Preben Kjølhede

Preoperative and intraoperative assessment of myometrial invasion in endometrial cancer—A Swedish Gynecologic Cancer Group (SweGCG) study

AbstractIntroductionDeep myometrial invasion (≥50%) is a prognostic factor for lymph node metastases and decreased survival in endometrial cancer. There is no consensus regarding which pre/intraoperative diagnostic method should be preferred. Our aim was to explore the pattern of diagnostic methods for myometrial invasion assessment in Sweden and to evaluate differences among magnetic resonance imaging (MRI), transvaginal sonography, frozen section, and gross examination in clinical practice.Material and methodsThis is a nationwide historical cohort study; women with endometrial cancer with data on assessment of myometrial invasion and FIGO stage I‐III registered in the Swedish Quality Registry for Gynecologic Cancer (SQRGC) between 2017 and 2019 were eligible. Data on age, histology, FIGO stage, method, and results of myometrial invasion assessment, pathology results, and hospital level were collected from the SQRGC. The final assessment by the pathologist was considered the reference standard.ResultsIn the study population of 1401 women, 32% (n = 448) had myometrial invasion of 50% of more. The methods reported for myometrial invasion assessment were transvaginal sonography in 59%, MRI in 28%, gross examination in 8% and frozen section in 5% of cases. Only minor differences were found for age and FIGO stage when comparing methods applied for myometrial invasion assessment. The sensitivity, specificity, and accuracy to find myometrial invasion of 50% or more with transvaginal sonography were 65.6%, 80.3%, and 75.8%, for MRI they were 76.9%, 71.9%, and 73.8%, for gross examination they were 71.9%, 93.6%, and 87.3%, and for frozen section they were 90.0%, 92.7%, and 92.0%, respectively.ConclusionsIn Sweden, the assessment of deep myometrial invasion is most often performed with transvaginal sonography, but the sensitivity is lower than for the other diagnostic methods. In clinical practice, the accuracy is moderate for transvaginal sonography and MRI.

The wait time to primary surgery in endometrial cancer – impact on survival and predictive factors: a population-based SweGCG study

Poor survival rates in different cancer types are sometimes blamed on diagnostic and treatment delays, and it has been suggested that such delays might be related to sociodemographic factors such as education and ethnicity. We examined associations of the wait time from diagnosis to surgery and survival in endometrial cancer (EC) and explored patient and tumour factors influencing the wait time. In this historical population-based cohort study, The Swedish Quality Registry for Gynaecologic Cancer (SQRGC) was used to identify EC patients who underwent primary surgery between 2010 and 2018. Factors associated with a wait time > 32 d were analysed with logistic regression. The 32-d time point was defined in accordance with the Swedish Standardisation Cancer Care programme. Adjusted Poisson regression analyses were used to analyse excess mortality rate ratio (EMRR). Out of 7366 women, 5535 waited > 32 d for surgery and 1098 > 70 d. The overall median wait time was 44 d. The factors most strongly associated with a wait time > 32 d were surgery at a university hospital (adjusted odds ratio [OR] 1.34, 95% confidence interval [CI] 1.08-1.66) followed by country of birth (OR 1.31, 95% CI 1.10-1.55) and year of diagnosis. There were no associations between wait time and histology or age. A wait time < 15 d was associated with higher mortality (adjusted EMRR 2.29,95% CI 1.36-3.84) whereas no negative survival impact was seen with a wait time of 70 d. Age, tumour stage, histology and risk group were highly associated with survival, whereas education, country of origin and hospital level did not have any impact on survival. Surgery within the first two weeks after EC diagnosis was associated with worsened survival. A prolonged wait time did not seem to have any significant adverse effect on prognosis.HighlightsSurgery within the first two weeks after diagnosis of endometrial cancer (EC) was associated with poorer survival.A prolonged wait time to surgery did not worsen prognosis.Delay in time to surgery was associated with sociodemographic factors.

