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Abstract Purpose of the review More than 50% of all gynaecological cancers can be classified as rare tumours (defined as an annual incidence of <6 per 100,000) and such tumours represent an important challenge for clinicians. Recent findings Rare cancers account for more than one fifth of all new cancer diagnoses, more than any of the single common cancers alone. Reviewing the RARECAREnet database, some of the tumours occur infrequently, whilst others because of their natural history have a high prevalence, and therefore appear to be more common, although their incidence is also rare. Harmonization of medical practice, guidelines and novel trials are needed to identify rare tumours and facilitate the development of new treatments. Ovarian tumours are the focus of this review, but we comment on other rare gynaecological tumours, as the diagnosis and treatment challenges faced are similar. Future This requires European collaboration, international partnerships, harmonization of treatment and collaboration to overcome the regulatory barriers to conduct international trials. Whilst randomized trials can be done in many tumour types, there are some for which conducting even single arm studies may be challenging. For these tumours alternative study designs, robust collection of data through national registries and audits could lead to improvements in the treatment of rare tumours. In addition, concentring the care of patients with rare tumours into a limited number of centres will help to build expertise, facilitate trials and improve outcomes. [ABSTRACT FROM AUTHOR]

The role of lymphadenectomy in the management of early endometrial cancer remains controversial. In the recent ESMO-ESGO-ESTRO guidelines, lymphadenectomy is recommended for patients with endometrioid adenocarcinoma Grade 3 with deep myometrial invasion, but complete agreement was not achieved. In Sweden, DNA aneuploidy has been included as a high-risk factor. The aim of our study was to evaluate the impact of tumor histology, FIGO grade, DNA ploidy and myometrial invasion (MI) on occurrence of lymph node metastasis (LNM) in patients with endometrial cancer. The study design is a retrospective cohort study based on prospectively recorded register data. Endometrial cancer patients registered in the Swedish Quality Registry for Gynecologic Cancer 2010-2015 with FIGO Stages I-III and verified nodal status were included. Data on DNA ploidy, histology, FIGO grade and MI were included in multivariable log-binomial regression analyses with LNM as dependent variable. 1,165 cases fulfilled the inclusion criteria. The multivariable analyses revealed increased risk of LNM in patients with tumors with MI ≥ 50% (risk ratio [RR] = 4.1; 95% confidence interval [CI] 3.0-5.6), nonendometrioid compared to endometrioid histology (RR 1.8; CI 1.4-2.4) and FIGO Grade 3 compared to Grade 1-2 tumors (RR 1.5; CI 1.1-2.0). No statistically significant association between DNA ploidy status and LNM was detected. This population-based, nation-wide study in women with endometrial cancer confirms a strong association between MI ≥ 50%, nonendometrioid histology and FIGO Grade 3, respectively, and LNM. DNA ploidy should not be included in the preoperative decision making of removing nodes or not. [ABSTRACT FROM AUTHOR]

1. Many observations in acute myocardial infarction are difficult to explain and are similar to those made in experimental intravascular sludging. 2. Intravascular sludging is a consistent observation in acute myocardial infarction. 3. This sludging was treated in a well-established manner with low molecular dextran in an effort to determine if the sludging was a significant factor in the pattern of infarction and whether its control would be beneficial to the patient. 4. The results indicate that the sludging is undoubtedly a factor in the pattern of myocardial infarction. 5. Clinical observations and mortality figures are encouraging and do not contraindicate further study in this problem. Any further conclusions regarding benefits to the patients are unjustified in this preliminary stage. [ABSTRACT FROM AUTHOR]

The impact of surgical learning curve on survival - reopening the door for minimally invasive surgery in the management of cervical cancer? Minimally invasive surgery has been widely adopted in gynaecological oncology with a significant surge since 2010 associated with the introduction of robot-assisted surgery. The unexpected results from the only randomised controlled trial (Ramirez et al. I N Engl J Med i 2018;379:1895-904) seriously challenge the use of minimally invasive surgery for cervical cancer. [Extracted from the article]

