COVID-19 and gynecological cancer: a review of the published … · 1424 uwins C etfial Int J Gynecol Cancer 202030:14241433 doi:101136igc-2020-001634 COVID-19 and gynecological cancer:

Uwins C, et al. Int J Gynecol Cancer 2020;30:1424–1433. doi:10.1136/ijgc-2020-0016341424

COVID-19 and gynecological cancer: a review of the published guidelines

Christina Uwins,1 Geetu Prakash Bhandoria ,2 TS Shylasree,3 Simon Butler- Manuel,1 Patricia Ellis,1 Jayanta Chatterjee,1 Anil Tailor,1 Alexandra Stewart,4 Agnieszka Michael5

For numbered affiliations see end of article.

Correspondence toDr Geetu Prakash Bhandoria, Obstetrics & Gynecology, Command Hospital Pune, Pune 411040, Maharashtra, India; doctor_ 071277@ yahoo. co. in

Received 18 May 2020Revised 4 June 2020Accepted 8 June 2020Published Online First 23 June 2020

To cite: Uwins C, Bhandoria GP, Shylasree TS, et al. Int J Gynecol Cancer 2020;30:1424–1433.

Review

© IGCS and ESGO 2020. No commercial re- use. See rights and permissions. Published by BMJ.

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INTERNATIONAL JOURNAL OF

GYNECOLOGICAL CANCER

AbstrACtOn March 11, 2020 the COVID-19 outbreak was declared a ‘pandemic’ by the World Health Organization. COVID-19 is associated with higher surgical morbidity and mortality. An array of guidelines on the management of cancer during this pandemic have been published since the first reports of the outbreak. This narrative review brings all the relevant information from the guidelines together into one document, to support patient care. We present a detailed review of published guidelines, statements, comments from peer- reviewed journals, and nationally/internationally recognized professional bodies and societies' web pages (in English or with English translation available) between December 1, 2019 and May 27, 2020. Search terms included combinations of COVID, SARS- COV-2, guideline, gynecology, oncology, gynecological, cancer. Recommendations for surgical and oncological prioritization of gynecological cancers are discussed and summarized. The role of minimally invasive surgery, patient perspectives, medico- legal aspects, and clinical trials during the pandemic are also discussed. The consensus is that elective benign surgery should cease and cancer surgery, chemotherapy, and radiotherapy should continue based on prioritization. Patient and staff face- to- face interactions should be limited, and health resources used efficiently using prioritization strategies. This review and the guidelines on which it is based support the difficult decisions currently facing us in gynecological cancer. It is a balancing act: limited resources and a hostile environment pitted against the time- sensitive nature of cancer treatment. We can only hope to do our best for our patients with the resources available to us.

bACkgrOunD

On March 11, 2020 the World Health Organization Director- General declared the outbreak of COVID-19 a pandemic on the basis of its spread and severity.1 Early reports in the first nationwide analysis from China, published in mid- February 2020, purported to indicate a 3.5 times higher risk of needing mechan-ical ventilation, intensive care admission, or dying in patients with a history of cancer compared with those without.2 The ongoing CovidSurg project, a new inter-national multi- center study, has provided data from 1129 patients with COVID-19 operated on during this time. Findings showed a high overall mortality rate of 24% and pulmonary complication rate of 51%. Most deaths followed pulmonary complications (83%), and elective surgery was associated with a 19% mortality

risk. These data support the cancelation or post-ponement of elective surgeries during the ongoing pandemic.3 Global predictive modeling estimates that 28 404 603 operations will have been canceled or postponed worldwide during the peak 12 weeks of disruption due to COVID-19.4 It is estimated that, if countries increase their normal surgical volume by 20% following the resolution of the pandemic, it will take a median of 45 weeks to clear the backlog of operations resulting from the COVID-19 disruption.4 There is an emergent need to better understand the impact of COVID-19 on the care of cancer patients requiring surgery. CovidSurg- Cancer and CovidSurg- Cancer Gynecological Oncology are international multi- center studies launched to understand this question. Data collection was ongoing for these studies at the time of submission of this review.5

Since the beginning of March 2020 an array of guidelines, statements, and comments have been published on the management of gynecological cancer during the COVID-19 pandemic. We have reviewed and summarized the surgical and oncolog-ical prioritization strategies in circumstances where capacity is limited. Capacity varies between countries and even within each country.

