Influence of chemoradiation on the immune microenvironment of cervical cancer patients.

PURPOSE: Cervical cancer remains a leading cause of cancer death in women. While immunotherapy has shown great success in combating cancer, the value of immunotherapy in cervical cancer is still only beginning to be explored. Thus, we performed a prospective analysis of patient blood and tumor samples at the beginning and end of conventional chemoradiation to assess changes in the immune cell and immunoreceptor compartments, and investigate if and when the addition of immunotherapy could be beneficial. METHODS: Patients with FIGO II-III cervical cancer receiving standard chemoradiation between January 2020 and December 2021 were included. We collected tumor and blood samples from patients before and at the end of therapy and analyzed immune cell composition and immune checkpoint receptor expression on both immune and tumor cells using multicolor flow cytometry. RESULTS: In all, 34 patients were eligible in the study period; 22 could be included and analyzed in this study. We found that chemoradiation significantly reduces T cell numbers in both tumors and blood, but increases macrophage and neutrophil numbers in tumors. Furthermore, we found that the percentage of immune checkpoint receptor PD­1 and TIGIT-expressing cells in tumors was significantly reduced at the end of therapy and that CD4 and CD8 memory T cell populations were altered by chemoradiation. In addition, we observed that while PD-L1 expression intensity was upregulated by chemoradiation on blood CD8 cells, PD-L1 expression frequency and the expression intensity of antigen-presenting molecule MHC­I were significantly reduced on tumor cells. CONCLUSION: Our data demonstrate that chemoradiation significantly alters the immune cell composition of human cervical tumors and the expression of immune checkpoint receptors on both lymphocytes and tumor cells. As our results reveal that the percentage of PD­1+ CD8 cells in the tumor as well as the frequency of PD-L1-expressing tumor cells were reduced at the end of therapy, neoadjuvant or simultaneous anti-PD­1 or anti-PD-L1 treatment might provide better treatment efficiency in upcoming clinical studies.

Radiation treatment of hemato-oncological patients in times of the COVID-19 pandemic : Expert recommendations from the radiation oncology panels of the German Hodgkin Study Group and the German Lymphoma Alliance.

PURPOSE: The coronavirus pandemic is affecting global health systems, endangering daily patient care. Hemato-oncological patients are particularly vulnerable to infection, requiring decisive recommendations on treatment and triage. The aim of this survey amongst experts on radiation therapy (RT) for lymphoma and leukemia is to delineate typical clinical scenarios and to provide counsel for high-quality care. METHODS: A multi-item questionnaire containing multiple-choice and free-text questions was developed in a peer-reviewed process and sent to members of the radiation oncology panels of the German Hodgkin Study Group and the German Lymphoma Alliance. Answers were assessed online and analyzed centrally. RESULTS: Omission of RT was only considered in a minority of cases if alternative treatment options were available. Hypofractionated regimens and reduced dosages may be used for indolent lymphoma and fractures due to multiple myeloma. Overall, there was a tendency to shorten RT rather than to postpone or omit it. Even in case of critical resource shortage, panelists agreed to start emergency RT for typical indications (intracranial pressure, spinal compression, superior vena cava syndrome) within 24 h. Possible criteria to consider for patient triage are the availability of (systemic) options, the underlying disease dynamic, and the treatment rationale (curative/palliative). CONCLUSION: RT for hemato-oncological patients receives high-priority and should be maintained even in later stages of the pandemic. Hypofractionation and shortened treatment schedules are feasible options for well-defined constellations, but have to be discussed in the clinical context.

The brave new world of endometrial cancer : Future implications for adjuvant treatment decisions.

