COVID‐19 and the impact on gynecologic cancer care

Abstract The COVID‐19 pandemic resulted in significant reconfiguration of gynecologic cancer services and care pathways across the globe, with a transformation of working practices. Services had to adapt to protect their vulnerable patients from infection, whilst providing care despite reduced resources/capacity and staffing. The international gynecologic cancer community introduced modified clinical care guidelines. Remote working, reduced hospital visiting, routine COVID‐testing, and use of COVID‐free surgical areas/hubs enabled the ongoing and safe delivery of complex cancer care, with priority levels for cancer treatments established to guide decision‐making by multidisciplinary tumor boards. Some 2.3 million cancer surgeries were delayed or cancelled during the first peak, with many patients reporting significant anxiety/concern for cancer progression and COVID infection. Although COVID trials were prioritized, recruitment to other cancer trials/research activity was significantly reduced. The impact of resultant protocol deviations on outcomes remains to be established. During the recovery healthcare services must maintain capacity and flexibility to manage future surges of infection, address the large backlog of patients with altered or delayed treatments, along with salvaging screening and prevention services. Training needs/mental well‐being of trainees need addressing and staff burnout prevented. Future research needs to fully evaluate the impact of COVID‐19 on long‐term patient outcomes.

expectancy 2 as well as a significant increase in all-cause mortality has recently been observed in some countries, with higher levels of excess deaths occurring in nonwhite populations. 3 All countries took multiple steps to reduce transmission of COVID-19, including public lockdowns, self-isolation for those with the disease and their contacts, contact tracing, and shielding of individuals with high-risk pre-existing medical conditions. Areas of high prevalence saw significant pressures on hospital inpatient beds including intensive care units (ITU), as well as staffing levels. 4 It led to reallocation of resources and an increase in hospital beds and ITU capacity for COVID-19 patients at the expense of both elective nonurgent patient care activity and urgent care activity including oncology services. Health systems and gynecologic cancer services have had to cope with a number of additional factors/stresses, including staff sickness and self-isolation, staff redeployment for COVID care, reduced theatre availability/capacity for elective oncology, reduced ITU access for complex surgery, reduced palliative care access, supply chain shortages (including personal protective equipment, PPE), reduced hospital visits, and moves toward remote consultations. 5,6 In the initial period, some patients refused surgery due to concerns around contracting COVID-19 and there was a fall in the number of patients seeking care via their general practitioners or emergency settings.
COVID-19 has a highly variable clinical presentation with approximately 44% of transmissions occurring in the presymptomatic stage, 7 while many carriers may never show symptoms 8,9 but can transmit the virus to others. 10,11 The majority of patients suffer no or mild upper respiratory tract symptoms, 11 whilst a minority are at highest risk of severe lower respiratory tract infection and need hospitalization. Mortality occurs predominantly through respiratory failure; however, sepsis, thromboembolism, and acute renal and multiorgan failure contribute to this complex clinical entity, requiring prolonged stays on ITUs. 12 Early in the pandemic, cancer patients were identified as being at higher risk for COVID infection, increased morbidity, ITU care, and mortality. [13][14][15] Other predictors of severe disease and mortality included age, comorbidities such as obesity, diabetes, asthma, other medical morbidities, and black/Asian ethnicity. 15 The gynecologic cancer patient population was thus considered vulnerable, with overlapping risk factors and immunosuppression arising from cancer and its treatments. An international study of 1128 patients undergoing surgery across all surgical disciplines found 30-day mortality rates in patients who develop COVID-19 in the perioperative period to be 19% following elective surgery, 26% following emergency surgery, and 27% following cancer surgery. 16,17 Gynecologic cancer services faced the dual challenge of continuing to provide oncological care often with capacity constraints, whilst protecting their vulnerable patients from the risk of COVID exposure and its sequelae. Thus, consideration was initially given to restricting surgery or chemotherapy to reduce COVID risk to patients. However, these initial concerns were not born out as subsequent evidence demonstrated such treatments did not increase the risk of hospitalization or death outside the perioperative period or during cytotoxic chemotherapy, beyond those of previously identified risk from age or comorbidities. 4,18 The unprecedented reallocation of healthcare services necessitated by the pandemic across high-, middle-, and low-income countries, 19 coupled with staff shortages and capacity constraints, forced an urgent re-evaluation of the clinical justification for each aspect of treatment, weighing oncological benefit against available resources. In terms of ethical principles, justice and nonmaleficence required due consideration alongside beneficence, autonomy, and equity, as clinicians learnt to practice in this unfamiliar situation. 20 Modified clinical guidelines for cancer care became necessary to provide a systematic, equitable, and evidence-led framework during the pandemic, given the adaptation of or reduction in usual services. Deviations from usual standard of care may be appropriate in the context of what can be safely delivered during the pandemic.
The international gynecologic oncology community developed modifications to clinical care across the spectrum of surgery, chemotherapy, radiotherapy, and treatment timelines from first presentation to relapse and palliation. National healthcare organizations in France, the UK, USA, Italy, and Australia issued guidance for general oncology services from March 2020, shortly followed by gynecologic cancer specific statements from organizations in the UK, USA, Europe, Canada, Asia, Australia, and New Zealand. 21 Pragmatic modifications to the gold standard of care were suggested according to availability of resources and clinical services, based primarily on expert opinion and review of pre-existing evidence of benefit. Initial considerations were given to reducing the number of surgical procedures associated with prolonged operative time, risk of major blood loss, ITU admission, or increased infection risk to staff. A global modelling analysis suggested that around 38% of cancer operations and 82% of benign surgical procedures may be postponed during the pandemic. 22 Other analysis highlighted the significant impact on survival even modest delays in surgery may incur on cancer outcomes. 23 The need for care of cancer patients to be prioritized over patients with benign diseases was universally recognized. Additionally, the need to tackle/minimize diagnostic delays occurring during the pandemic became apparent to prevent significant additional avoidable mortality. 24

