Recently, the safety of laparoscopic radical hysterectomy (LRH) has been called into question in early-stage cervical cancer. This study aimed to evaluate overall survival (OS) and disease-free ...survival (DFS) in patients treated with abdominal radical hysterectomy (ARH) and LRH for early-stage cervical cancer and to provide a literature review.
Patients diagnosed between 2010 and 2017 with International Federation of Gynaecology and Obstetrics (2009) stage IA2 with lymphovascular space invasion, IB1 and IIA1, were identified from the Netherlands Cancer Registry. Cox regression with propensity score, based on inverse probability treatment weighting, was applied to examine the effect of surgical approach on 5-year survival and calculate hazard ratios (HR) and 95% confidence intervals (CIs). Literature review included observational studies with (i) analysis on tumours ≤4 cm (ii) median follow-up ≥30 months (iii) ≥5 events per predictor parameter in multivariable analysis or a propensity score.
Of the 1109 patients, LRH was performed in 33%. Higher mortality (9.4% vs. 4.6%) and recurrence (13.1% vs. 7.3%) were observed in ARH than LRH. However, adjusted analyses showed similar DFS (89.4% vs. 90.2%), HR 0.92 95% CI: 0.52–1.60) and OS (95.2% vs. 95.5%), HR 0.94 95% CI: 0.43–2.04). Analyses on tumour size (<2/≥2 cm) also gave similar survival rates. Review of nine studies showed no distinct advantage of ARH, especially in tumours <2 cm.
After adjustment, our retrospective study showed equal oncological outcomes between ARH and LRH for early-stage cervical cancer – also in tumours <2 cm. This is in correspondence with results from our literature review.
•Oncological outcome is equal after abdominal and laparoscopic radical hysterectomy.•Disease-free survival and overall survival are equal in tumours <2 cm.•The exact role of laparoscopy should be examined in prospective randomised trials.
Correct identification of patients with lymph node metastasis from cervical cancer prior to treatment is of great importance, because it allows more tailored therapy. Patients may be spared ...unnecessary surgery or extended field radiotherapy if the nodal status can be predicted correctly. This review captures the existing knowledge on the identification of lymph node metastases in cervical cancer. The risk of nodal metastases increases per 2009 FIGO stage, with incidences in the pelvic region ranging from 2% (stage IA2) to 14–36% (IB), 38–51% (IIA) and 47% (IIB); and in the para-aortic region ranging from 2 to 5% (stage IB), 10–20% (IIA), 9% (IIB), 13–30% (III) and 50% (IV). In addition, age, tumor size, lymph vascular space invasion, parametrial invasion, depth of stromal invasion, histological type, and histological grade are reported to be independent prognostic factors for the risk of nodal metastases. Furthermore, biomarkers can contribute to predict a patient’s nodal status, of which the squamous cell carcinoma antigen (SCC-Ag) is currently the most widely used in squamous cell cervical cancer. Still, pre-treatment lymph node assessment is primarily performed by imaging, of which diffusion-weighted magnetic resonance imaging has the highest sensitivity and 2-deoxy-2-
18
Ffluoro-D-glucose positron emission computed tomography the highest specificity. Imaging results can be combined with clinical parameters in nomograms to increase the accuracy of predicting positives nodes. Despite all the progress regarding pre-treatment prediction of lymph node metastases in cervical cancer in recent years, prediction rates are not robust enough to safely abandon surgical staging of the pelvic or para-aortic region yet.
Introduction
Serous ovarian carcinomas constitute the largest group of epithelial ovarian cancer (60%–75%) and are further classified into high‐ and low‐grade serous carcinoma. Low‐grade serous ...carcinoma (LGSC) is a relatively rare subtype (approximately 5% of serous carcinomas) and epidemiologic studies of large cohorts are scarce. With the present study we aimed to report trends in stage, primary treatment and relative survival of LGSC of the ovary in a large cohort of patients in an effort to identify opportunities to improve clinical practice and outcome of this relatively rare disease.
