Identifying safe diagnostic algorithms for sentinel lymph node mapping in high-risk endometrial cancer: The SENTIREC-endo study.

INTRODUCTION: It is unclear if sentinel node (SLN) mapping can replace pelvic- (PLD) and paraaortic lymphadenectomy (PALD) for high-risk endometrial cancer (EC). A diagnostically safe surgical algorithm, taking failed mapping cases into account, is not defined. We aimed to investigate the diagnostic accuracy of SLN mapping algorithms in women with exclusively high-risk EC. METHODS: We undertook a prospective national diagnostic cohort study of SLN mapping in women with high-risk EC from March 2017 to January 2023. The power calculation was based on the negative predictive value (NPV). Women underwent SLN mapping, PLD and PALD besides removal of suspicious and any FDG/PET-positive lymph nodes. Accuracy analyses were performed for five algorithms. RESULTS: 170/216 included women underwent SLN mapping, PLD and PALD and were included in accuracy analyses. 42/170 (24.7%) had nodal metastasis. The algorithm SLN and PLD in case of failed mapping, demonstrated a sensitivity of 86% (95% CI 74-100) and an NPV of 96% (95% CI 91-100). The sensitivity increased to 93% (95% CI 83-100) and the NPV to 98% (95% CI 94-100) if PLD was combined with removal of any PET-positive lymph nodes. Equivalent results were obtained if PLD and PALD were performed in non-mapping cases; sensitivity 93% (95% CI 83-100) and NPV 98% (95% CI 95-100). CONCLUSION: SLN-mapping is a safe staging procedure in women with high-risk EC if strictly adhering to a surgical algorithm including removal of any PET-positive lymph nodes independent of location and PLD or PLD and PALD in case of failed mapping.

The SENTIREC-endo study - Risks and benefits of a national adoption of sentinel node mapping in low and intermediate risk endometrial cancer.

OBJECTIVE: The SENTIREC-endo study aims to investigate risks and benefits of a national protocolled adoption of sentinel lymph node (SLN) mapping in women with early-stage low-grade endometrial cancer (EC) with low- (LR) and intermediate-risk (IR) of lymph node metastases. METHODS: We performed a national multicenter prospective study of SLN-mapping in women with LR and IR EC from March 2017-February 2022. Postoperative complications were classified according to Clavien-Dindo. Lymphedema was assessed as a change score and as incidence of swelling and heaviness evaluated by validated patient-reported outcome measures at baseline and three months postoperatively. RESULTS: 627 women were included in the analyses; 458 with LR- and 169 with IR EC. The SLN detection rate was 94.3% (591/627). The overall incidence of lymph node metastases was 9.3% (58/627); 4.4% (20/458) in the LR- and 22.5% (38/169) in the IR group. Ultrastaging identified 62% (36/58) of metastases. The incidence of postoperative complications was 8% (50/627) but only 0.3% (2/627) experienced an intraoperative complication associated with the SLN procedure. The lymphedema change score was below the threshold for clinical importance 4.5/100 CI: (2.9-6.0), and the incidence of swelling and heaviness was low; 5.2% and 5.8%, respectively. CONCLUSION: SLN mapping in women with LR and IR EC carries a very low risk of early lymphedema and peri- and postoperative complications. The national change in clinical practice contributed to a more correct treatment allocation for both risk groups and thus supports further international implementation of the SLN technique in early stage, low grade EC.

Patient-initiated follow-up in women with early-stage endometrial cancer: A long-term follow-up of the OPAL trial.

OBJECTIVE: A long-term follow-up of the OPAL trial to compare the effect of patient-initiated (PIFU) versus hospital-based (HBFU) follow-up on fear of cancer recurrence (FCR), quality of life (QoL) and healthcare use after 34 months of follow-up. DESIGN: Pragmatic, multicentre randomised trial. SETTING: Four Danish departments of gynaecology between May 2013 and May 2016. POPULATION: 212 women diagnosed with stage I low-intermediate risk endometrial carcinoma. METHODS: The control group attended HBFU with regular outpatient visits (i.e., 8) for 3 years after primary treatment. The intervention group underwent PIFU with no prescheduled visits but with instructions about alarm symptoms and options of self-referral. MAIN OUTCOME MEASURES: The endpoints were FCR as measured by the Fear of Cancer Recurrence Inventory (FCRI) and QoL as measured by the European Organisation for Research and Treatment of Cancer Quality of Life Core Questionnaire C-30 (EORTC QLQ C-30), and healthcare use as measured by questionnaires and chart reviews after 34 months of follow-up. RESULTS: FCR decreased from baseline to 34 months in both groups and no difference was found between allocations (difference -6.31 [95% confidence interval -14.24 to 1.63]). QoL remained stable with no difference in any domains between the two arms at 34 months using a linear mixed model analysis. The use of healthcare was significantly lower in the PIFU group (P < 0.01). CONCLUSION: Patient-initiated follow-up is a valid alternative to hospital-based follow-up for people who have been treated for endometrial cancer and have low risk of recurrence.

