British Gynaecological Cancer Society recommendations for women with gynecological cancer who received non-standard care during the COVID-19 pandemic.

During the COVID-19 pandemic, pressures on clinical services required adaptation to how care was prioritised and delivered for women with gynecological cancer. This document discusses potential 'salvage' measures when treatment has deviated from the usual standard of care. The British Gynaecological Cancer Society convened a multidisciplinary working group to develop recommendations for the onward management and follow-up of women with gynecological cancer who have been impacted by a change in treatment during the pandemic. These recommendations are presented for each tumor type and for healthcare systems, and the impact on gynecological services are discussed. It will be important that patient concerns about the impact of COVID-19 on their cancer pathway are acknowledged and addressed for their ongoing care.

Chemotherapy versus surgery for initial treatment in advanced ovarian epithelial cancer.

BACKGROUND: Epithelial ovarian cancer presents at an advanced stage in the majority of women. These women require surgery and chemotherapy for optimal treatment. Conventional treatment has been to perform surgery first and then give chemotherapy. However, there may be advantages to using chemotherapy before surgery. OBJECTIVES: To assess whether there is an advantage to treating women with advanced epithelial ovarian cancer with chemotherapy before debulking surgery (neoadjuvant chemotherapy (NACT)) compared with conventional treatment where chemotherapy follows debulking surgery (primary debulking surgery (PDS)). SEARCH METHODS: We searched the following databases on 11 February 2019: CENTRAL, Embase via Ovid, MEDLINE (Silver Platter/Ovid), PDQ and MetaRegister. We also checked the reference lists of relevant papers that were identified to search for further studies. The main investigators of relevant trials were contacted for further information. SELECTION CRITERIA: Randomised controlled trials (RCTs) of women with advanced epithelial ovarian cancer (Federation of International Gynaecologists and Obstetricians (FIGO) stage III/IV) who were randomly allocated to treatment groups that compared platinum-based chemotherapy before cytoreductive surgery with platinum-based chemotherapy following cytoreductive surgery. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed risk of bias in each included trial. MAIN RESULTS: We found 1952 potential titles, with a most recent search date of February 2019, of which five RCTs of varying quality and size met the inclusion criteria. These studies assessed a total of 1713 women with stage IIIc/IV ovarian cancer randomised to NACT followed by interval debulking surgery (IDS) or PDS followed by chemotherapy. We pooled results of the three studies where data were available and found little or no difference with regard to overall survival (OS) (1521 women; Hazard Ratio (HR) 0.95, 95% CI 0.84 to 1.07; I2 = 0%; moderate-certainty evidence) or progression-free survival in four trials where we were able to pool data (1631 women; HR 0.97, 95% CI 0.87 to 1.07; I2 = 0%; moderate-certainty evidence). Adverse events, surgical morbidity and quality of life (QoL) outcomes were poorly and incompletely reported across studies. There may be clinically meaningful differences in favour of NACT compared to PDS with regard to serious adverse effects (SAE grade 3+). These data suggest that NACT may reduce the risk of need for blood transfusion (risk ratio (RR) 0.80; 95% CI 0.64 to 0.99; four studies,1085 women; low-certainty evidence), venous thromboembolism (RR 0.28; 95% CI 0.09 to 0.90; four studies, 1490 women; low-certainty evidence), infection (RR 0.30; 95% CI 0.16 to 0.56; four studies, 1490 women; moderate-certainty evidence), compared to PDS. NACT probably reduces the need for stoma formation (RR 0.43, 95% CI 0.26 to 0.72; two studies, 581 women; moderate-certainty evidence) and bowel resection (RR 0.49, 95% CI 0.26 to 0.92; three studies, 1213 women; moderate-certainty evidence), as well as reducing postoperative mortality (RR 0.18; 95% CI 0.06 to 0.54:five studies, 1571 women; moderate-certainty evidence). QoL on the EORTC QLQ-C30 scale produced inconsistent and imprecise results in two studies (MD -1.34, 95% CI -2.36 to -0.32; participants = 307; very low-certainty evidence) and use of the QLQC-30 and QLQC-Ov28 in another study (MD 7.60, 95% CI 1.89 to 13.31; participants = 217; very low-certainty evidence) meant that little could be inferred. AUTHORS' CONCLUSIONS: The available moderate-certainty evidence suggests there is little or no difference in primary survival outcomes between PDS and NACT. NACT may reduce the risk of serious adverse events, especially those around the time of surgery, and the need for bowel resection and stoma formation. These data will inform women and clinicians and allow treatment to be tailored to the person, taking into account surgical resectability, age, histology, stage and performance status. Data from an unpublished study and ongoing studies are awaited.