Many recommendations are pragmatic deviations from 'standard of care' management, aiming to balance the risk of treatment and available resources during this pandemic. It remains to be seen how short- term and long- term oncological outcomes will be affected. Treatment escalation plans and patients’ wishes regarding resuscitation should therefore be discussed openly with patients for a range of different eventualities and documented in the medical notes. The guidelines reviewed here reflect choices made by clinicians during the current pandemic and help with the decision- making process.

MethODs

We performed electronic searches of Embase, Medline, and Google Scholar for guidelines, state-ments, or comments (in English or with English translation available) published between December 1, 2019 and May 27, 2020. Those published in peer- reviewed journals or on nationally/internation-ally recognized professional bodies’/societies’ web

on June 19, 2021 by guest. Protected by copyright.

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Table 1 Timeline of guidelines

General oncology guidelinesDate of issue/publication (year 2020)

Haut Conseil de Santé Publique6 March 14

National Institute for Health and Care Excellence39 March 20

National Health Service (NHS)12 March 23

American College of Surgeons (Statement)60 March 24

Society of American Gastrointestinal and Endoscopic Surgeons & European Association for Endoscopic Surgery30

March 29

Italian Society of Surgical Oncology, Italian Association of Medical Oncology and Italian Association of Radiation Oncology joint statement9 (Statement)

March 23

National Comprehensive Care Network10 April 5 (accepted for publication March 16)

American Society of Clinical Oncology36 April 28 (accepted for publication April 8)

Medical Oncology Group of Australia8 April 16 (published May 13)

Gynecological cancer statements/guidelines

British Gynaecological Cancer Society7 March 22 (updated v2.0 April 13, v3.0 May 5)

Society of Gynecologic Oncology49 March 23

European Network of Gynaecological Oncological Trial Groups45 March 23

International Journal of Gynecological Cancer51 March 27 (accepted March 24)

American Association of Gynecologic Laparoscopists (Statement)32 March 27

Australia New Zealand Gynecological Oncology Group47 March 31

European Society of Gynecological Oncology (ESGO) Statement61 March 31

Groupe de Recherche en chirurgie Oncologique et Gynécologique interest group of Collège National des Gynécologues Obstétriciens Français15

April 1

Society of European Robotic Gynecological Surgery31 April 3

Society of Gynecologic Oncology of Canada16 April 7

Italian Society for Colposcopy and Cervico- Vaginal Pathology55 April 8

British Society of Colposcopy and Cervical Pathology54 April 9

European Society of Medical Oncology56 62 63 April (accessed April 19)

Asian Society of Gynecologic Oncology17 May 8

European Federation for Colposcopy (EFC)- European Society of Gynecologic Oncology (ESGO)59

May

pages were included (first guideline published on 14 March, 2020). Reference lists were hand- searched to identify any pertinent arti-cles that had been missed. Search terms included combinations of: COVID, SARS- COV-2, guideline, gynecology, oncology, gyneco-logical, cancer, and variant spellings. Comments, perspectives, and correspondence published in various journals have not been incor-porated in this review.

results

evolution of the guidelinesThe first set of publicly available guidelines appeared in France. The French High Council for Public Health (Haut Conseil de Santé Publique) formally released their guidelines on March 14, 2020. These were followed by a series of guidelines/recommendations

published by several national/international professional societies/bodies, as listed in Table 1.6 Due to the rapidly evolving nature of this pandemic, guidelines are based on expert opinion because of the lack of available robust scientific evidence.

recommendations on reduction of infection rate ► Identification of patients: COVID-19 screening clinics ► Testing patients admitted for treatment/surgery depending on

available resources or based on symptoms within 14 days ► Strict tracing of patients' contacts ► Establishing isolated areas for COVID patients ► 'Clean/COVID-19- free' hospital sites for cancer surgery7

► Work from home/separated teams to maintain the workforce ► Travel restrictions


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► Fever/severe acute respiratory syndrome coronavirus 2 (SARS- COV-2) screening for staff and visitors

