Management of advanced ovarian cancer in Leicester: The benefits of a paradigm shift in surgical approach.

AIM: Surgery for advanced ovarian cancer (AOC) has evolved over the past decade to ingeminate the need to offer maximum effort surgery (MES). The aim of this study is to analyze the implementation of a paradigm shift in the surgical management of women with AOC at the University Hospitals of Leicester NHS Trust (UHL) in 2015, until 2020, compared to 2011-2014. METHODS: Retrospective cohort study of women with AOC who underwent cytoreductive surgery (CRS) in the UHL. The two groups were: 153 women from January 2011 to December 2014 (group 1), 136 women from January 2015 to January 2020 (group 2). RESULTS: In group 1, the 1, 3, and 5 years overall survival rates (OS) were, 90.4%, 33.7%, and 19.3%, compared to 90.2%, 55.4%, and 29.7%, respectively, in group 2 (p = 0.012). Significantly more women had CRS in group 2: 45-Primary debulking surgery (PDS) and 57-interval debulking surgery (IDS) versus 17-PDS & 67-IDS in group 1 (p < 0.001). Surgical complexity score (modified Aletti score) was higher in group 2 compared to group 1 (p = <0.001). No significant difference was noted in the postoperative complications, in group 2, in women who underwent PDS versus IDS, yet PDS was associated with higher OS. CONCLUSIONS: MES/CRS in women with AOC significantly improves OS. Our data highlights the importance of a dedicated team to implement this change in cancer centers. Where possible, suitable women with AOC likely to have complete cytoreduction based on preoperative assessment, should be offered PDS.

Tumor size: a better independent predictor of distant failure and death than depth of myometrial invasion in International Federation of Gynecology and Obstetrics stage I endometrioid endometrial cancer.

OBJECTIVE: Depth of myometrial invasion is considered as the strongest predictor of distant failure and death from disease in stage I endometrial cancer. The aim of this study was to determine whether tumor size (TS) is an independent prognostic indicator of survival and a better predictor than depth (%) of myometrial invasion, in stage I endometrioid endometrial cancer. METHODS: This was a retrospective study of all women with International Federation of Gynecology and Obstetrics stage I endometrioid endometrial carcinoma from January 2000 to December 2007, who had surgery at the Northern Gynaecological Oncology Centre. Surgicopathological, follow-up, and survival data were collected. Tumor size (a continuous variable) was defined as the maximum tumor dimension. Univariate and multivariate analyses to predict distant recurrence and death from disease were performed comparing known risk factors. The prognostic accuracy of TS was then assessed by receiver operating characteristic curve analyses, and an optimum cutoff was proposed. RESULTS: A total of 216 women were identified. Pelvic lymphadenectomy was performed in 51 women (24%). The median follow-up time was 80 months (95% confidence interval [95% CI], 34-131 months), with 9 distant recurrences and 11 disease-related deaths. Tumor size was the only independent predictor of both distant recurrence (hazard ratio [HR], 1.05; 95% CI, 1.02-1.08; P = 0.004) and death from disease (HR, 1.03; 95% CI, 1.00-1.07; P = 0.05). Myometrial invasion only predicted distant failure (HR, 1.03, 95% CI, 1.00-1.05; P = 0.03). In women who did not have pelvic lymph node dissection (n = 165), only TS retained its independent prognostic value to predict both distant failure (HR, 1.08; 95% CI, 1.03-1.13; P = 0.002) and death from disease (HR, 1.05; 95% CI, 1.01-1.10; P = 0.02). In women who underwent pelvic lymphadenectomy, none of the variables predicted the above outcomes. CONCLUSIONS: Tumor size could play a significant role in risk stratification and planning adjuvant treatment in women with International Federation of Gynecology and Obstetrics stage I endometrioid endometrial cancer.

The role of intraoperative fluid optimization using the esophageal Doppler in advanced gynecological cancer: early postoperative recovery and fitness for discharge.