Impact of lymphadenectomy and lymphoedema on health‐related quality of life 1 year after surgery for endometrial cancer. A prospective longitudinal multicentre study

ObjectiveTo assess the impact of lymphadenectomy and lymphoedema of the lower limbs (LLL) on health‐related quality of life (HRQoL) 1 year after surgery for endometrial cancer (EC).DesignProspective longitudinal cohort multicentre study.SettingDepartments of obstetrics and gynaecology at four university hospitals, six central hospitals and four county hospitals in Sweden.PopulationTwo‐hundred‐and‐thirty‐five women with early stage EC were included; 116 with high‐risk EC underwent surgery including lymphadenectomy (+LA), and 119 with low‐risk EC had surgery without lymphadenectomy (−LA).MethodsThe generic SF‐36 and EQ‐5D‐3L and the lymphoedema‐specific LYMQOL questionnaire were used to assess HRQoL. LLL was assessed by systematic circumferential measurements of the legs enabling volume estimation, clinical evaluation and patient‐reported perception of leg swelling. All assessments were carried out on four occasions; preoperatively, and 4–6 weeks, 6 months and 1 year postoperatively.Main outcome measureHRQoL scores.ResultsNo significant differences were seen in HRQoL between the +LA and –LA groups 1 year postoperatively. Irrespective of method of determining LLL, women with LLL were significantly more affected in the LYMQOL domains Function, Appearance/body image and Physical symptoms, but not in the domain Emotion/mood, than women without LLL. No such differences were seen in the generic HRQoL or in the LYMQOL global score between the groups with and without LLL.ConclusionsLymphadenectomy did not seem to affect generic HRQoL adversely. Irrespective of the method of measuring, LLL affected the lymphoedema‐specific HRQoL negatively, mainly in physical domains, but had no impact on the generic HRQoL.Tweetable abstractLymphoedema has impact on lymphoedema‐specific, but not on generic, HRQoL, 1 year after surgery for EC.

Markers of tissue damage and inflammation after robotic and abdominal hysterectomy in early endometrial cancer: a randomised controlled trial

AbstractThe aim of this study was to analyse the dynamics of tissue damage and inflammatory response markers perioperatively and whether these differ between women operated with robotic and abdominal hysterectomy in treating early-stage endometrial cancer. At a Swedish university hospital fifty women with early-stage low-risk endometrial cancer were allocated to robotic or abdominal hysterectomy in a randomiszed controlled trial. Blood samples reflecting inflammatory responses (high sensitivity CRP, white blood cells (WBC), thrombocytes, IL-6, cortisol) and tissue damage (creatine kinase (CK), high-mobility group box 1 protein (HMGB1)) were collected one week preoperatively, just before surgery, postoperatively at two, 24 and 48 hours, and one and six weeks postoperatively. High sensitivity CRP (p = 0.03), WBC (p &lt; 0.01), IL-6 (p = 0.03) and CK (p = 0.03) were significantly lower in the robotic group, but fast transitory. Cortisol returned to baseline two hours after robotic hysterectomy but remained elevated in the abdominal group comparable to the preoperative high levels for both groups just before surgery (p &lt; 0.0001). Thrombocytes and HMGB1 were not affected by the mode of surgery. Postoperative inflammatory response and tissue damage were lower after robotic hysterectomy compared to abdominal hysterectomy. A significant remaining cortisol elevation two hours after surgery may reflect a higher stress response in the abdominal group.

Risk factors for lymph ascites after surgery for endometrial cancer and impact on lymphedema of the legs. A prospective longitudinal Swedish multicenter study

AbstractIntroductionThe primary aim was to determine the occurrence of lymph ascites 4–6 weeks after surgery for endometrial cancer. Secondary aims were to assess risk factors for lymph ascites and the association with lymphedema of the legs.Material and MethodsThis was a post hoc analysis of an observational prospective multicenter study, performed in 14 Swedish hospitals that included 235 women undergoing surgery for early‐stage endometrial cancer between June 2014 and January 2018; 116 underwent surgery including pelvic and para‐aortic lymphadenectomy and 119 had surgery without lymphadenectomy. Lymph ascites (free intraabdominal fluid or encapsulated pelvic or para‐aortic fluid) was assessed by vaginal ultrasound 4–6 weeks postoperatively. Lymphedema was assessed using circumferential measurements of the legs preoperatively and 1 year postoperatively, enabling estimation of leg volume. A BMI‐standardized leg volume increase ≥10% was classified as lymphedema. Evaluation of risk factors was performed using multiple logistic regression.ResultsLymph ascites 4‐6‐weeks postoperatively occurred in 28.5% (67/235) of the women. The estimated volume of the lymph ascites in these women was mean 28 mL (standard deviation 48 mL) and median 14 mL (interquartile range 2–36 mL). Lymphadenectomy was a risk factor for lymph ascites (aOR 9.97; 95% CI 4.53–21.97) whereas the use of minimally invasive surgery (aOR 0.50; 95% CI 0.25–0.99) reduced the risk. Twenty‐two of 231 women (9.5%) developed lymphedema of the legs 1 year after surgery. The presence of lymph ascites was predictive of lymphedema (aOR 3.90; 95% CI 1.52–9.96).ConclusionsLymph ascites was common 4–6 weeks after surgery but in a low and clinically insignificant volume. Lymphadenectomy was a strong risk factor for lymph ascites and the use of minimally invasive surgery seemed to reduce the risk. Detection of lymph ascites at early postoperative follow‐up may be a means of selecting patients at high risk of developing lymphedema after treatment with endometrial cancer for preventive measures against lymphedema progression.

