PREDICT-GTN 2: Two-factor streamlined models match FIGO performance in gestational trophoblastic neoplasia.

OBJECTIVE: The International Federation of Gynecology and Obstetrics (FIGO) scoring system uses the sum of eight risk-factors to predict single-agent chemotherapy resistance in Gestational Trophoblastic Neoplasia (GTN). To improve ease of use, this study aimed to generate: (i) streamlined models that match FIGO performance and; (ii) visual-decision aids (nomograms) for guiding management. METHODS: Using training (n = 4191) and validation datasets (n = 144) of GTN patients from two UK specialist centres, logistic regression analysis generated two-factor models for cross-validation and exploration. Performance was assessed using true and false positive rate, positive and negative predictive values, Bland-Altman calibration plots, receiver operating characteristic (ROC) curves, decision-curve analysis (DCA) and contingency tables. Nomograms were developed from estimated model parameters and performance cross-checked upon the training and validation dataset. RESULTS: Three streamlined, two-factor models were selected for analysis: (i) M1, pre-treatment hCG + history of failed chemotherapy; (ii) M2, pre-treatment hCG + site of metastases and; (iii) M3, pre-treatment hCG + number of metastases. Using both training and validation datasets, these models showed no evidence of significant discordance from FIGO (McNemar's test p > 0.78) or across a range of performance parameters. This behaviour was maintained when applying algorithms simulating the logic of the nomograms. CONCLUSIONS: Our streamlined models could be used to assess GTN patients and replace FIGO, statistically matching performance. Given the importance of imaging parameters in guiding treatment, M2 and M3 are favoured for ongoing validation. In resource-poor countries, where access to specialist centres is problematic, M1 could be pragmatically implemented. Further prospective validation on a larger cohort is recommended.

Efficacy analysis of single-agent carboplatin AUC4 2-weekly as second-line therapy for methotrexate-resistant (MTX-R) low risk gestational trophoblastic neoplasia (GTN).

BACKGROUND: Approximately one-third of patients with low-risk Gestational Trophoblastic Neoplasia (WHO 0-6) develop methotrexate-resistance (MTX-R). In the UK, subsequent treatment with either actinomycin-D (ActD) or multi-agent combination chemotherapy has depended on whether the hCG was above or below an hCG threshold. To reduce exposure to combination chemotherapy (CC), over the years the UK service has raised this threshold as well as using single-agent carboplatin AUC6 3-weekly at MTX-R instead of CC. Updated results for carboplatin demonstrate an 86% complete hCG response (hCG CR) but associated with haematological dose-limiting toxicity. METHODS: In 2017, single-agent carboplatin became the national standard second-line treatment following MTX-R at hCG of >3000 IU/L. Carboplatin was changed to two-weekly AUC4 scheduling and continued until normal hCG plus 3 consolidation cycles. For patients failing to respond, CC (Etoposide-Actinomycin-D or EMA-CO) was introduced. RESULTS: 22 evaluable patients with a median hCG at MTX-R of 10,147 IU/L (IQR 5527-19,639) received carboplatin AUC4 2-weekly (median no. of cycles = 6, IQR 2-8). Of these, 36% achieved a hCG CR. All 14 non-CR patients were cured with subsequent CC; 11 and 2 patients with 3rd line and 4th line CC respectively and 1 patient following 5th line CC and hysterectomy. Overall survival remains 100%. CONCLUSION: Carboplatin is not sufficiently active in the second-line treatment of low-risk MTX-resistant GTN. New strategies are required to increase hCG CR and spare more toxic CC regimens.

Flat-dose versus weight or body surface area-based methotrexate dosing in low-risk gestational trophoblastic neoplasia.

