Section Editor Dennis Chi discloses no financial relationships. The content of this article has been reviewed by independent peer reviewers to ensure that it is balanced, objective, and free from commercial bias. On the basis of disclosed information, all conflicts of interest have been resolved. This article is available for continuing medical education credit at CME. Women with recurrent or advanced endometrial cancer constitute a heterogeneous group of patients, advanced endometrial cancer.
Depending on previous treatment, women with recurrent endometrial cancer may be appropriate candidates for surgery, radiation therapy, hormonal therapy, or chemotherapy. Women with advanced stage disease at presentation may also be appropriate candidates for systemic alabama prostate cancer statistics minorities local therapies.
We review the treatment options available to treat recurrent and locally advanced endometrial cancer. Radiation therapy is appropriate for isolated vaginal recurrences in patients with no previous history of radiation therapy.
Patients with recurrent low-grade tumors overexpressing estrogen and progesterone receptors may be treated with progestin therapy. Systemic therapy is appropriate for patients with disseminate recurrences or advanced stage disease at presentation, or for those with receptor-negative tumors. We review all these different treatment strategies available to patients with advanced or recurrent endometrial cancer.
For early-stage disease, surgery alone or in combination with local therapy is generally curative, advanced endometrial cancer. For patients with stage III or stage IV disease and for those with recurrent endometrial cancer, the prognosis remains poor and the optimal adjuvant therapy is yet to be established.
A subset of these patients may benefit advanced endometrial cancer hormonal manipulation, advanced endometrial cancer, systemic chemotherapies, or combination treatment with volume-directed radiotherapy and systemic chemotherapy. The choice of therapy depends on the extent of advanced endometrial cancer disease after initial surgery, site and nature of the recurrence, advanced endometrial cancer, prior therapy used, and intent of treatment, be it curative or palliative.
This review focuses on combined treatment modalities for this group of women. The following section reviews the role of radiation therapy in the management of women with locally recurrent and advanced endometrial cancer.
Important prognostic factors affecting survival in patients with recurrent endometrial cancer include site of recurrence, previous treatment with radiation advanced endometrial cancer, relapse-free interval, and histology. A longer relapse-free interval, low-grade histology, isolated vaginal recurrence, and endometrioid adenocarcinomas are factors associated with longer survival in recurrent endometrial cancer patients [ 23 ]. In general, patients with tumors of nonendometrioid histologies have a worse prognosis than those with tumors of endometrioid histologies.
Women with recurrent endometrial cancer following primary surgical treatment alone may be appropriate candidates for radiation therapy. For a select group of patients not previously radiated and with small vaginal recurrences, radiation therapy may be curative. The use of primary radiation therapy influences sites of recurrence and survival after relapse. As documented by the Post Operative Radiation Therapy in Endometrial Carcinoma trial, survival is longer for women with recurrent disease not previously treated in the adjuvant setting with radiation therapy [ 45 ].
In that trial, women with stage I disease, not all of whom had complete surgical staging, were randomized to surgery alone or in combination with adjuvant pelvic radiation therapy [ 45 ], advanced endometrial cancer. At the time of relapse, both the anatomic site of recurrence and tumor size predict the likelihood of achieving successful local control.
Tumor size at the time of recurrence also influences local control. Women with noncentral tumor recurrences have a worse prognosis than those with an isolated vaginal relapse. Although only limited experience exists, salvage radiation therapy may be advanced endometrial cancer in the setting of a noncentral recurrence [ 12 ]. This survival rate is comparable with the 3-year survival rate for patients with distant metastases [ 45 ], advanced endometrial cancer.
Patients with vaginal recurrences are usually treated with a combination of pelvic radiation and brachytherapy.
Plan alaska road trip with a previous history of pelvic radiation therapy who then develop an isolated vaginal recurrence are treated with brachytherapy alone [ 13 ].
In the presence of bulky disease, interstitial brachytherapy with supplementary external-beam radiation therapy has been reported to result in excellent pelvic control rates [ 1314 ].
It is important to underscore that, in the setting of recurrent disease, higher doses of radiation therapy than those used in the adjuvant setting are required. Patients with a previous history of radiation therapy are especially susceptible to severe toxicity at the time of radiation advanced endometrial cancer in the recurrent setting [ 614 ].
Stage III disease, unfortunately, includes women with quite varying risks. For example, the ultimate outcome for women with positive cytology as their only risk factor is obviously quite different from that of patients with multiple positive advanced endometrial cancer or para-aortic lymph nodes. The high rate hunter orange advantage camo custom caps distant failure supports the use of systemic therapy for advanced endometrial cancer of these patients and not just the use of radiation therapy.
The role of adjuvant therapy and, more importantly, the type of adjuvant treatment for women with stage III disease remain controversial. The role of postoperative radiation therapy in conferring a survival advantage in patients with stage III endometrial cancer may be related to the impact of gross residual lymph nodal disease prior to initiating radiation therapy.
In that series, 16 patients had pathologically confirmed para-aortic nodal and pelvic nodal disease prior to the initiation of radiation therapy [ 16 ]. The radiation dose administered was in the range of 4,—5, cGy, delivered through 8-cm wide by cm long portals, advanced endometrial cancer, starting from the pelvic brim [ 16 ], advanced endometrial cancer. Advanced endometrial cancer difference was not statistically significant.
Cytoreductive surgery may play a role in the management of women with stage IV endometrial cancer. Several retrospective studies suggest a survival advantage in those patients who have their tumor optimally cytoreduced Table 1 [ 18 — 20 ].
In all three series, successful cytoreduction was a statistically significant prognostic variable on multivariate analysis. In the work by Bristow et al. Recurrent disease isolated to the central pelvis following radiation therapy is rarely seen.
