Baseline knowledge on risk factors, symptoms and intended behavior of women and men towards screening and treatment of cervical cancer in rural Uganda: a cross-sectional study.

BACKGROUND: Knowledge of risk factors and symptoms of cervical cancer has been found to promote uptake of screening of cervical cancer. Most interventions targeted women without much involvement of men (husbands/decision makers) who are often decision makers in many low- and middle-income countries. This study aimed at assessing baseline knowledge and intended behavior of both women and men to enable design specific targeted messages to increase uptake of cervical cancer screening and promote early detection of women with symptoms. METHODS: This cross-sectional study was conducted in two districts in Western Uganda using the modified African Women Awareness of CANcer (AWACAN) questionnaire. Women aged 30-49 years and their husbands/decision makers were interviewed. Knowledge on risk factors and symptoms, intended behavior and barriers towards participation in cervical cancer screening and treatment were assessed. Descriptive and logistic regression analyses were done to establish the association between knowledge levels and other factors comparing women to men. RESULTS: A total of 724 women and 692 men were enrolled. Of these, 71.0% women and 67.2% men had ever heard of cervical cancer and 8.8% women had ever been screened. Knowledge of risk factors and symptoms of cervical cancer was high and similar for both women and men. Lack of decision making by women was associated with low knowledge of risk factors (X2 = 14.542; p = 0.01), low education (X2 = 36.05, p < 0.01) and older age (X2 = 17.33, p < 0.01). Men had better help seeking behavior than women (X2 = 64.96, p < 0.01, OR = 0.39, 95% CI: 0.31-0.50) and were more confident and skilled in recognising a sign or symptom of cervical cancer (X2 = 27.28, p < 0.01, OR = 0.52, CI (0.40-0.67). CONCLUSION: The baseline knowledge for cervical cancer was high in majority of participants and similar in both women and men. Their intended behavior towards screening was also positive but screening uptake was very low. This study suggests developing messages on multiple interventions to promote screening behavior in addition to education, consisting of male involvement, women empowerment and making services available, accessible and women friendly.

Diagnostic accuracy of MRI, CT, and [18F]FDG-PET-CT in detecting lymph node metastases in clinically early-stage cervical cancer - a nationwide Dutch cohort study.

OBJECTIVES: Imaging is increasingly used to assess lymph node involvement in clinically early-stage cervical cancer. This retrospective study aimed to evaluate the diagnostic accuracy of MRI, CT, and [18F]FDG-PET-CT. METHODS: Women with International Federation of Gynaecology and Obstetrics (FIGO) 2009 stage IA2-IIA cervical cancer and pretreatment imaging between 2009 and 2017 were selected from the Netherlands Cancer Registry. Patient-based and region-based (i.e. pelvic and common iliac) nodal status was extracted from radiology reports. Pathology results were considered the reference standard for calculating accuracy indices. Multiple imputation was used for missing pathology to limit verification bias risk. RESULTS: Nodal assessment was performed in 1676 patients with MRI, 926 with CT, and 379 with [18F]FDG-PET-CT, with suspicious nodes detected in 17%, 16%, and 48%, respectively. [18F]FDG-PET-CT was used to confirm MRI/CT results in 95% of patients. Pathology results were imputed for 30% of patients. [18F]FDG-PET-CT outperformed MRI and CT in detecting patient-based nodal metastases with sensitivities of 80%, 48%, and 40%, and AUCs of 0.814, 0.706, and 0.667, respectively, but not in specificity: 79%, 92%, and 92%. Region-based analyses showed similar indices in the pelvic region, but worse performance in the common iliac region with AUCs of 0.575, 0.554, and 0.517, respectively. CONCLUSIONS: [18F]FDG-PET-CT outperformed MRI and CT in detecting nodal metastases, which may be related to its use as a verification modality. However, MRI and CT had the highest specificity. As MRI is generally performed routinely to assess local and regional spread of cervical cancer, [18F]FDG-PET-CT can be used to confirm suspicious nodes. CRITICAL RELEVANCE STATEMENT: Accurate assessment of the nodal status in clinically early-stage cervical cancer is essential for tumour staging, treatment decision making and prognosis. KEY POINTS: • The accuracy of MRI, CT or [18F]FDG-PET-CT for nodal staging in early cervical cancer is a subject of discussion. • Overall, [18F]FDG-PET-CT outperformed MRI, followed by CT, when used as a verification modality. • Staging with MRI and the addition of [18F]FDG-PET-CT to verify high-risk cases seems to be a good approach.

Optimising follow-up strategy based on cytology and human papillomavirus after fertility-sparing surgery for early stage cervical cancer: a nationwide, population-based, retrospective cohort study.