BACKGROUND: Single-agent methotrexate (MTX) is commonly used as first-line treatment for low-risk gestational trophoblastic neoplasia (LR-GTN), although no international consensus exists on the optimal treatment regimen to maximise complete hCG response (CR) and minimise relapse rates. Current regimens differ in the route of administration, dose scheduling, and use of flat-dose, body surface area (BSA)- or weight-based dosing. In the UK a methotrexate-folinic acid (MTX-FA) 8-day 50 mg intramuscular flat-dose regimen is used, with 15 mg oral folinic acid rescue. In LR-GTN patients, we aim to determine the effect of MTX dose adjustment by BSA and weight upon chemotherapy response and disease relapse. METHODS: Between January 1973 and August 2020, 935 LR-GTN patients treated with first-line MTX-FA were identified from a single UK specialist trophoblastic centre. Of these, 364 were included, of which 178 (49%) had a CR to first-line MTX-FA. Subgroup analyses were performed upon: (i) patients who changed chemotherapy due to MTX toxicity (n = 33); and (ii) patients with a FIGO score of 5-6 (n = 85). Logistic regression analysis explored the relationship between BSA or weight adjusted MTX dosing and: (i) CR to first-line chemotherapy; (ii) incidence of disease relapse. Linear regression analyses assessed the correlation of BSA and weight with the number of MTX-FA cycles required to achieve CR. RESULTS: In LR-GTN patients, BSA and weight adjusted MTX-FA dosing did not influence CR to first-line chemotherapy or the incidence of disease relapse. The number of MTX cycles required to achieve CR was not associated with BSA or weight. These findings were maintained in a subgroup analysis of FIGO 5-6 patients. The incidence of MTX toxicity was not influenced by BSA or weight. CONCLUSIONS: In the treatment of LR-GTN, dose individualisation using BSA or weight is not required, and fixed dosing continues to be preferred as the UK standard.

PREDICT-GTN 1: Can we improve the FIGO scoring system in gestational trophoblastic neoplasia?

Gestational trophoblastic neoplasia (GTN) patients are treated according to the eight-variable International Federation of Gynaecology and Obstetrics (FIGO) scoring system, that aims to predict first-line single-agent chemotherapy resistance. FIGO is imperfect with one-third of low-risk patients developing disease resistance to first-line single-agent chemotherapy. We aimed to generate simplified models that improve upon FIGO. Logistic regression (LR) and multilayer perceptron (MLP) modelling (n = 4191) generated six models (M1-6). M1, all eight FIGO variables (scored data); M2, all eight FIGO variables (scored and raw data); M3, nonimaging variables (scored data); M4, nonimaging variables (scored and raw data); M5, imaging variables (scored data); and M6, pretreatment hCG (raw data) + imaging variables (scored data). Performance was compared to FIGO using true and false positive rates, positive and negative predictive values, diagnostic odds ratio, receiver operating characteristic (ROC) curves, Bland-Altman calibration plots, decision curve analysis and contingency tables. M1-6 were calibrated and outperformed FIGO on true positive rate and positive predictive value. Using LR and MLP, M1, M2 and M4 generated small improvements to the ROC curve and decision curve analysis. M3, M5 and M6 matched FIGO or performed less well. Compared to FIGO, most (excluding LR M4 and MLP M5) had significant discordance in patient classification (McNemar's test P < .05); 55-112 undertreated, 46-206 overtreated. Statistical modelling yielded only small gains over FIGO performance, arising through recategorisation of treatment-resistant patients, with a significant proportion of under/overtreatment as the available data have been used a priori to allocate primary chemotherapy. Streamlining FIGO should now be the focus.

Investigating the Impact of Ultra-Radical Surgery on Survival in Advanced Ovarian Cancer Using Population-Based Data in a Multicentre UK Study.

We investigated URS and impact on survival in whole patient cohorts with AOC treated within gynaecological cancer centres that participated in the previously presented SOCQER 2 study. National cancer registry datasets were used to identify FIGO Stage 3,4 and unknown stage patients from 11 cancer centres that had previously participated in the SOCQER2 study. Patient outcomes' association with surgical ethos were evaluated using logistic regression and Cox proportional hazards. Centres were classified into three groups based on their surgical complexity scores (SCS); those practicing mainly low complexity, (5/11 centres with >70% low SCS procedures, 759 patients), mainly intermediate (3/11, 35−50% low SCS, 356 patients), or mainly high complexity surgery (3/11, >35% high SCS, 356 patients). Surgery rates were 43.2% vs. 58.4% vs. 60.9%. across mainly low, intermediate and high SCS centres, respectively, p < 0.001. Combined surgery and chemotherapy rates were 39.2% vs. 51.8% vs. 38.3% p < 0.000 across mainly low, intermediate and high complexity groups, respectively. Median survival was 23.1 (95% CI 19.0 to 27.2) vs. 22.0 (95% CI 17.6 to 26.3) vs. 17.9 months (95% CI 15.7 to 20.1), p = 0.043 in mainly high SCS, intermediate, and low SCS centres, respectively. In an age and deprivation adjusted model, compared to patients in the high SCS centres, patients in the low SCS group had an HR of 1.21 (95% CI 1.03 to 1.40) for death. Mainly high/intermediate SCS centres have significantly higher surgery rates and better survival at a population level. Centres that practice mainly low complexity surgery should change practice. This study provides support for the utilization of URS for patients with advanced OC.