OBJECTIVE: To determine the effect of fluid optimization using esophageal Doppler monitoring (EDM) when compared to standard fluid management in women who undergo major gynecological cancer surgery and whether its use is associated with reduced postoperative morbidity. METHODS: From January 2009 to December 2010, women undergoing laparotomy for pelvic masses or uterine cancer had either fluid optimization using intraoperative EDM or standard fluid replacement without using EDM. Cases were selected from 2 surgeons to control for variability in surgical practice. Demographic and surgical details were collected prospectively. Univariate and multivariate analyses were performed to quantify the association between the use of EDM with "early postoperative recovery" and "early fitness for discharge." RESULTS: A total of 198 women were operated by the 2 prespecified surgeons; 79 women had fluid optimization with EDM, whereas 119 women had standard anesthetic care. The use of ODM was associated with earlier postoperative recovery (adjusted odds ratio, 2.83; 95% confidence interval, 1.20-6.68; P = 0.02) and earlier fitness for discharge (adjusted odds ratio, 2.81; 95% confidence interval, 1.01-7.78; P = 0.05). Women with advanced-stage disease in the "EDM" group resumed oral diet earlier than women in the "no EDM" group (median, 1 day vs 2 days; P = 0.02). These benefits with EDM did not extend to women with early-stage disease/benign/borderline tumors. No significant difference in postoperative complications was noted. CONCLUSIONS: Intraoperative fluid optimization with EDM in women with advanced gynecological cancer may be associated with improved postoperative recovery and early fitness for discharge. Studies with adequate power are needed to investigate its role in reducing postoperative complications.

Surgical cytoreduction for recurrent epithelial ovarian cancer.

BACKGROUND: The standard management of primary ovarian cancer is optimal cytoreductive surgery followed by platinum-based chemotherapy. Most women with primary ovarian cancer achieve remission on this combination therapy. For women achieving clinical remission after completion of initial treatment, most (60%) with advanced epithelial ovarian cancer will ultimately develop recurrent disease. However, the standard treatment of women with recurrent ovarian cancer remains poorly defined. Surgery for recurrent ovarian cancer has been suggested to be associated with increased overall survival. OBJECTIVES: To evaluate the effectiveness and safety of optimal secondary cytoreductive surgery for women with recurrent epithelial ovarian cancer. To assess the impact of various residual tumour sizes, over a range between 0 cm and 2 cm, on overall survival. SEARCH METHODS: We searched the Cochrane Gynaecological Cancer Group Trials Register, MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL) up to December 2012. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. For databases other than MEDLINE, the search strategy has been adapted accordingly. SELECTION CRITERIA: Retrospective data on residual disease, or data from randomised controlled trials (RCTs) or prospective/retrospective observational studies that included a multivariate analysis of 50 or more adult women with recurrent epithelial ovarian cancer, who underwent secondary cytoreductive surgery with adjuvant chemotherapy. We only included studies that defined optimal cytoreduction as surgery leading to residual tumours with a maximum diameter of any threshold up to 2 cm. DATA COLLECTION AND ANALYSIS: Two review authors (KG, TA) independently abstracted data and assessed risk of bias. Where possible the data were synthesised in a meta-analysis. MAIN RESULTS: There were no RCTs; however, we found nine non-randomised studies that reported on 1194 women with comparison of residual disease after secondary cytoreduction using a multivariate analysis that met our inclusion criteria. These retrospective and prospective studies assessed survival after secondary cytoreductive surgery in women with recurrent epithelial ovarian cancer.Meta- and single-study analyses show the prognostic importance of complete cytoreduction to microscopic disease, since overall survival was significantly prolonged in these groups of women (most studies showed a large statistically significant greater risk of death in all residual disease groups compared to microscopic disease).Recurrence-free survival was not reported in any of the studies. All of the studies included at least 50 women and used statistical adjustment for important prognostic factors. One study compared sub-optimal (> 1 cm) versus optimal (< 1 cm) cytoreduction and demonstrated benefit to achieving cytoreduction to less than 1 cm, if microscopic disease could not be achieved (hazard ratio (HR) 3.51, 95% CI 1.84 to 6.70). Similarly, one study found that women whose tumour had been cytoreduced to less than 0.5 cm had less risk of death compared to those with residual disease greater than 0.5 cm after surgery (HR not reported; P value < 0.001).There is high risk of bias due to the non-randomised nature of these studies, where, despite statistical adjustment for important prognostic factors, selection is based on retrospective achievability of cytoreduction, not an intention to treat, and so a degree of bias is inevitable.Adverse events, quality of life and cost-effectiveness were not reported in any of the studies. AUTHORS' CONCLUSIONS: In women with platinum-sensitive recurrent ovarian cancer, ability to achieve surgery with complete cytoreduction (no visible residual disease) is associated with significant improvement in overall survival. However, in the absence of RCT evidence, it is not clear whether this is solely due to surgical effect or due to tumour biology. Indirect evidence would support surgery to achieve complete cytoreduction in selected women. The risks of major surgery need to be carefully balanced against potential benefits on a case-by-case basis.