Improved stratification of stage-specific survival for cervical uterine cancer by integrating FDG-PET/CT and MRI for lymph node staging in 2018 FIGO classification.

OBJECTIVE: Staging carcinoma of the uterine cervix (CCU) by FIGO-2018 suggests stage migration of FIGO-2009 stage I-III patients with lymph node metastasis into FIGO-2018 stage IIIC. We aimed to investigate the prognostic value of lymph node metastases identified by imaging. METHODS: We enrolled all patients with biopsy-verified CCU from 2007 to 2016 at Odense University Hospital, Denmark. FDG-PET/CT and MRI were performed before clinical examination in general anesthesia. Disease-specific mortality was compared between women with lymph node-positive and lymph node-negative imaging. RESULTS: In total, 488 patients underwent clinical staging according to FIGO-2009. Lymph node-positive imaging was identified in 146 (30%) patients: 0/36 (0%) in stage IA, 22/195 (11%) in IBI, 14/30 (47%) in IB2, 70/164 (43%) in II and 40/63 (63%) in III. The 5-year cumulative incidence of death due to CCU lymph node-negative vs. lymph node-positive patients was 0.8% vs. 7.1% (p = 0.034) in stage IBI, 0% vs. 34.5% (p = 0.003) in stage IB2, 15.1% vs. 41.4% (p < 0.0001) in stage II, and 33.3% vs. 46.6% (p = 0.28) in stage III by FIGO-2009. CONCLUSIONS: One of three women with FIGO-2009 stage I-III CCU had suspected lymph node metastasis on imaging and is upstaged to stage IIIC according to FIGO-2018. The cancer-specific mortality by CCU was significantly lower in the lymph node-negative women stages IBI-II, thus supporting stage migration due to suspected lymph node metastasis. However, the exact prognostic value within stage IIIC is challenged, and future revision of FIGO stages may include new sub-stages.

Use of hypnotics among women diagnosed with cervical cancer - A population-based cohort study.

OBJECTIVE: Previous studies suggest that sleeping problems are frequent after cervical cancer. However, the evidence on the use of hypnotics is sparse. We investigated if women diagnosed with cervical cancer have an increased risk of using hypnotics and identified risk factors for prolonged use. METHODS: In this nationwide register-based cohort study, 4264 women diagnosed with cervical cancer from 1997 to 2013 and 36,632 cancer-free women were followed in registers until 2016. Prolonged use of hypnotics was defined as more than three prescriptions with no more than three months in between. Data were analysed using Cox proportional hazards regression models and multistate Markov models separately for women with localized and advanced cervical cancer. RESULTS: The rate of first use of hypnotics was substantially increased during the first year after cervical cancer diagnosis compared to cancer-free women (HRlocalized 4.4, 95% CI 3.9-5.1; HRadvanced 8.9, 95% CI 7.5-10.6) and remained markedly increased for up to five years after diagnosis. Dependent on stage of disease and age, 1.4 to 4.7 excess women per 100 with cervical cancer were prolonged users of hypnotics compared to cancer-free women one year after diagnosis. Risk factors for prolonged use of hypnotics were higher age, short education, previous use of antidepressants or anxiolytics, and advanced disease. CONCLUSIONS: Women diagnosed with cervical cancer are at increased risk of prolonged use of hypnotics. For the majority, treatment with hypnotics is initiated within the first year after cancer diagnosis, but the rate of first use is increased for up to five years.

SENTIREC - The sentinel node mapping in women with cervical cancer study - Patient-reported early lymphedema and its impact on quality of life.