Neoadjuvant chemotherapy before surgery versus surgery followed by chemotherapy for initial treatment in advanced ovarian epithelial cancer.

BACKGROUND: Epithelial ovarian cancer presents at an advanced stage in the majority of women. These women require a combination of surgery and chemotherapy for optimal treatment. Conventional treatment has been to perform surgery first and then give chemotherapy. However, there may be advantages to using chemotherapy before surgery. OBJECTIVES: To assess whether there is an advantage to treating women with advanced epithelial ovarian cancer with chemotherapy before debulking surgery (neoadjuvant chemotherapy (NACT)) compared with conventional treatment where chemotherapy follows debulking surgery (primary debulking surgery (PDS)). SEARCH METHODS: We searched the following databases up to 9 October 2020: the Cochrane Central Register of Controlled Trials (CENTRAL), Embase via Ovid, MEDLINE (Silver Platter/Ovid), PDQ and MetaRegister. We also checked the reference lists of relevant papers that were identified to search for further studies. The main investigators of relevant trials were contacted for further information. SELECTION CRITERIA: Randomised controlled trials (RCTs) of women with advanced epithelial ovarian cancer (Federation of International Gynaecologists and Obstetricians (FIGO) stage III/IV) who were randomly allocated to treatment groups that compared platinum-based chemotherapy before cytoreductive surgery with platinum-based chemotherapy following cytoreductive surgery. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed risk of bias in each included trial. We extracted data of overall (OS) and progression-free survival (PFS), adverse events, surgically-related mortality and morbidity and quality of life outcomes.  We used GRADE methods to determine the certainty of evidence. MAIN RESULTS: We identified 2227 titles and abstracts through our searches, of which five RCTs of varying quality and size met the inclusion criteria. These studies assessed a total of 1774 women with stage IIIc/IV ovarian cancer randomised to NACT followed by interval debulking surgery (IDS) or PDS followed by chemotherapy. We pooled results of the four studies where data were available and found little or no difference with regard to overall survival (OS) (Hazard Ratio (HR) 0.96, 95% CI 0.86 to 1.08; participants = 1692; studies = 4; high-certainty evidence) or progression-free survival in four trials where we were able to pool data (Hazard Ratio 0.98, 95% CI 0.88 to 1.08; participants = 1692; studies = 4; moderate-certainty evidence). Adverse events, surgical morbidity and quality of life (QoL) outcomes were variably and incompletely reported across studies. There are probably clinically meaningful differences in favour of NACT compared to PDS with regard to overall postoperative serious adverse effects (SAE grade 3+): 6% in NACT group, versus 29% in PDS group, (risk ratio (RR) 0.22, 95% CI 0.13 to 0.38; participants = 435; studies = 2; heterogeneity index (I2) = 0%; moderate-certainty evidence). NACT probably results in a large reduction in the need for stoma formation: 5.9% in NACT group, versus 20.4% in PDS group, (RR 0.29, 95% CI 0.12 to 0.74; participants = 632; studies = 2; I2 = 70%; moderate-certainty evidence), and probably reduces the risk of needing bowel resection at the time of surgery: 13.0% in NACT group versus 26.6% in PDS group (RR 0.49, 95% CI 0.30 to 0.79; participants = 1565; studies = 4; I2 = 79%; moderate-certainty evidence). NACT reduces postoperative mortality: 0.6% in NACT group, versus 3.6% in PDS group, (RR 0.16, 95% CI 0.06 to 0.46; participants = 1623; studies = 5; I2 = 0%; high-certainty evidence). QoL on the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) scale produced inconsistent and imprecise results in three studies (MD -0.29, 95% CI -2.77 to 2.20; participants = 524; studies = 3; I2 = 81%; very low-certainty evidence) but the evidence is very uncertain and should be interpreted with caution. AUTHORS' CONCLUSIONS: The available high to moderate-certainty evidence suggests there is little or no difference in primary survival outcomes between PDS and NACT. NACT probably reduces the risk of serious adverse events, especially those around the time of surgery, and reduces the risk of postoperative mortality and the need for stoma formation. These data will inform women and clinicians (involving specialist gynaecological multidisciplinary teams) and allow treatment to be tailored to the person, taking into account surgical resectability, age, histology, stage and performance status. Data from an unpublished study and ongoing studies are awaited.