| ADAP TATI ON STOCLINI C ALS ERVI CE S ANDPATHWAYS
There has been significant service reconfiguration, transformation of working practices, and changes to cancer care delivery pathways as a result of the COVID-19 pandemic. 25 An important reason was to reduce the risk of infection to patients and staff, from other patients, staff members, and visitors. Key steps included reduction in people attending a given clinical site, along with use of handwashing, face masks, public distancing, PPE, and safe hygiene practices.
Staff struggled with PPE shortages in both low-and high-income countries-an issue leaving many staff at higher risk of infection. 26 Visiting was reduced for all hospital attendances for inpatient and outpatient care. It was restricted to new patients or essential consultations for acute oncologic issues or those undergoing active treatment and the most vulnerable patients. 19 Attendance of family members was restricted. Remote or telemedicine/telephone outpatient consultations were undertaken to reduce hospital attendance. Routine clinics such as regular follow-up and preassessment were conducted remotely. The use of patient-initiated follow-up was advocated where appropriate. Patients who required definite examination or breaking of bad news were advised to attend in person and benefitted from support from specialist nurses as usual. Multidisciplinary team or tumor board meetings were conducted remotely or, where not possible, sufficient distancing between staff was ensured to reduce the risk of staff transmission. As testing capacity became established, universal testing of patients prior to and upon admission was implemented.
Preoperative COVID-19 testing and self-isolation protocols (e.g. 14-day self-isolation and COVID-19 swab 72 hours before surgery) were introduced prior to gynecologic cancer surgery. Additionally, over time, surveillance testing of healthcare staff was introduced and has become a key tool in reducing transmission within some hospitals. 27 The use of "COVID-free" areas within hospitals or COVID-free hospitals/surgical hubs with separate staff enabled surgical and nonsurgical cancer services to continue. This approach of establishing COVID-19-free surgical pathways with segregation of the operating theater, ITU, and inpatient ward areas was shown to reduce postoperative SARS-CoV-2 infection and postoperative pulmonary complication rates. 28 In some centers, surgery was allocated through centralized triage and decisionmaking based on newly established national guidelines. 29 The introduction of vaccination from December 2020 for staff and more recently for patients is a key step forward in minimizing infections and reducing treatment morbidity.

| ADAP TATI ON STOD IAG NOS TI C S ERV I CE S
Changes to diagnostic pathways aimed to simplify the process, reducing hospital attendance and demand on clinical time, whilst still providing a safe process for patients. Greater flexibility was incorporated into triaging suspected cancer referrals from primary care.

Examples of changes introduced include:
• Telephone or virtual assessment without the need for clinical examination followed by direct investigation with hysteroscopy and ultrasound in women with postmenopausal bleeding.
• Maximizing out-patient hysteroscopy due to the reduced availability of operating theatres.
• Insertion of the levonorgestrel-releasing intrauterine system (LNG-IUS) at the time of initial hysteroscopy in case of abnormal findings, to minimize face-to-face visits and treatment delays where surgical treatment is constrained.
• One-stop clinics preferred over multiple visits.
• Patient-initiated follow-up to ensure those with multiple episodes of bleeding could attend for clinical examination when required.
• Evaluation of adnexal masses using ultrasound or MRI and established rules for triage, e.g. International Ovarian Tumour Analysis or the Risk of Malignancy Index (RMI) etc. In cases of low index of suspicion for malignancy (e.g. RMI <200), surgery could be deferred for 3-6 months, with virtual follow-up.
• For those requiring assessment in secondary care, such as patients with postmenopausal bleeding, telephone or virtual assessment followed by direct investigation with hysteroscopy and ultrasound is preferred without the need for clinical examination if possible (given a normal cervical smear history).
• For those with suspected ovarian cancer, using cytology to guide treatment decisions if there was inadequate or restricted access to usual image-guided biopsies.