OBJECTIVE: To evaluate patient-reported incidence and severity of early lymphedema and its impact on quality of life (QoL) after sentinel lymph node (SLN) mapping only and after SLN and pelvic lymphadenectomy (PL) in women undergoing surgery for early-stage cervical cancer. METHODS: In a national prospective multicenter study, we included women with early-stage cervical cancer from March 2017-January 2021 to undergo radical surgery including SLN mapping. Women with tumors >20 mm underwent completion PL. The incidence and severity of early lymphedema and its influence on QoL were evaluated using validated patient-reported outcome measures before surgery and three months postoperative. We investigated changes over time using linear regression. RESULTS: Two hundred of 245 (81.6%) included women completed questionnaires at baseline and three months postoperatively. The incidence of early lymphedema was 5.6% (95% CI 2.1-11.8%) and 32.3% (95% CI 22.9-42.7%) in women who underwent SLN mapping only and SLN + PL, respectively. Lymphedema symptoms in the legs, genitals, and groins increased in both groups postoperatively but three times more in women who underwent PL. Lymphedema symptoms after SLN + PL significantly impaired physical performance (p = 0.001) and appearance (p = 0.007). Reporting lymphedema was significantly associated with impaired body image, physical-, role-, and social functioning, and a high level of fatigue. CONCLUSIONS: SLN mapping alone carries a low risk of lymphedema in women undergoing surgery for early-stage cervical cancer. In contrast, completion PL is associated with a high incidence of early lymphedema. Reporting lymphedema is associated with significant impairment of several physical, psychological, and social aspects of QoL.

Human papillomavirus vaccination in women undergoing excisional treatment for cervical intraepithelial neoplasia and subsequent risk of recurrence: A systematic review and meta-analysis.

INTRODUCTION: In this review and meta-analysis we aimed to investigate whether human papilloma virus (HPV) vaccination administered after excisional treatment of cervical intraepithelial neoplasia (CIN) is associated with a reduced risk of recurrence of CIN grade 2 or worse (CIN2+). MATERIAL AND METHODS: We performed a systematic literature search in three online databases through June 2021. Observational studies and randomized controlled trials (RCTs) were eligible for inclusion if the prophylactic HPV vaccine was administered after excisional treatment for histologically verified CIN. Only English language literature was included. The primary outcome measure was recurrence of CIN2+ after treatment. A meta-analysis was performed using fixed and random-effects models, and results were reported as pooled odds ratios (OR) with 95% confidence intervals (95% CI). Quality assessment was performed using ROB2-tool for RCTs and ROBINS-I for observational studies. The protocol was registered in PROSPERO (CRD42021238257). RESULTS: A total of 1561 studies were identified, of which nine, including 19 971 women, were included. Two studies were RCTs and seven were observational studies. Using the fixed-effect model on the two RCTs, the OR for recurrence of CIN2+ was 0.29 (95% CI 0.16-0.53). Due to considerable heterogeneity in observational studies, the random-effects model was used to estimate pooled OR for CIN2+ recurrence in these studies. Thus, using unadjusted data from observational studies, the OR for CIN2+ recurrence was 0.35 (95% CI 0.18-0.67), whereas when using adjusted data, the OR for CIN2+ recurrence was 0.54 (95% CI 0.21-1.35). However, quality assessment revealed a serious risk of bias for the majority of the studies included. CONCLUSIONS: HPV vaccination post-treatment was associated with a significantly reduced risk of CIN2+ recurrence when using unadjusted estimates from observational studies and RCTs. We found no significant effect of HPV vaccination on risk of CIN2+ recurrence when using the outcome measure from observational studies with the least risk of bias. Large, well-designed randomized placebo-controlled trials are needed to determine whether post-treatment HPV vaccination should be recommended to all women undergoing excisional treatment for CIN.

Cervical cancer survivors and health care use: A Danish population-based register study.

