Current Approaches to the Management of Patients with Endometrial Cancer.

The incidence of endometrial cancer (EC) is rising and healthcare professionals need to be informed about the latest data on the constant developments in the field of its management. With particular interest in the classification and management of EC, we surveyed current literature, national and international data, and guidelines, as well as the latest studies to present the most recent data regarding the management of EC. It became evident that despite the consensus on low-risk EC, there are still controversies surrounding the management of high-risk EC, especially regarding the role of sentinel lymph node biopsy (SLNB). Our aim is to present the old and new perspectives in the management of EC, the different available surgical routes, the possible desire for fertility preservation, the role of adjuvant therapies and the focus on the advantages and the limitations of the implementation of SLNB in therapeutic strategies. It became evident throughout our search and based on literature data that minimally invasive surgery (MIS) leads to satisfying outcomes, thus becoming gradually the preferred route of surgery, while SLNB could provide essential information and guidance about the overall management needed in cases of both low-risk and high-risk EC.

Definitive chemoradiotherapy for cervical cancer: A 11-year population-based study.

PURPOSE: To assess the recurrence pattern and survival in women treated with definitive chemoradiotherapy for cervical cancer. METHODS: A retrospective cohort study of women FIGO (2012) stage IB2 to IVA from the Grampian region of Scotland between February 2000 and March 2011. These women were followed up until April 2018. RESULTS: A total of 121 eligible women allocated with mean age at treatment 50.59 years (SD = 13.98, range 22-82). Tumours staged: IB2: n = 24 (19.8%), II: n = 45 (37.2%), III: n = 43 (35.5%) and IVA: n = 7 (5.8%). Two (1.7%) women had no available data. Fifty-five (45.5%) women had recurrence after treatment, and 51 (42.15%) women died from the disease. The sites of recurrence were as follows: central pelvic only (n = 4, 7.27%), pelvic and distant (n = 39, 70.91%) and distant only (n = 12, 21.82%) with median time from end of treatment to first recurrence 44 months (range 2-98), 26 months (range 1-146) and 22 months (range 3-66) respectively. 5-and 8-year overall survival was 76.0% (95% CI: 68.8%-84.0%) and 64.4% (95% CI: 56.4%-73.5%) respectively. CONCLUSIONS: Though overall survival is better than with radiotherapy alone, recurrence occurs up to 10 years after treatment. This raises the issues of how to reduce late recurrence and the appropriateness of current follow-up protocols.

Endometrial cancer after endometrial ablation or resection for menorrhagia.

OBJECTIVE: To assess the incidence of endometrial cancer after endometrial ablation or resection (EA/R) for menorrhagia. METHOD: The present retrospective observational cohort study included women who underwent EA/R for menorrhagia at Aberdeen Royal Infirmary between February 1, 1990 and December 31, 1997. Follow-up data until 2015 were examined. To assess risk of endometrial cancer, each woman was matched by age to the annual observed incidence of endometrial cancer in northeast Scotland for each year from the date of EA/R until 2015. RESULTS: During the 7-year study period, 901 eligible women (mean age 42.3 ± 5.7 years; range 26-50 years) underwent EA/R. Of these patients, 204 (22.6%) subsequently had a hysterectomy for reasons other than endometrial cancer, and 695 (77.1%) did not. The overall incidence of endometrial cancer was 0.2% (2/901); the risk of developing endometrial cancer after EA/R was calculated as 11.1 per 100 000 women years. The mean expected incidence for all women and the subgroup with no hysterectomy was estimated to be 26.5 and 35.6 occurrences per 100 000 women years, respectively. The observed incidence was significantly lower versus the mean expected risk for both groups (P<0.001). CONCLUSION: The findings indicate that the risk of endometrial cancer could be significantly reduced but not eliminated by EA/R.

Surgical Outcomes and Morbidity After Radical Surgery for Ovarian Cancer in Aberdeen Royal Infirmary, the Northeast of Scotland Gynaecologic Oncology Centre.