| ADAP TATI ON STOTRE ATMENT
The disruption to cancer services and capacity constraints have required prioritization of treatment for those patients who are most in need. Three priority levels were recommended by the British Gynaecological Cancer Society (BGCS) and UK National Health Service (NHS) to determine the timescales required for surgical treatments during the pandemic (Table 1). 29 Patients are advised of the risks of perioperative COVID-19 infection as well as the risk of reduced survival with delayed treatment. It is important that any delays or changes to gold standard treatment should be recorded, communicated clearly with patients, and made with multidisciplinary input.
Patients whose treatment is deferred should be tracked. The BGCS has devised a harms template that can be used. 29 Considerations were made to improve the safety of procedures undertaken. 30 COVID-19 testing should occur prior to surgery; where a patient tests positive their treatment should be delayed by 2-4 weeks to allow recovery owing to the heightened morbidity from perioperative COVID-19 infection. Vaccination for COVID-19 significantly reduces the risks of infection and is recommended for all women planned for and undergoing cancer treatment. [31][32][33] Routine primary or interval debulking surgery for advanced ovarian cancer was delayed at the start of the pandemic, with neoadjuvant chemotherapy given due to initial concerns regarding surgical morbidity as well as the increased resource requirements, including  (Table 2) 35

| IMPAC TONSURG ERY
The COVID-19 pandemic has severely disrupted cancer care across the whole spectrum of prevention, diagnosis, surgery, oncology treatments, and palliative care. Modelling has estimated that approximately 2.3 million cancer surgeries will have been delayed or cancelled during the pandemic's first peak (March-May 2020). 22,37 The impact on cancer diagnostics is also estimated to be substantial, with more than 350 000 fewer people than usual being referred for a rapid referral for suspected cancer in the UK between March and September 2020, largely owing to fewer people seeking primary care advice. 38 The uptake of screening programs has been reduced and elective preventive surgery has been delayed.
The COVIDSurg gynaecological cancer study investigating outcomes in first-line management of women with gynecologic cancer reports that at least 15% of women with gynecologic cancer have suffered disruption/change to usual first-line surgery. 39 Current data show that major morbidity and mortality from gynecologic cancer surgery in patients selected to undergo surgery during the pandemic is comparable to pre-COVID times. 28 Studies have also clearly shown that introduction of safe COVID-free pathways and establishing cancer care in COVID-free elective care hospitals that do not provide care for COVID-19 patients ensure that cancer care can safely continue even during the pandemic. Nevertheless, cancer surgery has been severely tested and the resilience of the healthcare system to provide cancer care must be boosted by investment from both government and private sector players worldwide.
Prioritization frameworks issued by the BGCS and NICE (Tables 1   and 2), as well as other international societies, have attempted to balance the risk from treatment in COVID-19 exposed environments and the availability of resources, including intensive care beds, against the impact of such delays on oncological outcomes.
Long-term data on the impact of such prioritization frameworks are awaited from the UKCOGS study (www.ukcogs.org.uk).

| IMPAC TONPATIENTS
Fifty-four percent of women with ovarian cancer report that their treatment has been impacted due to the COVID-19 pandemic, and 27% of women could not access care as they did before the pandemic. A patient experience survey conducted by the charity Cancer Research UK investigating the overall impact of care reported that gynecologic cancers were among the most affected, with 78% patients with gynecologic cancers reporting an impact. 40 Questionnaire surveys investigating patient perceptions show that fear about COVID-19 and anxiety about cancer progression due to a change in cancer care during COVID-19 is a frequent and serious concern for cancer patients. 41 It is important to understand that healthcare givers and patients/ carers can perceive the impact of change very differently. Changes in care such as telephone follow-up rather than face-to-face follow-up, earlier discharge from hospital, and stopping visiting may all be seen by healthcare providers as relatively minor changes to overall outcome. However, these are seen as major changes to usual care by patients. It is difficult to quantify the impact these changes may make on the relationship of trust between doctor and patient/ carer. Clinical staff too are constrained by their own psychological response to risks brought on by the pandemic, including the ongoing risk of becoming infected with COVID-19, which placed them in an uncertain position. Healthcare staff are also vulnerable to the impact of COVID-19; it is vital that this is recognized and burnout is prevented.
Patients also seek information amongst themselves and conduct lay risk assessments through online patient groups; for instance, regarding what they can or cannot do during periods when they were advised to shield from COVID-19 exposure. 42  Important messages: • It is possible to operate safely on gynecologic cancer patients during the COVID-19 pandemic, with precautions.
• Hospitals and health systems should have resilient elective care pathways so that cancer is managed in safe areas, away from where patients with COVID-19 are being looked after.
• It is critical to ensure COVID-19 vaccination for all cancer patients.
• Counter misinformation by working with cancer charities and patient support groups, developing a clear communications plan to reach patients.
• It is important to focus on salvaging screening and prevention services as this will have long-term impact, especially for cervical cancer.
• We must plan for the recovery and backlog of patients whose treatments have been delayed or altered.
• We need to prepare for additional surges or outbreaks of infection.
• Steps need to be taken to minimize staff burnout and attrition.
• Trainees need additional support that addresses both their training needs as well as mental well-being.
• Research is needed to evaluate the impact of COVID-19 on changes to gynecologic cancer patient care and long-term patient outcomes.

AUTH O RCO NTR I B UTI O N S
All authors contributed to manuscript writing, review, and approval.