OBJECTIVE: To evaluate the impact of a cervical cancer (CC) diagnosis on use of health care and prescription drugs. METHODS: This population-based register-study included Danish women aged 23-59 years and diagnosed with CC in 2001-2005. Women with a cervical screening outcome were used as comparison group. We obtained number of contacts to general practitioners (GPs), hospitals, psychologists/psychiatrists and defined daily doses (DDD) of analgesic/psychotropic prescription drugs. A difference-in-differences-design was used to estimate effect of a CC diagnosis on health-care use from five-year periods before and after the diagnosis/screening outcome. RESULTS: In total, 926 women with CC and 1,004,759 women without cancer were included. In five years following the date of CC diagnosis, CC patients had increased their use of GPs with 8.6 (95% CI 4.8-12.4) contacts more than women in the comparison group, and with 4.12 (95% CI 3.99-4.25) more hospital contacts. In contrast, use of psychologists/psychiatrists was low and largely unaffected by the CC diagnosis. For use of prescription drugs, analgesics increased with 80 (95% CI 60-100) DDD more in CC patients than in comparison women, and for psychotropics with 304 (95% CI 261-347) DDD more. CONCLUSIONS: A CC diagnosis was followed by an increase in use of GPs, hospitals, and analgesic/psychotropic prescription drugs, while use of psychologist/psychiatrist was largely unaffected. This pattern may indicate that pain/mental health concerns after CC either persisted or were alleviated by other means only.

From FIGO-2009 to FIGO-2018 in women with early-stage cervical cancer; Does the revised staging reflect risk groups?

OBJECTIVES: We aimed to evaluate if the revised staging according to FIGO-2018 in early-stage cervical cancer correctly predicts the risk for nodal metastases. METHODS: We reallocated 245 women with early-stage cervical cancer from FIGO-2009 to FIGO-2018 stages using data from a national, prospective cohort study on sentinel lymph node (SLN) mapping. We used univariate and multivariate binary regression models to investigate the association between FIGO-2018 stages, tumor characteristics, and nodal metastases. RESULTS: Stage migration occurred in 54.7% (134/245) (95% CI 48.2-61.0), due to tumor size or depth of invasion (71.6%, 96/134) and nodal metastases (28.4%, 38/134). Imaging preoperatively upstaged 7.3% (18/245); seven had nodal metastatic disease on final pathology. Upstaging occurred in 49.8% (122/245) (95% CI 43.4-56.2%) and downstaging to FIGO-2018 IA stages in 4.9% (12/245) (95% CI 2.6-8.4). The tumor size ranged from 3.0-19.0 mm in women with FIGO-2018 IA tumor characteristics, and none of the 14 women had nodal metastases. In multivariate analysis, risk factors significantly associated with nodal metastases were FIGO-2018 ≥ IB2 (RR 5.01, 95% CI 2.30-10.93, p < 0.001), proportionate depth of invasion >2/3 (RR 1.88, 95% CI 1.05-3.35, p = 0.033), and lymphovascular space invasion (RR 5.56, 95% CI 2.92-10.62, p < 0.001). CONCLUSIONS: The FIGO-2018 revised staging system causes stage migration for a large proportion of women with early-stage cervical cancer. Women who were downstaged to FIGO-2018 IA stages did not have nodal metastatic disease. The attention on depth of invasion rather than horizontal dimension seems to correctly reflect the risk of nodal metastases.

Sentinel lymph node mapping in early-stage cervical cancer - A national prospective multicenter study (SENTIREC trial).

OBJECTIVES: Sentinel lymph node (SLN) mapping may replace staging radical pelvic lymphadenectomy in women with early-stage cervical cancer. In a national multicenter setting, we evaluated SLN mapping in women with early-stage cervical cancer and investigated the accuracy of SLN mapping and FDG-PET/CT in tumors >20 mm. METHODS: We prospectively included women with early-stage cervical cancer from March 2017-January 2021 to undergo SLN mapping. Women with tumors >20 mm underwent completion pelvic lymphadenectomy and removal of FDG-PET/CT positive nodes. We determined SLN detection rates, incidence of nodal disease, sensitivity and negative predictive value (NPV) of SLN mapping, and the sensitivity, specificity, NPV, and positive predictive value (PPV) of FDG-PET/CT. RESULTS: We included 245 women, and 38 (15.5%) had nodal metastasis. The SLN detection rate was 96.3% (236/245), with 82.0% (201/245) bilateral detection. In a stratified analysis of 103 women with tumors >20 mm, 27 (26.2%) had nodal metastases. The sensitivity of SLN mapping adhering to the algorithm was 96.3% (95% CI 81.0-99.9%) and the NPV 98.7% (95% CI 93.0-100%). For FDG-PET/CT imaging the sensitivity was 14.8% (95% CI 4.2-33.7%), the specificity 85.5% (95% CI 75.6-92.5%), the NPV 73.9% (95% CI 63.4-82.7%), and the PPV 26.7% (95% CI 7.8-55.1%). CONCLUSIONS: SLN mapping seems to be an adequate staging procedure in early-stage cervical cancer tumors ≤20 mm. In tumors >20 mm, SLN mapping is highly sensitive but demands full adherence to the SLN algorithm. We recommend completion pelvic lymphadenectomy in tumors >20 mm until the oncological safety is established. FDG-PET/CT for nodal staging of women with early-stage cervical cancer seems limited.