Objective: Patients with TNM T1a cervical cancer have excellent prognosis; however, the risk for recurrence remains an issue of concern and management guidelines are based on limited data. Here we performed subgroup analysis of the Surveillance in Cervical Cancer (SCCAN) consortium with the objective of defining the prognosis of T1a cervical cancer patients., Methods: SCCAN was an international, multicentric, retrospective cohort study of patients with cervical cancer undergoing surgical treatment in tertiary centers. Inclusion criteria included: histologically confirmed cervical cancer treated between 2007 and 2016; TNM T1a; primary surgical management; and at least 1-year of follow-up data availability. Exclusion criteria included treatment with primary chemo-radiation, and missing treatment-related or clinical data., Results: Out of 975 patients included, 554 (57 %) were T1a1 and 421 (43 %) T1a2. The majority had squamous-cell carcinoma (78 %). 79 patients (8.1 %) had lymphovascular space invasion (LVSI). 455 patients (47 %) underwent radical hysterectomy/ parametrectomy. Laparoscopic and open surgery was performed in 401 (41 %) and in 361 (37 %) patients, respectively. Adjuvant treatment was administered to 56 patients (5.7 %). Assessment of lymph nodes (LN) was performed in 524 patients (54 %), with LN involvement found in 15 (2.9 %). There were 40 (4.1 %) recurrences, occurring at a median of 26 months (4-106), out of which 33 (82.5 %) occurred in pelvis. Among T1a1 cases, there were 10 recurrences (2.0 %) if LVSI was negative, and 3 recurrences (6.7 %) if LVSI was positive. Among T1a2 cases, there were 23 recurrences (6.7 %) if LVSI was negative, and 4 recurrences (5.1 %) if LVSI was positive. There were 3 recurrences in the LN+ group (recurrence rate 20 %)., Conclusions: The risk of recurrence in T1a cervical cancer was 4.1 % corresponding to the rates seen in patients with FIGO 1B cancer in recently published prospective trials. LN involvement represents a risk factor for disease recurrence. Our results indicate that stage T1a cervical cancer, apart from T1a1 LVSI negative disease, should follow the same principles in the management as that of FIGO stage 1B cancer., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest for this research publication., (Copyright © 2024. Published by Elsevier Inc.)

Background: In the FIGO 2018 classification, women with cervical cancer and a depth of invasion ≤ 5 mm and a horizontal spread of > 7 mm in excisional biopsy with tumour-free margins, are now classified as stage IA instead of IB. This stage shift may reduce the likelihood of surgical lymph node staging. It is therefore crucial to estimate the risk and risk factors of lymph node metastasis (pN+) in this group., Methods: Women diagnosed with cervical cancer between 2005 and 2022 were identified from nationwide population-based registries from the Netherlands, Denmark, and Sweden. Inclusion criteria were squamous cell carcinoma or adenocarcinoma, FIGO 2009 stage IB1, a depth of invasion ≤ 5 mm and horizontal spread of > 7-≤ 40 mm. All cases underwent radical hysterectomy or radical trachelectomy, and surgical lymph node staging. Logistic regression was used to identify risk factors of pN+., Results: We included 992 women (pN+ 4.1 %; n = 41). Lymphovascular space invasion (LVSI) was a significant risk factor of pN+ (odds ratio 4.26, 95 % confidence interval 2.24-8.32). Accordingly, the risk of pN+ was ≥ 7.3 % in LVSI-positive tumours. The risk was lowest in LVSI-negative tumours with a size of > 7-≤ 20 mm (2.2 %), although this varied by depth of invasion and histological subtype (pN+ range 0.6-5.1 %)., Conclusion: Women with LVSI-positive FIGO 2018 IA cervical cancer and a horizontal spread > 7 mm, should undergo surgical lymph node staging. In LVSI-negative tumours, lymph node staging should not be routinely performed; tumour size, depth of invasion and histology should be considered., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: HF: Board Member Surgical Science, PJ: MSD Advisory Board for cervical cancer, All other authors declare that they have no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Assessment of retroperitoneal nodes is an important part of the surgical staging of gynecologic cancers. Although pelvic and paraaortic lymphadenectomy have been widely described by different authors, there is little consensus on the description of the different surgical steps for each procedure. An Intergroup Committee on Onco-Gyn Minimally Invasive Surgery has been established with members of the European Society for Gynecological Endoscopy (ESGE), European Society of Gynaecological Oncology (ESGO) and the Society of European Robotic Gynaecological Surgery (SERGS). The Intergroup Committee has various objectives: writing down a surgical description of the technique, which will be assessed by a group of experts following a formal consensus method and developing a specific Objective Structured Assessment of Technical Skills (OSATS) scale for each procedure., Methods: A hierarchical task analysis was conducted by a working group of eight experts from the three societies in order to identify the surgical steps of transperitoneal and extraperitoneal approach in paraaortic lymphadenectomy. The selection of the definitive surgical steps was confirmed by a group of 19 experts from the different societies, following a formal consensus method. Two rounds of Delphi panel rating were considered necessary for achieving an agreement. The consensus agreement identified 29 surgical steps in transperitoneal and 17 surgical steps in extraperitoneal approach to complete a paraaortic lymphadenectomy. Once the description of the procedure and the consensus were established, an Objective specific Scale for the Assessment of Technical Skills for Paraaortic lymphadenectomy (PA-OSATS) in the transperitoneal and extraperitoneal approach was developed., Results: In the first round of rating we found that 28 steps out of 29 in the transperitoneal approach and 13 out of 17 in the extraperitoneal approach did not reach a strong degree of agreement. They were reformulated based on comments made by the experts, and submitted to a second round of rating and this finally achieved an agreement., Conclusion: We defined a list of surgical steps in transperitoneal and extraperitoneal approach in paraaortic lymphadenectomy and a specific PA-OSATS scale for these procedures. This tool will be useful for teaching, assessing and standardizing this surgical procedure., Competing Interests: Competing interests: AEB has reported grants for travelling from Olympus; AF has reported advisory boards for Johnson & Johnson, Fondazione Internazionale Menarini and Oncoinvent, research support from AstraZeneca/MSD, and speakers bureau for GlaxoSmithKline and Covidien/Medtronic; RR, LM, FP, HF, MB, DQ, and CT have reported no conflicts of interest., (© IGCS and ESGO 2024. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

After the publication of the Laparoscopic Approach to Cervical Cancer (LACC) trial, open surgery has become the standard approach for radical hysterectomy in early stage cervical cancer. Recent studies assessed the role of a non-radical approach in low risk cervical cancer and showed no survival difference compared with radical hysterectomy. However, there is a gap in knowledge regarding the oncologic outcomes of minimally invasive simple hysterectomy in low risk cervical cancer. This review offers an overview of the current evidence on the role of the minimally invasive approach in low risk cervical cancer and raises the need for a new clinical trial in this setting., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Aim: The aim of this study was to assess whether the use of sentinel lymph node (SLN) in addition to lymphadenectomy was associated with survival benefit in patients with early-stage cervical cancer., Methods: International, multicenter, retrospective study., Inclusion Criteria: cervical cancer treated between 01/2007 and 12/2016 by surgery only; squamous cell carcinoma, adenocarcinoma, adenosquamous carcinoma, FIGO 2009 stage IB1-IIA2, negative surgical margins, and laparotomy approach. Patients undergoing neo-adjuvant and/or adjuvant treatment and/or with positive para-aortic lymph nodes, were excluded. Women with positive pelvic nodes who refused adjuvant treatment, were included. Lymph node assessment was performed by SLN (with ultrastaging protocol) plus pelvic lymphadenectomy ('SLN' group) or pelvic lymphadenectomy alone ('non-SLN' group)., Results: 1083 patients were included: 300 (27.7 %) in SLN and 783 (72.3 %) in non-SLN group. 77 (7.1 %) patients had recurrence (N = 11, 3.7 % SLN versus N = 66, 8.4 % non-SLN, p = 0.005) and 34 (3.1 %) (N = 4, 1.3 % SLN versus N = 30, 3.8 % non-SLN, p = 0.033) died. SLN group had better 5-year disease-free survival (DFS) (96.0 %,95 %CI:93.5-98.5 versus 92.0 %,95 %CI:90.0-94.0; p = 0.024). No 5-year overall survival (OS) difference was shown (98.4 %,95 %CI:96.8-99.9 versus 96.8 %,95 %CI:95.4-98.2; p = 0.160). SLN biopsy and lower stage were independent factors associated with improved DFS (HR:0.505,95 %CI:0.266-0.959, p = 0.037 and HR:2.703,95 %CI:1.389-5.261, p = 0.003, respectively). Incidence of pelvic central recurrences was higher in the non-SLN group (1.7 % versus 4.5 %, p = 0.039)., Conclusion: Adding SLN biopsy to pelvic lymphadenectomy was associated with lower recurrence and death rate and improved 5-year DFS. This might be explained by the lower rate of missed nodal metastasis thanks to the use of SLN ultrastaging. SLN biopsy should be recommended in patients with early-stage cervical cancer., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Abu-Rustum received research funding paid to the institution from GRAIL. Memorial Sloan Kettering Cancer Center also has equity in GRAIL. All remaining authors have declared no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: According to international guidelines, standard treatment (ST) with curative intent in cervical cancer (CC) comprises radical hysterectomy and pelvic lymphadenectomy in early stages (International Federation of Gynecology and Obstetrics (FIGO) 2009 IB1, IIA1), adjuvant chemoradiation is recommended based on risk factors upon final pathology. Definitive chemoradiation is recommended in locally advanced stages (FIGO 2009 IB2, IIA2, IIB). Total mesometrial resection (TMMR) with therapeutic lymph node dissection (tLND) without adjuvant radiation has emerged as a promising treatment. Here we compare oncologic outcome by TMMR + tLND or ST., Methods: In this observational cohort study, women treated according to international guidelines were identified in the population-based registries from Sweden and women treated with TMMR were identified in the Leipzig Mesometrial Resection (MMR) Study Database (DRKS 0001517) 2011-2020. Relevant clinical and tumour related variables were extracted. Recurrence-free survival (RFS) and overall survival (OS) by ST or TMMR was analysed with log-rank test, cumulative incidence function and proportional hazard regression yielding hazard ratios (HR) with 95% confidence intervals (CI), adjusted for relevant confounders., Findings: Between 2011 and 2020, 1007 women were included in the final analysis. 