BACKGROUND/AIM: Ovarian cancer (OC) has a high mortality rate and usually presents late in advanced stage, which poses challenges to management. Better understanding of the disease biology and application of radical surgery (RS) to achieve no visible residual tumor, alongside with chemotherapy, may lead to longer survival amongst these patients. Our purpose was to examine the demographic characteristics, surgical morbidity and outcomes of patients undergoing RS for OC. MATERIALS AND METHODS: A retrospective cohort study of women undertaking surgery for OC between February 2014 and September 2016 in Aberdeen Royal Infirmary. RESULTS: A total of 121 women had surgery for OC of whom 78 (64.5%) were stage II and above. Of these, 40 (51.3%) women had primary and 38 (48.7%) had interval debulking surgery with 42 (53.8%) having radical surgery. The most common procedures that were performed as part of RS included rectosigmoid resection (n=20, 47.6%), small bowel resection (n=10, 23.8%), splenectomy (n=9, 21.4%). Morbidity outcomes included blood loss >1.5 lt. (n=14, 33.3%), hospitalization >7days (n=31, 73.8%), sepsis (n=8, 19%). There was no short-term mortality. Debulking outcomes were: no macroscopic residual disease (n=36, 85.7%), ≤10 mm disease (n=2, 4.8%), and ≥10 mm disease (n=3, 7.1%). CONCLUSION: Our findings support the practise where RS for OC can be offered to selected patients, with good surgery outcomes and low morbidity rates.

Long-term incidence of hysterectomy following endometrial resection or endometrial ablation for heavy menstrual bleeding.

OBJECTIVE: To estimate the incidence of hysterectomy following endometrial resection or endometrial ablation (ERA). METHODS: The present retrospective study enrolled women who underwent ERA for benign heavy menstrual bleeding (HMB) at Aberdeen Royal Infirmary, UK, between February 1, 1990, and December 31, 1997; follow-up data to the end of 2015 were included from the pathology laboratory report system from the single pathology laboratory in the region. Data were compared between patients who did or did not require a hysterectomy after ERA. RESULTS: There were 901 patients who underwent ERA for HMB during the study period. The mean age of patients was 42.3 ± 5.7 years; of the patients included, 206 (22.9%) women underwent hysterectomy and these patients had a mean age of 40.1 years. Of the patients who had hysterectomies, 155 (75.2%) did so in the first 5 years following ERA, 31 (15.0%) did within 6-10 years, 11 (5.3%) did within 11-15 years, and 9 (4.4%) did within 16-20 years. In total, 51 (24.8%) of these patients had hysterectomies within 6-25 years of ERA. CONCLUSIONS: A significant majority of women who underwent ERA for HMB did not require hysterectomy up to 25 years after the procedure.

An update on the management of uterine carcinosarcoma.

UNLABELLED: Carcinosarcomas are rare aggressive neoplasms with a poor prognosis. The recent International Federation of Gynecology and Obstetrics (FIGO) 2009 categorizes uterine carcinosarcoma into the endometrial carcinoma group. This review highlights the prognosis, recurrence rate, and the treatment modalities. The primary treatment is surgery. Lymphadenectomy as part of the surgical procedure has shown to prolong survival even for early-stage disease. A combined chemo-radiotherapeutic approach has shown a survival benefit. Radiotherapy from various studies has shown a significant effect on local control of the disease, with no obvious benefit on overall survival. Various trials led by the gynecologic oncology group looking into different chemotherapeutic combinations have showed differing response rates. In the future, the emergence of combination of chemotherapeutic agents with molecular-targeted agents may show promising results. TARGET AUDIENCE: Obstetricians & Gynecologists and Family Physicians. LEARNING OBJECTIVES: After completing this CME activity, physicians should be better able to appraise the aggressive nature of uterine carcinosarcoma and factors which would help in delaying or preventing recurrence, assess the importance of lymphadenectomy for uterine carcinosarcoma and its effect on survival, and evaluate various recent trials addressing the chemo-radiotherapeutic combinations as adjuvant therapy.