Validation of data quality in the Swedish quality register of gynecologic cancer for cervical cancer and vulvar cancer—a Swedish gynecologic cancer group (Swe‐GCG) study

AbstractIntroductionPopulation‐based registers provide an important source of real‐world data. The growing number of large cohort studies using data from cancer registers makes validation of such registers important. The Swedish Quality Register of Gynecologic Cancer (SQRGC) is a nationwide population‐based register containing data on patient and tumor characteristics, treatment, and follow‐up. To ensure that the results from research and quality assurance reports using SQRGC data are robust and reliable, the accuracy and completeness of the register need to be validated. The aim of this study was to evaluate the quality of data on cervical cancer and vulvar cancer in the SQRGC.Material and MethodsQuality of data in the SQRGC was investigated by evaluating completeness, timeliness, comparability, and validity in accordance with recommendations from the International Agency for Research on Cancer and the national Swedish guidelines on validation of cancer registers. Completeness was evaluated by coverage relative to the Swedish National Cancer Register, and timeliness as the time from diagnosis until entry into the SQRGC. We randomly selected 276 women diagnosed with cervical cancer (n = 138) and vulvar cancer (n = 138) between 2014 and 2019 for validation. An external monitor manually re‐abstracted data on 10 core variables per sub‐register from the patients' medical records. Comparability was assessed by reviewing the adherence to international standards regarding coding. Validity was evaluated by the agreement between re‐abstracted data and original data in the SQRGC. Correlations were estimated using Pearson's correlation coefficient and Cohen's kappa coefficient.ResultsFor cervical cancer, the completeness was 99% and the timeliness was 87.1% within 12 months. The corresponding figures for vulvar cancer were 100% and 87.9%, respectively. Adherence to international coding standards was satisfactory. The median degree of agreement between re‐abstracted data and data in the SQRGC was 90.8% (range 73.2%–100%) for cervical cancer, and 85.4% (range 59.6%–98.2%) for vulvar cancer.ConclusionsThe data on cervical and vulvar cancer in the SQRGC are of adequate quality and may well be used for research and clinical purposes.

The impact of local symptoms on health‐related quality of life in vulvar cancer survivors—A nationwide prospective study

AbstractIntroductionVulvar cancer may cause serious local symptoms that may impact negatively on the woman's health‐related quality of life (HRQOL). However, knowledge about the prevalence of vulvar and lymphedema symptoms at diagnosis and during follow‐up is limited. The aim of this study was to evaluate the longitudinal development of vulvar and lymphedema symptoms as well as the trajectory of HRQOL in women with vulvar cancer. Furthermore, associations between vulvar symptoms and HRQOL were investigated.Material and MethodsIn this nationwide prospective cohort study, women completed validated patient‐reported outcome measures; the EORTC‐QLQ C30 and the EORTC‐QLQ‐VU34 at diagnosis, three, and 12 months post‐treatment. Mean scores of symptom‐ and functioning scales were calculated over time. Heatmaps were used to visualize proportional changes in the prevalence of symptoms at baseline and 12 months after treatment. Linear mixed‐effects models with patient‐specific random intercepts were specified to estimate changes in mean scores of HRQOL over time. Additionally, adjusted linear mixed‐effects models were applied to investigate the effect of the most prevalent vulvar symptom on HRQOL. The study has been registered at ClinicalTrials.gov (NCT 04152512).ResultsBetween 2019 and 2021, 153 women consented to participate in the study, and 140 (92%) completed the patient‐reported outcome measures at least once. In total, 105 (69%) completed the patient‐reported outcome measures at all three time points. The most prevalent reported symptom was itchy, irritated skin in the vulva, which decreased from 82% at diagnosis to 56% 12 months after treatment. All vulvar symptoms, except narrowing of the vaginal entrance, improved over time but persisted in large proportions of the women. Women with severe vulvar symptoms reported a significant decline in HRQOL. A deterioration of leg swelling symptoms was reported by 33% of the women. Emotional‐, role‐, social‐, and cognitive functioning, global and mental health improved significantly after treatment.ConclusionLocal vulvar symptoms were highly prevalent at diagnosis; however, as most aspects of HRQOL, they improved significantly during the first year of follow‐up. Severe vulvar symptoms were associated with impaired HRQOL. Symptoms of leg lymphedema increased after treatment. © 2025 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley &amp; Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).