► Social distancing ► Frequent disinfection of areas which are touched frequently

such as door knobs, elevator buttons, or railings8

► Limitation of family and friends visiting the hospital

recommendations for outpatient clinics ► Minimize face- to- face appointments9

► Telephone/video consultations ► Maintaining ‘social distancing’ in outpatient waiting areas ► Adequate protection equipment

recommendations for healthcare personnel safety ► Personal protection equipment whenever and wherever

applicable ► Staff training in using personal protection equipment ► Staff training in the identification of suspected COVID patients ► Ensuring that staff have access to psychological support ► Reassignment of clinical duties to administrative roles for immu-

nocompromised staff or those with significant co- morbidities10

► Strict ‘stay at home when ill’ policy10

► Improving awareness among professionals through regular webinars with a national and international presence to learn from others

recommendations on inpatient management ► COVID designated wards/intensive care units/operating rooms/

hospitals ► Blood bank balancing operating room transfusion needs with

shortage of blood products due to a reduction in blood donation ► Pooling of resources such as shifting patients to COVID- free

units/hospitals ► Restricting the number of visitors to ‘none’ or ‘single- only'In addition to changes in day- to- day practice relating to hospital

visits and minimizing risk of infection, guidelines advise on prioriti-zation of treatment when faced with low capacity in intensive care units and staff absence due to COVID-19 infection. As COVID-19 has had a global effect these guidelines vary, with some countries and societies defining priorities and others providing various options.11

surgical prioritizationThe general consensus is that elective surgery for benign indica-tions should cease during this pandemic.12 Recommendations for the surgical prioritization of gynecological cancer cases may be broadly divided into four main groups.7 9 12–17

Priority level 11a Emergency required within 24 hours to save a life

1b Urgent required


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Table 2 Surgery: ovarian cancer

1b7 or High62 27 or Medium62 3 or Low62

Mechanical intestinal obstruction/impending perforation where lines of life- prolonging treatment exist.7

Pelvic mass with torsion or causing urinary or intestinal obstruction35

Malignant germ cell tumors in young patients should take priority. Complete staging procedure should be performed with nodal evaluation.49

Image- guided/diagnostic laparoscopy for tissue biopsy/assess operability if high suspicion of cancer35

Elective surgery with the expectation of cure to be performed within 4 weeks to save a life/prevent progression of disease beyond operabilityPriority- based on:

► Urgency of symptoms ► Complications ► Expected growth rate

Primary debulking surgery for ovarian cancer, particularly cell types unlikely to respond to neoadjuvant chemotherapy (low grade serous, clear cell, or mucinous)16 35

Presumed early- stage ovarian cancer based on adnexectomy: completion/staging surgery may be deferred for 1–2 months15

Ovarian mass with adverse features but normal tumor markers: ideally operated on within 4 weeks but could be delayed following multidisciplinary tumor board discussion16

Interval debulking surgerySecondary surgery in recurrent ovarian cancer: patients should be managed with chemotherapy unless surgery would relieve symptoms7

Pelvic masses following multidisciplinary tumor board discussion, including using MRI/International Ovarian Tumor Analysis ultrasound/Risk of Malignancy Index to decide on the likelihood of malignancy:

► Thought to be benign: can defer surgery for 3–6 months

► Risk of Malignancy Index


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Table 3 Chemotherapy: ovarian cancer

High62 Medium62 Low62

For advanced ovarian cancer, neoadjuvant chemotherapy may be preferred to primary cytoreductive surgery and be effective in delaying surgery and inpatient hospitalization7 14–16 Interval surgery may then follow if local capacity permits, or in some centers clinicians may consider continuing to six cycles to delay surgery7 15 51

Patients should undergo at least two new cycles of chemotherapy after their surgery.15

Test for Breast Cancer Antigen (BRCA) mutations, germline and somatic so that patients may access poly ADP ribose polymerase inhibitorsPoly ADP ribose polymerase inhibitors should be started at the end of chemotherapy, if possible, patients may access Poly ADP ribose polymerase inhibitors before the opportunity for surgery arises7 16

Consider the routine use of Filgrastim (granulocyte colony stimulating factor) to reduce the incidence of neutropenia in patients receiving combination therapy7

Malignant germ cell tumors high priority if requiring chemotherapy49

Chemotherapy for platinum- sensitive relapse should be considered for symptomatic patients and delayed where possible for asymptomatic patients7 16