BACKGROUND: The optimal follow-up strategy to detect recurrence after fertility-sparing surgery for early stage cervical cancer is unknown. Tailored surveillance based on individual risks could contribute to improved efficiency and, subsequently, reduce costs in health care. The aim of this study was to establish the predictive value of cervical cytology and high-risk human papillomavirus (HPV) testing to detect recurrent cervical intraepithelial neoplasia grade 2 or worse (CIN2+; including recurrent cervical cancer) after fertility-sparing surgery. METHODS: In this nationwide, population-based, retrospective cohort study, we used data from the Netherlands Cancer Registry and the Dutch Nationwide Pathology Databank. All patients aged 18-40 years with cervical cancer of any histology who received fertility-sparing surgery (ie, large loop excision of the transformation zone, conisation, or trachelectomy) between Jan 1, 2000, and Dec 31, 2020, were included. Pathology data from diagnosis, treatment, and during follow-up were analysed. The primary and secondary outcomes were the cumulative incidence of recurrent CIN2+ and recurrence-free survival, overall and stratified by results for cytology and high-risk HPV. FINDINGS: 1548 patients were identified, of whom 1462 met the inclusion criteria. Of these included patients, 19 568 pathology reports were available. The median age at diagnosis was 31 years (IQR 30-35). After a median follow-up of 6·1 years (IQR 3·3-10·8), recurrent CIN2+ was diagnosed in 128 patients (cumulative incidence 15·0%, 95% CI 11·5-18·2), including 52 patients (cumulative incidence 5·4%, 95% CI 3·7-7·0) with recurrent cervical cancer. The overall 10-year recurrence-free survival for CIN2+ was 89·3% (95% CI 87·4-91·3). By cytology at first follow-up visit within 12 months after fertility-sparing surgery, 10-year recurrence-free survival for CIN2+ was 92·1% (90·2-94·1) in patients with normal cytology, 84·6% (77·4-92·3) in those with low-grade cytology, and 43·1% (26·4-70·2) in those with high-grade cytology. By high-risk HPV status at first follow-up visit within 12 months after surgery, 10-year recurrence-free survival for CIN2+ was 91·1% (85·3-97·3) in patients who were negative for high-risk HPV and 73·6% (58·4-92·8) in those who were positive for high-risk HPV. Cumulative incidence of recurrent CIN2+ within 6 months after any follow-up visit (6-24 months) in patients negative for high-risk HPV with normal or low-grade cytology was 0·0-0·7% and with high-grade cytology was 0·0-33·3%. Cumulative incidence of recurrence in patients positive for high-risk HPV with normal or low-grade cytology were 0·0-15·4% and with high-grade cytology were 50·0-100·0%. None of the patients who were negative for high-risk HPV without high-grade cytology, at 6 months and 12 months, developed recurrence. INTERPRETATION: Patients who are negative for high-risk HPV with normal or low-grade cytology at 6-24 months after fertility-sparing surgery, could be offered a prolonged follow-up interval of 6 months. This group comprises 80% of all patients receiving fertility-sparing surgery. An interval of 12 months seems to be safe after two consecutive negative tests for high-risk HPV with an absence of high-grade cytology, which accounts for nearly 75% of all patients who receive fertility-sparing surgery. FUNDING: KWF Dutch Cancer Society.

Artificial intelligence and visual inspection in cervical cancer screening.

INTRODUCTION: Visual inspection with acetic acid is limited by subjectivity and a lack of skilled human resource. A decision support system based on artificial intelligence could address these limitations. We conducted a diagnostic study to assess the diagnostic performance using visual inspection with acetic acid under magnification of healthcare workers, experts, and an artificial intelligence algorithm. METHODS: A total of 22 healthcare workers, 9 gynecologists/experts in visual inspection with acetic acid, and the algorithm assessed a set of 83 images from existing datasets with expert consensus as the reference. Their diagnostic performance was determined by analyzing sensitivity, specificity, and area under the curve, and intra- and inter-observer agreement was measured using Fleiss kappa values. RESULTS: Sensitivity, specificity, and area under the curve were, respectively, 80.4%, 80.5%, and 0.80 (95% CI 0.70 to 0.90) for the healthcare workers, 81.6%, 93.5%, and 0.93 (95% CI 0.87 to 1.00) for the experts, and 80.0%, 83.3%, and 0.84 (95% CI 0.75 to 0.93) for the algorithm. Kappa values for the healthcare workers, experts, and algorithm were 0.45, 0.68, and 0.63, respectively. CONCLUSION: This study enabled simultaneous assessment and demonstrated that expert consensus can be an alternative to histopathology to establish a reference standard for further training of healthcare workers and the artificial intelligence algorithm to improve diagnostic accuracy.

Sentinel lymph node procedure in early-stage vulvar cancer: Correlation of lymphoscintigraphy with surgical outcome and groin recurrence.