Impact of Patient Body Mass Index on Post-Operative Recovery from Robotic-Assisted Hysterectomy.

A longitudinal, descriptive, prospective, and prolective study of individuals with endometrial or cervical cancer/pre-cancer diagnoses and high BMI (over 35 kg/m2) undergoing RH was conducted. Of the 53 participants recruited, 3 (6%) were converted to open surgery. The 50 RH participants had median BMI 42 kg/m2 (range 35 to 60): the range 35-39.9 kg/m2 had 17 cases; the range 40-44.9 kg/m2 had 15 cases; 45-49.9 kg/m2 8 cases; and those ≥50 kg/m2 comprised 10 cases. The mean RH operating time was 128.1 min (SD 25.3) and the median length of hospital stay was 2 days (range 1-14 days). Increased BMI was associated with small, but statistically significant, increases in operating time and anaesthetic time, 65 additional seconds and 37 seconds, respectively, for each unit increase in BMI. The median self-reported time for individuals who underwent RH to return to their pre-operative activity levels was 4 weeks (range 2 to >12 weeks). There was a significant improvement in pain and physical independence scores over time (p = 0.001 and p < 0.001, respectively) and no significant difference in scores for overall QOL, pain, or physical independence scores was found between the BMI groups. Patient-reported recovery and quality of life following RH is high in individuals with high BMI (over 35 kg/m2) and does not appear to be impacted by the severity of obesity.

Small volume stage 1B1 cervical cancer: Is radical surgery still necessary?

OBJECTIVE: Current surgical treatment of FIGO stage 1B1 cervical cancer is radical surgery. However, several reports have shown that for small tumours a more conservative approach can be as effective in terms of survival, whilst at the same time reducing the morbidity associated with removing the parametrium. The objective of our study was to report survival and obstetric outcomes following conservative management of small-volume stage 1B1 disease. METHODS: All patients with FIGO stage 1B1 cancer and estimated tumour volume of less than 500 mm(3) in a loop biopsy specimen were included in the study, irrespective of other histological characteristics. A second loop biopsy was performed to rule out residual disease in 79% of patients. RESULTS: Sixty two women were identified with a median age of 35 years (range 27-67). Median tumour length was 9.75 mm (7.2-20) and median depth of invasion was 1.55 mm (0.3-5). Thirty five women (56.4%) were treated with loop biopsy, whilst 27 (45.6%) had simple hysterectomy. Fifty seven women (92%) had pelvic lymphadenectomy and one positive node was recorded. After a median follow up of 56 months (16-132) no recurrence was noted. Seven full term pregnancies have been achieved. There were no preterm deliveries or mid-term miscarriages. CONCLUSION: Cervical loop biopsy or simple hysterectomy combined with negative pelvic lymphadenectomy for small-volume stage 1B1 cervical cancer offers excellent prognosis in terms of survival. Postoperative morbidity is reduced and obstetric outcomes may be improved. Should these results be verified by further prospective studies, radical surgery for these women may be avoided.

Endometrial Cancer Incidence in Patients With Atypical Endometrial Hyperplasia According to Mode of Management.

BACKGROUND/AIM: It is well established that around one-third of patients with atypical endometrial hyperplasia (AEH) go on to develop endometrial cancer (EC). PATIENTS AND METHODS: This retrospective cohort study included 119 patients recruited from the University Hospitals of Leicester from 01/01/2015 to 01/01/2020 with a diagnosis of AEH by endometrial biopsy. Patients were divided into two groups according to the management modality: Primary surgery (n=99), and conservative treatment (n=20). The aim of this study was to determine the incidence of EC in patients with AEH in University Hospitals of Leicester, UK, and to explore the reasons why patients with AEH opted for conservative management. RESULTS: EC was diagnosed in 34.4% of patients with AEH managed by primary surgery. Moreover, the incidence of EC in patients with AEH managed conservatively was 25%. The main reason for opting for conservative management was that patients were unfit for surgery when assessed in the high-risk Anaesthetic Clinic (35%). CONCLUSION: AEH is a pre-malignant lesion that has high risk of EC regardless of the mode of management. Total hysterectomy is the safest first line of treatment in AEH due to the high risk of concurrent EC and progression to EC. Currently, there is no reliable follow-up intervention to distinguish between concurrent EC and progression of AEH. Adequate discussion and counselling are essential when discussing conservative management for women with complex AEH. Patients should be counselled regarding the high risk of developing concurrent EC and risk of progression to EC.