733 women were treated according to ST and 274 with TMMR. RFS at five years was 77.9% (95% CI 74.3-81.1) and 82.6% (95% CI 77.2-86.9) for the ST and TMMR cohorts respectively (p = 0.053). In early-stage CC, RFS was higher after TMMR as compared to ST, 91.2% vs 81.8% (p = 0.002). In the adjusted analysis, TMMR was associated with a lower hazard of recurrence (HR 0.39; 95% CI 0.22-0.69) and death (HR 0.42; 95% CI 0.21-0.86) compared to ST. The absolute difference in risk of recurrence at 5 years was 9.4% (95% CI 3.2-15.7) in favor of TMMR. In locally advanced CC, no significant differences in RFS or OS was observed., Interpretation: Compared to ST, TMMR without radiation therapy was associated with superior oncologic outcomes in women with early-stage cervical cancer whereas no difference was observed in locally advanced disease. Our findings together with previous evidence suggest that TMMR may be considered the primary option for both early-stage and locally advanced cervical cancer confined to the Müllerian compartment., Funding: This study was supported by grants from Centre for Clinical Research Sörmland (Sweden) and Region Stockholm (Sweden)., Competing Interests: HF is a board member of Surgical Science Inc. No other author declared any conflict of interest., (© 2024 The Author(s).)

Background: Risk assessment for ischemic stroke (IS) and myocardial infarction (MI) is done routinely before surgery, but the increase in risks associated with surgery is not known. The aim of this study is to assess the risk of arterial ischemic events during the first year after oncological surgery., Methods: We used Swedish healthcare databases to identify 443,300 patients who underwent cancer surgery between 1987 and 2016 and 4,127,761 matched comparison subjects. We estimated odds ratios (ORs) for myocardial infarction and ischemic stroke during the hospitalization with logistic regression and calculated 1-year cumulative incidences and hazard ratios (HRs) with 95% confidence intervals (CIs) for the outcomes after discharge., Results: The cumulative incidences of myocardial infarction and ischemic stroke during the first postoperative year were 1.33% and 1.25%, respectively. In the comparison cohort, the corresponding 1-year cumulative incidences were 1.04% and 1.00%. During the hospitalization, the OR for myocardial infarction was 8.81 (95% CI 8.24-9.42) and the OR for ischemic stroke was 6.71 (95% CI 6.22-7.23). After discharge, the average HR during follow-up for 365 days was 0.90 (95% CI 0.87-0.93) for myocardial infarction and 1.02 (95% CI 0.99-1.05) for ischemic stroke., Conclusions: We found an overall increased risk of IS and MI during the first year after cancer surgery that was attributable to events occurring during the hospitalization period. After discharge from the hospital, the overall risk of myocardial infarction was lower among the cancer surgery patients than among matched comparison subjects., (© 2023. The Author(s).)

Importance: The risks and benefits of thromboprophylaxis therapy after cancer surgery are debated. Studies that determine thrombosis risk after cancer surgery with high accuracy are needed., Objectives: To evaluate 1-year risk of venous thromboembolic events after major cancer surgery and how these events vary over time., Design, Setting, and Participants: This register-based retrospective observational matched cohort study included data on the full population of Sweden between 1998 and 2016. All patients who underwent major surgery for cancer of the bladder, breast, colon or rectum, gynecologic organs, kidney and upper urothelial tract, lung, prostate, or gastroesophageal tract were matched in a 1:10 ratio with cancer-free members of the general population on year of birth, sex, and county of residence. Data were analyzed from February 13 to December 5, 2023., Exposure: Major surgery for cancer., Main Outcomes and Measures: The main outcome was incidence of venous thromboembolic events within 1 year after the surgery. Crude absolute risks and risk differences of events within 1 year and adjusted time-dependent cause-specific hazard ratios (HRs) of postdischarge events were calculated., Results: A total of 432 218 patients with cancer (median age, 67 years [IQR, 58-75 years]; 68.7% women) and 4 009 343 cancer-free comparators (median age, 66 years [IQR, 57-74 years]; 69.3% women) were included in the study. The crude 1-year cumulative risk of pulmonary embolism was higher among the cancer surgery population for all cancers, with the following absolute risk differences: for bladder cancer, 2.69 percentage points (95% CI, 2.33-3.05 percentage points); for breast cancer, 0.59 percentage points (95% CI 0.55-0.63 percentage points); for colorectal cancer, 1.57 percentage points (95% CI, 1.50-1.65 percentage points); for gynecologic organ cancer, 1.32 percentage points (95% CI, 1.22-1.41 percentage points); for kidney and upper urinary tract cancer, 1.38 percentage points (95% CI, 1.21-1.55 percentage points); for lung cancer, 2.61 percentage points (95% CI, 2.34-2.89 percentage points); for gastroesophageal cancer, 2.13 percentage points (95% CI, 1.89-2.38 percentage points); and for prostate cancer, 0.57 percentage points (95% CI, 0.49-0.66 percentage points). The cause-specific HR of pulmonary embolism comparing patients who underwent cancer surgery with matched comparators peaked just after discharge and generally plateaued 60 to 90 days later. At 30 days after surgery, the HR was 10 to 30 times higher than in the comparison cohort for all cancers except breast cancer (colorectal cancer: HR, 9.18 [95% CI, 8.03-10.50]; lung cancer: HR, 25.66 [95% CI, 17.41-37.84]; breast cancer: HR, 5.18 [95% CI, 4.45-6.05]). The hazards subsided but never reached the level of the comparison cohort except for prostate cancer. Similar results were observed for deep vein thrombosis., Conclusions and Relevance: This cohort study found an increased rate of venous thromboembolism associated with cancer surgery. The risk persisted for about 2 to 4 months postoperatively but varied between cancer types. The increased rate is likely explained by the underlying cancer disease and adjuvant treatments. The results highlight the need for individualized venous thromboembolism risk evaluation and prophylaxis regimens for patients undergoing different surgery for different cancers.