PURPOSE: For many decades, endometrial cancer (EC) has been considered as a homogenous tumor entity with good prognosis. The currently valid risk stratification considers clinical and pathological factors. Treatment recommendations differ considerably from country to country. MATERIALS AND METHODS: The Cancer Genome Atlas (TCGA) Research Network has shown that ECs should be reclassified into four novel molecular prognostic groups, with the potential of changing adjuvant management of EC patients: ultra-mutated, hyper-mutated, copy-number low, and copy-number high. Clinical examples are shown, and the available literature has been highlighted. The European Society of Gynaecological Oncology (ESGO) guideline for endometrial cancer takes the new classification system into consideration for adjuvant treatment decisions and will be published this year. RESULTS: In the near future, we expect new treatment recommendations that may differ considerably from the clinicopathologically driven recommendations on the basis of our deeper insight and better understanding of molecular markers in endometrial cancer. The PORTEC 4a study is the only recruiting study which randomizes patients to adjuvant or no adjuvant treatment on the basis of the aforementioned new classification system. CONCLUSION: The aim of the new classification is a more personalized adjuvant radio(chemo)therapy decision and better oncologic outcomes or avoidance of overtreatment.

Age-corrected hearing loss after chemoradiation in cervical cancer patients.

OBJECTIVE: This study aimed to evaluate subjective and objective hearing loss in cervical cancer patients after chemoradiation with cisplatin (mono). PATIENTS AND METHODS: A total of 51 cervical cancer patients with indication for chemoradiation were included. Pure tone and impedance audiometry were performed before and after chemoradiation. Hearing loss was scaled according to ASHA criteria. Subjective hearing was assessed with the Oldenburger Sentence Test. To consider age-dependent changes, hearing loss was corrected for age and the time interval between measurements. RESULTS: Median age at diagnosis was 46 years, 46% were active/former smokers (n = 24), 28 (54%) patients were never-smokers. Median total weekly cisplatin dose was 70 ± 14.2 mg. Cumulative doses of cisplatin during chemoradiation ranged between 115.2 and 400 mg cisplatin (mean 336.1 mg, median 342 ± 52.7 mg). The median interval between last chemotherapy and second audiometry was 320 ± 538 days (35-2262 days). Changes in hearing threshold ≥20 dB were experienced by 32/52 patients (62%) following chemoradiation, 55% of them for frequencies ≥6000 Hz. No statistically significant hearing loss remained after chemoradiation upon correction for age and time interval. Patients >40 years had a higher risk of hearing loss than younger patients. Objective data on hearing function did not correlate with subjective hearing loss and did not impair daily activity in any patient. CONCLUSION: Chemoradiation with cumulative cisplatin doses up to 400 mg did not lead to significant impairment of objective or subjective hearing. For cervical cancer patients undergoing chemoradiation, standard audiometry is not indicated.

Evolution of adjuvant treatment in endometrial cancer-no evidence and new questions?

PURPOSE: For endometrial cancer (EC), clinical and pathological risk factors are taken to triage patients and estimate their prognosis. Lymph node involvement (pN+), lymphovascular space involvement (LSVI), grading, age of the patients, and T classification are internationally accepted parameters for treatment decisions. MATERIALS AND METHODS: Studies on adjuvant radiation, chemotherapy, and chemoradiation are discussed against the background of risk stratification and clinical decision-making in early-to-advanced stage endometrial cancer. Recent publications on adjuvant treatment in high-risk disease and its implications for the patients with regard to expected oncologic benefit and treatment-related toxicity are discussed. RESULTS: Surgery is the mainstay of treatment of EC patients. Well-differentiated tumors and early disease (FIGO IA) should be followed up without further treatment. In FIGO I stage without risk factors, VBT remains the standard treatment after surgery. FIGO I, II patients with one or more risk factors (MI ≥ 50%, Grading[G]3, age >60 years, LVSI) benefit from external beam radiotherapy (EBRT) in terms of survival. There are no data of acceptable quality demonstrating that chemotherapy is superior to radiation in locally advanced carcinomas. Therefore, even in locally advanced disease (FIGO III, IV), EBRT remains the standard of care after surgery. EBRT contributes to the very low rate of local relapses and better DFS in these patients and should not be replaced by chemotherapy only. Whether and which subgroups of patients benefit from an additional (concomitant and/or adjuvant) chemotherapy in terms of disease-free survival remains a controversial issue. The recently published PORTEC-3 trial could not create clear evidence. With a high rate of isolated tumors cells and micrometastases in the specimens, the increasing use of unvalidated sentinel concepts in endometrial cancer raises more questions with regard to indications for adjuvant treatment. In the future, integrated genomic characterization of tumors might be helpful for treatment individualization in the adjuvant setting.