Material and Methods
Patients diagnosed with LGSC between 2000 and 2019 were identified from the Netherlands Cancer Registry (n = 855). Trends in FIGO stages and primary treatment were analyzed with the Cochran–Armitage trend test, and differences in and trends of 5‐year relative survival were analyzed using multivariable Poisson regression.
Results
Over time, LGSC was increasingly diagnosed as stage III (39.9%–59.0%) and IV disease (5.7%–14.4%) and less often as stage I (34.6%–13.5%; p < 0.001). Primary debulking surgery was the most common strategy (76.2%), although interval debulking surgery was preferred more often over the years (10.6%–31.1%; p < 0.001). Following primary surgery, there was >1 cm residual disease in only 15/252 patients (6%), compared with 17/95 patients (17.9%) after interval surgery. Full cohort 5‐year survival was 61% and survival after primary debulking surgery was superior to the outcome following interval debulking surgery (60% vs 34%). Survival following primary debulking surgery without macroscopic residual disease (73%) was better compared with ≤1 cm (47%) and >1 cm residual disease (22%). Survival following interval debulking surgery without macroscopic residual disease (51%) was significantly higher than after >1 cm residual disease (24%). Except FIGO stage II (85%–92%), survival did not change significantly over time.
Conclusions
Over the years, LGSC has been diagnosed as FIGO stage III and stage IV disease more often and interval debulking surgery has been increasingly preferred over primary debulking in these patients. Relative survival did not change over time (except for stage II) and worse survival outcomes after interval debulking surgery were observed. The results support the common recommendation to perform primary debulking surgery in patients eligible for primary surgery.
Neoadjuvant chemotherapy for low‐grade serous ovarian carcinoma increased over time. Overall 5‐year relative survival was 61% and did not change over time, except for FIGO stage II disease. Survival after primary surgery was superior to interval surgery.
Introduction
To establish the impact of the number of lymph node metastases (nLNM) and the lymph node ratio (LNR) on survival in patients with early‐stage cervical cancer after surgery.
Material and ...methods
In this nationwide historical cohort study, all women diagnosed between 1995 and 2020 with International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IA2–IIA1 cervical cancer and nodal metastases after radical hysterectomy and pelvic lymphadenectomy from the Netherlands Cancer Registry were selected. Optimal cut‐offs for prognostic stratification by nLNM and LNR were calculated to categorize patients into low‐risk or high‐risk groups. Kaplan–Meier overall survival analysis and flexible parametric relative survival analysis were used to determine the impact of nLNM and LNR on survival. Missing data were imputed.
Results
The optimal cut‐off point was ≥4 for nLNM and ≥0.177 for LNR. Of the 593 women included, 500 and 501 (both 84%) were categorized into the low‐risk and 93 and 92 (both 16%) into the high‐risk groups for nLNM and LNR, respectively. Both high‐risk groups had a worse 5‐year overall survival (p < 0.001) compared with the low‐risk groups. Being classified into the high‐risk groups is an independent risk factor for relative survival, with excess hazard ratios of 2.4 (95% confidence interval 1.6–3.5) for nLNM and 2.5 (95% confidence interval 1.7–3.8) for LNR.
Conclusions
Presenting a patient's nodal status postoperatively by the number of positive nodes, or by the nodal ratio, can support further risk stratification regarding survival in the case of node‐positive early‐stage cervical cancer.
To investigate and compare overall survival (OS), disease-free survival (DFS) and toxicity of women who underwent either chemoradiotherapy with or without prior lymph node debulking or upfront ...chemotherapy followed by radiotherapy and hyperthermia (triple therapy) for locally advanced cervical cancer (LACC) to identify a potential role for triple therapy.
Women with histologically proven LACC and with International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IB2 and IIA2 to IVA were included. Cox regression analyses were used for calculating hazard ratios and to adjust for confounding variables. A multivariable logistic regression analysis was used to examine the influence of covariates on toxicity.
A total of 370 patients were included of whom 58% (
= 213) received chemoradiotherapy (CRT), 18% (
= 66) received node-debulking followed by chemoradiotherapy (LND-CRT) and 25% (
= 91) received triple therapy (TT). Five-year OS was comparable between the three treatment groups, with 53% (95% confidence interval 46-59%) in the CRT group, 45% (33-56%) in the LND-CRT group and 53% (40-64%) in the TT group (
= 0.472). In the adjusted analysis, 5-year OS and DFS were comparable between the three treatment groups. No chemotherapy-related differences in toxicity were observed.