Introduction: Our objective was to investigate the trajectories of anxiety, depression, emotional and social functioning in women with newly diagnosed vulvar cancer from the time of diagnosis to 12 months after treatment. A further aim was to identify risk factors for high levels of anxiety., Material and Methods: PROVE (PROspective Vulvar Cancer Evaluation) is a nationwide longitudinal cohort study investigating quality of life in women with newly diagnosed vulvar cancer by the following validated patient-reported outcome measures at diagnosis, and 3 and 12 months after treatment: The Hospital Anxiety and Depression Scale, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30, and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Vulvar module VU34. Mean scores, changes over time and associations were analyzed by generalized estimated equations and log-linear regression models, adjusted for possible confounders., Results: Between 2019 and 2021, 105 (69%) women completed the questionnaires at all three time points. At diagnosis, 42% of the women reported elevated anxiety levels, decreasing significantly to 30% during the first 12 months. Insomnia, persisting vulvar symptoms and high information needs were significantly associated with a high level of anxiety (relative risk [RR] 2.1, 95% CI 1.2-3.7 for insomnia; RR 2.8, 95% CI 1.7-4.6 for vulvar symptoms, RR 2.7, 95% CI 1.5-4.9 for information needs). We found a trend towards a higher level of anxiety in younger women (<65 years: RR 1.5, 95% CI 1.0-2.5). Participants reported a low and stable prevalence of depression (14%) and high social functioning throughout the study period., Conclusions: Women with newly diagnosed vulvar cancer report a high level of anxiety at diagnosis. Despite a significant improvement, anxiety remains widely prevalent during the first year of follow-up. Targeting insomnia, vulvar symptoms and unmet needs may decrease anxiety during surveillance., (© 2023 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Introduction: Women with advanced ovarian cancer commonly present with peritoneal disease both at primary diagnosis and relapse, with risk of subsequent bowel obstruction. The aims of this study were to assess the cumulative incidence of and survival after intervention for bowel obstruction in women with advanced ovarian cancer, to identify factors predictive of survival and the extent to which the intended outcome of the intervention was achieved., Material and Methods: Women diagnosed with advanced ovarian cancer stages III and IV in 2009-2011 and 2014-2016 in the Stockholm-Gotland Region in Sweden were identified in the Swedish Quality Registry for Gynecologic Cancer. Through hospital records, types of intended and executed interventions for bowel obstruction were assessed, and as well as when in the course of oncologic treatment, the intervention was performed. Time from first intervention to death was analyzed with survival methodology and proportional hazard regression was used., Results: Of 751 identified women, 108 had an intervention for bowel obstruction. Laparotomy was the most prevalent intervention and was used in 87% (94/108) of all women, with a success rate of 87% (82/94). An intervention for bowel obstruction was performed before or during first line treatment in 32% (35/108) with a cumulative incidence in the whole cohort of 14% (108/751, 95% confidence interval [CI] 11-16). Median survival after intervention for bowel obstruction was 4 months (95% CI 3-6). The hazard of death increased when the intervention was performed after completion of primary treatment (HR 4.46, 95% CI 1.61-12.29, P < 0.01), with a median survival of 3 months. In women subjected to radical surgery during primary treatment, the hazard of death after intervention for bowel obstruction decreased (hazard ratio [HR] 0.54, 95% CI 0.32-0.91, P = 0.02)., Conclusions: Women with advanced ovarian cancer undergoing intervention for bowel obstruction have a dismal prognosis, regardless of which line of oncologic treatment the intervention was performed. In the majority of women an intervention for bowel obstruction was performed in a relapse situation with an even worse survival. Our findings emphasize the importance of a holistic approach in the decision-making before an intervention for bowel obstruction in women with advanced ovarian cancer., (© 2023 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Background: International guidelines recommend tailoring the radicality of hysterectomy according to the known preoperative tumor characteristics in patients with early-stage cervical cancer., Objective: This study aimed to assess whether increased radicality had an effect on 5-year