Health-related quality of life metrics as endpoints in surgical trials: hype or hope?

The management of gynecological cancer has evolved considerably over the past decades in almost every field of treatment. Surgery plays a major role in the treatment algorithm. However, these invasive interventions can have profound implications for the quality of life (QoL) of affected individuals. The routine implementation of QoL measurements in clinical trials has become common, reflecting a new research 'standard', despite the fact that all available QoL instruments were not designed nor validated prospectively for surgical trials. This review seeks to address whether patient reported outcomes and QoL measurements rightfully take center stage in current surgical trials, leading to direct implementation for the benefit of patient care, or are they simply more of a researcher's hope. We will also provide an 'action plan' to better implement QoL measurements in future surgical trials.

Ovarian cancer management in an ESGO ovarian cancer center of excellence: a systematic case study of the interprofessional and interdisciplinary interaction.

PURPOSE: With growing knowledge about ovarian cancer over the last decades, diagnosis, evaluation and treatment of ovarian cancer patients have become highly specialized, and an individually adapted approach should be made in each woman by interdisciplinary cooperation. The present study aims to show the variety and extent of medical specialties involved at our institution according to the European Society of Gynecologic Oncology (ESGO) Quality indicators (QI). METHODS: A woman, diagnosed with high-grade ovarian cancer, International Federation of Gynecology and Obstetrics (FIGO) class IVb was selected for a single case observational study. The observation period (total = 22d) comprised preoperative diagnostic procedures, including imaging, the in-patient stay for cytoreductive surgery, and the postoperative course and case discussion at our interdisciplinary tumor board. Data were obtained by self-reporting and by patient file review. RESULTS: Patient tracking demonstrated an interdisciplinary cooperation of 12 medical specialties [62 physicians (63% male, 37% female)], 8 different types of nursing staff [n = 59 (22% male, 78% female)], and 9 different types of perioperative/administrative staff (n = 23; male 17,4%, female n = 19, 82,6%). Contact with the patient was direct (n = 199; 76%) or without face-to-face interaction (n = 63; 24%). CONCLUSION: The present study demonstrates the high diversity of physicians and the affiliated medical staff, as well as interdisciplinary intersections within teams of a specialized hospital. Matching the ESGO QIs, this report underlines the requirement of an adequate infrastructure for the complex management of advanced ovarian cancer patients. Future prospective studies are warranted to evaluate the specific procedures and actions to optimize the interprofessional and interdisciplinary workflows.

Prognostic value of CA125 kinetics, half-life, and nadir in the treatment of epithelial ovarian cancer: a systematic review and meta-analysis.

OBJECTIVE: To investigate the prognostic value of cancer antigen 125 (CA125) related variables on progression free survival and overall survival in primary and recurrent ovarian cancers. METHOD: A comprehensive review of the Medline, Embase, and Cochrane Library databases was conducted to identify relevant literature on survival outcomes according to the ELIMination Rate Constant K (KELIM), Gynecologic Cancer InterGroup (GCIG) CA125 response criteria, CA125 half-life, and CA125 nadir levels during first line or later line chemotherapy. The search included articles published before February 2023. Cut-off values determining the favorable/unfavorable score of each study were extracted, and pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were analyzed using a random effects model to identify the relationship between survival outcomes of the favorable/unfavorable groups, which was determined by an individual model using CA125 kinetics. RESULTS: A total of 27 studies with 14 444 patients with epithelial ovarian cancer were included in this meta-analysis. In primary ovarian cancer, a favorable KELIM score, determined by individual modeled cut-off values, was associated with a significant progression free survival (HR 0.53, 95% CI 0.45 to 0.62) and overall survival (HR 0.51, 95% CI 0.43 to 0.62) benefit in the primary setting. The favorable KELIM scored group also correlated with a better progression free survival (HR 0.54, 95% CI 0.47 to 0.62) in relapsed disease. We failed to demonstrate a better prognostic value of the GCIG response criteria and the CA125 half-life for progression free survival and overall survival. CONCLUSION: Novel chemotherapy response scores, such as KELIM, may be more clinically relevant than other prognostic models using CA125 kinetics, being directly associated with a more favorable survival in both the primary and relapsed setting in patients with epithelial ovarian cancer. STUDY REGISTRATION: The systemic review and meta-analysis were registered in PROSPERO (CRD42023385512).