Breast conserving surgery in combination with intraoperative radiotherapy after previous external beam therapy: an option to avoid mastectomy.

PURPOSE: Mastectomy is the standard procedure in patients with in-breast tumor recurrence (IBTR) or breast cancer after irradiation of the chest due to Hodgkin's disease. In certain cases a second breast conserving surgery (BCS) in combination with intraoperative radiotherapy (IORT) is possible. To date, data concerning BCS in combination with IORT in pre-irradiated patients are limited. This is the first pooled analysis of this special indication with a mature follow-up of 5 years. METHODS: Patients with IBTR after external beam radiotherapy (EBRT; treated in two centers) for breast cancer were included. Patients with previous EBRT including the breast tissue due to other diseases were also included. IORT was performed with the Intrabeam™-device using low kV X-rays. Clinical data including outcome for all patients and toxicity for a representative cohort (LENT-SOMA scales) were obtained. Statistical analyses were done including Kaplan-Meier estimates for local recurrence, distant metastasis and overall survival. RESULTS: A total of 41 patients were identified (39 patients with IBTR, 2 with Hodgkin`s disease in previous medical history). Median follow-up was 58 months (range 4-170). No grade 3/4 acute toxicity occurred within 9 weeks. Local recurrence-free survival rate was 89.9% and overall survival was 82.7% at 5 years. Seven patients developed metastasis within the whole follow-up. CONCLUSIONS: BCS in combination with IORT in IBTR in pre-irradiated patients is a feasible method to avoid mastectomy with a low risk of side effects and an excellent local control and good overall survival.

[CyberKnife®: new treatment option for uveal melanoma]. / CyberKnife®: Eine neue Therapieoption bei uvealem Melanom.

BACKGROUND: CyberKnife® stereotactic radiosurgery is a new treatment option for uveal melanoma. OBJECTIVE: This review outlines the technique of robot-assisted CyberKnife® therapy, as well as the pros and cons in the treatment of uveal melanoma. METHODS: The study provides a PubMed literature review and own preliminary clinical experiences. RESULTS: CyberKnife® therapy for choroidal and ciliary body melanomas shows comparable results concerning local tumor control and overall survival matching those of conventional therapies. With only low complication rates, a high level of quality of life can be conserved by possible preservation of visual acuity as well as the ocular globe. CONCLUSION: Stereotactic radiosurgery using CyberKnife® seems to be an efficient and safe therapeutic option for malignant melanomas affecting the choroid and ciliary body. Comparative studies with conventional radiation strategies are now a high priority.

Risk-adapted robotic stereotactic body radiation therapy for inoperable early-stage non-small-cell lung cancer.