The PROMova study comparing active and passive use of patient-reported outcome measures in ovarian cancer follow-up: effect on patient-perceived involvement, satisfaction with care, and usefulness.

BACKGROUND: Patients with ovarian cancer often experience substantial health problems and side effects resulting in reduced quality of life (QoL). Different models of using patient-reported outcome measures (PROMs) during follow-up may improve the quality of care. This national, multicenter observational study investigated the effect of active use of PROMs on patient-perceived involvement, satisfaction with care, unmet needs, and QoL during follow-up of ovarian cancer. MATERIAL AND METHODS: Ovarian cancer patients were recruited at the end of primary treatment at eight centers in Denmark. During 18 months of follow-up patients repeatedly completed European Organization for Research and Treatment of Cancer (EORTC) questionnaires covering health related QoL and symptoms. At the sites using PROMs actively (ACT), the clinician had access to an overview of the patient's scores during the clinical encounter. Clinicians using PROMs passively were alerted in case of severe development of symptoms. Following each encounter, patients evaluated their health service experience by completing the CollaboRATE scale of involvement in decision making, the Patient Experience Questionnaire, and ad hoc questions covering patient-perceived usefulness of the PROMs. RESULTS: A total of 223 patients were enrolled, i.e., 168 (75.3%) at five sites using ACT and 53 (23.8%) at three sites using them passively. We found no statistically significant difference in involvement in the decision making, satisfaction with care, unmet needs, and QoL between the two groups. The majority of patients found it useful to complete the PROMs, although it did not seem to significantly support them in raising issues with the oncologist. CONCLUSION: Active use of PROMs did not improve patients' experience of involvement in follow-up care as compared to passive use.

Self-management and adherence to recommended follow-up after gynaecological cancer: results from the international InCHARGE study.

OBJECTIVE: To assess the relationship between self-management skills and adherence to follow-up guidelines among gynecological cancer survivors in the Netherlands, Norway, and Denmark, and to assess the relationship between adherence to follow-up programs and use of additional healthcare services. METHODS: For this international, multicenter, cross-sectional study, we recruited gynecological cancer survivors 1-5 years after completion of treatment. Information on follow-up visits, use of healthcare resources, self-management (measured by the Health Education Impact Questionnaire), clinical characteristics, and demographics were obtained by validated questionnaires. Participants were categorized as adherent if they attended the number of follow-up visits recommended by national guidelines, non-adherent if they had fewer visits than recommended, or over-users if they had more visits than recommended. RESULTS: Of 4455 invited survivors, 2428 (55%) returned the questionnaires, and 911 survivors were included in the analyses. Survivors with high self-management most frequently adhered to recommended follow-up. Non-adherent survivors showed lower self-management in the health-directed activity domain (OR 1.54, 95% CI 1.03 to 2.32) than adherent survivors. No other associations between self-management and follow-up adherence were revealed. Non-adherent survivors tended to have endometrial cancer, surgical treatment only, be older, and be Danish residents. Over-users reported more follow-up visits and also used additional healthcare services more frequently than adherent survivors. CONCLUSION: Low self-management appears to reduce the likelihood of adherence to national guidelines for gynecological cancer follow-up. Focusing on patient education for survivors at risk of low self-management to ensure adherence to recommended follow-up may improve personalization of follow-up.

Association of patient-reported outcomes and ovarian cancer recurrence.