Clinical value of pre-operative scoring systems to predict leiomyosarcoma: results of a validation study in 177 patients from the NOGGO-REGSA Registry.

OBJECTIVES: Benign leiomyomas are the most common uterine tumors. In contrast, uterine leiomyosarcomas are malignancies with a poor prognosis due to difficulties in early diagnosis and inappropriate surgical treatment. Most often they are diagnosed incidentally after surgery performed for treatment of leiomyoma. As the appropriate surgical treatment is crucial for survival of the patient, there is a high demand to predict leiomyosarcoma pre-operatively. Available scoring systems to discriminate leiomyoma from leiomyosarcoma are based on retrospective studies with limited numbers of patients and are not implemented in routine clinical practice. METHODS: The aim of our study was to evaluate a recently published score-the pre-operative leiomyosarcoma (pLMS) score-to determine whether it would have been predictive of leiomyosarcoma in 177 patients from the NOGGO-REGSA study, a German register of histologically proven gynecological sarcoma detected during routine clinical investigation. RESULTS: The threshold of the pLMS score for 'leiomyosarcoma not probable' (< -3) failed for 7.5% of the patients and the threshold 'indicator for leiomyosarcoma' (>+1) was true for 39.1% of the patients. 53.4% of the patients were attributed to the group 'additional investigations are recommended' (-3 to +1). The most relevant parameters in our analysis were suspicious sonography and rapid growth, but neither have been quantitatively defined. CONCLUSION: In our validation cohort, the pLMS score seems not to be a reliable tool to predict leiomyosarcoma and therefore we do not recommend its clinical implementation to identify leiomyosarcoma.

Frailty Index for prediction of surgical outcome in ovarian cancer: Results of a prospective study.

BACKGROUND: Complete macroscopic tumor resection is the strongest prognostic factor for patients with ovarian cancer, which requires complex surgery for achievement. Based on the mostly advanced tumor stage and high symptom burden many patients are classified as frail which may limit optimal surgical outcome. Aim of this study is to evaluate the predictive ability of Frailty Index for surgical outcomes in patients with ovarian cancer. METHODS: This prospective study enrolled patients with ovarian cancer undergoing cytoreductive surgery. We classified frailty proposed by Mitnitski et al. regarding the cumulative deficit model of frailty. Utilizing Receiver Operator Characteristic (ROC) analysis and logistic regression, we determined predictive clinical factors for severe postoperative complications. The Kaplan-Meier method and log-rank test were used for overall survival analysis. RESULTS: Out of f 144 enrolled patients, the overall prevalence of frailty based on a Frailty Index >0.26 and Frailty Index >0.15 was 33% and 74%, respectively. The logistic regression shows that frail patients with a Frailty Index >0.26 (Odds ratio (OR): 3.64, 95% CI: 1.34-9.85, p = 0.01), ECOG PS > 1 (OR 6.33, 95% CI:1.31-30.51, p = 0.02) and high surgical complexity score (OR 8.86, 95% CI:1.88-41.76, p = 0.006) had a significant higher risk for severe postoperative complications. According to multivariable cox regression Frailty Index >0.15 (hazard ratio (HR) (HR 1.87, 95% CI: 1.01-3.47, p = 0.048), residual tumor <1 cm (HR 2.75, 95%CI: 1.53-4.99, p = 0.001), residual tumor >1 cm (HR 5.00, 95% CI: 2.74-9.13, p < 0.001) and albumin<35.5 g/dl (HR 1.92, 95% CI: 1.08-3.43, p = 0.03) resulted as significant parameters for poor overall survival. Resulted as significant parameters for poor overall survival. CONCLUSION: Next to surgical complexity score, ECOG PS > 1 and recurrent surgery, Frailty Index >0.26 is associated with severe postoperative complications in patients with ovarian cancer. Besides tumor residuals and low albumin levels a Frailty Index >0.15 predicts poor survival.