Increased detection of high grade CIN, when using electrical impedance spectroscopy as an adjunct to routine colposcopy, is maintained when used across international boundaries: Prospective data from nine European countries.

OBJECTIVE: To evaluate the performance of EIS (ZedScan) with colposcopy in the detection of high grade CIN (HG-CIN) in different health care settings. METHOD: Pooled analysis of data from 26 colposcopy centres in 9 countries. All women underwent colposcopy and ZedScan examination. Data was recorded prospectively via a proforma. Indications for referral to colposcopy were according to national guidelines. Pathology was reported according to national guidelines. RESULTS: 5257 women were examined by 82 colposcopists, median 93 women per centre (range 41 - 2684), 3 users per centre (range 1-8). Referral indications were; 19.3% high grade cytology, 50.4% low grade, 30.3% clinical or HPV positive / cytology negative. The prevalence of HG-CIN was 26.5%; 79.1% in high grade referrals, 16.7% low grade, 9.4% clinical or HPV positive / cytology negative. The use of ZedScan detected an extra 269 cases of high grade CIN (24% increase) (7.5% increase for high grade referrals, 57.9% for low grade and 52% for clinical or HPV positive/cytology negative). Based upon colposcopic impression (CI), the sensitivity of colposcopy for CIN2 + was 74.1% compared with 91.6% for colposcopy with ZedScan (Chi2 p < 0.0001). The PPV for a ZedScan directed biopsy varied according to referral cytology and colposcopic impression (19.5% to 85.7%). 489 women underwent treatment at first visit, when ZedScan suggested treatment, 95.1% had HG-CIN/HG-CGIN or cervical cancer. The pooled results for the whole 26 centres were consistent with the results obtained for the largest centre (Sheffield) alone and also with the results with this largest centre excluded. CONCLUSIONS: The addition of EIS (ZedScan) increases detection of HG-CIN with the PPV for a ZedScan directed biopsy consistent with the published literature. Results were similar in multiple healthcare settings. With more women being referred to colposcopy at low risk of HG-CIN, due to HPV vaccination and primary HPV screening, this study confirms the value of a real time adjunctive technology.

Are we managing our patients correctly following treatment for cervical glandular intraepithelial neoplasia? A review of practice at the Jessop Wing Colposcopy Unit.

OBJECTIVE: Women diagnosed with cervical glandular intraepithelial neoplasia (CGIN) remain at risk of further pre-malignant and malignant disease and require rigorous post-treatment follow-up. We assess the effectiveness and safety of community cervical sampling follow-up in women treated for CGIN. METHODS: A retrospective study was conducted of women diagnosed with CGIN between April 1, 2013, and March 31, 2019, at Jessop Wing Colposcopy Unit, Sheffield, UK. RESULTS: Of 140 women diagnosed with CGIN, 76 had co-existing cervical intraepithelial neoplasia (CIN). Cytologists were significantly more likely to report glandular neoplasia in the absence of co-existing CIN, and high-grade dyskaryosis in its presence (Ps < 0.0001). Co-existing CIN was significantly more likely to be present with high or low-grade compared to normal colposcopy findings (P < 0.0001). The 6-month test of cure (TOC) was attended by 67% of women (84% within 12 months), and the 18-month post-treatment sampling by 52.5% of women (70% within 24 months). Colposcopy recalled 96% of women correctly for the 18-month sampling, but 20% of women undertaking primary care samples were incorrectly recalled at 3 years instead. CONCLUSIONS: When CGIN is diagnosed, two dates for recall should be provided at 6 and 18 months post-treatment to the Cervical Screening Administration Service and the centralised screening laboratory ensuring the 18-month post-treatment sample is correctly appointed, preventing women with HPV-negative TOC samples being returned to 3-year recall. Follow-up of CGIN should be closely audited by the centralised laboratories ensuring women with CGIN are not put at additional risk.