BACKGROUND: The vast majority of patients with advanced ovarian cancer experience disease recurrence after primary treatment. OBJECTIVE: To explore the diagnostic accuracy of repeated measurement of patient-reported outcomes and quality-of-life scores in relation to ovarian cancer recurrence. METHODS: Patients with ovarian cancer were recruited to the PROMova study by the end of their primary treatment at eight centers in Denmark. The purpose of the PROMova study was to explore the applicability of repeated use of patient-reported outcomes, which consisted of the European Organization for Research and Treatment of Cancer generic questionnaire and the ovarian specific questionnaire. The patient-reported outcomes were completed 3, 6, 9, 12, and 15 months after enrollment or until recurrence. The 3-month interval between completions was the period in which recurrence was assessed. Imaging and the biomarker CA125 were used as reference modality for recurrence. Mixed effects logistic regression was used to investigate the association between mean patient-reported outcome scores and recurrence. Receiver operating curves were used to establish cut-off scores. The diagnostic accuracy of patient-reported outcomes, including sensitivity, specificity, and positive and negative predictive values was estimated based on the Youden index. For combined scales, diagnostic accuracy was investigated based on multivariate analysis. RESULTS: The analysis included 196 patients with an overall recurrence rate of 50.5% and an overall mean time to recurrence of 302 days. With imaging as reference, patients with recurrence reported significantly lower global health, worse physical functioning, and more abdominal symptoms preceding recurrence. With CA125 as reference, global health, physical and emotional functioning were impaired. Despite the worsening of a number of symptoms prior to recurrence whichever reference modality was applied, the patient-reported outcome scores did not provide adequate diagnostic accuracy. CONCLUSION: Repeated use of patient-reported outcomes during surveillance of ovarian cancer was not of diagnostic value. Future efforts should be directed at improving the administration of patient-reported outcomes as well as exploring the potential of using these outcomes as an indicator of clinical relevance.

Use of PROM during follow-up of patients with ovarian cancer: the PROMova study protocol.

BACKGROUND: There is a paucity of high-level evidence on the optimal follow-up of patients with ovarian cancer after primary treatment. A debate is ongoing on the extent to which follow-up should consider patient preferences and patient-reported outcome measures. Incorporation of patient-reported outcome measures supports the dialog between patient and clinician and may be instrumental in symptom monitoring and detection of underlying issues, especially when used actively during the clinical consultation. PRIMARY OBJECTIVE AND ENDPOINT: The PROMova study aims to assess whether proactive use of patient-reported outcome measures during follow-up care increases patient involvement as perceived by the patient compared with standard care. Another objective is to measure satisfaction with the care provided. STUDY HYPOTHESIS: It is hypothesized that proactive use of patient-reported outcome measures during the clinical encounter will improve patients' experience of involvement in follow-up care. TRIAL DESIGN: PROMova is a multi-center, observational cohort study collecting data from eight departments in Denmark. Five departments use the patient-reported outcome measures proactively during the consultation and three provide standard care. Participants are followed up with patient-reported outcome measures for up to 3 years. The patient-reported outcome measures package comprises EORTC QLQ-C30, EORTC QLQ-OV28, a questionnaire screening tool for recurrence, CollaboRATE, and selected questions from the Patient Experience Questionnaire. MAJOR INCLUSION/EXCLUSION CRITERIA: Patients older than 18 years diagnosed with ovarian, fallopian tube, or primary peritoneal cancer are eligible when entering the follow-up program after primary treatment. Participants must be able to speak and read Danish. SAMPLE SIZE: 223 patients with ovarian cancer. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: The protocol closed for enrollment in 2019. Publication of final results is expected in spring 2022. TRIAL REGISTRATION: PROMova was registered with ClinicalTrials.gov November 2016 Identifier: NCT02916875.

Surgery Is Physically Demanding and Associated With Multisite Musculoskeletal Pain: A Cross-Sectional Study.

BACKGROUND: Performing surgery involves well-known risk factors for developing musculoskeletal pain. Multisite musculoskeletal pain has shown to have an even higher adverse impact on the individual. We examined prevalence and intensity of multisite musculoskeletal pain in surgeons and identified characteristics associated with two or more painful body sites. MATERIALS AND METHODS: Information on sociodemographic, work experience, work demands, health status, physical capacity, and prevalence and intensity of musculoskeletal pain were collected from an internet-based questionnaire in 284 surgeons. Descriptive statistics were used to report prevalence and intensity of musculoskeletal pain. A logistic regression model was conducted to assess the characteristics associated with multisite musculoskeletal pain. RESULTS: Musculoskeletal pain was reported by 93% of the surgeons and 77% experienced multisite pain. The reported median pain intensities ranged from 2 to 4. Multisite musculoskeletal pain was significantly associated with being a female surgeon (OR: 3.4; 95% CI: 1.5-7.4), physical work demands (OR: 1.5 95% CI: 1.2-1.7), work ability (OR: 3.4; 95% CI: 1.6-7.0), and feeling a sense of heaviness in the head/headache (OR:4.8; 95% CI: 2.0-11.5). In addition, 21%-40% of the surgeons who experienced multisite pain reported that pain influenced their work, leisure time, and sleep negatively. CONCLUSIONS: The observed high prevalence of multisite musculoskeletal pain and high pain intensities adds new knowledge to the emerging literature on surgeons' health. In addition, several characteristics, for example, work ability, were significantly associated with multiple pain sites. This is concerning as pain could ultimately shorten a surgeon's career. Therefore, it is pertinent to develop preventive and rehabilitating strategies.