Mode of Referral of Ovarian Cancer Patients: Does it Alter Treatment and Survival?

BACKGROUND/AIM: Some studies have shown that ovarian cancer patients admitted after referral to the emergency department had a worse prognosis than those referred through non-emergency pathways. We believe that our study is the first in the UK to explore this difference and aimed to compare the 1-year, 3-year, and 5-year overall survival rates of ovarian cancer patients referred non-urgently from the general practitioner (GP) vs. patients referred urgently to the emergency department (ED). PATIENTS AND METHODS: This was a retrospective cohort study conducted at the University Hospitals of Leicester (UHL) from 1st January 2015 to 31st December 2019 involving 298 ovarian cancer patients: 197 referred non-urgently from the GP and 101 patients referred to the ED. RESULTS: There was no significant difference in the 1-year, 3-year, and 5-year overall survival in ovarian cancer patients referred from the GP compared to patients referred to the ED, 84.8%, 62.2%, and 48.4% versus 80.2%, 64.8%, and 43.5%, respectively (p=0.732). CONCLUSION: The mode of referral for ovarian cancer patients may not affect their prognosis. Prompt referral to the gynaecological oncology multidisciplinary team, a good acute oncology service, early imaging and image-guided diagnostic pathways, timely appointment, and timely initiation of treatment in our centre may have minimized the difference in outcome in the two groups.

Effect of New RCOG 2019 Curriculum and COVID 19 on Gynaecological Training in the U.K.

BACKGROUND/AIM: The Royal College of Obstetricians and Gynaecologists (RCOG) introduced a new curriculum in 2019. Furthermore, the National Health Service was hit by the COVID 19 pandemic in 2020. Our survey aims to find how the new RCOG curriculum and COVID 19 pandemic affected gynaecological training amongst specialist trainees in the UK. PATIENTS AND METHODS: A cross sectional study was conducted using the University of Leicester online survey platform involving the RCOG trainees in the UK from the 1st of June 2021 to the 1st of October 2021. The survey was divided into two main categories: 1) new RCOG curriculum and gynaecology training, 2) COVID 19 pandemic and gynaecology training. RESULTS: We received replies from 10% of trainees. The quality of gynaecology training under the new RCOG curriculum was described as less than good in 75.6% of respondents. Around one-third (29.2%) of trainees did not have local gynaecology simulation training. The COVID 19 pandemic adversely affected all aspects of gynaecology training. Benign gynaecology, subfertility, urogynaecology, and gynaeoncology modules training were affected in 94.0%, 85.1%, 89.7%, and 83.5% of trainees, respectively. During the pandemic, gynaecology teaching was affected in 84.9% of trainees, redeployment occurred in 11.8% of trainees, and 16% suffered adverse ARCP outcomes. CONCLUSION: The new RCOG curriculum and COVID 19 pandemic have simultaneously compromised the gynaecology training amongst the UK trainees. RCOG and GMC-led more comprehensive survey would be welcomed to incorporate our findings and take necessary actions.

Peri-operative Variables Associated With Prolonged Intensive Care Stay Following Cytoreductive Surgery for Ovarian Cancer.

BACKGROUND: Peri-operative variables associated with prolonged Intensive Care Unit (ICU) admission following cytoreductive surgery for ovarian cancer were investigated. PATIENTS AND METHODS: A retrospective review was carried out of patients admitted to the ICU following cytoreductive surgery for ovarian cancer in a single tertiary referral centre from 2015-2019. Patients were categorized according to length of ICU stay (<48 h and ≥48 h), and peri-operative variables were compared across the two groups. RESULTS: A total of 56 patients were admitted to the ICU post-operatively, 37 for <48 h and 19 for ≥48 h (range=3-11 days). Greater duration of procedure and estimated blood loss, bowel resection, higher post-operative lactate level, lower post-operative albumin level and requirement for post-operative blood products were associated with prolonged ICU stay. Increased intraoperative fluid requirement was an independent predictor of extended ICU stay. CONCLUSION: Utilizing identified intra-operative risk factors to perform individualized risk assessments might improve planning of ICU resources. Optimizing intraoperative fluid management may improve short-term patient outcomes.