Patient-initiated follow-up after treatment for low risk endometrial cancer: a prospective audit of outcomes and cost benefits.

OBJECTIVE: Recurrence of low-risk endometrioid endometrial cancer is rare, and traditional hospital follow-up has a cost to both the patient and the healthcare system, without evidence of benefit. We examined the uptake of patient-initiated follow-up, pattern of recurrences, and survival for women following surgical treatment of low-risk endometrial cancer and compared estimated costs with hospital follow-up. METHODS: This study was a prospective audit of outcomes following implementation of a patient-initiated follow-up policy in a UK-based gynecological cancer center for women with low-risk endometrial cancer treated surgically (International Federation of Gynecology and Obstetrics (FIGO) stage 1A, G1-2) from January 2010 to December 2015. Women were identified following multidisciplinary team meetings and data were collected from the electronic cancer register, paper, and electronic clinical records. Health service costs were calculated based on standard tariffs for follow-up appointments; patient costs were estimated from mileage traveled from home postcode and parking charges. Progression-free survival and overall survival were assessed. Estimated financial costs to the health service and patients of hospital follow-up were compared with actual patient-initiated follow-up costs. RESULTS: A total of 129 women were offered patient-initiated follow-up (declined by four; accepted by another 11 after hospital follow-up for 6 months to 3.5 years) with median follow-up of 60.7 months (range 1.4-109.1 months). Ten women recurred: four vaginal vault recurrences (all salvaged), three pelvic recurrences (all salvaged), and three distant metastatic disease (all died). Five-year disease-specific survival was 97.3%. Ten women in the cohort died: three from endometrial cancer and seven from unrelated causes. The cost saving to the health service of patient-initiated follow-up compared with a traditional hospital follow-up regimen was £116 403 (median £988.60 per patient,range £0-£1071). Patients saved an estimated £7122 in transport and parking costs (median £57.22 per patient,range £4.98-£147.70). CONCLUSION: Patient-initiated follow-up for low risk endometrial cancer has cost benefits to both health service and patients. Those with pelvic or vault recurrence had salvageable disease, despite patient-initiated follow-up.

Management of Malignant Vulval Melanoma: A Retrospective Case Series and Review of the Literature.

OBJECTIVES: The aims of the study were to evaluate clinicopathologic features, management, and outcomes in vulval melanoma and to review the literature. MATERIALS AND METHODS: Data were collected retrospectively on patients with vulval melanoma from 2001 to 2017 in 5 gynecological oncology cancer centers (Bristol, Taunton, Truro, Plymouth, and Cheltenham). SPSS software was used for univariate and multivariate statistical analysis. Disease-specific median survival was calculated using Kaplan-Meier curves. RESULTS: Forty-four patients with vulval melanoma were included, with a median age of 71 years. Forty-three of 44 had wide local excision with full inguinal lymphadenectomy if abnormal lymph nodes. Seven patients had sentinel lymph nodes. However, 2 patients with negative sentinel lymph nodes had distant recurrences within 16 months.On univariate analysis, presence of ulceration (p = .012), perineural invasion (p = .03), and area of lesion (p = .016) were associated with risk of recurrence but only presence of microsatellites (p = .01) was associated with risk of death.There were 31 deaths (70%): 29 (94%) of 31 from melanoma and 28 (64%) of 44 recurrences: 17 local (10 groin, 7 vulval) and 9 distant. Overall median survival was 32.5 months (95% CI, 17.8-46.5 months) and median recurrence-free survival 12.6 months (95% CI, 7.7-17.4 months). CONCLUSIONS: This retrospective multicenter study highlights the high recurrence rate and poor prognosis of vulval melanoma. Lymph node surgery did not make any difference to recurrence-free survival or overall survival. The presence of microsatellites was associated with a statistically increased risk of death.