First-line therapy for ovarian cancer with carboplatin followed by paclitaxel-gemcitabine (SCOTROC5): a feasibility study and comparative analysis of the SCOTROC series.

BACKGROUND: We have conducted a series of four feasibility studies in stage Ic-IV ovarian cancer exploring six sequential first-line schedules with the same entry criteria in a total of 339 patients. Here we present the results of the sixth study, and an analysis of the overall series. METHODS: In this trial patients received 4 cycles of carboplatin AUC 7 every 3 weeks, followed by 4 cycles of concurrent paclitaxel 175 mg/m(2) (day 1) and gemcitabine 1000 mg/m(2) (days 1 and 8) every 3 weeks. The primary end-point of the trial was feasibility of administering all cycles of planned chemotherapy to >60% of patients. RESULTS: Fifty-four patients were recruited to the trial between June 05 and June 06. A total of 40 (74.1%) patients received all 8 cycles of treatment. Reasons for early discontinuation included toxicity (n=8) and disease progression (n=4). The overall response rate was 73.7%, and the median progression free survival (PFS) was 14.2 months with a median follow-up of 24 months. A comparative analysis of all six regimens from the SCOTROC series suggests that the sequential schedule in which paclitaxel was given weekly (median PFS 19.5m) is most effective. CONCLUSION: The sequential schedule explored in this trial is feasible, but comparative efficacy analysis suggests that trials involving weekly paclitaxel should be prioritised for further study.

Use of new imaging techniques to predict tumour response to therapy.

Imaging of tumour response to therapy has steadily evolved over the past few years as a result of advances in existing imaging modalities and the introduction of new functional techniques. The use of imaging as an early surrogate biomarker of response is appealing, because it might allow for a window of opportunity during which treatment regimens can be tailored accordingly, depending on the expected response. The clinical effect of this would ultimately result in a reduction in morbidity and undue costs. The aim of this review is to describe the potential of various new imaging techniques as biomarkers of early tumour response. We have reviewed the literature and identified studies that have assessed these techniques, such as diffusion-weighted MRI, dynamic contrast-enhanced MRI, magnetic resonance spectroscopy, and 18-fluorodeoxyglucose-PET as early response indicators, and highlight the current clinical awareness of their use.

A combined pharmacokinetic and radiologic assessment of dynamic contrast-enhanced magnetic resonance imaging predicts response to chemoradiation in locally advanced cervical cancer.

PURPOSE: To investigate the combination of pharmacokinetic and radiologic assessment of dynamic contrast-enhanced magnetic resonance imaging (MRI) as an early response indicator in women receiving chemoradiation for advanced cervical cancer. METHODS AND MATERIALS: Twenty women with locally advanced cervical cancer were included in a prospective cohort study. Dynamic contrast-enhanced MRI was carried out before chemoradiation, after 2 weeks of therapy, and at the conclusion of therapy using a 1.5-T MRI scanner. Radiologic assessment of uptake parameters was obtained from resultant intensity curves. Pharmacokinetic analysis using a multicompartment model was also performed. General linear modeling was used to combine radiologic and pharmacokinetic parameters and correlated with eventual response as determined by change in MRI tumor size and conventional clinical response. A subgroup of 11 women underwent repeat pretherapy MRI to test pharmacokinetic reproducibility. RESULTS: Pretherapy radiologic parameters and pharmacokinetic K(trans) correlated with response (p < 0.01). General linear modeling demonstrated that a combination of radiologic and pharmacokinetic assessments before therapy was able to predict more than 88% of variance of response. Reproducibility of pharmacokinetic modeling was confirmed. CONCLUSIONS: A combination of radiologic assessment with pharmacokinetic modeling applied to dynamic MRI before the start of chemoradiation improves the predictive power of either by more than 20%. The potential improvements in therapy response prediction using this type of combined analysis of dynamic contrast-enhanced MRI may aid in the development of more individualized, effective therapy regimens for this patient group.