Computed tomography chest imaging offers no advantage over chest X-ray in the initial assessment of gestational trophoblastic neoplasia.

BACKGROUND: The International Federation of Gynaecology and Obstetrics (FIGO) score identifies gestational trophoblastic neoplasia (GTN) patients as low- or high-risk of single-agent chemotherapy resistance (SACR). Computed tomography (CT) has greater sensitivity than chest X-ray (CXR) in detecting pulmonary metastases, but effects upon outcomes remain unclear. METHODS: Five hundred and eighty-nine patients underwent both CXR and CT during GTN assessment. Treatment decisions were CXR based. The number of metastases, risk scores, and risk category using CXR versus CT were compared. CT-derived chest assessment was evaluated as impact upon treatment decision compared to patient outcome, incidence of SACR, time-to-normal human chorionic gonadotrophin hormone (TNhCG), and primary chemotherapy resistance (PCR). RESULTS: Metastasis detection (p < 0.0001) and FIGO score (p = 0.001) were higher using CT versus CXR. CT would have increased FIGO score in 188 (31.9%), with 43 re-classified from low- to high-risk, of whom 23 (53.5%) received curative single-agent chemotherapy. SACR was higher when score (p = 0.044) or risk group (p < 0.0001) changed. Metastases on CXR (p = 0.019) but not CT (p = 0.088) lengthened TNhCG. Logistic regression analysis found no difference between CXR (area under the curve (AUC) = 0.63) versus CT (AUC = 0.64) in predicting PCR. CONCLUSIONS: CT chest would improve the prediction of SACR, but does not influence overall treatment outcome, TNhCG, or prediction of PCR. Lower radiation doses and cost mean ongoing CXR-based assessment is recommended.

M-EA (methotrexate, etoposide, dactinomycin) and EMA-CO (methotrexate, etoposide, dactinomycin / cyclophosphamide, vincristine) regimens as first-line treatment of high-risk gestational trophoblastic neoplasia.

High-risk gestational trophoblastic neoplasia (GTN) is highly chemosensitive with an excellent prognosis with treatment. Historically in the United Kingdom, the high-risk regimens used have been M-EA (methotrexate, etoposide, dactinomycin) (Sheffield) and EMA-CO (methotrexate, etoposide, dactinomycin / cyclophosphamide, vincristine) (Charing Cross, London) with prior published data suggesting no difference in survival between these. Our Sheffield treatment policy changed in 2014, switching from M-EA to EMA-CO, aiming to reduce time in hospital, and harmonise UK practice. We aimed to report the toxicities, response rates and survival outcomes for 79 patients with high-risk GTN treated in the first-line setting with either M-EA (n = 59) or EMA-CO (n = 20) from 1998 to 2018. Median duration of treatment was similar (M-EA, 17.3 weeks (IQR 13.9-22.6) and 17.6 weeks (IQR 13.4-20.7) with EMA-CO. For M-EA, overall human chorionic gonadotrophin (hCG) complete response (CR) rate was 84.7% (n = 50/59). Two patients died of drug-resistant disease after several lines of multiagent chemotherapy; overall survival is 96.6% (median follow-up 10.4 years). For EMA-CO, overall hCG CR rate was 70%, overall survival is 100% (median follow-up 4 years). In our experience, patients treated with EMA-CO experienced an apparent increased incidence of neutropenia, non-neutropenic Grade 3-4 infection, peripheral neuropathy and more treatment delays and nights in hospital. Granulocyte-colony stimulating factor, after both EMA and CO arms, titrated to baseline neutrophil count improved the toxicity profile. Both treatment regimens are associated with excellent prognosis; selection of regimen may be further guided by individual patients' personal, social and family circumstances. There is further rationale to explore whether these regimens can be refined, such as 2-weekly EMA, to optimise patient experience and reduce toxicity while maintaining efficacy.