Guidelines for vulvar and vaginal surgery: Enhanced Recovery After Surgery Society recommendations.

This is the first collaborative Enhanced Recovery After Surgery Society guideline for optimal perioperative care for vulvar and vaginal surgeries. An Embase and PubMed database search of publications was performed. Studies on each topic within the Enhanced Recovery After Surgery vulvar and vaginal outline were selected, with emphasis on meta-analyses, randomized controlled trials, and prospective cohort studies. All studies were reviewed and graded according to the Grading of Recommendations, Assessment, Development and Evaluation system. All recommendations on the Enhanced Recovery After Surgery topics are based on the best available evidence. The level of evidence for each item is presented.

Results of the interprofessional and interdisciplinary Berlin round table on patient-reported outcomes, quality of life, and treatment expectations of patients with gynecological cancer under maintenance treatment.

BACKGROUND: Patients' reported outcomes and their perspectives around their therapeutic management is a field of continuously increasing relevance in gynecological oncology. We report the results of the Berlin dialog on seven patient-reported parameters and outcomes concerning chemotherapy and maintenance treatment in patients with gynecological cancer. METHODS: Key opinion leaders in gynecological oncology from different European counties and representatives of leading patients' advocate groups in Berlin held a consensus meeting in Berlin on April 6, 2019. Seven topics of interest were identified in advance around quality of life, iatrogenic toxicity, treatment decision-making processes, sexuality, participation in clinical trials, second opinion, and long-term survivors with the the following standard operating procedure for processing and discussion: (1) agreement on its relevance; (2) literature review, and (3) discussion and consensus statements. RESULTS: All main topics reached a consensus approval. The defined statements emphasized the importance of patients' role in incorporating and establishing quality of life as an outcome parameter in clinical trials. Furthermore, discussants raised the importance of identifying new tools for reflecting patient-reported iatrogenic toxicity as well as emphasizing patients' rights in providing personal information, access to second opinion in the decision-making process, and their participation in clinical trials. CONCLUSION: The results of this round table meeting could help redefine perspectives on the discussed topics and the importance for therapeutic management as well as for trial designs.

Prehabilitation programs and ERAS protocols in gynecological oncology: a comprehensive review.

PURPOSE: The "Enhanced recovery after surgery" (ERAS) concept has been continuously developed for many surgical disciplines. Shorter length of stay (LOS) and associated cost savings have been achieved without an increase in the complication or readmission rate. Current guidelines helped to support an increasing standardisation of care. One innovation of the recently published update is the proposal to integrate prehabilitation (PREHAB) into the ERAS concept. On this basis, the authors provide an overview of the current data on ERAS concepts in gynecological oncology and review the evidence of prehabilitation concepts. METHODS: Systematic literature review of all comparative studies on ERAS concepts in gynecological oncology and prehabilitation undergoing abdominal cancer surgery was performed using the standard databases. Outcomes of interest included prehabilitation program composition (exercise, nutritional, and psychological interventions), duration and outcome measures used to determine impact of prehabilitation vs. standard care. RESULTS: Five studies reported on PREHAB programs in gynecology (three RCTs, one study protocol, one pilot study). There is no trial evaluating a pathway for patients with extensive ovarian or cervical cancer. Study protocols were heterogenous, but showed improvements in both physical and psychological parameters. ERAS protocols in ovarian cancer patients were investigated in 12 observational studies, mostly single center and only 1 RCT, in 4 studies patients with ovarian cancer or patients. Most studies showed improvement in complication rate and shorter LOS. DISCUSSION: PREHAB programs seem feasible in abdominal cancer surgery and may improve surgical outcome. However, there is no prospective trial in gynecological oncology so far. Furthermore, there is no concept combining ERAS and PREHAB interventions. Therefore, the authors encourage the further development of both by describing in a novel treatment algorithm.

Patients' perspectives towards malignant ascites: results of a prospective observational trial regarding expectations, characteristics and quality of life-a study of the North-Eastern-German Society of Gynecological Oncology.