Predicting the response of advanced cervical and ovarian tumors to therapy.

UNLABELLED: The management of advanced cervical and ovarian cancers remains a significant challenge as many women fail to respond to recommended therapy, resulting in disease progression and ultimately patient death. Because of tumor heterogeneity, it is rare for all cancers of a particular type to respond to a specific therapy; and, as a result, many patients receive treatment from which they derive little or no benefit, leading to increased morbidity and undue costs. A marker that could rapidly predict or forecast disease outcome would clearly be beneficial in allowing the administration of a tailored regime for each patient while reducing toxicity and cost. Traditional prognostic factors of tumor size, grade, and stage are not ideal for predicting patient outcome, whereas the use of in vitro assays to detect chemosensitivity or resistance has not yet translated into routine clinical practice. Similarly, biomarkers and tumor markers vary in their predictive ability. DNA array technology offers great promise in predicting the response to therapy based on gene expression profiles, and can allow for targeted therapies against specific molecular alterations that cause disease. Imaging techniques, particularly those with the ability to characterize biological tissues and provide functional, structural, and molecular information, have the potential to noninvasively integrate physical and metabolic information. These include F-18-fluorodeoxyglucose positron emission tomography, dynamic contrast-enhanced magnetic resonance imaging, and diffusion weighted magnetic resonance imaging, all techniques that attempt to evaluate and predict therapy response and so influence clinical outcome. This review examines different methods of predicting the response to treatment in advanced cervical and ovarian tumors. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader should be able to describe why prediction of response to therapy for cervical and ovarian cancers is important, describe obstacles to use of in vitro assays to predict outcomes for therapy for ovarian and cervical cancers, and explain potentially new predictive markers.

Magnetic resonance imaging in gynecological oncology.

Magnetic resonance imaging (MRI) has become an indispensable tool in the assessment of malignant disease. With increasingly sophisticated systems and technical advancements, MRI has continued to expand its role in providing crucial information regarding cancer diagnosis and management. In gynecological malignancies, this modality has assumed greater responsibility, particularly in the evaluation of cervical and endometrial cancers. In addition to conventional imaging, innovative techniques such as dynamic contrast-enhanced MRI and diffusion-weighted MRI show promise in offering early assessment of tumor response. This paper reviews the current role of MRI in gynecological cancers and highlights the potential of novel techniques in improving patient care.

Diffusion-weighted magnetic resonance imaging in the early detection of response to chemoradiation in cervical cancer.

OBJECTIVE: To investigate diffusion-weighted magnetic resonance imaging (DWI) as an early and reproducible response indicator in women receiving concurrent radiotherapy and chemotherapy (chemoradiation) for advanced cervical cancer. METHODS: Twenty women with advanced cervical cancer were included in a prospective cohort study. DWI was carried out prior to chemoradiation, repeated after 2 weeks of therapy and at the conclusion of therapy using a 1.5 T MRI scanner. The apparent diffusion coefficient (ADC) was calculated from the diffusion data at each assessment. This was correlated with final tumour response as determined by change in tumour size using MRI and conventional clinical response. Twelve women also underwent 2 separate pre-treatment DWI examinations to test for reproducibility of the ADC measurements. RESULTS: ADC values after 2 weeks of therapy showed a significant correlation with eventual MR response (p=0.048, rho=0.448, Spearman's correlation) and clinical response (p=0.009, rho=0.568) as did the change in ADC after 2 weeks of therapy (p=0.01, rho=0.56 for MR response, p=0.03, rho=0.48 for clinical response). Reproducibility of ADC measurements was confirmed with a mean difference in ADC of -0.003 between consecutive pre-therapy MRI assessments and 95% confidence intervals of -0.12 and 0.11. CONCLUSION: DWI has potential to provide a surrogate biomarker of treatment response in advanced cervical cancers. The use of ADC offers an early and reproducible indication of tumour response which may ultimately allow the development of individualised regimens.

Is this the end of the line for the moderate dyskaryotic smear?