The diagnostic accuracy of colposcopy - A review of research methodology and impact on the outcomes of quality assurance.

OBJECTIVE: To review the published diagnostic accuracy figures for the performance of colposcopy and to assess how the various forms of bias might explain the very wide range of reported values and the impact they have on quality assurance of cervical screening. METHODS: Publications were only selected where they contained sufficient raw data to enable diagnostic accuracy statistics to be calculated for the detection of cervical intraepithelial neoplasia grade 2+ (CIN2+), as determined by punch biopsy. In addition, both the colposcopic impression at the time of examination and the disease threshold used to determine the need for biopsy must have been reported. RESULTS: Large differences in diagnostic accuracy figures were found when the output of colposcopy was defined either, on the basis that the colposcopist thought there was CIN2+ present or, that the colposcopist considered there to be some disease present and so took a biopsy to confirm this. Weighted mean sensitivity was 68.5% (95% CI 59.9-77.1) for the first method but 95.7% (95% CI 93.4-98.0) for the second method. Weighted mean specificity was 75.9% (95% CI 69.3-82.5) for the first method but 34.2% (95% CI 27.0-41.4) for the second method. Weighted mean PPV was 68.9% (95% CI 64.2-73.6) for the first method but 54.3% (95% CI 46.5-62.1) for the second method. CONCLUSION: The main reason for the wide range of published diagnostic accuracy figures, arises from the use of two different methods of assessing the output of colposcopy. Colposcopic Impression is appropriate when assessing the performance of a colposcopist at the time of examination, but the taking of a biopsy to confirm that Disease is Present should be used when assessing patient management. Accurate assessment of both outcomes is fundamental to any quality assurance programme.

Systematic review of health-related quality of life and patient-reported outcome measures in gestational trophoblastic disease: a parallel synthesis approach.

Gestational trophoblastic disease is a rare complication of pregnancy that can develop into cancer. Medical outcomes of gestational trophoblastic disease are well researched, but the effect of the disease on health-related quality of life (HRQOL) requires attention if care is to be improved. This systematic review was designed to establish the effect of gestational trophoblastic disease and its treatment on HRQOL and to identify the appropriateness of HRQOL measures. Quantitative studies found HRQOL in long-term survivors of gestational trophoblastic disease to be at or above population norms. The disease had a negative effect on HRQOL for patients who experienced physical, psychological, and social sequelae related to the condition. Clinically significant levels of anxiety, depression, sexual dysfunction, and fertility-related distress were found in these patients. The results should be treated with caution because the evidence base was limited to small heterogeneous samples, data were retrospective, and a range of measures was used. Within qualitative studies on HRQOL for survivors of gestational trophoblastic disease, new conditions emerged, including nerve damage, fatigue, amenorrhoea, and grief. These areas are not captured in existing patient-reported outcome measures, and the content might not be valid for this population. Further qualitative research might lead to the development of a specific patient-reported outcome measure for gestational trophoblastic disease, providing reliable, meaningful, and valid assessments, and allowing longitudinal data to be obtained.

Conservative management of CIN2: National Audit of British Society for Colposcopy and Cervical Pathology members' opinion.