INTRODUCTION: In early-stage vulvar squamous cell carcinoma (VSCC) a sentinel lymph node (SLN) procedure is regarded successful if at least one SLN is removed with minimal residual radioactivity. An inguinofemoral lymphadenectomy is considered if not all SLNs visualized on lymphoscintigraphy can be found, with subsequent increased morbidity. We correlated lymphoscintigraphy findings with surgical outcome and groin recurrence with focus on number of SLNs found. METHODS: This study concerns a retrospective cohort of 171 women treated for early-stage VSCC who underwent a SLN procedure between 2000 and 2020. The risk of groin recurrence was compared after either a successful or complete SLN procedure, i.e. removal of all SLNs that were visualized on lymphoscintigraphy. RESULTS: In 13 (7.6%) groins of 171 patients SLN visualization on lymphoscintigraphy failed. In 230 of the 246 (93.5%) groins in which a SLN was visualized, at least one SLN was found during surgery. In 224 of the 246 (91.1%) groins the SLN procedure was regarded either successful (n = 14) or complete (n = 210). An isolated groin recurrence was documented in 5 out of 192 (2.6%, 95%-CI; 0.34 to 4.9) SLN-negative groins after a median follow-up of 47.0 months. All recurrences were noted in the complete SLN group (5/180 groins). The difference with the successful SLN group (0/12 groins) was not significant. CONCLUSION: Risk of groin recurrence was 2.6% after SLN negative biopsy in early-stage VSCC. The risk appeared not increased if at least one SLN was found with minimal residual radioactivity, in case more SLNs were visualized on lymphoscintigraphy.

Involving men in cervical cancer prevention; a qualitative enquiry into male perspectives on screening and HPV vaccination in Mid-Western Uganda.

INTRODUCTION: Evidence-based preventive strategies for cervical cancer in low-resource setting have been developed, but implementation is challenged, and uptake remains low. Women and girls experience social and economic barriers to attend screening and human papillomavirus (HPV) vaccination programs. Male support has been proven successful in uptake of other reproductive healthcare services. This qualitative study with focus groups aimed to understand the perspectives of males on cervical cancer screening and HPV vaccination in Western-Uganda This knowledge could be integrated into awareness activities to increase the attendance of cervical cancer screening and HPV vaccination programs. MATERIALS AND METHODS: Focus group discussions were conducted with men aged 25 to 60 years, who were married and/or had daughters, in Kagadi district, Mid-Western Uganda. All interviews were transcribed verbatim and thematically analyzed using an inductive approach. RESULTS: Eleven focus group discussions were conducted with 67 men. Men were willing to support their wives for screening and their daughters for HPV vaccination. Misperceptions such as family planning and poor personal hygiene leading to cervical cancer, and misperception of the preventative aspect of screening and vaccination were common. Women with cervical cancer suffer from stigmatization and family problems due to loss of fertility, less marital sexual activity, domestic violence and decreased economic productivity. CONCLUSIONS: Ugandan men were willing to support cervical cancer prevention for their wives and daughters after being informed about cervical cancer. Limited knowledge among men about the risk factors and causes of cervical cancer, and about the preventative aspect of HPV vaccination and screening and their respective target groups, can limit uptake of both services. Screening and vaccination programs should actively involve men in creating awareness to increase uptake and acceptance of prevention.

Investigating feasibility of 2021 WHO protocol for cervical cancer screening in underscreened populations: PREvention and SCReening Innovation Project Toward Elimination of Cervical Cancer (PRESCRIP-TEC).

BACKGROUND: High-risk human papillomavirus (hrHPV) testing has been recommended by the World Health Organization as the primary screening test in cervical screening programs. The option of self-sampling for this screening method can potentially increase women's participation. Designing screening programs to implement this method among underscreened populations will require contextualized evidence. METHODS: PREvention and SCReening Innovation Project Toward Elimination of Cervical Cancer (PRESCRIP-TEC) will use a multi-method approach to investigate the feasibility of implementing a cervical cancer screening strategy with hrHPV self-testing as the primary screening test in Bangladesh, India, Slovak Republic and Uganda. The primary outcomes of study include uptake and coverage of the screening program and adherence to follow-up. These outcomes will be evaluated through a pre-post quasi-experimental study design. Secondary objectives of the study include the analysis of client-related factors and health system factors related to cervical cancer screening, a validation study of an artificial intelligence decision support system and an economic evaluation of the screening strategy. DISCUSSION: PRESCRIP-TEC aims to provide evidence regarding hrHPV self-testing and the World Health Organization's recommendations for cervical cancer screening in a variety of settings, targeting vulnerable groups. The main quantitative findings of the project related to the impact on uptake and coverage of screening will be complemented by qualitative analyses of various determinants of successful implementation of screening. The study will also provide decision-makers with insights into economic aspects of implementing hrHPV self-testing, as well as evaluate the feasibility of using artificial intelligence for task-shifting in visual inspection with acetic acid. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05234112 . Registered 10 February 2022.

Treatment of bulky lymph nodes in locally advanced cervical cancer: boosting versus debulking.

