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Objective: Several European and American guidelines recommend to perform an additional hysterectomy in patients with cervical adenocarcinoma in situ (AIS), who initially received conservative treatment and who completed childbearing during follow-up. This study aimed to evaluate cost-effectiveness of performing an additional hysterectomy in comparison to expectative management., Methods: This post-hoc analysis was based on a retrospective cohort of patients diagnosed with AIS, who were conservatively treated by a radical (i.e., negative surgical margins) large loop excision of the transformation zone (LLETZ) or cold-knife conisation (CKC) in the Netherlands between 1990 and 2021. Based on these data, we estimated and compared the harms, benefits, and costs in 1000 simulated patients, both with and without an additional hysterectomy five years after conservative treatment for AIS. In the sensitivity analyses, we varied the timing of the additional hysterectomy, the risk of recurrent high-grade cervical dysplasia and cervical cancer risk after AIS treatment, and the utility loss for hysterectomy., Results: Less than 2 % of the patients who did not receive an additional hysterectomy after AIS developed cervical cancer. When an additional hysterectomy was performed, no quality adjusted life-years (QALYs) were gained and costs were 863 % higher (€6203,485 versus €644,238). Only when assuming no utility loss for a hysterectomy, QALYs were gained resulting in a cost-effectiveness ratio of €144,273, which is far above the cost-effectiveness threshold of €20,000., Conclusion: It is not cost-effective to perform an additional hysterectomy after completion of childbearing in patients who were primarily treated by a radical LLETZ or CKC., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: RB: gives lectures for MSD. All other authors declare that they have no competing interests., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: The majority of high-grade serous carcinomas (HGSC) of the ovary, fallopian tube, and peritoneum arise from the precursor lesion called serous tubal intraepithelial carcinoma (STIC). It has been postulated that cells from STICs exfoliate into the peritoneal cavity and give rise to peritoneal HGSC several years later. While co-existent STICs and HGSCs have been reported to share similarities in their mutational profiles, clonal relationship between temporally distant STICs and HGSCs have been infrequently studied and the natural history of STICs remains poorly understood., Methods: We performed focused searches in two national databases from the Netherlands and identified a series of BRCA1/2 germline pathogenic variant (GPV) carriers (n = 7) who had STIC, and no detectable invasive carcinoma, at the time of their risk-reducing salpingo-oophorectomy (RRSO), and later developed peritoneal HGSC. The clonal relationship between these STICs and HGSCs was investigated by comparing their genetic mutational profile by performing next-generation targeted sequencing., Results: Identical pathogenic mutations and loss of heterozygosity of TP53 were identified in the STICs and HGSCs of five of the seven patients (71%), confirming the clonal relationship of the lesions. Median interval for developing HGSC after RRSO was 59 months (range: 24-118 months)., Conclusion: Our results indicate that cells from STIC can shed into the peritoneal cavity and give rise to HGSC after long lag periods in BRCA1/2 GPV carriers, and argues in favor of the hypothesis that STIC lesions may metastasize., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to analyze morbidity and survival after pelvic exenteration for gynecologic malignancies and evaluate prognostic factors influencing postoperative outcome., Methods: We retrospectively reviewed all patients who underwent a pelvic exenteration at the departments of gynecologic oncology of three tertiary care centers in the Netherlands, the Leiden University Medical Centre, the Amsterdam University Medical Centre, and the Netherlands Cancer Institute, during a 20-year period. We determined postoperative morbidity, 2- and 5-year overall survival (OS) and 2- and 5-year progression free survival (PFS), and investigated parameters influencing these outcomes., Results: A total of 90 patients were included. The most common primary tumor was cervical cancer (n = 39, 43.3%). We observed at least one complication in 83 patients (92%). Major complications were seen in 55 patients (61%). Irradiated patients had a higher risk of developing a major complication. Sixty-two (68.9%) required ≥1 readmission. Re-operation was required in 40 patients (44.4%). Median OS was 25 months and median PFS was 14 months. The 2-year OS rate was 51.1% and the 2-year PFS rate was 41.5%. Tumor