There is no doubt that organised cervical screening programmes have significantly reduced the rates of cervical cancer by detection and treatment of high-grade cervical intraepithelial neoplasia (CIN2, CIN3). National UK guidelines do not differentiate between CIN2 and CIN3 as separate entities and recommend treatment for both, although a degree of uncertainty exists regarding the natural history of CIN2. This national survey of British Society for Colposcopy and Cervical Pathology members aimed to assess attitudes towards conservative management (CM) of CIN2 in the UK and identify potential selection criteria. In total, 511 members responded (response rate 32%); 55.6% offered CM for selective cases; 12.4% for all cases; 16.4% had formal guidelines. Most agreed age group was >40yrs (83%), HPV 16/18 positive (51.4%), smoking (60%), immuno-compromise (74.2%), and large lesion size (80.8%) were relative contraindications for CM. 75.9% favoured six-monthly monitoring, with 80.2% preferring excisional treatment for persistent high-grade disease. Many UK colposcopists manage CIN2 conservatively without formal guidelines. Potential selection criteria should be investigated by a multicentre study. Impact statement Although anecdotally some colposcopists manage many women with CIN2 conservatively, this National Audit of British Society for Colposcopy and Cytopathology members, we believe, is the first time this has been formally recorded. The survey assesses current attitudes towards conservative management (CM) of CIN2 and seeks to identify potential selection criteria that could be used to identify suitable women. It received over 500 responses and significantly, identified many colposcopists recommending CM of CIN2 for patients despite the lack of any formal guidance regarding this approach. The greater majority of respondents were keen to consider participating in a multicentre trial on CM of CIN2 targeting the UK screening population (25-64 years). The paper has international relevance as ACOG and ASCCP have recently changed their guidance for the management of CIN2 in younger women and now recommend CM with monitoring rather than first line ablative or excisional treatment due to concerns regarding overtreatment, especially in women who have not yet completed their family.

Development and Psychometric Testing of an Electronic Patient-Reported Outcome Tool for Vulval Disorders (ePAQ-Vulva).

OBJECTIVE: Development of an electronic patient-reported outcome measure (PROM) specifically designed for vulval disorders. Psychometric testing of the components of the questionnaire, which assess vulval symptoms, sexual function, and quality of life (QoL). MATERIALS AND METHOD: Development and programming of the instrument (ePAQ-Vulva) was informed by national guidelines for the assessment of vulval disorders, an expert panel, and a survey of 61 vulval clinic patients. The PROM assesses frequency and impact of vulval symptoms, sexual function, and QoL. It also records conditions and behaviors related to vulval disorders and patient concerns/goals.Scale generation and psychometric testing were undertaken for the vulval symptoms, sexual function, and QoL components of the PROM with 91 participants; descriptive statistics, factor analysis and internal reliability of identified domains, and agreement between free-text and multiple-choice items to assess convergent validity and interrater reliability of picture items were assessed. RESULTS: Descriptive statistics showed high floor effects for seven questionnaire items. Factor analysis identified 5 principal components. These were reviewed and amended to provide a putative domain structure of 6 domains. Internal reliability of these domains was assessed using Cronbach α, producing values of 0.715 to 0.917. Interrater reliability of the picture items produced a κ statistic of 0.405. Spearman rank showed moderate correlation between multiple-choice answers and free-text concerns (r = 0.364-0.462) in 3 of the 6 domains (pain, sex, and dyspareunia). CONCLUSIONS: ePAQ-Vulva offers the first patient-reported outcome tool, specifically designed for vulval disorders. The instrument requires further validation and testing, including evaluation of the stability, responsiveness, and reliability.

Influence of high risk HPV genotype on colposcopic performance: A large prospective study demonstrates improved detection of disease with ZedScan I, particularly in non-HPV 16 patients.

OBJECTIVE: To assess the influence of high-risk Human Papilloma Virus (hrHPV) genotyping on the detection of high-grade disease (CIN2+) using colposcopic impression both with and without electrical impedance spectroscopy (ZedScan I) as an adjunct. STUDY DESIGN: A prospective cohort of women with a known hrHPV genotype referred to a single colposcopy service. RESULTS: 839 women underwent colposcopy and ZedScan I examination. 613 women were referred with abnormal cytology; 411 (67%) with low-grade dyskaryosis (67%) and 202 (33%) with high-grade dyskaryosis. 187 were referred with persistent hrHPV but negative cytology. 35 were attended for follow up and 4 for a clinical indication. 159 (19%) women were positive for HPV16 only; 54 (6%) with HPV18 only, 443 (53%) women were positive for hrHPV other types (HPV O). 183 (22%) were positive for multiple hrHPV genotypes. CIN2+ was present in 170 (84.2%) of high-grade and 69 (16.7%) of low-grade cytology referrals. Colposcopy was better at detecting HPV16 associated CIN2+ than that associated with HPV18 or HPV O (86.9% vs 79.7%, p=0.0191). ZedScan I increased the detection of CIN2+ from 85.6% to 96% irrespective of hrHPV genotype status (p<0.0001). CONCLUSION: The use of an electrical impedance spectroscopic device (ZedScan I) increases detection of CIN2+ irrespective of hrHPV genotype.