disease-free survival in patients with early-stage cervical cancer undergoing radical hysterectomy. The secondary aims were 5-year overall survival and pattern of recurrence., Study Design: This was an international, multicenter, retrospective study from the Surveillance in Cervical CANcer (SCCAN) collaborative cohort. Patients with the International Federation of Gynecology and Obstetrics 2009 stage IB1 and IIA1 who underwent open type B/C1/C2 radical hysterectomy according to Querleu-Morrow classification between January 2007 and December 2016, who did not undergo neoadjuvant chemotherapy and who had negative lymph nodes and free surgical margins at final histology, were included. Descriptive statistics and survival analyses were performed. Patients were stratified according to pathologic tumor diameter. Propensity score match analysis was performed to balance baseline characteristics in patients undergoing nerve-sparing and non-nerve-sparing radical hysterectomy., Results: A total of 1257 patients were included. Of note, 883 patients (70.2%) underwent nerve-sparing radical hysterectomy, and 374 patients (29.8%) underwent non-nerve-sparing radical hysterectomy. Baseline differences between the study groups were found for tumor stage and diameter (higher use of non-nerve-sparing radical hysterectomy for tumors >2 cm or with vaginal involvement; P<.0001). The use of adjuvant therapy in patients undergoing nerve-sparing and non-nerve-sparing radical hysterectomy was 27.3% vs 28.6%, respectively (P=.63). Five-year disease-free survival in patients undergoing nerve-sparing vs non-nerve-sparing radical hysterectomy was 90.1% (95% confidence interval, 87.9-92.2) vs 93.8% (95% confidence interval, 91.1-96.5), respectively (P=.047). Non-nerve-sparing radical hysterectomy was independently associated with better disease-free survival at multivariable analysis performed on the entire cohort (hazard ratio, 0.50; 95% confidence interval, 0.31-0.81; P=.004). Furthermore, 5-year overall survival in patients undergoing nerve-sparing vs non-nerve-sparing radical hysterectomy was 95.7% (95% confidence interval, 94.1-97.2) vs non-nerve-sparing 96.5% (95% confidence interval, 94.3-98.7), respectively (P=.78). In patients with a tumor diameter ≤20 mm, 5-year disease-free survival was 94.7% in nerve-sparing radical hysterectomy vs 96.2% in non-nerve-sparing radical hysterectomy (P=.22). In patients with tumors between 21 and 40 mm, 5-year disease-free survival was 90.3% in non-nerve-sparing radical hysterectomy vs 83.1% in nerve-sparing radical hysterectomy (P=.016) (no significant difference in the rate of adjuvant treatment in this subgroup, P=.47). This was confirmed after propensity match score analysis (balancing the 2 study groups). The pattern of recurrence in the propensity-matched population did not demonstrate any difference (P=.70)., Conclusion: For tumors ≤20 mm, no survival difference was found with more radical hysterectomy. For tumors between 21 and 40 mm, a more radical hysterectomy was associated with improved 5-year disease-free survival. No difference in the pattern of recurrence according to the extent of radicality was observed. Non-nerve-sparing radical hysterectomy was associated with better 5-year disease-free survival than nerve-sparing radical hysterectomy after propensity score match analysis., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Tumor cells release fragments of their DNA into the circulation, so called cell-free tumor DNA (ctDNA), allowing for analysis of tumor DNA in a simple blood test, that is, liquid biopsy. Cervical cancer is one of the most common malignancies among women worldwide and high-risk human papillomavirus (HR-HPV) is the cause of the majority of cases. HR-HPV integrates into the host genome and is often present in multiple copies per cell and should thus also be released as ctDNA. Such ctHPV DNA is therefore a possible biomarker in cervical cancer. In this review, we first give a background on ctDNA in general and then a comprehensive review of studies on ctHPV DNA in cervical cancer and pre-malignant lesions that may develop in cervical cancer. Furthermore, studies on ctHPV DNA in other HPV related malignancies (eg, head-and-neck and anogenital cancers) are briefly reviewed. We conclude that detection of ctHPV DNA in plasma from patients with cervical cancer is feasible, although optimized protocols and ultra-sensitive techniques are required for sufficient sensitivity. Results from retrospective studies in both cervical cancer and other HPV-related malignancies suggests that ctHPV DNA is a promising prognostic biomarker, for example, for detecting relapses early. This paves the way for larger, preferably prospective studies investigating the clinical value of ctHPV DNA as a biomarker in cervical cancer. However, there are conflicting results whether ctHPV DNA can be found in blood from patients with pre-malignant lesions and further studies are needed to fully elucidate this question., (© 2022 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Objective: 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., Methods: 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+., Results: 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%)., Conclusion: 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., (Copyright © 2023 Elsevier Ltd. 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.)