Prevalence and possible predictors of sexual dysfunction and self-reported needs related to the sexual life of advanced cancer patients.

Background: Sexual dysfunction and problems are common late effects after treatment of cancer. However, little is known about the prevalence and risk factors for sexual dysfunction in patients with advanced cancer. The aim of this study was to investigate the prevalence and predictors of sexual problems and needs in a large sample of Danish patients with advanced cancer. Methodology: The data derived from a representative cross-sectional study of patients with advanced cancer. Patients who had been in contact with 1 of 54 hospital departments were invited to fill out a questionnaire on symptoms and problems. Five items asked about sexuality. Ordinal logistic regression was used to identify variables associated with sexual functioning in explorative analyses. Results: A total of 1,447 patients completed the questionnaire and of those, 961 patients (66%) completed the sexuality items. More than half of the patients (60%) had not been sexually active within the previous month, despite a high prevalence of desire for sexual intimacy (62%). More than half of the patients (57%) experienced that their physical condition or treatment had impaired their sex life. Of those, 52% experienced an unmet need for help with sexual problems from the health care system. Older patients were less likely to report sexual problems than younger patients. Having prostate or gynecologic cancer was associated with the feeling that one's sexual life was negatively influenced. Conclusion: Sexual problems are common among patients with advanced cancer and should be addressed by the health care system.

Robot-assisted approach to cervical cancer (RACC): an international multi-center, open-label randomized controlled trial.

BACKGROUND: Radical hysterectomy with pelvic lymphadenectomy represents the standard treatment for early-stage cervical cancer. Results from a recent randomized controlled trial demonstrate that minimally invasive surgery is inferior to laparotomy with regards to disease-free and overall survival. PRIMARY OBJECTIVE: To investigate the oncologic safety of robot-assisted surgery for early-stage cervical cancer as compared with standard laparotomy. STUDY HYPOTHESIS: Robot-assisted laparoscopic radical hysterectomy is non-inferior to laparotomy in regards to recurrence-free survival with the advantage of fewer post-operative complications and superior patient-reported outcomes. TRIAL DESIGN: Prospective, multi-institutional, international, open-label randomized clinical trial. Consecutive women with early-stage cervical cancer will be assessed for eligibility and subsequently randomized 1:1 to either robot-assisted laparoscopic surgery or laparotomy. Institutional review board approval will be required from all participating institutions. The trial is coordinated from Karolinska University Hospital, Sweden. MAJOR INCLUSION/EXCLUSION CRITERIA: Women over 18 with cervical cancer FIGO (2018) stages IB1, IB2, and IIA1 squamous, adenocarcinoma, or adenosquamous will be included. Women are not eligible if they have evidence of metastatic disease, serious co-morbidity, or a secondary invasive neoplasm in the past 5 years. PRIMARY ENDPOINT: Recurrence-free survival at 5 years between women who underwent robot-assisted laparoscopic surgery versus laparotomy for early-stage cervical cancer. SAMPLE SIZE: The clinical non-inferiority margin in this study is defined as a 5-year recurrence-free survival not worsened by >7.5%. With an expected recurrence-free survival of 85%, the study needs to observe 127 events with a one-sided level of significance (α) of 5% and a power (1-ß) of 80%. With 5 years of recruitment and 3 years of follow-up, the necessary number of events will be reached if the study can recruit a total of 768 patients. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Trial launch is estimated to be May 2019 and the trial is estimated to close in May 2027 with presentation of data shortly thereafter. TRIAL REGISTRATION: The trial is registered at ClinicalTrials.gov (NCT03719547).

Using an intervention mapping approach to develop prevention and rehabilitation strategies for musculoskeletal pain among surgeons.