OBJECTIVE: Treatment strategies for bulky lymph nodes in patients with locally advanced cervical cancer scheduled for definitive chemoradiation include nodal boosting with radiotherapy, surgical debulking, or both. The aim of this retrospective cohort study was to compare survival and toxicity in patients receiving these treatments and to compare them with a group that received neither form of treatment. METHODS: Women diagnosed between January 2009 and January 2017 with International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IB2, IIA2-IVA cervical cancer with lymph nodes ≥1.5 cm without upper limit on pretreatment imaging and treated with definitive chemoradiation were selected from the Netherlands Cancer Registry. Patients were categorized by intention-to-treat strategy: boosting, debulking, or neither treatment, with subgroup analysis for patients receiving both treatments, that is, debulking with boosting. Overall and relapse-free survival outcomes were compared by Kaplan-Meier and Cox regression analyses and toxicity by logistic regression analysis. RESULTS: Of 190 patients, 101 (53%) received only nodal boosting, 31 (16%) debulking alone, 29 (15%) debulking combined with boosting, and 29 (15%) received neither treatment. The 5 year overall and relapse-free survival for the treatment groups were 58%, 45% and 45% (p=0.19), and 47%, 44% and 46% (p=0.87), respectively. Multivariable Cox regression analyses demonstrated no differences in overall and relapse-free survival. Combination of debulking with boosting was associated with decreased overall and relapse-free survival compared with debulking alone (HR 2.47, 95% CI 1.22 to 5.00; and HR 2.37, 95% CI 1.14 to 4.93). Nodal boosting was independently associated with a decreased toxicity risk compared with debulking strategy (OR 0.37, 95% CI 0.16 to 0.83). CONCLUSIONS: This study showed no survival benefit from either nodal boosting or debulking strategy in patients with suspicious bulky nodes. Nodal boosting might, however, be associated with less toxicity. Dual treatment with debulking and boosting showed a worse survival outcome because this group probably represents patients with poor prognostic factors.

SUCCOR cone study: conization before radical hysterectomy.

OBJECTIVE: To evaluate disease-free survival of cervical conization prior to radical hysterectomy in patients with stage IB1 cervical cancer (International Federation of Gynecology and Obstetrics (FIGO) 2009). METHODS: A multicenter retrospective observational cohort study was conducted including patients from the Surgery in Cervical Cancer Comparing Different Surgical Aproaches in Stage IB1 Cervical Cancer (SUCCOR) database with FIGO 2009 IB1 cervical carcinoma treated with radical hysterectomy between January 1, 2013, and December 31, 2014. We used propensity score matching to minimize the potential allocation biases arising from the retrospective design. Patients who underwent conization but were similar for other measured characteristics were matched 1:1 to patients from the non-cone group using a caliper width ≤0.2 standard deviations of the logit odds of the estimated propensity score. RESULTS: We obtained a weighted cohort of 374 patients (187 patients with prior conization and 187 non-conization patients). We found a 65% reduction in the risk of relapse for patients who had cervical conization prior to radical hysterectomy (hazard ratio (HR) 0.35, 95% confidence interval (CI) 0.16 to 0.75, p=0.007) and a 75% reduction in the risk of death for the same sample (HR 0.25, 95% CI 0.07 to 0.90, p=0.033). In addition, patients who underwent minimally invasive surgery without prior conization had a 5.63 times higher chance of relapse compared with those who had an open approach and previous conization (HR 5.63, 95% CI 1.64 to 19.3, p=0.006). Patients who underwent minimally invasive surgery with prior conization and those who underwent open surgery without prior conization showed no differences in relapse rates compared with those who underwent open surgery with prior cone biopsy (reference) (HR 1.94, 95% CI 0.49 to 7.76, p=0.349 and HR 2.94, 95% CI 0.80 to 10.86, p=0.106 respectively). CONCLUSIONS: In this retrospective study, patients undergoing cervical conization before radical hysterectomy had a significantly lower risk of relapse and death.

Radical hysterectomy in early cervical cancer in Europe: characteristics, outcomes and evaluation of ESGO quality indicators.

