive lymphadenectomy improves survival in comparison with no lymphadenectomy. Risk factors are used to determine the indication for adjuvant radiation therapy, as the majority of patients are at low risk of recurrence. Low-risk disease (Stage I, grade 1 or 2 with no or superficial myometrial invasion) does not require adjuvant radiation therapy, as demonstrated in a Danish cohort study of low-risk women, with 96% five-year survival after surgery alone [40]. A seminal Norwegian trial [41], which included 621 women treated after surgery with vaginal brachytherapy, indicated that overall survival was not improved by additional external beam radiation therapy (EBRT), although it did reduce the risk of pelvic recurrence. Three large randomized trials of pelvic radiation therapy versus no further treatment after surgery have determined the role of radiation therapy based on risk factors, and have led to reduced indications for adjuvant radiation therapy: the PORTEC trial [42], the US GOG#99 trial [43], and the UK MRC ASTEC trial [44]. All of these trials reported a significant reduction in the rates of vaginal and pelvic recurrence with EBRT, but without survival benefit. EBRT added to the risk of long-term morbidity. PORTEC and ASTEC trials had similar recurrence and survival rates without lymphadenectomy, compared with GOG#99 that included patients with documented node-negative disease. PORTEC-1 showed that most pelvic relapses were located in the vaginal vault (75%), and that salvage rates were high in women who had not had previous radiation therapy [45]. The PORTEC-2 trial randomized 427 women with high–intermediate risk factors to EBRT or vaginal brachytherapy alone [46]. This trial showed that vaginal brachytherapy had excellent vaginal control rates (< 2% at 5 years for both EBRT and vaginal brachytherapy groups), with minimal adverse effects and significantly better quality of life. Quality of life of patients in the brachytherapy group remained the same as those of an age-matched normal population [47]. Vaginal brachytherapy has replaced EBRT as standard adjuvant treatment for patients with high–intermediate risk factors. That omission of any EBRT or vaginal brachytherapy for (high)intermediate risk disease increases recurrence rates (22% for intermediate risk disease, of which 15% locoregional) but without a difference in survival has been confirmed by a Danish population study [48]. A patient preference study showed that patient's preferences are biased to a treatment preventing relapse [49]. The seminal NSGO-9501 trial investigated the use of both EBRT and adjuvant platinum-based chemotherapy compared with EBRT alone for patients with risk factors (grade 3 or deep invasion or adverse histologies). This trial was published in a pooled analysis with the Italian ILIADE trial [50]. While trials comparing adjuvant EBRT alone with adjuvant cisplatin-based chemotherapy alone have not shown any difference in overall or relapse-free survival [51,52], the pooled NSGO-EC9501/EORTC55991 and ILIADE trial analysis reported a significant 9% improvement in progression-free survival (69% vs 78% at 5 years; Hazard Ratio [HR] 0.63) with the addition of chemotherapy to EBRT, and a trend for a 7% improvement in five-year overall survival (75% vs 82%; HR 0.69, P = 0.07). Ongoing and recently completed trials are currently investigating the roles of EBRT or chemotherapy alone or combined EBRT and chemotherapy for patients with high-risk or advanced stage disease (GOG#249, GOG#258, PORTEC-3, Danish/EORTC trials). First results of the randomised GOG-249 trial (601 patients with Stage I − II endometrial cancer with high − intermediate or high-risk factors, comparing vaginal brachytherapy plus three cycles of carboplatin-paclitaxel with pelvic EBRT) showed no differences in relapse-free survival (84% vs 82%) or overall survival (92% vs 93%) between the arms at a median follow-up of 24 months [53]. About 50% of the trial population had grade 1–2 disease with a baseline five-year survival of 86% − 91%. In the PORTEC-3 trial, patients with high-risk Stage I − II or with Stage III endometrial cancer were randomized to pelvic EBRT alone or EBRT with two cycles of cisplatin followed by four cycles of carboplatin and paclitaxel. PORTEC-3 completed accrual (686 patients enrolled) in late 2013 and results are expected in 2016. In the ongoing ENGOT-EN2-DGCG-trial patients with node-negative endometrial cancer with high-risk features are randomized to adjuvant chemotherapy (six cycles of carboplatin-paclitaxel) or observation, with or without brachytherapy in both arms. These trials will answer many of the questions regarding optimal use and optimal schedules of adjuvant therapy for women with high-risk endometrial cancer. In summary, adjuvant radiation therapy is not indicated for patients with grade 1–2 tumors and no more than 50% myometrial invasion, or for those with only a single risk factor. For patients with high–intermediate risk factors (at least two of the factors: age > 60 years, deep myometrial invasion, grade 3, serous or clear cell histology, LVSI), vaginal brachytherapy alone is preferable to EBRT, providing excellent vaginal control without impacting on quality of life. In patients with higher-risk disease (3 or more risk factors, Stages II and III), the role of adjuvant chemotherapy, with or without radiation therapy, is currently being investigated. This has been widely prescribed in the past, but a meta-analysis of six randomized trials involving a total of 3339 women has shown no survival benefit for adjuvant progestogen therapy in endometrial cancer [54]. A subsequently published randomized trial of 1012 women also failed to demonstrate any survival benefit [55]. Patients with clinically occult Stage II disease are generally managed in a similar