This study suggests that the toxicity and survival of TT is similar to CRT or LND-CRT.
This study aims to report trends in primary treatment and survival in cervical cancer (CC) to identify opportunities to improve clinical practice and disease outcome.
Patients diagnosed with CC ...between 1989 and 2018 were identified from the Netherlands Cancer Registry (N = 21,644). Trends in primary treatment and 5-year relative survival were analysed with the Cochran-Armitage trend test and multivariable Poisson regression, respectively.
In early CC, surgery remains the preferred treatment for ages 15–74. Overall, it was applied more often in younger than in older patients (92% in 15–44; 64% in 65–74). For 75+, surgery use was stable over time (38%–41%, p=0.368), while administration of radiotherapy decreased (57%–29%, p < 0.001). In locally advanced CC, chemoradiation use increased over time (5%–65%, p < 0.001). It was applied least often for 75+, in which radiotherapy remains most common (54% in 2014–2018). In metastatic CC, chemotherapy use increased over time (11%–28%, p < 0.001), but varied across age groups (6%–40% in 2014–2018). In patients treated with primary chemoradiation, regardless of stage, brachytherapy use increased over time (p ≤ 0.001). Full cohort 5-year survival increased from 68% to 74% (relative excess risk 0.55; 95% confidence interval 0.50–0.62). Increases were most significant in locally advanced CC (38%–60%; 0.55 0.47–0.65). Survival remained stable in 75+ (38%–34%; 0.82 0.66–1.02).
Relative survival for cervical cancer increased over the last three decades. The proportion of older patients receiving preferred treatment lags behind. Consequently, survival did not improve in the oldest patients.
•Relative survival of cervical cancer increased from 68% to 74%, over three decades.•Relative survival increased across all stages, but most in locally advanced stage.•Relative survival increased in ages 15–74, but remained stable in those aged 75+.•Chemoradiation use increased for all age groups, but the least in those aged 75+.•Brachytherapy use increased significantly, in combination with chemoradiation.
A multi‐active‐region bipolar‐cascade edge‐emitting laser emitting at nearly 900 nm is presented. The three active regions and two tunnel junctions located in a single waveguide core share the same ...third‐order vertical mode. A slope efficiency of 3.6 W/A was measured with a threshold current density of 230 A/cm2. The epitaxial layer stack developed features with very low internal optical losses of 0.7 cm−1. The voltage extrapolated to vanishing current is only 0.3 V larger than 3 times the voltage of 1.4 V originating from the photon energy.
•Similar oncological outcome and total proportions of adverse events between treatment strategies.•Strategies affect adverse events, quality of life and sexual functioning in different ...ways.•Differences allow room for personalised treatment.
Upon discovery of lymph node metastasis during radical hysterectomy with pelvic lymphadenectomy in early-stage cervical cancer, the gynaecologist may pursue one of two treatment strategies: abandonment of surgery followed by primary (chemo)radiotherapy (PRT) or completion of radical hysterectomy, followed by adjuvant (chemo)radiotherapy (RHRT). Current guidelines recommend PRT over RHRT, as combined treatment is presumably associated with increased morbidity. However, this review of literature suggests there are no significant differences in survival and recurrence and total proportions of adverse events between treatment strategies. Additionally, both strategies are associated with varying types of adverse events, and affect quality of life and sexual functioning differently, both in the short and long term. Although total proportions of adverse events were comparable between treatment strategies, lower extremity lymphoedema was reported more often after RHRT and symptom experience (e.g. distress from bladder or bowel problems) and sexual dysfunction more often after PRT. As reporting of adverse events, quality of life and sexual functioning were not standardised across the articles included, and covariate adjustment was not conducted in most of the analyses, comparability of studies is hampered. Accumulating retrospective evidence suggests no major differences on oncological outcome and morbidity after PRT and RHRT for intraoperatively discovered lymph node metastasis in cervical cancer. However, conclusions should be considered cautiously, as all studies were of retrospective design with small sample sizes. Still, treatment strategies seem to affect adverse events, quality of life and sexual functioning in different ways, allowing room for shared decision-making and personalised treatment.