INTRODUCTION: Comprehensive updated information on cervical cancer surgical treatment in Europe is scarce. OBJECTIVE: To evaluate baseline characteristics of women with early cervical cancer and to analyze the outcomes of the ESGO quality indicators after radical hysterectomy in the SUCCOR database. METHODS: The SUCCOR database consisted of 1272 patients who underwent radical hysterectomy for stage IB1 cervical cancer (FIGO 2009) between January 2013 and December 2014. After exclusion criteria, the final sample included 1156 patients. This study first described the clinical, surgical, pathological, and follow-up variables of this population and then analyzed the outcomes (disease-free survival and overall survival) after radical hysterectomy. Surgical-related ESGO quality indicators were assessed and the accomplishment of the stated recommendations was verified. RESULTS: The mean age of the patients was 47.1 years (SD 10.8), with a mean body mass index of 25.4 kg/m2 (SD 4.9). A total of 423 (36.6%) patients had a previous cone biopsy. Tumor size (clinical examination) <2 cm was observed in 667 (57.7%) patients. The most frequent histology type was squamous carcinoma (794 (68.7%) patients), and positive lymph nodes were found in 143 (12.4%) patients. A total of 633 (54.8%) patients were operated by open abdominal surgery. Intra-operative complications occurred in 108 (9.3%) patients, and post-operative complications during the first month occurred in 249 (21.5%) patients, with bladder dysfunction as the most frequent event (119 (10.3%) patients). Clavien-Dindo grade III or higher complication occurred in 56 (4.8%) patients. A total of 510 (44.1%) patients received adjuvant therapy. After a median follow-up of 58 months (range 0-84), the 5-year disease-free survival was 88.3%, and the overall survival was 94.9%. In our population, 10 of the 11 surgical-related quality indicators currently recommended by ESGO were fully fulfilled 5 years before its implementation. CONCLUSIONS: In this European cohort, the rate of adjuvant therapy after radical hysterectomy is higher than for most similar patients reported in the literature. The majority of centers were already following the European recommendations even 5 years prior to the ESGO quality indicator implementations.

Palliative care needs and preferences of female patients and their caregivers in Ethiopia: A rapid program evaluation in Addis Ababa and Sidama zone.

INTRODUCTION: In Ethiopia there is an extensive unmet need for palliative care, while the burden of non-communicable diseases and cancer is increasing. This study aimed to explore palliative care needs and preferences of patients, their caregivers, and the perspective of stakeholders on service provision in palliative programs for women, mostly affected by cervical cancer and breast cancer. METHODS: A rapid program evaluation using a qualitative study approach was conducted in three home-based palliative care programs in Addis Ababa and Yirgalem town, Ethiopia. Female patients enrolled in the programs, and their primary caregivers were interviewed on palliative care needs, preferences and service provision. We explored the views of purposely selected stakeholders on the organization of palliative care and its challenges. Audio-taped data was transcribed verbatim and translated into English and an inductive thematic analysis was applied. Descriptive analyses were used to label physical signs and symptoms using palliative outcome scale score. RESULTS: A total of 77 interviews (34 patients, 12 primary caregivers, 15 voluntary caregivers, 16 stakeholders) were conducted. The main physical complaints were moderate to severe pain (70.6%), followed by anorexia (50.0%), insomnia, nausea and vomiting (41.2%). Social interaction and daily activities were hampered by the patients' condition. Both patients and caregivers reported that programs focus most on treatment of symptoms, with limited psychosocial, emotional, spiritual and economic support. Lack of organizational structures and policy directions limit the collaboration between stakeholders and the availability of holistic home-based palliative care services. CONCLUSIONS: Although female patients and caregivers appreciated the palliative care and support provided, the existing services did not cover all needs. Pain management and all other needed supports were lacking. Multi-sectorial collaboration with active involvement of community-based structures is needed to improve quality of care and access to holistic palliative care services.

Impact of Medical Doctors Global Health and Tropical Medicine on decision-making in caesarean section: a pre- and post-implementation study in a rural hospital in Malawi.

BACKGROUND: Medical doctors with postgraduate training in Global Health and Tropical Medicine (MDGHTM) from the Netherlands, a high-income country with a relatively low caesarean section rate, assist associate clinicians in low-income countries regarding decision-making during labour. Objective of this study was to assess impact of the presence of MDGHTMs in a rural Malawian hospital on caesarean section rate and indications. METHODS: This retrospective pre- and post-implementation study was conducted in a rural hospital in Malawi, where MDGHTMs were employed from April 2015. Indications for caesarean section were audited against national protocols and defined as supported or unsupported by these protocols. Caesarean section rates and numbers of unsupported indications for the years 2015 and 2016 per quarter for different staff cadres were assessed by linear regression. RESULTS: Six hundred forty-five women gave birth by caesarean section in the study period. The caesarean rate dropped from 20.1 to 12.8% (p < 0.05, R2 = 0.53, y = - 0.0086x + 0.2295). Overall 132 of 501 (26.3%) auditable indications were not supported by documentation in medical records. The proportion of unsupported indications dropped significantly over time from 47.0 to 4.4% (p < 0.01, R2 = 0.71, y = - 0.0481x + 0.4759). Stratified analysis for associate clinicians only (excluding caesarean sections performed by medical doctors) showed a similar decrease from 48.3 to 6.5% (p < 0.05, R2 = 0.55, y = - 0.0442x + 0.4805). CONCLUSIONS: Our results indicate that presence of MDGHTMs was accompanied by considerable decreases in caesarean section rate and proportion of unsupported indications for caesarean section in this facility. Their presence is likely to have influenced decision-making by associate clinicians.