PURPOSE: Malignant ascites (MA) is a frequent and common symptom in (gyneco-) oncological patients. The present trial evaluated and assessed patients' characteristics, clinical features and the possible influence of MA on QoL measurements. METHODS: A prospective observational trial was conducted from Oct 2013 until Nov 2016. Therefore an interdisciplinary questionnaire was developed. Overall 250 patients with histological confirmed MA were included with different cancer entities (gynecological, gastrointestinal). The correlation of MA caused symptoms and QoL measurements was assessed using Kendall's tau b. Multivariable logistic regression models were applied to analyze the risks of symptoms or severe limitation in daily activities. RESULTS: 125 questionnaires could be analyzed. The majority of patients with MA had diagnosis of ovarian cancer (68.8%) and were under current cancer treatment (57.6%), mostly chemotherapy. Over 50% reported abdominal tension as major symptom, around 56% of the patients had MA when cancer was firstly diagnosed. Regression analysis showed that patients with MA above 2l were significantly more likely to be harmed in everyday activities. However, the age, gender, type of malignancy and the current treatment (chemotherapy vs. no chemotherapy) had no significant influence. CONCLUSION: MA has a significantly impact on QoL measurements in cancer patients and might influence everyday activities including basic needs like eating, walking and body care. There is a high need for more information and education of patients with MA.

The growth of uterine myomas in untreated women: influence factors and ultrasound monitoring.

PURPOSE: Until now there are no systematic studies about the long-term course of myoma growth. Therefore, the aims of the present study were: (1) ultrasound monitoring of the natural course of growth of uterine leiomyomas; (2) assessment of whether the growth of myomas depends on the age of the patients, the location, or the initial size (possible co-factors/predictor criteria for increase of growth); influence of oral contraceptives (OC). METHODS: Patient records (2010-May 2016) were retrospectively and systematically evaluated in regards to their growth and clinical course. The patients received a follow-up questionnaire by mail about the further history. Linear regression analysis and generalized regression analysis were performed to determine the influence of various factors on the growth of myomas. RESULTS: Overall, 152 met the further inclusion criteria. Most of the myomas increased in size but 10% of the myomas became smaller without therapy. There is a significant dependency between the initial myoma size, and the first and second measurements, but not between those measures and myoma localization. In regression analysis, there was also a significant association between the growth of the myomas and the initial size but no association with age, complaint symptoms, and use of OC. However, the use of OC waas significantly associated with myoma growth in GEE. CONCLUSIONS: The course of growth of myomas has large variance, so this should not be taken as a sign for a malignant event (sarcoma or the so-called STUMP). The growth takes place with considerable individual variability and ultimately is not predictable.

Correlation of intrapartum translabial ultrasound parameters with computed tomographic 3D reconstruction of the female pelvis.

AIMS: Intrapartum translabial ultrasound [ITU] can be an objective, reproducible and more reliable method than digital vaginal examination when evaluating fetal head position and station in prolonged second stage of labor. However, two-dimensional (2D) ultrasound is not sufficient to demonstrate the ischial spines and other important "landmarks" of the female pelvis. Therefore, the purpose of this study was to evaluate the distance of the interspinous plane as a parallel line to the infrapubic line in 2D ITU with the help of 3D computed tomography and digital reconstruction. RESULTS: Mean distance between the infrapubic plane and the tip of the ischiadic spine was 32.35 (±4.46) mm. The mean height was 166 (±7) cm; the mean weight was 67.5 (±18.4) kg. Body height and the measured distance were significantly correlated (P=0.025; correlation coefficient of 0.5), whereas body weight was not (P=0.37; correlation coefficient of -0.214). CONCLUSIONS: With the present results, clinicians were enabled to transfer the reproducible measurements of the "head station" by ITU to the widespread but observer-depending vaginal examination. Furthermore, ITU can be verified as an objective method in comparison to subjective palpation with the ability to optimize the evaluation of the head station according to bony structures as landmarks in a standardized application.

Sonographic Monitoring of Growth of Uterine Myomas in Untreated Women and Respective Influence Factors.