BACKGROUND: The aim of the present study was to describe the development of strategies to prevent and rehabilitate musculoskeletal pain among surgeons. Musculoskeletal pain affects surgeons' life, and evidence on interventions for effective prevention and rehabilitation is lacking for this occupational group. METHODS: An Intervention Mapping approach was used to develop intervention strategies specifically tailored to surgeons. This approach entailed conducting a systematic scoping literature search and semi-structured interviews with six surgeons. RESULTS: The first step was to develop a logic model of the problem of musculoskeletal pain among surgeons. Step two was to formulate health-enhancing outcomes and performance objectives for the intervention, while in step three theory-based methods and practical strategies for the intervention were identified. CONCLUSION: The present Intervention Mapping study demonstrated that musculoskeletal pain among surgeons is a complex area that needs attention. Our findings highlight a need for individual behavioural changes as well as organisational, attitudinal, and management changes.

Assessing Patient-reported Quality of Life Outcomes in Vulva Cancer Patients: A Systematic Literature Review.

OBJECTIVES: Vulva cancer (VC) treatment carries a high risk of severe late effects that may have a negative impact on quality of life (QoL). Patient-reported outcome measures (PROMs) are increasingly used when evaluating disease- and treatment-specific effects. However, the adequacy of measures used to assess sequelae and QoL in VC remains unclear. The aims of the present study were to evaluate disease- and treatment-related effects as measured by PROMs in VC patients and to identify available VC-specific PROMs. METHODS/MATERIALS: A systematic literature search from 1990 to 2016 was performed. The inclusion criterion was report of disease- and treatment-related effects in VC patients using PROMs in the assessment. Methodological and reporting quality was in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. This systematic review was performed as part of phase 1 of the development of a European Organisation for Research and Treatment of Cancer QoL questionnaire for VC patients. RESULTS: The search revealed 2299 relevant hits, with 11 articles extracted including a total of 535 women with VC; no randomized controlled trials were identified. The selected studies exhibited great heterogeneity in terms of PROMs use. Twenty-one different instruments assessed QoL. Most of the questionnaires were generic. Different issues (sexuality, lymphedema, body image, urinary and bowel function, vulva-specific symptoms) were reported as potentially important, but the results were not systematically collected. Only one VC-specific questionnaire was identified but did not allow for assessment and reporting on a scale level. CONCLUSIONS: Vulva cancer treatment is associated with considerable morbidity deteriorating QoL. To date, there is no validated PROM available that provides adequate coverage of VC-related issues. The study confirms the need for a VC-specific QoL instrument with sensitive scales that allows for broad cross-cultural application for use in clinical trials.

Detection of recurrence in early stage endometrial cancer - the role of symptoms and routine follow-up.

BACKGROUND: Considerable controversy remains as to the optimal organization of endometrial cancer follow-up. AIM: To evaluate the relationship between the way recurrence was detected and survival after treatment for endometrial cancer. Further, to identify characteristics associated with a pre-scheduled examination in women with symptomatic recurrence. MATERIAL AND METHODS: All women with early stage endometrial cancer during 2005-2009 were included in a population-based historical cohort derived from the Danish Gynecological Cancer Database. Women diagnosed with recurrence within three years after primary surgery and the mode of recurrence detection were identified from hospital charts: asymptomatic recurrence detected at regular follow-up, symptomatic recurrence detected at regular follow-up or symptomatic recurrence detected in between follow-up. Survival of women with symptomatic and asymptomatic disease was compared. Furthermore, characteristics associated with self-referral as compared to presenting symptoms at regular follow-ups were identified using univariate analyses. RESULTS: In total, 183 cases of recurrence (7%) were identified in the cohort of 2612 women. Of these, 65.5% were symptomatic with vaginal bleeding as the most prevalent symptom. Asymptomatic women had a significantly better three-year survival rate compared to symptomatic women (80.3% vs. 54.3%, p < 0.01). A total of 2.3% of the entire population had an asymptomatic recurrence. Women diagnosed at a pre-scheduled visit due to symptoms had a higher educational level (p = 0.03) and more often high-risk disease (p = 0.02) than symptomatic women diagnosed at regular follow-up. CONCLUSION: Early stage endometrial cancer carries a low risk of recurrence. Survival appears to be superior in asymptomatic patients, but length-time bias, i.e. the effect of aggressive tumor biology in symptomatic recurrences, may bias results in non-randomized controlled trials. Well educated patients with symptoms of recurrence more often sought medical attendance compared to less educated counterparts. This should be considered if patient-initiated follow-up is the standard care.