Chemotherapy for non- serous, non- endometrioid ovarian cancers and low- grade cancers offers limited benefit and adjuvant chemotherapy in these patients is of lower priority Consider hormonal therapy (letrozole, anastrozole, tamoxifen)7 8

Maintenance bevacizumab used with caution as it has low survival benefit and may be associated with a higher risk of bowel perforation7

Following up- front adjuvant chemotherapy; consideration may be given to oral maintenance therapy, such as PARPi, as maintenance intravenous therapy requires repeated visits to the hospital51,16

Table 4 Surgery, chemotherapy and radiotherapy: endometrial cancer

1b7or High63 263or Medium7 363or Low7

Surgery

► Hemorrhage7 63

► Peritonitis63

► Radiotherapy complications63

► (Fistula/perforation) ► Post- operative bleeding/ureteric injury63

► Hydatiform mole curettage or hysterectomy64

► High- risk or high- grade disease7

► Uterus confined disease63

► Grade 3 endometrioid/grade 2 p53 mutated/serous/carcinosarcoma/undifferentiated/clear cell16

► Known/suspicion of high- grade uterine sarcoma16

► Low- grade, early stage7

► Risk- reducing surgery in genetically predisposed63

► Complex atypical hyperplasia not controlled with hormonal therapy63

► Repair of asymptomatic fistula63

► Resection of slow growing central recurrence63

Chemotherapy and radiotherapy

► Adjuvant treatment after curative intent surgery

► Priority to high- grade disease (including ovarian cancer, sarcomas, gestational trophoblastic neoplasia, and type II endometrial cancers). Recurrent cancer patients with symp-toms needing urgent treatment or end of life discussion14

► Where possible, chemotherapy for platinum- sensitive relapse should be considered for symptomatic patients and delayed, if possible, for patients without symptoms or with small- volume disease unlikely to lead to significant pathophysiological complications in the next 3 months

► Utilization of chemotherapy regimens that will avoid frequent patient visits

► For patients with metastatic disease, treatment delays may lead to worsening performance status; however, chemotherapy for a platinum- resistant disease would be of low priority, particu-larly in the absence of symptoms; consideration should include how such delays may lead to admission for symptom palliation, which further stresses inpatient resources.10 Alternative strate-gies to manage symptoms should be considered

For patients found to be COVID-19- positive, do not start chemo-therapy until their symptoms resolve±they test negative (depending on resources).16 Advance care planning discussions should be documented during discussions with patients. This should include goals of care and end- of- life care.36 When chemotherapy is offered,

a decision should be made together with patients, counseling about the risks of delaying chemotherapy versus the risks of developing COVID-19 while on treatment.

radiotherapyPrioritization for radiotherapy patients is based on principles similar to those in chemotherapy patients. Curative radiotherapy should be prioritized over adjuvant therapy for local disease control. Where adjuvant radiotherapy is likely to reduce local recurrence but not prolong survival, radiotherapy may be withheld following careful consideration and counseling.7 17 The recommendations are summarized below12 40 41:

Priority level 1Rapidly growing tumors12 40

► Curative intent chemoradiotherapy ► Treatment already underway—external beam radiotherapy and

brachytherapy combined treatment plan

Priority level 2Urgent palliative radiotherapy12 40

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► Radiotherapy is the first- line definitive treatment ► Post- operative radiotherapy in known residual disease

following surgery for rapidly growing tumors

Priority level 4Palliative radiotherapy to reduce the burden on the healthcare service12 40

Priority level 5Adjuvant radiotherapy following complete resection of disease (


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Figure 1 Pre- invasive cervical lesions.