Near-infrared fluorescence imaging compared to standard sentinel lymph node detection with blue dye in patients with vulvar cancer - a randomized controlled trial.

OBJECTIVE: The aim of this study was to assess the superiority of ICG-99mTc-nanocolloid for the intraoperative visual detection of sentinel lymph nodes (SLNs) in vulvar squamous cell carcinoma (VSCC) patients compared to standard SLN detection using 99mTc-nanocolloid with blue dye. METHODS: In this multicenter, randomized controlled trial, VSCC patients underwent either the standard SLN procedure or with the hybrid tracer ICG-99mTc-nanocolloid. The primary endpoint was the percentage of fluorescent SLNs compared to blue SLNs. Secondary endpoints were successful SLN procedures, surgical outcomes and postoperative complications. RESULTS: Forty-eight patients were randomized to the standard (n = 24) or fluorescence imaging group (n = 24) using ICG-99mTc-nanocolloid. The percentage of blue SLNs was 65.3% compared to 92.5% fluorescent SLNs (p < 0.001). A successful SLN procedure was obtained in 92.1% of the groins in the standard group and 97.2% of the groins in the fluorescence imaging group (p = 0.33). Groups did not differ in surgical outcome, although more short-term postoperative complications were documented in the standard group (p = 0.041). CONCLUSIONS: Intraoperative visual detection of SLNs in patients with VSCC using ICG-99mTc-nanocolloid was superior compared to 99mTc-nanocolloid and blue dye. The rate of successful SLN procedures between both groups was not significantly different. Fluorescence imaging has potential to be used routinely in the SLN procedure in VSCC patients to facilitate the search by direct visualization. CLINICAL TRIAL REGISTRATION: Netherlands Trial Register (Trial ID NL7443).

SUCCOR study: an international European cohort observational study comparing minimally invasive surgery versus open abdominal radical hysterectomy in patients with stage IB1 cervical cancer.

BACKGROUND: Minimally invasive surgery in cervical cancer has demonstrated in recent publications worse outcomes than open surgery. The primary objective of the SUCCOR study, a European, multicenter, retrospective, observational cohort study was to evaluate disease-free survival in patients with stage IB1 (FIGO 2009) cervical cancer undergoing open vs minimally invasive radical hysterectomy. As a secondary objective, we aimed to investigate the association between protective surgical maneuvers and the risk of relapse. METHODS: We obtained data from 1272 patients that underwent a radical hysterectomy by open or minimally invasive surgery for stage IB1 cervical cancer (FIGO 2009) from January 2013 to December 2014. After applying all the inclusion-exclusion criteria, we used an inverse probability weighting to construct a weighted cohort of 693 patients to compare outcomes (minimally invasive surgery vs open). The first endpoint compared disease-free survival at 4.5 years in both groups. Secondary endpoints compared overall survival among groups and the impact of the use of a uterine manipulator and protective closure of the colpotomy over the tumor in the minimally invasive surgery group. RESULTS: Mean age was 48.3 years (range; 23-83) while the mean BMI was 25.7 kg/m2 (range; 15-49). The risk of recurrence for patients who underwent minimally invasive surgery was twice as high as that in the open surgery group (HR, 2.07; 95% CI, 1.35 to 3.15; P=0.001). Similarly, the risk of death was 2.42-times higher than in the open surgery group (HR, 2.45; 95% CI, 1.30 to 4.60, P=0.005). Patients that underwent minimally invasive surgery using a uterine manipulator had a 2.76-times higher hazard of relapse (HR, 2.76; 95% CI, 1.75 to 4.33; P<0.001) and those without the use of a uterine manipulator had similar disease-free-survival to the open surgery group (HR, 1.58; 95% CI, 0.79 to 3.15; P=0.20). Moreover, patients that underwent minimally invasive surgery with protective vaginal closure had similar rates of relapse to those who underwent open surgery (HR, 0.63; 95% CI, 0.15 to 2.59; P<0.52). CONCLUSIONS: Minimally invasive surgery in cervical cancer increased the risk of relapse and death compared with open surgery. In this study, avoiding the uterine manipulator and using maneuvers to avoid tumor spread at the time of colpotomy in minimally invasive surgery was associated with similar outcomes to open surgery. Further prospective studies are warranted.

Efficacy and toxicity of postoperative external beam radiotherapy or chemoradiation for early-stage cervical cancer.