PURPOSE: To evaluate efficacy and toxicity of stereotactic body radiation therapy (SBRT) with CyberKnife® (Accuray, Sunnyvale, CA, USA) in a selected cohort of primary, medically inoperable early-stage non-small cell lung cancer (NSCLC) patients. METHODS: From 2012 to 2016, 106 patients (median age 74 years, range 50-94 years) with primary NSCLC were treated with SBRT using CyberKnife®. Histologic confirmation was available in 87 patients (82%). For mediastinal staging, 92 patients (87%) underwent 18F-fluorodeoxyglucose positron-emission tomography (18-FDG-PET) and/or endobronchial ultrasound (EBUS)-guided lymph node biopsy or mediastinoscopy. Tumor stage (UICC8, 2017) was IA/B (T1a-c, 1-3 cm) in 86 patients (81%) and IIA (T2a/b, 3-5 cm) in 20 patients (19%). Depending on tumor localization, three different fractionation schedules were used: 3 fractions of 17Gy, 5 fractions of 11Gy, or 8 fractions of 7.5 Gy. Tracking was based on fiducial implants in 13 patients (12%) and on image guidance without markers in 88%. RESULTS: Median follow-up was 15 months (range 0.5-46 months). Acute side effects were mild (fatigue grade 1-2 in 20% and dyspnea grade 1-2 in 17%). Late effects were observed in 4 patients (4%): 3 patients developed pneumonitis requiring therapy (grade 2) and 1 patient suffered a rib fracture (grade 3). In total, 9/106 patients (8%) experienced a local recurrence, actuarial local control rates were 88% (95% confidence interval, CI, 80-96%) at 2 years and 77% (95%CI 56-98%) at 3 years. The median disease-free survival time was 27 months (95%CI 23-31 months). Overall survival was 77% (95%CI 65-85%) at 2 years and 56% (95%CI 39-73%) at 3 years. CONCLUSION: CyberKnife® lung SBRT which allows for real-time tumor tracking and risk-adapted fractionation achieves satisfactory local control and low toxicity rates in inoperable early-stage primary lung cancer patients.

The relevance of the lymph node ratio as predictor of prognosis is higher in HPV-negative than in HPV-positive oropharyngeal squamous cell carcinoma.

OBJECTIVES: Lymph node ratio (LNR) is an established predictor in different entities of carcinoma, including head and neck malignancies. In oropharyngeal squamous cell carcinoma (OPSCC), lymph node involvement differs between human papilloma virus (HPV)-positive and HPV-negative tumours. Herein, we evaluate the impact of HPV association on the concept of LNR. METHODS: 88 surgically treated patients were included in this retrospective chart review. HPV-positive and HPV-negative OPSCC were evaluated for prediction of outcome by LNR separately. The endpoints were 5-year overall survival (OS) and recurrence-free survival (RFS). RESULTS: The OS of all patients was 60.1%. In univariate analysis, LNR was a significant predictor of overall survival rate (P=.008) in OPSCC independently of the HPV status, as well as extracapsular spread (ECS). T-classification was only a significant predictor in the univariate analysis in HPV-positive OPSCC carcinoma. However, in the multivariate analysis LNR remained predictor of prognosis in all OPSCC and in HPV-negative OPSCC. In patients with HPV-positive OPSCC, only T-classification reached significance to predict OS. CONCLUSION: Prognosis of primarily operated HPV-positive patients might be more dependent on the extent of primary tumour site, whereas prognosis of HPV-negative patients is based more on cervical metastatic spread, represented by LNR.

Checkpoint inhibitors and radiation treatment in Hodgkin's lymphoma : New study concepts of the German Hodgkin Study Group.

BACKGROUND: Patients with classical Hodgkin's lymphoma (cHL) have a good prognosis even in advanced stages. However, combined chemo- and radiotherapy, as the standard of care, is also associated with treatment-related toxicities such as organ damage, secondary neoplasias, infertility, or fatigue and long-term fatigue. Many patients suffer from this burden although their cHL was cured. Therefore, the efficacy of immune checkpoint inhibitors like anti-PD1/PD-L1 antibodies in the treatment of solid cancers and also in HL offers new options. A remarkable and durable response rate with a favorable toxicity profile was observed in heavily pretreated cHL patients. METHODS: Planning to perform prospective randomized clinical trials in the content of radio-immune treatment in patients with Hodgkin's lymphoma (HL), we transferred the results of preliminary clinical studies and basic research in clinical relevant study concepts. RESULTS: Based on these promising early phase trial data, the German Hodgkin Study Group (GHSG) will investigate innovative treatment regimens in upcoming phase II trials. CONCLUSION: The therapeutic efficacy and potential synergies of anti-PD1 antibodies in combination with chemo- or radiotherapy will be investigated in various settings of HL.