size, resection margins and pelvic sidewall involvement had a negative impact on OS (HR = 2.159, HR = 2.376, and HR = 1.200, respectively). Positive resection margins and pelvic sidewall involvement resulted in decreased PFS (HR = 2.567 and HR = 3.969, respectively)., Conclusion: Postoperative complications after pelvic exenteration for gynecologic malignancies are common, especially in irradiated patients. In this study, a 2-year OS rate of 51.1% was observed. Positive resections margins, tumor size, and pelvic sidewall involvement were related to poor survival outcomes. Adequate selection of patients who will benefit from pelvic exenteration is important., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare and there is no financial interest to report. We certify that the submission is original work and is not under review at any other publication., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: The "intermediate-risk" (IR) group of early-stage cervical cancer patients is characterized by negative pelvic lymph nodes and a combination of tumor-related prognostic risk factors such as tumor size ≥2 cm, lymphovascular space invasion (LVSI), and deep stromal invasion. However, the role of adjuvant treatment in these patients remains controversial. We investigated whether adjuvant (chemo)radiation is associated with a survival benefit after radical surgery in patients with IR cervical cancer., Methods: We analyzed data from patients with IR cervical cancer (tumor size 2-4 cm plus LVSI OR tumor size >4 cm; N0; no parametrial invasion; clear surgical margins) who underwent primary curative-intent surgery between 2007 and 2016 and were retrospectively registered in the international multicenter Surveillance in Cervical CANcer (SCCAN) study., Results: Of 692 analyzed patients, 274 (39.6%) received no adjuvant treatment (AT-) and 418 (60.4%) received radiotherapy or chemoradiotherapy (AT+). The 5-year disease-free survival (83.2% and 80.3%; P DFS = 0.365) and overall survival (88.7% and 89.0%; P OS = 0.281) were not significantly different between the AT- and AT+ groups, respectively. Adjuvant (chemo)radiotherapy was not associated with a survival benefit after adjusting for confounding factors by case-control propensity score matching or in subgroup analyses of patients with tumor size ≥4 cm and <4 cm. In univariable analysis, adjuvant (chemo)radiotherapy was not identified as a prognostic factor in any of the subgroups (full cohort: P DFS = 0.365; P OS = 0.282)., Conclusion: Among patients with IR early-stage cervical cancer, radical surgery alone achieved equal disease-free and overall survival rates to those achieved by combining radical surgery with adjuvant (chemo)radiotherapy., Competing Interests: Declaration of Competing Interest The authors declared no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: The value of serum human epididymis protein 4 (HE4) in guiding referral decisions in patients with an ovarian mass remains unclear, because the majority of studies investigating HE4 were performed in oncology hospitals. However, the decision to refer is made at general hospitals with a low ovarian cancer prevalence. We assessed accuracies of HE4 in differentiating benign or borderline from malignant tumors in patients presenting with an ovarian mass at general hospitals., Method: Patients with an ovarian mass were prospectively included between 2017 and 2021 in nine general hospitals. HE4 and CA125 were preoperatively measured and the risk of malignancy index (RMI) was calculated. Histological diagnosis was the reference standard., Results: We included 316 patients, of whom 195 had a benign, 39 had a borderline and 82 had a malignant ovarian mass. HE4 had the highest AUC of 0.80 (95%CI 0.74-0.86), followed by RMI (0.71, 95%CI 0.64-0.78) and CA125 (0.69, 95%CI 0.62-0.75). Clinical setting significantly influenced biomarker performances. Applying age-dependent cut-off values for HE4 resulted in a better performance than one cut-off. Addition of HE4 to RMI resulted in a 32% decrease of unnecessary referred patients, while the number of correctly referred patients remained the same., Conclusion: HE4 is superior to RMI in predicting malignancy in patients with an ovarian mass from general hospitals. The addition of HE4 to the RMI improved HE4 alone. Although, there is still room for improvement, HE4 can guide referral decisions in patients with an ovarian mass to an oncology hospital., Competing Interests: Declaration of Competing Interest All authors declare no conflict of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: Compliance of physicians with guidelines has emerged as an important indicator for quality of care. We evaluated compliance of physicians with adjuvant therapy guidelines for endometrial cancer patients in the Netherlands