OBJECTIVE: The British Society for Clinical Cytology has recently proposed that the terminology for cervical smear reporting is to be changed from a 3-tier system (mild, moderate, severe dyskaryosis) to a 2-tier system of low-grade and high-grade dyskaryosis. This modification eliminates the central category of moderate dyskaryosis which would be incorporated into the high-grade group. The aim of this study was to investigate the role of the moderate dyskaryotic smear in clinical practice. MATERIALS AND METHODS: A retrospective review of all women who were referred for colposcopy because of a moderate dyskaryotic smear was carried out for a 6-month period. Data collected included colposcopic impression, procedure performed and final histopathology. Two cytologists who were unaware of the original smear report were asked to reclassify these smears using the new 2-tier system. Their findings were compared with the documented colposcopic and histopathology results. RESULTS: One hundred women with moderate dyskaryotic smears were referred for colposcopy during the study period. Most of these were reclassified as high-grade dyskaryosis using the new system. Fifty-six (72%) of the moderate dyskaryotic smears which were correctly regraded as high grade by cytologist 1 were found to have cervical intraepithelial neoplasia 2/3 on final histopathology, whereas for cytologist 2, 66 (68%) were found to have high-grade cervical intraepithelial neoplasia. CONCLUSION: There is no clinical benefit in retaining the term moderate dyskaryosis. This study emphasizes the need for a uniform 2-tier system.

Isolated clear cell adenocarcinoma in scar endometriosis mimicking an incisional hernia.

BACKGROUND: The development of a mass in association with a previous surgical scar can pose a diagnostic dilemma due to similarities in appearance to hernias, abscesses, hematomas, or desmoid tumors. Scar endometriosis is an uncommon cause of such a lump, but malignant change within this ectopic tissue is exceptionally rare. CASE: We present a case of a 55-year-old woman who was found to have an isolated clear cell adenocarcinoma in an area of scar endometriosis more than 30 years after an open tubal sterilization. This mass was initially thought to be an incisional hernia, but was later diagnosed intraoperatively by frozen section and then incompletely excised, highlighting the difficulties in preoperative diagnosis as well as surgical treatment. CONCLUSION: Malignant change within scar endometriosis is rare, but increased awareness of this phenomenon is required. Vigilance is paramount and a mass located in or close to a surgical scar should be treated with suspicion.

Auditing the use of colposcopy versus general gynecology clinics to investigate women with postcoital or intermenstrual bleeding: a case for a new outpatient service.

OBJECTIVE: The aim of this audit was to determine whether initial referral to a general gynecology clinic (GOPD) or a colposcopy clinic is the most efficient means of managing women with postcoital (PCB) or intermenstrual (IMB) bleeding. MATERIALS AND METHODS: A prospective audit of women with PCB or IMB was conducted. Sixty referrals from primary care were note-logged and alternatively allocated to either clinic. Data were collected by case note review. RESULTS: Sixty women were referred for abnormal bleeding, 33 (55%) of which were seen at the GOPD and 27 (45%) at the colposcopy clinic. Investigations included Chlamydia testing, which was deficient in both settings, whereas ultrasound scans and hysteroscopies were performed in 9% of patients attending the GOPD compared with none in the colposcopy clinic. The most common finding at the GOPD was cervical ectopy in 14 (42%) patients. No abnormality was found in 9 (28%) patients. At colposcopy, 14 (52%) had no abnormality detected, whereas 8 (30%) had cervical ectopy and 3 (11%) had cervical intraepithelial neoplasia. There were no cases of malignancy found in this study. CONCLUSION: Most patients with PCB and IMB will not have a serious abnormality. Our study proposes that a new PCB/IMB outpatient service can improve the efficiency of treatment of these women by providing appropriate guidelines to standardize their care.

Profiling cytochrome P450 expression in ovarian cancer: identification of prognostic markers.