Diagnosis, Therapy and Follow-up Care of Vulvar Cancer and its Precursors. Guideline of the DGGG and DKG (S2k-Level, AWMF Registry Number 015/059, November 2015.

Purpose: This is an official guideline, published and coordinated by the Arbeitsgemeinschaft Gynäkologische Onkologie (AGO, Study Group for Gynecologic Oncology) of the Deutsche Krebsgesellschaft (DKG, German Cancer Society) and the Deutsche Gesellschaft für Gynäkologie und Geburtshilfe (DGGG, German Society for Gynecology and Obstetrics). The number of cases with vulvar cancer is on the rise, but because of the former rarity of this condition and the resulting lack of literature with a high level of evidence, in many areas knowledge of the optimal clinical management still lags behind what would be required. This updated guideline aims to disseminate the most recent recommendations, which are much clearer and more individualized, and is intended to create a basis for the assessment and improvement of quality care in hospitals. Methods: This S2k guideline was drafted by members of the AGO Committee on Vulvar and Vaginal Tumors; it was developed and formally completed in accordance with the structured consensus process of the Association of Scientific Medical Societies in Germany (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften, AWMF). Recommendations: 1. The incidence of disease must be taken into consideration. 2. The diagnostic pathway, which is determined by the initial findings, must be followed. 3. The clinical and therapeutic management of vulvar cancer must be done on an individual basis and depends on the stage of disease. 4. The indications for sentinel lymph node biopsy must be evaluated very carefully. 5. Follow-up and treatment for recurrence must be adapted to the individual case.

[S3 guidelines on diagnostics and treatment of cervical cancer: Demands on pathology]. / S3-Leitlinie Diagnostik und Therapie des Zervixkarzinoms.

Between 2011 and the end of 2014 the former consensus S2k guidelines for the diagnostics and treatment of cervical cancer were updated and upgraded to S3 level, methodologically based on the regulations of the German Cancer Society (DKG). The present article summarizes the relevant aspects for the sectioning, histopathological workup, diagnostics and reporting for the pathology of invasive cancer of the uterine cervix. The recommendations are based on the most recent World Health Organization (WHO) and TNM classification systems and consider the needs of the clinician for appropriate surgical and radiotherapeutic treatment of patients. Detailed processing rules of colposcopy-guided diagnostic biopsies, conization and trachelectomy as well as for radical hysterectomy specimens and lymph node resection (including sentinel lymph node resection) are given. In the guidelines deep stromal invasion in macroinvasive cervical cancer is defined for the first time as tumor infiltration of > 66% of the cervical stromal wall. Furthermore, morphological prognostic factors for microinvasive and macroinvasive cervical cancer are summarized.

Combined measurement of tumor perfusion and glucose metabolism for improved tumor characterization in advanced cervical carcinoma. A PET/CT pilot study using [15O]water and [18F]fluorodeoxyglucose.

BACKGROUND AND PURPOSE: The aim of this pilot study was (1) to evaluate the combination of [(18)F]fluorodeoxyglucose (FDG) and [(15)O]water for detection of flow-metabolism mismatch in advanced cervical carcinomas, i.e., increased glycolysis at low blood flow, as a possible parameter for prediction of response to treatment, and (2) to propose a method for automated quantification of its spatial extent. PATIENTS AND METHODS: The study retrospectively included 10 women with advanced cervical carcinoma in whom PET with both FDG and [(15)O]water had been performed prior to therapy. The metabolically active tumor volume was delineated automatically in the FDG images. For computation of the regional blood flow in the tumor, a recovery corrected image-derived arterial input function was used. A tumor voxel was classified as mismatched when the voxel SUV of FDG was larger than the median tumor SUV and the voxel perfusion (K1) was smaller than the median perfusion. The absolute mismatch volume (aMMV) was defined as the volume of all mismatched voxels in ml, and the relative mismatch volume (rMMV) as the ratio of the aMMV to the metabolic tumor volume in percent. RESULTS: The tumors were quite heterogeneous with respect to both FDG uptake and perfusion. The aMMV clustered into 2 groups: "large aMMV" ≥ 10 ml in 40 % of patients and "small aMMV" ≤ 5 ml in 60 % of patients. The rMMV ranged from 12.7-24.9 %. There was no correlation between rMMV and metabolic tumor volume. There was a tendency (p = 0.126) for an association between rMMV and histological grading, rMMV being about 20 % higher in G3 than in G2 tumors. rMMV did not correlate with SUV or perfusion. CONCLUSION: These results suggest that combined PET with FDG and [(15)O]water allows detection and quantitative characterization of flow-metabolism mismatch in advanced cervical carcinomas.

Patterns of care in patients with cervical cancer 2012: results of a survey among German radiotherapy departments and out-patient health care centers.

BACKGROUND: Platinum-based primary or adjuvant chemoradiation is the treatment of choice for patients with cervical cancer. However, despite national guidelines and international recommendations, many aspects in diagnosis, therapy, and follow-up of patients with cervical cancer are not based on valid data. METHODS: To evaluate the current patterns of care for patients with cervical cancer in Germany, a questionnaire with 25 items was sent to 281 radiooncologic departments and out-patient health care centers. RESULTS: The response rate was 51%. While 87% of institutions treat 0-25 patients/year, 12 % treat between 26 and 50 and only 1% treat more than 50 patients/year. In 2011, the stage distribution of 1,706 treated cervical cancers were IB1, IB2, IIA, IIB, IIIA/IIIB, and IV in 11, 12, 11, 22, 28, and 16%, respectively. CT (90%) and MRI (86%) are mainly used as staging procedures in contrast to PET-CT with 14%. Interestingly, 27% of institutions advocate surgical staging prior to chemoradiation. In the majority of departments 3D-based (70%) and intensity-modulated radiotherapy (76%) are used for percutaneous radiation, less frequently volumetric arc techniques (26%). Nearly all colleagues (99.3%) apply conventional fractioning of 1.8-2 Gy for external-beam radiotherapy, in 19% combined with a simultaneous integrated boost. Cisplatinum mono is used as a radiosensitizer with 40 mg/m(2) weekly by 90% of radiooncologists. For boost application in the primary treatment, HDR (high-dose rate) brachytherapy is the dominant technique (84%). In patients after radical hysterectomy pT1B1/1B2, node negative and resection in sound margins adjuvant chemoradiation is applied due to the occurrence of 1-4 other risk factors in 16-97%. There is a broad spectrum of recommended primary treatment strategies in stages IIB and IVA. CONCLUSION: Results of the survey underline the leading role but also differences in the use of chemoradiation in the treatment of cervical cancer patients in Germany.

Aspects of Therapy for Cervical Cancer in Germany 2012 - Results from a Survey of German Gynaecological Hospitals.