Chemotherapy versus surgery for initial treatment in advanced ovarian epithelial cancer.

BACKGROUND: Epithelial ovarian cancer presents at an advanced stage in the majority of women. These women require surgery and chemotherapy for optimal treatment. Conventional treatment has been to perform surgery first and then give chemotherapy. However, there may be advantages to using chemotherapy before surgery. OBJECTIVES: To assess whether there is an advantage to treating women with advanced epithelial ovarian cancer with chemotherapy before debulking surgery (neoadjuvant chemotherapy (NACT)) compared with conventional treatment where chemotherapy follows debulking surgery (primary debulking surgery (PDS)). SEARCH METHODS: We searched the following databases on 11 February 2019: CENTRAL, Embase via Ovid, MEDLINE (Silver Platter/Ovid), PDQ and MetaRegister. We also checked the reference lists of relevant papers that were identified to search for further studies. The main investigators of relevant trials were contacted for further information. SELECTION CRITERIA: Randomised controlled trials (RCTs) of women with advanced epithelial ovarian cancer (Federation of International Gynaecologists and Obstetricians (FIGO) stage III/IV) who were randomly allocated to treatment groups that compared platinum-based chemotherapy before cytoreductive surgery with platinum-based chemotherapy following cytoreductive surgery. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed risk of bias in each included trial. MAIN RESULTS: We found 1952 potential titles, with a most recent search date of February 2019, of which five RCTs of varying quality and size met the inclusion criteria. These studies assessed a total of 1713 women with stage IIIc/IV ovarian cancer randomised to NACT followed by interval debulking surgery (IDS) or PDS followed by chemotherapy. We pooled results of the three studies where data were available and found little or no difference with regard to overall survival (OS) (1521 women; hazard ratio (HR) 1.06; 95% confidence interval (CI) 0.94 to 1.19, I2 = 0%; moderate-certainty evidence) or progression-free survival in four trials where we were able to pool data (1631 women; HR 1.02; 95% CI 0.92 to 1.13, I2 = 0%; moderate-certainty evidence). Adverse events, surgical morbidity and quality of life (QoL) outcomes were poorly and incompletely reported across studies. There may be clinically meaningful differences in favour of NACT compared to PDS with regard to serious adverse effects (SAE grade 3+). These data suggest that NACT may reduce the risk of need for blood transfusion (risk ratio (RR) 0.80; 95% CI 0.64 to 0.99; four studies,1085 women; low-certainty evidence), venous thromboembolism (RR 0.28; 95% CI 0.09 to 0.90; four studies, 1490 women; low-certainty evidence), infection (RR 0.30; 95% CI 0.16 to 0.56; four studies, 1490 women; moderate-certainty evidence), compared to PDS. NACT probably reduces the need for stoma formation (RR 0.43, 95% CI 0.26 to 0.72; two studies, 581 women; moderate-certainty evidence) and bowel resection (RR 0.49, 95% CI 0.26 to 0.92; three studies, 1213 women; moderate-certainty evidence), as well as reducing postoperative mortality (RR 0.18; 95% CI 0.06 to 0.54:five studies, 1571 women; moderate-certainty evidence). QoL on the EORTC QLQ-C30 scale produced inconsistent and imprecise results in two studies (MD -1.34, 95% CI -2.36 to -0.32; participants = 307; very low-certainty evidence) and use of the QLQC-30 and QLQC-Ov28 in another study (MD 7.60, 95% CI 1.89 to 13.31; participants = 217; very low-certainty evidence) meant that little could be inferred. AUTHORS' CONCLUSIONS: The available moderate-certainty evidence suggests there is little or no difference in primary survival outcomes between PDS and NACT. NACT may reduce the risk of serious adverse events, especially those around the time of surgery, and the need for bowel resection and stoma formation. These data will inform women and clinicians and allow treatment to be tailored to the person, taking into account surgical resectability, age, histology, stage and performance status. Data from an unpublished study and ongoing studies are awaited.