PURPOSE: The cytochromes P450 are a multigene family of enzymes with a central role in the oxidative metabolism of a wide range of xenobiotics, including anticancer drugs and biologically active endogenous compounds. The purpose of this study was to define the cytochrome P450 profile of ovarian cancer and identify novel therapeutic targets and establish the prognostic significance of expression of individual cytochrome P450s in this type of cancer. EXPERIMENTAL DESIGN: Immunohistochemistry for a panel of 23 cytochrome P450s and cytochrome P450 reductase was done on an ovarian cancer tissue microarray consisting of 99 primary epithelial ovarian cancers, 22 peritoneal metastasis, and 13 normal ovarian samples. The intensity of immunoreactivity in each sample was established by light microscopy. RESULTS: In primary ovarian cancer, several P450s (CYP1B1, CYP2A/2B, CYP2F1, CYP2R1, CYP2U1, CYP3A5, CYP3A7, CYP3A43, CYP4Z1, CYP26A1, and CYP51) were present at a significantly higher level of intensity compared with normal ovary. P450 expression was also detected in ovarian cancer metastasis and CYP2S1 and P450 reductase both showed significantly increased expression in metastasis compared with primary ovarian cancer. The presence of low/negative CYP2A/2B (log rank = 7.06, P = 0.008) or positive CYP4Z1 (log rank = 6.19, P = 0.01) immunoreactivity in primary ovarian cancer were each associated with poor prognosis. Both CYP2A/2B and CYP4Z1 were also independent markers of prognosis. CONCLUSIONS: The expression profile of individual P450s has been established in ovarian cancer. Several P450s show increased expression in ovarian cancer and this provides the basis for developing P450-based therapeutics in ovarian cancer. Expression of CYP2A/2B or CYP4Z1 in primary ovarian cancer were independent markers of prognosis.

Surgical treatment of bleeding problems in perimenopausal women.

Bleeding problems are common in perimenopausal women. They affect quality of life. Traditionally, hysterectomy was the definitive 'cure'; however, the past two decades have seen the emergence of less invasive and safer alternatives, in the form of endometrial ablation. Like hysterectomy, these treatments have a high satisfaction rate. Endometrial ablation employing resection techniques may be the procedure of choice in perimenopausal women because the majority of the endometrial cavity is sampled, which may reduce the risk of undetected endometrial cancer. Since no operation is without risk, women should be appropriately selected and counselled.

A randomised comparison of microwave endometrial ablation with transcervical resection of the endometrium; follow up at a minimum of five years.

OBJECTIVE: To compare long term outcomes following microwave endometrial ablation (MEA) or transcervical resection of the endometrium (TCRE). DESIGN: Follow up of a randomised controlled trial. SETTING: Gynaecology department of a large UK teaching hospital. POPULATION/SAMPLE: Two hundred and thirty-nine participants in a randomised comparison of MEA with TCRE. METHODS: Collection of patient completed postal questionnaires and operative databank review. MAIN OUTCOME MEASURES: Women's satisfaction with and acceptability of treatment, menstrual symptoms, changes in health-related quality of life and additional treatments received. RESULTS: Two hundred and thirty-six of the original 263 women returned questionnaires (90%) after a minimum of five years post-treatment. Women allocated to MEA were significantly more likely to be totally or generally satisfied with treatment (86% vs 74%; difference 12%, 95% CI 2% to 23%), to find it acceptable (97% vs 91%; difference 6%, 95% CI 1% to 13%) and would recommend it (97% vs 89%; difference 8%, 95% CI 1% to 14%). Bleeding and pain scores were highly significantly reduced following both MEA and TCRE, achieving amenorrhoea rates of 65% and 69%, respectively. The hysterectomy rate after a minimum of five years was 16% in the MEA and 25% in the TCRE arm. CONCLUSIONS: Both techniques achieve significant and comparable improvements in menstrual symptoms, and health-related quality of life. While high rates of satisfaction with treatment and acceptability of treatment are achieved by TCRE, these are significantly lower than levels following MEA. These long term data, when combined with the trials' operative findings and known costs of both procedures, now inform us that MEA is a more effective and efficient treatment for heavy menstrual loss than TCRE.