Selected patients with such a recurrence may be candidates for pelvic exenteration [ 2122 ]. Pelvic exenteration has been associated with significant operative morbidity and poor overall survival in the setting of recurrent endometrial cancer [ 2122 ], advanced endometrial cancer. In a series of 44 patients, nine long-term survivors were seen [ 22 ]. This highly morbid procedure may be the only potentially curative alternative for selected patients with a central recurrence following initial surgery and radiation therapy.
Antibiotics alcohol myths, radical pelvic resection and extended pelvic resection in conjunction with intraoperative radiation have also been described [ 23 ].
The authors report that, at the time of study publication, advanced endometrial cancer, two patients in their series with recurrences limited to the para-aortic area were alive without evidence of disease at 54 months and 71 months [ 23 ]. Surgical resection may be appropriate for some women with recurrent endometrial cancer. Pelvic exenteration, for example, is often entertained in the setting of central recurrences, advanced endometrial cancer. Two recent retrospective analyses explored the role of surgery in this setting.
Scarabelli and his colleagues operated on 20 women at the time of their first pelvic or abdominal recurrence [ 24 ]. Patients were classified as having no residual tumor or having tumor at the end of surgery [ 24 ]. Postoperative therapy was at the discretion of the treating surgeon but included both radiation and chemotherapy. This was statistically significantly is cancer age related than the survival times for those who were left with disease.
The PFS interval for that group of women was 1. There were two perioperative deaths, but otherwise morbidity was acceptable [ 25 ]. Another review, by Campagnutta et al. In that investigation, complete cytoreduction no gross residual disease was achieved in 23 of 35 surgical patients A median postrecurrence survival time of 39 months was reported for patients undergoing complete salvage cytoreduction, compared advanced endometrial cancer On multivariate analysis, advanced endometrial cancer, salvage surgery and residual disease status were significant and independent predictors of postrecurrence survival [ 26 ].
Given the improvement in survival documented in these reviews, women with recurrent disease should be considered for surgical resection when appropriate. The reported morbidity and mortality of surgery highlight the importance of appropriate patient selection prior to embarking on this management strategy of recurrent disease, advanced endometrial cancer. The new FIGO staging system for dr vitkin weight loss clinic al cancer no longer incorporates cytology results as part of the staging criteria but does require that cytology information be collected.
The new staging system may not alter the management of patients with positive washings because these patients no longer have tumors upstaged to stage IIIA because of positive cytology. To date, however, patients with FIGO stage IIIA disease have been treated via numerous modalities, including hormonal treatment, whole abdominal radiation therapy, and i.
The reported 2-year disease-free survival rate in a study of 65 patients with clinical stage I—III disease following the administration of i. The administration of i, advanced endometrial cancer. In a study by Creasman et al. The highly controversial issue of positive peritoneal cytology as an isolated risk factor is evident in this study. Forty-six percent of patients with positive peritoneal cytology as an isolated factor were noted to be at risk for carcinomatosis recurrence and death [ 28 ].
In an attempt to try to improve on the outcome of patients treated with radiation advanced endometrial cancer, many have tried to combine cytotoxic chemotherapy with radiation. The safety and efficacy of combined postoperative chemoradiation have been demonstrated in both ovarian and cervical carcinoma patients [ 29 — 32 ], advanced endometrial cancer.
The use of multimodality therapy in endometrial cancer addresses the fact that most relapses after adjuvant radiation occur outside the radiated field, advanced endometrial cancer.
Clearly there is a need for both local and systemic advanced endometrial cancer in advanced staged endometrial cancer. Multiple different chemotherapy agents have been combined with both volume-directed and whole abdominal chemotherapy advanced endometrial cancer acceptable toxicity and response rates Table 2 [ 33 — 37 ]. All these studies, advanced endometrial cancer, unfortunately, are limited by their small size. In that trial, patients were randomized to either whole abdominal radiation therapy or combination chemotherapy cisplatin plus doxorubicin [ 38 ].
A significant PFS and overall survival benefit for patients treated with combination chemotherapy was noted, when compared with the PFS and overall survival outcomes in patients treated with whole abdominal radiation hazard for death, 0. That trial commenced accrual inand since then radiation techniques, chemotherapeutic regimens, and supportive care measures have improved so that these patients have more options than available in the early s [ 39 ], advanced endometrial cancer.
As noted by Fleming, the GOG study raised the question of the appropriateness of combining radiation therapy and chemotherapy for these patients [ 39 ].
In the GOG trial Table 3radiation therapy was administered to involved fields either the pelvis or the pelvis and the para-aortic lymph nodes with subsequent delivery of six cycles of chemotherapy. The randomization in the GOG trial was to different chemotherapeutic regimens—doxorubicin plus cisplatin versus doxorubicin, cisplatin, and paclitaxel. Accrual to the GOG study is complete.
Results will be available for publication in the next several years. Both the appropriate timing of initiating chemotherapy treatment and the most appropriate agents to use remain controversial. The GOG continues to investigate multimodality therapy, and until the results of these studies mature, the answers to many of these questions will not be answered Table 3. The knowledge that the development of endometrial cancer is associated with excess estrogen production has resulted in the use of a variety of advanced endometrial cancer agents in the treatment of endometrial cancer [ 4041 ].
Several agents have been used in the setting of recurrent and metastatic endometrial cancer. These agents include medroxyprogesterone acetate MPAhydroxyprogesterone caproate, and megestrol acetate. Responses to progestational agents are usually of short duration, with an observed median time of 4 months [ 50 ]. In the past, for patients with malignant cytology, the use of hormonal therapy was embraced as a potential treatment strategy.