Research Question What are the growth patterns of uterine myomas in untreated premenopausal women? Which factors influence the growth rate of uterine myomas in premenopausal women? Method All premenopausal women who presented to the outpatient myoma consultation clinic between January 2005 and March 2022 at least twice were screened. Exclusion criteria were hormonal therapy, pregnancy, and postmenopausal status. Results A total of 189 patients were included in our study which focused on the respective largest uterine myoma of each woman. An ideal linear growth over time was assumed. Most myomas (82%) increased in size. The mean annual growth of these myomas was 68.42 cm 3 . The most important prognostic factor for growth was the initial size of the myoma. The absolute annual growth of myomas measuring > 50 cm 3 at first presentation was higher compared to smaller myomas (p < 0.001). The relative annual growth rate was highest for myomas measuring between 20 and 50 cm 3 at the initial presentation (p = 0.003). The relative annual growth rate in women older than 40 years was significantly lower than that in women below the age of 40 years (p = 0.003). Conclusion Overall, it is difficult to make an individual prognosis about the growth pattern of a uterine myoma in a specific patient. It should be noted especially in asymptomatic patients that spontaneous regression of myoma size can also occur in premenopausal women.

Primary Treatment Results in Patients with Ovarian, Fallopian or Peritoneal Cancer-Results of a Clinical Cancer Registry Database Analysis in Germany.

Background: The current therapy of ovarian cancer is based on the so-called "Three-Pillar-Model", consisting of surgery, chemotherapy and maintenance therapy. This study represents the first major analysis of a federal cancer database of OC patients from the states Berlin/Brandenburg in Germany. The primary objective was to evaluate the prevailing established quality indicators surgical outcome, adjuvant chemotherapy and integrity of surgical staging in early stages. Methods: Data from the Clinical Cancer Registry for Brandenburg and Berlin of the years 2009−2019 were analyzed. Objectives were defined by a working group of selected physicians. Descriptive statistics were performed, as well as survival analysis. Results: A total of 2771 primary OC cases were included. Results regarding histological subtype met the suspected allocation with predominantly high-grade serous OC in advanced stage. The rate of complete surgical staging in FIGO stages I−IIA was 57%, and the rate of macroscopic complete resection in >FIGO III was 53%. Five-year survival rate varied from 79% (FIGO I) to 40% (FIGO III). Rate of adjuvant chemotherapy was above 50%. Conclusion: The results elucidate quality measurements and treatment results and show good treatment outcomes in patients with primary diagnosis. However, they also indicate deficits and can help to establish new quality indicators to further improve the treatment.

Sentinel Lymph Node Staging with Indocyanine Green for Patients with Cervical Cancer: The Safety and Feasibility of Open Approach Using SPY-PHI Technique.

(1) Background: Sentinel lymph node staging (SLN) with indocyanine green (ICG) in cervical cancer is the standard of care in most national and international guidelines. However, the vast majority of relevant studies about the safety and feasibility of this method are conducted on minimally invasive surgery; (2) Methods: This study is a retrospective analysis of a retrospective collected database of 76 consecutive patients with cervical cancers, who were operated laparoscopically (50%), or laparotomy (50%). Sentinel nodes were defined as the ICG-positive pelvic nodes in the first and second echelons. False negative cases were defined as positive non-sentinel lymph nodes despite successful sentinel mapping or failed mapping bilaterally by per-patient assessment or unilaterally by pelvic sidewall assessment; (3) Results: Regardless of the approach (open or laparoscopic), the SLN technique achieved a total sensitivity, specificity, and negative predictive value (NPV) of 94.7%, 98.6%, and 94.7%, respectively in the entire sample. The bilateral detection rate was as high as 93.4% with identical results in both approaches. The sensitivity and NPV for SNL in open surgery was found to be similar to minimal access surgery; (4) Conclusions: ICG and SPY-PHI technique is a reliable tool to detect sentinel lymph nodes in cervical cancer during laparotomy.

Results of a German wide survey towards current surgical approach in early stage cervical cancer NOGGO MONITOR 11.