Improving the uptake of cervical screening in pregnant and recently postnatal women: a quality improvement project.

BACKGROUND: In 2018, cervical screening uptake was at its lowest level since screening began, particularly in those aged 25-35, coinciding with the peak incidence of cervical cancer and average age at first delivery. PROBLEM: Retrospective baseline data of pregnant women found 47.3% (n=123/260) were overdue for screening by delivery, of whom 74% (n=91/123) remained overdue by 6 months postnatal. METHODS: We undertook a quality improvement project from April 2018 to April 2019 to improve cervical screening uptake in pregnant and postnatal women. We mapped out the screening process and canvassed stakeholders. The main theme was inconsistency of advice received by women. From February 2018 to May 2020, we undertook a prospective audit of 10 women per week who gave birth in our maternity department, recording screening status at delivery and 6 months postnatal.Interventions included introducing evidence-based guidelines about cervical screening in pregnancy and the postnatal period, flow charts for maternity staff, multiprofessional teaching for all maternity staff and information dissemination to women (via the HANDiApp platform, a social media campaign and adapting results letters following colposcopy, highlighting dates when screening would be due). Primary care opening hours were extended for screening and women received a letter from their midwives, if they required cervical screening in pregnancy. RESULTS: Locally, the percentage of women overdue for cervical screening by 6 months postnatal improved by 8.0% during this project, compared with a 1.6% change in national screening rates in women aged 25-49. CONCLUSIONS: We increased the percentage of local pregnant and postnatal women attending cervical screening by introduction of a package of information, targeted education and widening access to screening appointments.

Small cell neuroendocrine tumour of the cervix in pregnancy: the importance of multidisciplinary management.

A woman in her mid-20s presented with bleeding at 18 weeks gestation from a cervical 'polyp'. Histopathology demonstrated a rare small cell neuroendocrine of the cervix. There were only 18 cases of neuroendocrine tumours of the cervix in and around pregnancy in the literature, so the evidence base for treatment was scarce. She was treated with neoadjuvant chemotherapy, using a regimen used for small cell neuroendocrine tumours of the lung, to allow for fetal lung maturity. Disease initially responded, then progressed and she was delivered at 32 weeks by caesarean radical hysterectomy. Adjuvant treatment included further chemotherapy and radical pelvic radiotherapy. The woman and her child are doing well over 6 years after treatment, although the woman has significant side effects of both radical surgery and radiotherapy. This case emphasises the need for excellent communication between multidisciplinary professionals, patients and their families and using external colleagues to help with rare clinical problems.

Relationship between vulvar symptoms and incidence of vulvar cancer in women referred to a rapid access clinic.

OBJECTIVE: We performed a study to estimate incidence of vulvar cancer in women with vulvar symptoms (irritation, pain, bleeding +/- presence of lesion) referred to a secondary care, rapid-access clinic. METHODS: Prospective data collection of all direct referrals from a primary to a secondary care gynecological oncology clinic from 2011 to 2016, for women with suspicious vulvar symptoms. RESULTS: 32/393 (8.1%) women had vulvar cancer, and 24/393 (6.1%) had a premalignant lesion. Multivariate logistic regression showed that women referred without a specific lesion had considerably lower odds of a diagnosis of vulvar cancer than those with a lesion (OR=0.11, 95% CI: 0.03-0.49). In total, 30/234 (12.8%) women with a vulvar lesion (mass or ulcer), had vulvar cancer, compared with 2/159 (1.3%) of those referred without a lesion (these patients had vulvar irritation and bleeding but had a visible lesion on examination). None of the 140 women with irritation alone, in the absence of a visible lesion or bleeding, had pre-invasive disease or cancer. CONCLUSION: Presence of a vulvar lesion, especially if painful/bleeding, has a high positive predictive value for vulvar cancer and 12.8% of women presenting with any vulvar lesion to secondary care had cancer.