Objective: Our objective was to examine oncologic outcome in women with advanced epithelial ovarian cancer (aEOC) receiving an intestinal stoma (IS) at the time of cytoreductive surgery (CRS), probability of stoma reversal (SR) and variables affecting odds of SR., Methods: This population-based cohort study included all women diagnosed with aEOC between 2009 and 2018 in the Stockholm/Gotland Region of Sweden. The association between IS formation at CRS and survival was analyzed with proportional hazards regression yielding hazard ratios (HR) with 95% confidence intervals (CI), adjusted for predefined confounders. Cumulative incidence functions, with death or recurrence as competing risk, were used to estimate chance of SR. The association between clinical factors and SR was analyzed with logistic regression yielding odds ratios (OR) with 95% CI., Results: The final analysis included 888 women undergoing CRS for aEOC. Of these, 129 (14,5%) received an IS of which 74% (n = 95) were defunctioning and 26% (n = 34) permanent. IS was associated with an increased hazard of death (HR 1.30, CI 95%, 1.05-1.61; p = 0.02) in the univariate analysis, however not in the adjusted analysis. The probability of SR of defunctioning IS within 2 years was 48% (95% CI, 38-58). Median time to SR was 10 months. High surgical complexity score (SCS) was associated with increased odds of reversal (OR 3.43, 95% CI, 1.06-11.05; p = 0.04)., Conclusions: IS formation does not seem to affect prognosis in women with aEOC. We could not identify any factor, known at time of CRS, that may predict the odds of SR except a high SCS., Competing Interests: Declaration of Competing Interest All authors declare no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: In cervical cancer, presence of lymph-node macrometastases (MAC) is a major prognostic factor and an indication for adjuvant treatment. However, since clinical impact of micrometastases (MIC) and isolated tumor-cells (ITC) remains controversial, we sought to identify a cut-off value for the metastasis size not associated with negative prognosis., Methods: We analyzed data from 967 cervical cancer patients (T1a1L1-T2b) registered in the SCCAN (Surveillance in Cervical CANcer) database, who underwent primary surgical treatment, including sentinel lymph-node (SLN) biopsy with pathological ultrastaging. The size of SLN metastasis was considered a continuous variable and multiple testing was performed for cut-off values of 0.01-1.0 mm. Disease-free survival (DFS) was compared between N0 and subgroups of N1 patients defined by cut-off ranges., Results: LN metastases were found in 172 (18%) patients, classified as MAC, MIC, and ITC in 79, 54, and 39 patients, respectively. DFS was shorter in patients with MAC (HR 2.20, P = 0.003) and MIC (HR 2.87, P < 0.001), while not differing between MAC/MIC (P = 0.484). DFS in the ITC subgroup was neither different from N0 (P = 0.127) nor from MIC/MAC subgroups (P = 0.449). Cut-off analysis revealed significantly shorter DFS compared to N0 in all subgroups with metastases ≥0.4 mm (HR 2.311, P = 0.04). The significance of metastases <0.4 mm could not be assessed due to limited statistical power (<80%). We did not identify any cut-off for the size of metastasis with significantly better prognosis than the rest of N1 group., Conclusions: In cervical cancer patients, the presence of LN metastases ≥0.4 mm was associated with a significant negative impact on DFS and no cut-off value for the size of metastasis with better prognosis than N1 was found. Traditional metastasis stratification based on size has no clinical implication., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: To evaluate the association of number of radical hysterectomies performed per year in each center with disease-free survival and overall survival., Methods: We conducted an international, multicenter, retrospective study of patients previously included in the Surveillance in Cervical Cancer collaborative studies. Individuals with International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IB1-IIA1 cervical cancer who underwent radical hysterectomy and had negative lymph nodes at final histology were included. Patients were treated at referral centers for gynecologic oncology according to updated national and international guidelines. Optimal cutoffs for surgical volume were identified using an unadjusted Cox proportional hazard model, with disease-free survival as the outcome and defined as the value that minimizes the P-value of the split in groups in terms of disease-free survival. Propensity score matching was used to create statistically similar cohorts at baseline., Results: A total of 2,157 patients were initially included. The two most significant cutoffs for surgical volume were identified at seven and 17 surgical procedures, dividing the entire cohort into low-volume, middle-volume, and high-volume centers. After propensity score matching, 1,238 patients were