Table 5 Surgery: cervical cancer

1b7or High56 27or Medium56 37or Low56

► Life- threatening hemorrhage with failed conservative measures, especially surgery likely curative7 56

► Peritonitis56

► Radiotherapy complications56 (fistula/perforation)

► Post- operative bleeding/ureteric injury56

► Early- stage (unspecified)7 51

► Stage 1A, 1B1–IIA: radical hysterectomy ± bilateral salpingo- oophorectomy + lymphadenectomy (level not specified)51 56

► Stage 1A: trachelectomy/hysterectomy ± sentinel lymph node sampling (postpone 2 months)51 56

► Low volume cervical cancer completely excised at loop excision7

► Cervical intra- epithelial neoplasia 3 conisation56

► Repair of asymptomatic fistula56

► Resection of slow growing central recurrence56

► Pelvic exenteration (consider postponing)56

Brachytherapy is an essential component of the treatment for cervical cancer, with poorer outcomes resulting when it is not used. Brachytherapy should be prioritized whenever possible.17 41

Vaginal cancerMost patients with vaginal cancer present at an advanced stage. Treatment is based around radiotherapy/chemotherapy/brachytherapy treatment. The added benefit of lymph node staging will be patient- dependent based on disease stage, location, and results of imaging investigations.15 For the majority of cases, prior-itization of treatment of vaginal cancer is as for cervical cancer.

Vulvar cancerIf all surgery, including cancer surgery, is suspended or a patient is not suitable for surgery, radical radiotherapy with concurrent chemotherapy is the treatment of choice. Chemotherapy may be omitted for elderly patients or those with co- morbidities .41

DIsCussIOn

Restrictions imposed during lockdown,59 including advice over social distancing and self- isolation, have reduced access to health-care services. Many of the guidelines focus on limiting patient and staff interactions by limiting the number and length of clinical visits, and thus limiting exposure. Delays and non- standard treatment pathways will undoubtedly be resorted to. Delays could be detri-mental to patients' health and, in the worst cases, lead to wors-ening performance and missing the treatment window.10

Multidisciplinary team outcomes should document what the standard of care is and how it has been modified due to the COVID-19 pandemic. When surgery is offered, a decision should be made together with patients, counseling about the risks of delaying surgery versus the risks of increased mortality and morbidity from developing COVID-19 peri- operatively in hospital. A supplementary consent form describing the increased mortality and morbidity


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Table 6 Chemotherapy and radiotherapy: cervical cancer


Chemotherapy

► Part of concurrent chemo- radiotherapy7 15 49

► Stage IB3, IIB- IVA: chemo- radiotherapy56

► Continuation of standard chemoradiotherapy, with proven benefit56

► Consider neoadjuvant chemotherapy for patients with visible tumor49 51

► Stage IVB: first line, first central recurrence, >12 months disease- free56

► First recurrence with good performance status or advanced previous untreated disease (Priority 4*)7

► Metastatic disease (Priority 6†)7 49

Radiotherapy: cervical cancer


► Part of chemoradiotherapy ‡7 15 49 56 ► Haemostatic radiotherapy7

► Salvage radiotherapy for symptomatic local recurrence56

► As adjuvant therapy in positive surgical margins7

► Palliation for unresectable, asymptomatic recurrence

*Curative therapy with a low (0%–15%) chance of success or non- curative therapy with an intermediate (15%–50%) chance of >1 year life extension.†Non- curative therapy with an intermediate (15%–50%) chance of palliation/temporary tumor control and


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Anaphylaxis management: a survey of school and day care nurses in LebanonAbstractMethodsDesignPopulationInstrumentData collectionStatistical analyses

ResultsStudy population characteristicsCurrent policies, processes and training sessionsPrevious experience in the management of anaphylaxis reaction

COVID-19 and gynecological cancer: a review of the published guidelinesAbstractBackgroundMethodsResultsEvolution of the guidelinesRecommendations on reduction of infection rateRecommendations for outpatient clinicsRecommendations for healthcare personnel safetyRecommendations on inpatient managementSurgical prioritizationPriority level 1Priority level 2Priority level 3

Patient perspectivesMinimally invasive surgeryOncological treatment guidelinesChemotherapyRadiotherapyPriority level 1Priority level 2Priority level 3Priority level 4Priority level 5

Other measuresClinical trialsOvarian cancerEndometrial cancerLow riskHigh risk

Gestational trophoblastic neoplasiaPre-invasive cervical diseaseCervical cancerVaginal cancerVulvar cancer

DiscussionReferences

Documents

COVID-19 and gynecological cancer: a review of the published … · 1424 uwins C etfial Int J Gynecol Cancer 202030:14241433 doi:101136igc-2020-001634 COVID-19 and gynecological cancer: