Neoadjuvant chemotherapy followed by surgery for advanced-stage endometrial cancer.

Background: Data showing the value of neoadjuvant chemotherapy (nact) followed by interval debulking surgery (ids) in the management of advanced-stage serous endometrial carcinoma (eca) are limited; the aim of the present study was to expand the knowledge about that treatment strategy in patients with advanced eca, including endometrioid eca. Methods: Data were collected retrospectively from all patients with advanced-stage eca treated with nact between 2005 and 2014 at 3 oncology referral centres. Primary outcomes were the radiologic response to nact and achievement of optimal or complete ids. Secondary outcomes were recurrence rate and progression-free and overall survival. Results: Of 102 eca cases included, a complete radiologic response was achieved in only 4 cases, with a partial response being achieved in 72% (64% of endometrioid cases, 80% of serous cases). Complete ids was achieved in 62% of the endometrioid cases and in 56% of the serous eca cases, with optimal ids achieved in 31% and 28% of those cases respectively. Survival rates were calculated for all patients with complete and optimal ids; recurrence was observed in 56% and 67% of the cases respectively, and progression-free survival was 18 months and 13 months respectively. Median survival duration was 24 months for endometrioid eca and 28 months for serous eca. Conclusions: For patients with advanced eca who are not suitable for primary debulking, nact followed by ids can be considered regardless of histologic subtype. The treatment options for this group of patients are limited and have to be explored.

Opportunistic salpingectomy in women undergoing hysterectomy: Results from the HYSTUB randomised controlled trial.

OBJECTIVE: To evaluate whether opportunistic salpingectomy in premenopausal women undergoing hysterectomy for benign indications is both hormonally and surgically safe, compared with hysterectomy without salpingectomy. STUDY DESIGN: In this multicentre randomised controlled trial, women were randomised to undergo either hysterectomy with opportunistic bilateral salpingectomy (intervention group) or standard hysterectomy with preservation of the Fallopian tubes (control group). MAIN OUTCOME MEASURES: The primary outcome was the difference in serum anti-Müllerian hormone concentration (ΔAMH), measured pre-surgery and 6 months post-surgery. Secondary outcomes were surgical outcomes and duration of hospital stay. The sample size was powered at 50 participants per group (n=100) to compare ΔAMH after hysterectomy with salpingectomy to ΔAMH after standard hysterectomy. RESULTS: Between March 2013 and December 2016, 104 women, aged 30-55 years, were randomly allocated to hysterectomy with opportunistic bilateral salpingectomy (n=52) or standard hysterectomy (n=52). The baseline characteristics did not differ between the two groups. The median ΔAMH was -0.14pmol/L (IQR -1.47-0.95) in the intervention group and 0.00pmol/L (IQR -1.05-0.80) in the control group (p=0.49). The addition of salpingectomy did not impair surgical results and it did not affect duration of hospital stay. CONCLUSION: Addition of opportunistic bilateral salpingectomy during hysterectomy did not result in a larger effect on ovarian reserve when compared with hysterectomy alone, neither did it affect surgical outcomes. Therefore, opportunistic salpingectomy seems to be a safe procedure in premenopausal women undergoing hysterectomy for benign gynaecological conditions.

Pitfall in the diagnosis of endometrial cancer: case report of an endometrioid adenocarcinoma arising from uterine adenomyosis.

BACKGROUND: The development of cancer from adenomyotic foci is a rare occurrence. The diagnosis is frequently delayed because of the absence of tumor in the eutopic endometrium. CASE REPORT: We present a case of a 64-year-old postmenopausal woman with irregular vaginal bleeding and dull abdominal pain. Hysteroscopy was negative and hormonal treatment was continued. Nine months later, persisting symptoms necessitated endometrial biopsy revealing an atrophic endometrium. Hydrosonography suggested an endometrial polyp of 14 x 7 mm with a surrounding regular thin endometrium and a diffusely inhomogeneous ultrasonographic pattern throughout the myometrium. Hysteroscopic excision of the endometrial polyp was performed. Biopsies obtained during operative hysteroscopy showed a well differentiated endometrioid endometrial carcinoma. A laparoscopically assisted vaginal hysterectomy with bilateral salpingo-oophorectomy, pelvic lymphadenectomy and peritoneal cytology was performed. Pathologic examination revealed an atrophic endometrium and a Stage IB (FIGO 2009) well differentiated endometrioid endometrial carcinoma with prominent squamous differentiation originating from nodular adenomyosis. This ectopic localization of the endometrioid carcinoma added to a diagnostic delay of 12 months. CONCLUSION: Endometrial cancer arising from uterine adenomyosis may be difficult to diagnose. Awareness of this entity and careful ultrasonography are likely to reduce diagnostic delay.

Clinicopathologic study in uterine cancer.

Patients with primary advanced or recurrent endometrial cancer are relatively uncommon and deserve better treatment options. Current treatment options are surgery, radiotherapy, and systemic therapy. Since the outcome is still poor, there is a need to improve our knowledge on molecular markers in order to personalize treatment. In addition, we need to continue the search for new treatment strategies with a better balance between efficacy and toxicity. In this doctoral thesis, we documented that among molecular and histological markers, blood vessel space involvement and chemotherapy induced regressive changes are new prognostic markers in endometrial cancer. We demonstrated that the tumour biology changes during tumour evolution. The optimal moment to decide on tumour biology is therefore the recurrent setting. A biopsy of the recurrent tumour is the best guarantee to characterize the tumour correctly. Furthermore, this study showed that neoadjuvant chemotherapy followed by interval debulking is a valuable treatment option for endometrial cancer with transperitoneal spread since optimal cytoreduction was achieved in 78% with a low morbidity. Future studies should look into new biomarkers that predict antitumoral activity and should search for mutations in endometrial cancer and analyse which mutation is sensitive for therapy.

Ineffective attempt to preserve fertility with a levonorgestrel-releasing intrauterine device in a young woman with endometrioid endometrial carcinoma: a case report and review of the literature.

BACKGROUND: The treatment of endometrial cancer in young women who want to preserve their fertility is challenging. CASE: A 25-year-old woman (A0P0G0) was diagnosed with grade 1 endometrioid endometrial carcinoma (EEC). Imaging studies including transvaginal ultrasound (TVS), computed tomography and magnetic resonance imaging (MRI) could not detect myometrial invasion or metastatic disease. The immunohistochemical expression of the estrogen and progesterone receptor in the tumor was strongly positive, whereas p53 staining was negative. After extensive counseling, we decided to use a levonorgestrel-releasing intrauterine device to preserve her fertility. Follow-up was organized every three months and consisted of serum CA125 levels, TVS, endometrial biopsy and MRI. The tumor regressed after ten months and the intrauterine device was removed. However, nine months later, recurrent EEC was diagnosed and a hysterectomy performed. Pathological examination confirmed Stage Ia EEC. CONCLUSION: Despite the presence of favorable prognostic factors of EEC as determined by grade and immunohistochemistry, the levonorgestrel-releasing intrauterine device was unable to preserve fertility.

Neoadjuvant chemotherapy followed by interval debulking surgery in patients with serous endometrial cancer with transperitoneal spread (stage IV): a new preferred treatment?

BACKGROUND: To investigate the value of neoadjuvant chemotherapy (NACT), followed by interval debulking surgery (IDS), in endometrial cancer with transperitoneal spread (stage IV). METHODS: Patients with endometrial cancer with transperitoneal spread, as determined by laparoscopy (+/-pleural effusion), were treated with NACT. Efficacy was determined according to the Response Evaluation Criteria in Solid Tumors, residual tumour at IDS and histopathological assessment of tumour regression. RESULTS: A total of 30 patients (median age: 65 years; range:44-81 years) received 3-4 cycles of NACT (83% paclitaxel/carboplatin). Histopathological subtypes were as follows: serous (90%), clear cell (3%) and endometrioid (6%) carcinoma. Response according to RECIST was as follows: 2 (7%) complete remission, 20 (67%) partial remission, 6 (20%) stable disease and 2 (7%) progressive disease (PD). Patients with PD were not operated upon. A total of 24 patients (80%) had optimal cytoreduction (R

Limited clinical benefit from trastuzumab in recurrent endometrial cancer: two case reports.

BACKGROUND: It is hypothesized that the HER-2/neu receptor could be used for targeted therapy in recurrent endometrial cancer. CASES: A patient with type II endometrial cancer (serous), showing strong HER-2/neu overexpression and gene amplification in both primary and recurrent tumor, received single-agent trastuzumab (3x weekly, 8 mg/kg loading, 6 mg/kg maintenance dose). Because of progression after 4 cycles, weekly paclitaxel-trastuzumab (80 mg/m(2) paclitaxel; trastuzumab 4 mg/kg loading, 2 mg/kg maintenance dose) was initiated. However, progressive disease was also noted after 11 weeks of combined treatment. A second patient, with recurrent type II endometrial cancer (grade III endometrioid), had HER-2/neu gene amplification in the primary tumor. However, biopsy from a lung metastasis 3 years later appeared to be HER-2/neu-negative. CONCLUSION: Based on lack of response and changes in tumor biology, trastuzumab was of little clinical value in 2 cases of recurrent type II endometrial cancer. This report underscores the importance of reassessment of a recurrent tumor before initiating targeted treatment.

Effectiveness of weekly topotecan in patients with recurrent epithelial ovarian cancer.

The objective of this study was to investigate the effectiveness and toxicity of weekly topotecan in patients with recurrent epithelial ovarian cancer. Twenty patients were treated with topotecan at a dose of 4 mg/m(2) weekly. Efficacy was determined according to the Response Criteria in Solid Tumors (RECIST) Gynecologic Cancer Inter Group criteria. Median age was 62 years (45-78). Patients had received 1-7 (median 3) prior chemotherapy lines. A total of 203 weekly treatments were administered. In 13 patients (65%) treatment delay was necessary due to bone marrow toxicity. Grade 3/4 neutropenia occurred in 11 patients (55%) and grade 3/4 thrombocytopenia in four patients (20%). Six patients (30%) needed a dose reduction, and 42 cycles (21%) were given with dose reduction. No neutropenia, fever, or sepsis was observed. There was one complete response and one partial response (response rate 10%). All patients with response had platin-sensitive disease (three out of eight). Six patients needed blood transfusion. None of the patients required granulocyte/granulocyte-macrophage colony-stimulating factor. The median duration of response was 13 months. In addition, there were four patients (20%) with a stable disease lasting at least for 4 months. Based on the results of this Phase II study, the toxicity of weekly topotecan seems to be lower than with the 3-weekly topotecan. The response rate of 10% is low but was not expected to be higher as these patients were heavily pretreated.

Endometrial carcinosarcoma with osteoclast-like giant cells.

We encountered a case of endometrial cancer with a poorly differentiated epithelial component, accompanied by a compact proliferation of atypical spindle cells and osteoclast-like giant cells. Immunohistochemically, the epithelial component was EMA and prekeratin positive with vimentin-positive spindle cells, whereas the osteoclast-like giant cells were strongly immunoreactive for CD68. The description of osteoclast-like giant cells adds to the knowledge of endometrial carcinosarcoma tumor biology.