Second Curettage for Low-Risk Nonmetastatic Gestational Trophoblastic Neoplasia.

OBJECTIVE: To evaluate the efficacy and safety of second uterine curettage in lieu of chemotherapy for patients with low-risk, nonmetastatic gestational trophoblastic neoplasia (GTN) and to evaluate whether response to second curettage is independent of patient age, World Health Organization (WHO) risk score, registration human chorionic gonadotropin (hCG) level, lesion size, and depth of myometrial invasion measured on ultrasound examination. METHODS: This was a cooperative group multicenter prospective phase II study. Prestudy testing included quantitative hCG level, pelvic ultrasonography, and chest radiography. Patients were categorized according to WHO risk scoring criteria (low risk with a score of 0-6). RESULTS: Sixty-four women with newly diagnosed low-risk, nonmetastatic GTN were enrolled. Four patients were excluded. Twenty-four patients (40%) (lower 95% confidence limit 27.6%) were cured after second curettage. An additional two patients (3%) achieved a complete response but did not complete follow-up. Overall, 26 of 60 patients were able to avoid chemotherapy. Surgical failure was observed in 34 women (59%) and was more common in women 19 years old or younger or 40 years old or older. One case of grade 1 uterine perforation was successfully managed by observation. Four grade 1 and one grade 3 uterine hemorrhages were reported. New metastatic disease (lung) was identified in one of these women after second curettage. In three patients (surgical failures), the second curettage pathology was placental site trophoblastic tumor, and it was placental nodule in one additional patient. CONCLUSION: Second uterine curettage as initial treatment for low-risk, nonmetastatic GTN cures 40% of patients without significant morbidity. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov/, NCT00521118.

Can We Be Less Radical with Surgery for Early Cervical Cancer?

Although a rare cancer in the developed world due to the success of cervical screening programmes, cervical cancer remains one of the most common cancers diagnosed in women under the age of 35 years old. Radical hysterectomy and more recently radical trachelectomy have been highly effective in curing the majority of women with early stage disease. Many, however, are left with long-term 'survivorship' issues including bowel, bladder and sexual dysfunction. In view of these chronic co-morbidities, many clinicians now consider whether a less radical approach to surgery may be an option for some women. This review focuses on the current evidence for the safety of conservative surgery for early stage cervical cancer with regard to cure rates in comparison to standard management, as well as any improvement in short and long-term morbidity associated with a more conservative approach.

The impact of surgery for vulval cancer upon health-related quality of life and pelvic floor outcomes during the first year of treatment: a longitudinal, mixed methods study.

OBJECTIVE: To measure the long-term impact of surgical treatment for vulval cancer upon health-related quality of life and pelvic floor outcomes during the first year of therapy. METHODS: Prospective, longitudinal, mixed-methods study. Twenty-three women aged >18 years with a new diagnosis of vulval cancer were recruited. The EORTC QLQ C30, SF-36 and an electronic pelvic floor assessment questionnaire (ePAQ-PF) were administered at baseline (pre-treatment) and 3, 6, 9 and 12 months post-treatment. Mixed effects repeated measures models (all adjusted for age and BMI) were used to investigate changes over time and differences between cancer stage. Qualitative interviews were carried out with 11 of the women and analysed using a thematic approach. RESULTS: Mean age was 59.9 years (SD = 15.3; range = 23.8-86.6 yrs). Mean BMI was 30.0 (SD = 4.5; range = 24.4-38.2). Sixteen women had early (Stage 1 to 2B), and seven women had advanced stage disease (Stage 3 to 4B). Questionnaire scores revealed that physical and social functioning, fatigue, pain and general sex life were significantly worse at 12 months than pre-treatment (p = < 0.05). Qualitative analysis revealed multiple treatment side effects which were perceived as severe and enduring. Women with advanced vulval cancer had significantly worse SF-36 mental health scores at 12 months compared to women with early stage disease (p = 0.037). CONCLUSIONS: Surgery for vulval cancer has long-term implications which can be persistent 12 months post-treatment. High rates of morbidity relating to lymphoedema and sexual function re-enforce the need for specialist clinics to support women who suffer these complications. © 2015 The Authors. Psycho-Oncology published by John Wiley & Sons Ltd.