Anxiety and depression among women with newly diagnosed vulvar cancer – A nationwide longitudinal study

AbstractIntroductionOur objective was to investigate the trajectories of anxiety, depression, emotional and social functioning in women with newly diagnosed vulvar cancer from the time of diagnosis to 12 months after treatment. A further aim was to identify risk factors for high levels of anxiety.Material and methodsPROVE (PROspective Vulvar Cancer Evaluation) is a nationwide longitudinal cohort study investigating quality of life in women with newly diagnosed vulvar cancer by the following validated patient‐reported outcome measures at diagnosis, and 3 and 12 months after treatment: The Hospital Anxiety and Depression Scale, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30, and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Vulvar module VU34. Mean scores, changes over time and associations were analyzed by generalized estimated equations and log‐linear regression models, adjusted for possible confounders.ResultsBetween 2019 and 2021, 105 (69%) women completed the questionnaires at all three time points. At diagnosis, 42% of the women reported elevated anxiety levels, decreasing significantly to 30% during the first 12 months. Insomnia, persisting vulvar symptoms and high information needs were significantly associated with a high level of anxiety (relative risk [RR] 2.1, 95% CI 1.2–3.7 for insomnia; RR 2.8, 95% CI 1.7–4.6 for vulvar symptoms, RR 2.7, 95% CI 1.5–4.9 for information needs). We found a trend towards a higher level of anxiety in younger women (&lt;65 years: RR 1.5, 95% CI 1.0–2.5). Participants reported a low and stable prevalence of depression (14%) and high social functioning throughout the study period.ConclusionsWomen with newly diagnosed vulvar cancer report a high level of anxiety at diagnosis. Despite a significant improvement, anxiety remains widely prevalent during the first year of follow‐up. Targeting insomnia, vulvar symptoms and unmet needs may decrease anxiety during surveillance.

The effect of tinzaparin on biomarkers in FIGO stages III-IV ovarian cancer patients undergoing neoadjuvant chemotherapy – the TABANETOC trial: study protocol for a randomized clinical multicenter trial

Background: Tinzaparin, a low-molecular weight heparin (LMWH), has shown anti-neoplastic properties in animal models and in in vitro studies of human cancer cell lines. The reduction of CA-125 levels during neoadjuvant chemotherapy (NACT) in patients with epithelial ovarian cancer (EOC) co-varies with the prognosis; the larger the decrease in CA-125, the better the prognosis. Purpose: This study aims to evaluate the potential anti-neoplastic effects of tinzaparin by investigating changes in serum CA-125 levels in advanced EOC patients who receive NACT. Material and methods: This is an open randomized multicenter pilot trial. Forty patients with EOC selected to receive NACT will be randomized 1:1 to receive daily addition of tinzaparin or no tinzaparin. The processing and treatment of the patients will otherwise follow the recommendations in the Swedish National Guidelines for Ovarian Cancer. Before every cycle of chemotherapy, preoperatively, and 3 weeks after the last cycle of chemotherapy, a panel of biomarkers, including CA-125, will be measured. Patients: Inclusion criteria are women aged 18 years or older, World Health Organization performance status 0–1, histologically confirmed high-grade serous, endometrioid or clear cell EOC, International Federation of Gynecology and Obstetrics (FIGO) stages III-IV. In addition, a CA-125 level of ≥ 250 kIE/L at diagnosis. Exclusion criteria are contraindications to LMWH, ongoing or recent treatment with unfractionated heparin, LMWH, warfarin or non-vitamin K antagonist oral anticoagulants. Interpretation: This study will make an important contribution to the knowledge of the anti-neoplastic effects of tinzaparin in EOC patients and may thus guide the planning of a future study on the impact of tinzaparin on survival in EOC.

Quality of Life, Unmet Needs and Satisfaction With Care After Vulvar Cancer

The aim of this prospective, longitudinal Swedish multi-center study is to assess the quality of life, treatment-related morbidity, unmet needs and satisfaction with care after treatment for vulvar cancer, evaluated by a validated questionnaire.