way to patients with Stage I disease. Historically, radical hysterectomy, bilateral salpingo-oophorectomy, bilateral pelvic lymphadenectomy, and selective aortic node dissection can be used as primary treatment for clinically overt cervical involvement. However, this strategy is poorly supported by the medical literature. Results from one of the rare retrospective studies could not find any survival benefit from radical hysterectomy for patients with suspected gross cervical involvement in comparison with simple or modified radical hysterectomy [56]. Since radical hysterectomy increases the risk of adverse events, surgical treatment in patients with suspected gross cervical involvement deserves further prospective evaluation. Preoperative MRI scanning is advisable to exclude bladder involvement and ensure local resectability. Studies indicate excellent results for this approach, with no benefit from the addition of radiation for patients with negative nodes [57,58]. Adjuvant radiotherapy is usually reserved for patients with involved nodes and/or close or involved surgical margins. However, neoadjuvant therapy followed by a less extensive simple hysterectomy can represent an alternative. The need for adjuvant radiotherapy has not been studied in a randomized trial, but a SEER study reported improved survival for patients with Stage II endometrial cancer when adjuvant radiotherapy was used after radical and simple hysterectomy [59,60]. If surgery is not considered feasible because of tumor extension, full pelvic radiotherapy and intracavitary brachytherapy, as in cervical cancer, may be employed. Most patients with Stage III endometrial cancer are managed by complete surgical resection of all metastatic disease, followed by postoperative EBRT and/or chemotherapy. The randomized GOG#122 trial included patients with Stages III and IV disease and residual tumor up to 2 cm, and compared whole abdominal radiation with intensive adjuvant chemotherapy (eight cycles of doxorubicin and cisplatin). It showed a survival benefit for chemotherapy (42% vs 53% estimated five-year survival), although event rates were high in both arms [28]. Adjuvant platin-based chemotherapy (more recently, carboplatin and paclitaxel) is increasingly used to reduce the risk of metastases. Retrospective studies have shown substantial pelvic recurrence rates when EBRT was omitted when using chemotherapy [61,62], and current ongoing trials are investigating the roles of chemotherapy, and combinations of chemotherapy and radiation therapy. A recent meta-analysis including four multicenter randomized controlled trials involving 1269 women with primary FIGO Stage III/IV endometrial cancer who received primary cytoreductive surgery showed that chemotherapy increases survival time after primary surgery by approximately 25% relative to radiotherapy [63]. Two trials, evaluating 620 women, mainly Stage III compared adjuvant chemotherapy with adjuvant radiotherapy [52,64], one trial evaluating 552 women mainly Stage III compared two chemotherapy regimens (cisplatin/doxorubicin/paclitaxel versus cisplatin/doxorubicin treatment) in women who had all undergone adjuvant radiotherapy (GOG 184) [65], and one trial contributed no data [51]. Overall and progression-free survivals were longer with adjuvant chemotherapy compared with adjuvant radiotherapy [63]. In subgroup analyses, the effects on survival in favor of chemotherapy were not different for Stage III and IV, or Stage IIIA and IIIC. This evidence was of moderate quality. Data from one trial showed that women receiving adjuvant chemotherapy were more likely to experience hematological and neurological adverse events and alopecia, and more likely to discontinue treatment, than those receiving adjuvant radiotherapy [63]. There was no statistically significant difference in treatment-related deaths between the chemotherapy and radiotherapy treatment arms [63]. There was no clear difference in progression free survival between intervention groups in the one trial that compared cisplatin/doxorubicin/paclitaxel versus cisplatin/doxorubicin [65]. A large trial evaluating adjuvant chemotherapy alone (six cycles of carboplatin-paclitaxel) compared with chemotherapy during and after radiation therapy (same schedule as used in PORTEC-3) for Stage III − IV endometrial cancer (GOG 0258) has recently completed accrual (804 patients) and results are expected in 2016. Patients with presumed Stage III disease because of adnexal involvement should have full surgical staging and expert pathologic examination of the specimen, as primary tumors of both the ovary and the endometrium may be present. Management should be individualized, and based on the stage of each tumor. Patients with clinical Stage III endometrial carcinoma that is not felt to be resectable by virtue of vaginal or parametrial extension are best treated primarily by pelvic irradiation, with or without chemotherapy [66]. Once therapy has been completed, exploratory laparotomy should be considered for those patients whose disease now appears to be resectable. Patients with Stage IV disease based on intraperitoneal spread benefit from cytoreductive surgery only if there is no residual tumor [67]. Neoadjuvant chemotherapy is an option, particularly if ascites is present, and/or postoperative morbidity is considered likely [68]. After surgery, platinum-based chemotherapy should be considered, based on the GOG#122 trial cited above [28]. Patients with evidence of extra-abdominal metastases are usually managed with systemic platinum-based chemotherapy, or hormonal therapy if grade 1 and/or receptor positive. Combination chemotherapy is the treatment of choice in advanced-stage disease as well as in relapsed disease. The combinations of doxorubicin, cisplatin, and paclitaxel (TAP) [69] and ca