Minimally invasive surgery (MIS) has become the standard approach in early stage cervical cancer (ECC). However, the recently published "LACC" trial and even others could show inferior PFS and OS of MIS compared to open radical hysterectomy. The results led to a widespread debate about the best surgical approach in ECC. The present survey aimed to get first insights after publication. NOGGO and AGE conducted a nationwide digital survey among 186 Gynecological Cancer Centers. Descriptive statistics and t-tests were performed using SPSS. A majority of the centers were of high expertise and/or experience in treatment of ECC and were highly aware of the LACC trial results. Trial quality and scientific value were rated as very good/good. However, still 40% would not change the standard of care to open surgery. Centers with higher volume and participating in clinical trials were more likely to change. This survey represents insights after the surprising results of recently published trials towards the surgical approach of ECC. There still seems to be a high need of future trials and possible explanations for the unexpected worse outcomes in the MIS group.

Bevacizumab Combined with Platinum-Taxane Chemotherapy as First-Line Treatment for Advanced Ovarian Cancer: Results of the NOGGO Non-Interventional Study (OTILIA) in 824 Patients.

In the single-arm non-interventional OTILIA study, patients with newly diagnosed International Federation of Gynecology and Obstetrics (FIGO) stage IIIB-IV ovarian cancer received bevacizumab (15 mg/kg every 3 weeks for up to 15 months) and standard carboplatin-paclitaxel. The primary aim was to assess safety and progression-free survival (PFS). Subgroup analyses according to age were prespecified. The analysis population included 824 patients (453 aged <70 years, 371 aged ≥70 years). At data cutoff, the median bevacizumab duration was 13.8 months. Grade ≥3 adverse events (AEs), serious AEs, and AEs leading to bevacizumab discontinuation were more common in older than younger patients, whereas treatment-related AEs were less common. Median PFS was 19.4 months, with no clear difference according to age (20.0 vs. 19.3 months in patients <70 vs. ≥70 years, respectively). One-year OS rates were 92% and 90%, respectively. Mean change from baseline in global health status/quality of life showed a clinically meaningful increase over time. In German routine oncology practice, PFS and safety were similar to reported randomized phase 3 bevacizumab trials in more selected populations. There was no notable reduction in effectiveness and tolerability in patients aged ≥70 years; age alone should not preclude use of bevacizumab-containing therapy. ClinicalTrials.gov: NCT01697488.

Nerve Sparing Radical Hysterectomy: Short-Term Oncologic, Surgical, and Functional Outcomes.

There is an obvious prevalence of disparity in opinions concerning the technique of nerve-sparing radical hysterectomy and its application, despite agreement on the need to spare the pelvic autonomic nerve system during such a radical operation. Understanding the precise three-dimensional anatomy of paracolpium and its close anatomical relationship to the components of the pelvic autonomic nervous system is the key in performing the nerve-sparing radical hysterectomy. A total of 42 consecutive patients with primary cervical cancers, who were operated upon in our institution between January 2017 and June 2019, were analyzed, concerning surgical, urinary functional, and short-term oncologic outcomes. Two thirds of the patients had locally advanced tumors (T > 40 mm or pT ≥ IIA2) with a median tumor size of 44.1 mm. The nerve-sparing radical hysterectomy was combined with the complete recovery of bladder function in 90% of patients directly after surgery and in 97% of patients in the first 2 weeks. The recurrence rate in a median follow-up time of 18 months was 9.5%. The nerve-sparing radical hysterectomy approach, which depends on the comprehensive understanding of the precise entire anatomy of paracolpium, was found to be feasible and applicable, even in locally advanced tumors, with good functional results and convincing short-term oncologic outcomes.

Case report of severe maternal hyponatremia complicating preeclampsia.

The incidence of preeclampsia associated maternal and neonatal hyponatremia is reportedly rare and can be life threatening in severe cases. The timely diagnosis and careful management requires a multidisciplinary approach between obstetric, neonatal, endocrinology, and intensive care teams. We report firstly, on a case of severe hyponatremia associated with preeclampsia, secondary to inappropriate Anti-Diuretic Hormone secretion, followed by a review of cases over a one year period at our institution.