analyzed-619 (50.0%) in the high-volume group, 523 (42.2%) in the middle-volume group, and 96 (7.8%) in the low-volume group. Patients who underwent surgery in higher-volume institutions had progressively better 5-year disease-free survival than those who underwent surgery in lower-volume centers (92.3% vs 88.9% vs 83.8%, P=.029). No difference was noted in 5-year overall survival (95.9% vs 97.2% vs 95.2%, P=.70). Cox multivariable regression analysis showed that FIGO stage greater than IB1, presence of lymphovascular space invasion, grade greater than 1, tumor diameter greater than 20 mm, minimally invasive surgical approach, nonsquamous cell carcinoma histology, and lower-volume centers represented independent risk factors for recurrence., Conclusion: Surgical volume of centers represented an independent prognostic factor affecting disease-free survival. Increasing number of radical hysterectomies performed in each center every year was associated with improved disease-free survival., Competing Interests: Financial Disclosure Henrik Falconer reports receiving payment from Intuitive Surgical and Surgical Science. The other authors did not report any potential conflicts of interest., (Copyright © 2022 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Tumor cells release fragments of their DNA into the circulation, so called cell-free tumor DNA (ctDNA) or liquid biopsy. Here, we analyze if cell-free human papillomavirus DNA (ctHPV DNA) is detectable before, during and after treatment, in patients with cervical cancer or pre-malignant lesions that may develop into cervical cancer, and whether ctHPV DNA levels were correlated to patient or tumor characteristics and outcome. Furthermore, total cell-free DNA load is studied using cfAlbumin DNA as a surrogate marker., Methods: 18 patients with locally advanced CC (LACC), 15 patients with early stage CC (ESCC) and 21 patients with pre-malignant lesions, all with verified HPV16, 18 or 45-positive lesions, were included. Pre- during- and post-treatment plasma were tested for HPV16, 18 & 45 and total cfDNA load using droplet digital PCR., Results: ctHPV DNA was found in 94.4% and 26.7% of pre-treatment plasma of patients with LACC and ESCC respectively, while all samples from patients with pre-malignant lesions were negative. Higher levels of ctHPV DNA were correlated to higher FIGO2018 stage. Patients with LACC and persistent ctHPV DNA at end-of-treatment had significantly worse progression-free survival (PFS) than patients who had cleared the ctHPV DNA (p = 0.007). Patients with total ctDNA-levels above median in pre-treatment plasma had a worse PFS (p = 0.026), compared to patients with total ctDNA-levels below median., Conclusion: ctHPV DNA is a promising prognostic biomarker in locally advanced cervical cancer that should be studied further for clinical use., Competing Interests: Declaration of Competing Interest The authors have no relevant conflicts of interest to disclose., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Study Objective: To examine whether objective bladder function after robot-assisted radical hysterectomy (RRH) for early-stage cervical cancer is correlated with subjective patient-reported outcomes and quality of life during the first year after RRH., Design: Prospective observational study., Setting: Karolinska University Hospital, Sweden., Patients: Women with early-stage cervical cancer (International Federation of Gynecology and Obstetrics stage IA2-IB1) between July 2017 and May 2019 were assessed for eligibility., Interventions: RRH., Measurements and Main Results: Subjective bladder function was evaluated with the Female Lower Urinary Tract Symptoms and Urinary Incontinence Quality of Life modules of the International Consultation on Incontinence Questionnaire. Objective urinary function was characterized with urodynamic tests, and the nerves ablated at RRH were quantified by using immunohistochemical staining of biopsies from the resected paracervix, vesicouterine, and sacrouterine ligaments. Twenty-seven women were included for analysis at baseline, 2 weeks, 3 months, and 12 months after surgery. RRH caused hypotonia of the urinary bladder (p <.05). Patient-reported outcomes of voiding and filling dysfunction were most significant 2 weeks after surgery (p <.05) but for most of the women, bladder function recovered within 3 months. No correlations were found with either subjective or objective urinary function and the number of ablated nerves., Conclusion: For most women, objective and subjective urinary bladder dysfunction recovered within 3 months after RRH. The absence of correlation between functional outcomes and ablated autonomous nerves suggests that other underlying causes play a significant role. Early detection of bladder overextension after RRH is paramount, and the role of postoperative bladder catheterization needs further investigation., (Copyright © 2022 AAGL. Published by Elsevier Inc. All rights reserved.)