OBJECTIVE: The aim of this study was to assess the impact of the evolving role of the addition of chemotherapy to postoperative radiotherapy on oncological outcomes and toxicity in patients with early-stage cervical cancer after radical hysterectomy. METHODS: Retrospective cohort study of patients with stage IB1-IIB FIGO 2009 cervical cancer treated from November 1999 to May 2015 by primary surgery and radiotherapy (46-50.4 Gy in 1.8-2.0 Gy fractions) with or without concurrent cisplatin (40 mg/m2, 5-6 weekly cycles) with or without a brachytherapy boost. Chemotherapy was allocated depending on the risk factors for recurrence. Incidences of all outcomes were calculated using Kaplan-Meier's methodology and compared by log-rank tests. Risk factors for recurrence and survival were identified using Cox's proportional hazards models. RESULTS: A total of 154 patients were included, median follow-up was 9.6 years (IQR: 6.1-12.8). Five-year pelvic recurrence-free survival was 75.3%; 74.7% in patients with high-risk factors treated with radiotherapy; and 77.3% in those treated with chemoradiation (P=0.43). Distant metastasis-free survival at 5 years was 63.4%; 63.6% in high-risk patients after radiotherapy; and 57.1% after chemoradiation (P=0.36). Five-year overall survival was 63.9%: 66.8% and 51.6% after radiotherapy and after chemoradiation in patients with high-risk factors (P=0.37), respectively. Large tumor size was a risk factor for vaginal and pelvic recurrence, ≥2 involved lymph nodes was a significant risk factor for para-aortic recurrence and death. Mild treatment-related late toxicity was observed in 53.9% of the patients. Five-year severe (grade 3-5) late rectal, bladder, bowel, and vaginal toxicities were, respectively, 1.3%, 0%, 3.4%, and 0.9%. Any late severe toxicity was observed in 5.5% of patients treated with radiotherapy and in 15.3% of those treated with chemoradiation (P=0.07). CONCLUSION: Postoperative (chemo)radiation for early-stage cervical cancer patients with risk factors for recurrence yields adequate pelvic tumor control, but overall survival is limited due to distant metastasis.

Survival of patients with early-stage cervical cancer after abdominal or laparoscopic radical hysterectomy: a nationwide cohort study and literature review.

AIM: Recently, the safety of laparoscopic radical hysterectomy (LRH) has been called into question in early-stage cervical cancer. This study aimed to evaluate overall survival (OS) and disease-free survival (DFS) in patients treated with abdominal radical hysterectomy (ARH) and LRH for early-stage cervical cancer and to provide a literature review. METHODS: Patients diagnosed between 2010 and 2017 with International Federation of Gynaecology and Obstetrics (2009) stage IA2 with lymphovascular space invasion, IB1 and IIA1, were identified from the Netherlands Cancer Registry. Cox regression with propensity score, based on inverse probability treatment weighting, was applied to examine the effect of surgical approach on 5-year survival and calculate hazard ratios (HR) and 95% confidence intervals (CIs). Literature review included observational studies with (i) analysis on tumours ≤4 cm (ii) median follow-up ≥30 months (iii) ≥5 events per predictor parameter in multivariable analysis or a propensity score. RESULTS: Of the 1109 patients, LRH was performed in 33%. Higher mortality (9.4% vs. 4.6%) and recurrence (13.1% vs. 7.3%) were observed in ARH than LRH. However, adjusted analyses showed similar DFS (89.4% vs. 90.2%), HR 0.92 [95% CI: 0.52-1.60]) and OS (95.2% vs. 95.5%), HR 0.94 [95% CI: 0.43-2.04]). Analyses on tumour size (<2/≥2 cm) also gave similar survival rates. Review of nine studies showed no distinct advantage of ARH, especially in tumours <2 cm. CONCLUSION: After adjustment, our retrospective study showed equal oncological outcomes between ARH and LRH for early-stage cervical cancer - also in tumours <2 cm. This is in correspondence with results from our literature review.

Fertility-sparing surgery of cervical cancer >2 cm (International Federation of Gynecology and Obstetrics 2009 stage IB1-IIA) after neoadjuvant chemotherapy.

OBJECTIVE: To assess the feasibility, safety, oncological, and obstetric outcomes in patients with cervical tumors >2 cm treated with neoadjuvant chemotherapy in preparation for abdominal radical trachelectomy. METHODS: A retrospective analysis of patients with cervical cancer >2 cm (up to 6 cm) was conducted in patients who were selected to receive neoadjuvant chemotherapy before abdominal radical trachelectomy. Surgical and clinical outcomes were examined in relation to radiological and pathological results. In addition, obstetric outcomes were described. The Mann-Whitney U test and Fisher's exact test were performed to compare radiological findings between successful and unsuccessful abdominal radical trachelectomy procedures. International Federation of Gynecology and Obstetrics (FIGO) 2009 staging classification was used for this study. RESULTS: A total of 19 women were treated with neoadjuvant chemotherapy for cervical tumors >2 cm at our institution between May 2006 and July 2018. The median age was 28 years (range 19-36). The distribution of FIGO stages was seven patients stage IB1 (37%), 10 patients stage IB2 (53%), and two patients (10%) stage IIA. Mean clinical tumor size was 4.4 cm (range 3.5-6.0). Histology revealed 74% cases of squamous cell carcinoma. The remaining patients had adenocarcinoma (21%) and only one patient had clear cell adenocarcinoma (5%). Chemotherapy consisted of six weekly cycles of cisplatin (70 mg/m2) and paclitaxel (70 mg/m2). In 15 of the 19 patients (74%) fertility was successfully preserved. In the four patients in whom fertility preservation failed, one patient had stable disease after three cycles and did not meet the criteria for fertility-sparing surgery and three patients had intra- or post-operative indications for adjuvant therapy. Three of the 19 patients (15.7%) had a relapse, two of whom died. One case was in the group of successful abdominal radical trachelectomy. CONCLUSION: Neoadjuvant chemotherapy followed by fertility-sparing surgery may be a feasible and safe option in select patients with cervical tumors >2 cm. Unfavorable prognostic factors are defined as non-responsiveness and non-squamous pathology, which can help in patient selection for fertility-sparing surgery.