Lymph node metastases (pN+) in presumed early-stage cervical cancer negatively impact prognosis. Using federated learning, we aimed to develop a tool to identify a group of women at low risk of pN+, ...to guide the shared decision-making process concerning the extent of lymph node dissection.
Women with cervical cancer between 2005 and 2020 were identified retrospectively from population-based registries: the Danish Gynaecological Cancer Database, Swedish Quality Registry for Gynaecologic Cancer and Netherlands Cancer Registry. Inclusion criteria were: squamous cell carcinoma, adenocarcinoma or adenosquamous carcinoma; The International Federation of Gynecology and Obstetrics 2009 IA2, IB1 and IIA1; treatment with radical hysterectomy and pelvic lymph node assessment. We applied privacy-preserving federated logistic regression to identify risk factors of pN+. Significant factors were used to stratify the risk of pN+.
We included 3606 women (pN+ 11%). The most important risk factors of pN+ were lymphovascular space invasion (LVSI) (odds ratio OR 5.16, 95% confidence interval CI, 4.59–5.79), tumour size 21–40 mm (OR 2.14, 95% CI, 1.89–2.43) and depth of invasion>10 mm (OR 1.81, 95% CI, 1.59–2.08). A group of 1469 women (41%)—with tumours without LVSI, tumour size ≤20 mm, and depth of invasion ≤10 mm—had a very low risk of pN+ (2.4%, 95% CI, 1.7–3.3%).
Early-stage cervical cancer without LVSI, a tumour size ≤20 mm and depth of invasion ≤10 mm, confers a low risk of pN+. Based on an international privacy-preserving analysis, we developed a useful tool to guide the shared decision-making process regarding lymph node dissection.
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•Federated learning was applied to analyse data while preserving privacy.•LVSI, tumour size, and depth of invasion were the most important risk factors of pN+.•41% of the women with early-stage cervical cancer were at low risk (2.4%) of pN+.
Cervical cancer with ≤5 mm depth of invasion and >7 mm horizontal spread is classified FIGO IA instead of FIGO IB in the revised staging system, as horizontal spread is no longer considered. We aimed ...to determine the incidence of lymph node metastasis (LNM) and, consequently, the necessity of pelvic lymph node assessment.
Patients diagnosed between January 2015 and May 2019 with cervical cancer FIGO (2009) stage IB with ≤5 mm depth of invasion and >7 mm horizontal spread, were identified from the Netherlands Cancer Registry. Associations between disease-characteristics and lymph node metastasis (LNM), and overall survival, were assessed.
Of 170 patients, six (3.5%) had LNM: 4/53 (7.6%) with adenocarcinoma and 2/117 (1.7%) with squamous cell carcinoma (p = .077). Four-year overall survival was 98.2%. LNM was observed more often in tumours with LVSI (4/43 patients, 9.3%) than without LVSI (2/117 patients, 1.7%) (p = .045). In adenocarcinoma with 3–5 mm depth of invasion LNM rate was 10% (4/40). None of the following tumours were observed with LNM: squamous cell carcinoma without LVSI (0/74); adenocarcinoma with <3 mm depth of invasion (0/13); <3 mm depth of invasion without LVSI (0/36).
Lymph node assessment is essential in any tumour with LVSI or in adenocarcinoma with 3–5 mm depth of invasion. It can be omitted in squamous cell carcinoma without LVSI, in adenocarcinoma with <3 mm depth of invasion and in any tumours without LVSI and with <3 mm depth of invasion.
•The necessity of pelvic lymph node assessment in microinvasive cervical cancer depends on LVSI and histological subtype•Lymph node assessment is essential in any tumour with LVSI•Lymph node assessment can be omitted in squamous cell carcinoma without LVSI•Lymph node assessment can be omitted in adenocarcinoma with <3 mm depth of invasion•Lymph node assessment can be omitted in tumours without LVSI and with <3 mm depth of invasion
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