in a population-based cohort over a period of 10years., Methods: Data from all patients diagnosed with endometrial cancer between 2005 and 2014, without residual tumor after surgical treatment, were extracted from the Netherlands Cancer Registry (N=14,564). FIGO stage, grade, tumor type and age were used to stratify patients into risk groups. Possible changes in compliance over time and impact of compliance on survival were assessed., Results: Patients were stratified into low/low-intermediate (52%), high-intermediate (21%) and high (20%) risk groups. Overall compliance with adjuvant therapy guidelines was 85%. Compliance was highest in patients with low/low-intermediate risk (98%, no adjuvant therapy indicated). The lowest compliance was determined in patients with high risk (61%, external beam radiotherapy with/without chemotherapy indicated). Within this group compliance decreased from 64% in 2005-2009 to 57% in 2010-2014. In high risk patients with FIGO stage III serous disease compliance was 55% (chemotherapy with/without radiotherapy indicated) and increased from 41% in 2005-2009 to 66% in 2010-2014., Conclusion: While compliance of physicians with adjuvant therapy guidelines is excellent in patients with low and low-intermediate risk, there is room for improvement in high risk endometrial cancer patients. Eagerly awaited results of ongoing randomized clinical trials may provide more definitive guidance regarding adjuvant therapy for high risk endometrial cancer patients., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: Objectives of this study were to evaluate the effect of changes in patterns of care, for example centralization and treatment sequence, on surgical outcome and survival in patients with epithelial ovarian cancer (EOC)., Methods: Patients diagnosed with FIGO stage IIB-IV EOC (2004-2013) were selected from the Netherlands Cancer Registry. Primary outcomes were surgical outcome (extent of macroscopic residual tumor after surgery) and overall survival. Changes in treatment sequence (primary debulking surgery and adjuvant chemotherapy (PDS+ACT) or neo-adjuvant chemotherapy and interval debulking surgery (NACT+IDS)), hospital type and annual hospital volume were also evaluated., Results: Patient and tumor characteristics of 7987 patients were retrieved. Most patients were diagnosed with stage III-IV EOC. The average annual case-load per hospital increased from 8 to 28. More patients received an optimal cytoreduction (tumor residue≤1cm) in 2013 (87%) compared to 2004 (55%, p<0.001). Complete cytoreduction (no macroscopic residual tumor), registered since 2010, increased from 42% to 52% (2010 and 2013, respectively, p<0.001). Optimal/complete cytoreduction was achieved in 85% in high volume (≥20 cytoreductive surgeries annually), 80% in medium (10-19 surgeries) and 71% in small hospitals (<10 surgeries, p<0.001). Within a selection of patients with advanced stage disease that underwent surgery the proportion of patients undergoing NACT+IDS increased from 28% (2004) to 71% (2013). Between 2004 and 2013 a 3% annual reduction in risk of death was observed (HR 0.97, p<0.001)., Conclusion: Changes in pattern of care for patients with EOC in the Netherlands have led to improvement in surgical outcome and survival., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objectives: In patients with a granulosa cell tumor of the ovary, the value of serum inhibin A and B concentrations for the assessment of disease status was investigated., Methods: In 30 consecutive patients with a stage I-III granulosa cell tumor, inhibin A and B concentrations were measured in pre- and post-treatment serum samples. Clinical data concerning diagnosis, treatment and follow-up of these patients were related to serum inhibin A and B concentrations. Serum samples from 41 premenopausal females with cervical dysplasia served as controls., Results: In 30 patients, 13 (43%) recurrences were observed during a median follow-up of 10 years (range 1-31 years). Serum inhibin A and B concentrations were elevated in respectively 67% and 89% of the patients at diagnosis, and in 58% and 85% at recurrence. Inhibin A and B concentrations were normal in all controls. Sensitivity of inhibin A testing for the diagnosis of granulosa cell tumor was 67% with a specificity of 100%, compared to 89% and 100% respectively for inhibin B (ns). Elevations in serum inhibin B concentrations predated recurrences by a median of 11 months. None of the patients in remission showed increased concentrations of inhibin A and B., Conclusion: Inhibin B seems to be the predominant form of inhibin secreted by granulosa cell tumors and appears to reflect disease status more accurately than inhibin A. Measurement of serum inhibin B concentrations may be preferred for the follow-up of granulosa cell tumors.