Management and Outcomes of Patients with Stage I and IlIl Low-Risk Gestational Trophoblastic Neoplasia Treated in Sheffield, UK, from 1997-2006.

OBJECTIVE: To review the outcome of patients treated for low-risk gestational trophoblastic neoplasia (GTN) over a 10-year period with the particular aim of assessing response to treatment in Stages I and III disease. Approximately 90% of women requiring treatment for GTN have low-risk disease. Methotrexate is the treat- ment of choice in the UK and achieves complete response rates of 50% and 90%. STUDY DESIGN: A retro- spective review of management and outcomes of patients treated for low-risk GTN at the Trophoblastic Disease Centre, Sheffield, UK, from 1997 to 2006. RESULTS: Overall 280 patients were treated for low- risk GTN during this time; 8.6% had stage III disease. Single-agent methotrexate was used as first-line therapy in 99% of cases, with a remission rate of 56%. There was no significant difference (p=0.67) in the complete response rate after first-line methotrexate between those with stage I and those with stage III disease. CONCLUSION: The overall cure rate for women with low-risk GTN was high (99.6%), and the complete response rate after first-line management was not sig- nificantly different between stages I and III disease.

Use of electrical impedance spectroscopy to detect malignant and potentially malignant oral lesions.

The electrical properties of tissues depend on their architecture and cellular composition. We have previously shown that changes in electrical impedance can be used to differentiate between different degrees of cervical dysplasia and cancer of the cervix. In this proof-of-concept study, we aimed to determine whether electrical impedance spectroscopy (EIS) could distinguish between normal oral mucosa; benign, potentially malignant lesions (PML); and oral cancer. EIS data were collected from oral cancer (n=10), PML (n=27), and benign (n=10) lesions. EIS from lesions was compared with the EIS reading from the normal mucosa on the contralateral side of the mouth or with reference spectra from mucosal sites of control subjects (n=51). Healthy controls displayed significant differences in the EIS obtained from different oral sites. In addition, there were significant differences in the EIS of cancer and high-risk PML versus low-risk PML and controls. There was no significant difference between benign lesions and normal controls. Study subjects also deemed the EIS procedure considerably less painful and more convenient than the scalpel biopsy procedure. EIS shows promise at distinguishing among malignant, PML, and normal oral mucosa and has the potential to be developed into a clinical diagnostic tool.

Ectopic gestational trophoblastic disease: a case series review.

OBJECTIVE: To highlight the clinical presentation, treatment, histological review and outcome of patients referred to the Sheffield Centre with possible ectopic gestational trophoblastic disease (GTD). STUDY DESIGN: A retrospective case note review of patients with possible ectopic GTD referred to the Sheffield Centre between 1997 and 2010 was performed. RESULTS: During the 13 years of this retrospective study 6,708 patients were registered at the Centre with GTD, of whom 42 had possible ectopic GTD. Most patients presented with abdominal pain and/or vaginal bleeding (67%). Ectopic pregnancy was diagnosed by ultrasound scan in 19%. Laparoscopic removal of ectopic pregnancy was carried out in 50% of cases; the rest underwent laparotomy for removal of ectopic conceptus. Histological review of slides was performed in 19 cases for whom there was clinical concern. This resulted in 12 confirmed cases of ectopic GTD: 4 choriocarcinomas, 5 partial moles and 3 complete moles. No evidence of metastasis was recorded in any of the cases. Three patients diagnosed with ectopic choriocarcinoma needed chemotherapy. Two responded to methotrexate and 1 needed second-line chemotherapy. All patients are alive and free of disease. CONCLUSION: Ectopic GTD is rare and still overdiagnosed. Presentation is the same as for conventional ectopic pregnancy. Central review of the histology should be undertaken, especially in cases where there is clinical, hCG level or histopathologic concern. Conventional chemotherapy for gestational trophoblastic neoplasia is effective. Prognosis remains excellent.