Local community networks in the fight against cervical cancer: the role of coffee ceremonies in the uptake of screening in Ethiopia.

Community mobilisation is an essential part of cervical cancer screening programmes to increase demand for screening services. While there are different methods of community mobilisation, in Ethiopia community conversations during traditional coffee ceremonies appear to be a context appropriate and effective method. Linkage of community mobilisation with existing community networks can increase uptake of cervical cancer screening and improve continuous support and care among community members.

A systematic review and meta-analysis of thermal coagulation compared with cryotherapy to treat precancerous cervical lesions in low- and middle-income countries.

BACKGROUND: Thermal coagulation is gaining popularity for treating cervical intraepithelial neoplasia (CIN) in screening programs in low- and middle-income countries (LMICs) due to unavailability of cryotherapy. OBJECTIVES: Assess the effectiveness of thermal coagulation for treatment of CIN lesions compared with cryotherapy, with a focus on LMICs. SEARCH STRATEGY: Papers were identified from previous reviews and electronic literature search in February 2018 with publication date after 2010. SELECTION CRITERIA: Publications with original data evaluating cryotherapy or thermal coagulation with proportion of cure as outcome, assessed by colposcopy, biopsy, cytology, and/or visual inspection with acetic acid (VIA), and minimum 6 months follow-up. DATA COLLECTION AND ANALYSIS: Pooled proportions of cure are presented stratified per treatment modality, type of lesion, and region. MAIN RESULTS: Pooled cure proportions for cryotherapy and thermal coagulation, respectively, were 93.8% (95% CI, 88.5-97.7) and 91.4% (95% CI, 84.9-96.4) for CIN 1; 82.6% (95% CI, 77.4-87.3) and 91.6% (95% CI, 88.2-94.5) for CIN 2-3; and 92.8% (95% CI, 85.6-97.7) and 90.1% (95% CI, 87.0-92.8) for VIA-positive lesions. For thermal coagulation of CIN 2-3 lesions in LMICs 82.4% (95% CI, 75.4-88.6). CONCLUSIONS: Both cryotherapy and thermal coagulation are effective treatment modalities for CIN lesions in LMICs.

Folate receptor-α targeted near-infrared fluorescence imaging in high-risk endometrial cancer patients: a tissue microarray and clinical feasibility study.

OBJECTIVE: Detection and resection of all malignant lesions is pivotal in staging and cytoreductive surgery (CRS) of endometrial cancer (EC). Intraoperative EC detection could be enhanced using OTL-38, a fluorescent-labelled folate receptor-α (FRα) targeted imaging agent. The objectives of this study were to investigate which subgroups of high-risk EC patients express FRα and assess feasibility of intraoperative EC detection using OTL-38. RESULTS: FRα expression on TMA was significantly correlated with tumor type (p < 0.01). Eighty-two percent of serous and clear cell carcinomas showed FRα expression. Four patients were enrolled in the clinical study. Using fluorescence imaging all omental (n = 3) and lymph node (LN) metastases (n = 16) could be clearly identified, including one otherwise undetected omental metastasis. However, false-positive fluorescence was identified in 17/50 non-metastatic LNs, caused by OTL-38 targeting of FRß, expressed by tumor-associated activated macrophages. CONCLUSIONS: This study describes high FRα expression in serous and clear cell EC and demonstrates the first experience of intraoperative FRα-targeted tumor detection in patients with these subtypes of EC. Although all metastases could be clearly identified using OTL-38, the role of tumor-associated macrophages should be further evaluated. METHODS: Immunohistochemical (IHC) staining of FRα expression was performed on tissue micro arrays (TMA) of 116 patients with high-risk EC features. Patients with either serous or clear cell EC, planned for staging or CRS, were eligible for inclusion in the clinical study and received an intravenous dose of 0.0125 mg/kg OTL-38, 2-3 hours prior to surgery. Resected lesions, identified by standard-of-care and/or fluorescence imaging, were histopathologically assessed for FRα and tumor status.