Introduction: In spite of the existence of guidelines and international recommendations, many aspects in the diagnosis, therapy and follow-up of patients with cervical cancer are not based on validated data. A broad spectrum of different opinions and procedures concerning the therapy for patients with cervical cancer is under controversial discussion by the responsible gynaecologists in German hospitals. Methods: The present study is intended to picture the current treatment situation for cervical cancer in Germany. For this purpose a specially developed questionnaire with questions divided into 19 subsections was sent to all 688 gynaecological hospitals in Germany. Results: The response rate to the questionnaire was 34 %. 91 % of the hospitals treated between 0 and 25 patients with cervical cancer per year. 7.5 % treated between 26 and 50 and 1.4 % of the hospitals more than 50 patients per year. The bimanual examination was the most frequently used staging method (98 %); PET-CT was the least used staging method (2.3 %). Interestingly 48 % of the hospitals used surgical staging. The great majority of the hospitals (71 %) used abdominal radical hysterectomy (Wertheim-Meigs operation) to treat their patients. TMMR via laparotomy was used by 13 %. 16 % of the hospitals performed laparoscopic or robot-assisted radical hysterectomies. The sentinel concept was hardly used even in the early stages. It must be emphasised that in 74 % of the hospitals radical hysterectomies were performed even in cases with positive pelvic lymph nodes and in 43 % also in cases with positive paraaortic lymph nodes. The therapy of choice for FIGO IIB cancers is primary radiochemotherapy (RCTX) in 21 % of the hospitals; operative staging followed by radiochemotherapy in 24 % and treatment by radical hysterectomy followed by adjuvant RCTX was employed in this situation by 46 % of the hospitals. In 15-97 % of the hospitals for node-negative and in sano resected patients in stage pT1B1/1B2 after radical hysterectomy, an adjuvant RCTX is recommended when further risk factors exist (LVSI, tumour > 4 cm, age < 40 years, adenocarcinoma, S3). Conclusion: A broad spectrum of differing staging and therapy concepts is in use for patients with cervical cancer in Germany. A standardisation of therapy is needed. An update of national guidelines could help to achieve more transparency and a standardisation of treatment for patients with cervical cancer.

From laparoscopic assisted radical vaginal hysterectomy to vaginal assisted laparoscopic radical hysterectomy.

Radical hysterectomy with pelvic lymphadenectomy is the standard surgical treatment for patients with early stage cervical cancer. The majority of radical hysterectomies are performed with the open technique. However, laparoscopic, combined laparoscopic and vaginal, and robotic-assisted approaches may also be used. Compared with the abdominal radical hysterectomy (ARH), laparoscopic techniques are associated with less blood loss, shorter hospital stay, better cosmesis, and faster recovery. A further breakthrough in laparoscopic technique can only be made if safety and oncological clearance are comparable with ARH. We describe the technique and results of laparoscopic assisted radical vaginal hysterectomy and the transition to vaginal assisted laparoscopic radical hysterectomy.

Current therapy of patients with endometrial carcinoma. A critical review.

Magnetic resonance imaging (MRI), 18-FDG positron emission tomography ((18)FDG PET-CT), and computed tomography (CT) have demonstrated disappointing detectability of lymph node metastases in endometrial cancer. The treatment of choice in patients with endometrial cancer is hysterectomy and bilateral salpingoophorectomy. Above all, obese patients with comorbidity have benefited the most from laparoscopically assisted approaches. For inoperable patients in FIGO stage I/II, radiation remains an alternative to hysterectomy. The role of pelvic and paraaortic lymphadenectomy is the most controversial issue in endometrial carcinoma treatment. The current spectrum of treatment ranges from no lymphadenectomy, exclusive pelvic or additional inframesentric paraaortic sampling, or complete pelvic to infrarenal paraaortic lymphadenectomy. The sentinel concept in patients with endometrial carcinoma is far from being introduced into routine clinical practice. Without a lymphadenectomy, decision making for adjuvant therapy remains a challenge, because no information is available from lymph node status and the reliability of pathologic grading is poor. For patients after hysterectomy with a low risk of local relapse (stage I/II without additional risk factors), vaginal brachytherapy is sufficient to prevent vaginal relapses. Adjuvant external beam irradiation (EBRT) in stage I/II demonstrated improved local control which impacted overall survival only in patients with high-risk features (higher age, grading myometrial infiltration). Stage IIIC patients seem to benefit from EBRT with regard to overall survival. In patients at high risk of progression (grade 3, MI > 50%, FIGO IIIC, unfavorable histology), multimodal treatment should be considered. The optimal substances and sequences are under investigation.