Dear Editor,
The novel coronavirus disease 2019 (COVID-19), viral respiratory illness, is developed by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its outbreak was firstly observed at Wuhan, China, in 2019 [1]. The World Health Organization (WHO) has developed practical recommendations for every specific situation [2]. In line with WHO's proposal, each country of the globe has announced applicable guidelines for the prevention of COVID-19 transmission. Despite strong quarantine, nationwide lockdown, social distancing, and hygiene education, the COVID-19 spread unfortunately continues with different patterns of occurrence in each country [3].
With these backgrounds, the standard of care in gynecologic cancers has been inevitably hampered by the COVID-19 crisis. As a result, patients and medical staffs are facing unprecedented challenges in treating cancer. In this letter, we have provided specialized recommendations beneficial for clinicians to take care of patients with gynecologic cancers during the pandemic of COVID-19. It is desirable to selectively apply this recommendation in consideration of the hospital's resources and the situation of COVID-19 transmission. For more clear understanding, we divided possible situation of diseases into three priorities, depending on the severity of patient's condition with gynecologic malignancies.
In Table 1, we described the priority of disease condition which was modified referring to the clinical guidelines from Ontario Health [4,5]. Management was indicated with A, B, and C in the order of higher priority to adequately cope with specific conditions in cervical, endometrial, and ovarian cancer (Tables 2, 3, 4) [6,7,8,9,10,11,12,13,14,15].
Table 1. The classification of priorities according to the severity of disease condition.
| Priority | Description of disease severity |
|---|---|
| A | Life-threatening or needs emergency care |
| B | Non-life threatening and could be deferred 6–8 weeks during the COVID-19 pandemic |
| C | Stable even in the discontinuation of treatment during the current COVID-19 crisis |
COVID-19, coronavirus disease 2019.
Table 2. Recommendations for cervical cancer care during the COVID-19 pandemic.
| Priority | Patient's status | Management |
|---|---|---|
| New diagnosis or screening test | ||
| A | Massive and/or persistent bleeding from cervix | Assessment should be performed as soon as possible based on the level of institution resources or regional circumstances of COVID-19 |
| C | Routine screening | It is preferable to discontinue all routine check-up during COVID-19 pandemic or consider to refer to the accessible local clinic |
| Abnormal Pap result | ||
| B | Suspected of low-grade cervical disease | Assessment could be deferred up to 6-12 months |
| B | Suspected of high-grade cervical disease without invasive cancer | It is appropriate to evaluate lesions within 3 months |
| B | Suspected of invasive cervical cancer | Diagnosis of the lesion could be prioritized within 2 weeks |
| Early-stage cervical cancer | ||
| C | Stage IA1 based on LLETZ pathology | It might be possible to observe the lesion without further treatment until COVID-19 outbreak wanes |
| B | Stage IA2 based on LLETZ pathology | It could be postponed to perform further treatment up to 6–8 weeks |
| B | Stage IB1, IB2, and IIA1 | Radical hysterectomy can be postponed up to 6–8 weeks and can be replaced by alternatives such as trachelectomy, neoadjuvant chemotherapy, or radiation therapy in consideration of fertility preservation, operation morbidity, and patient condition |
| C | Postoperative status - low risk of recurrence | Adjuvant therapy might be discontinued during the crisis of COVID-19 |
| B | Postoperative status - intermediate risk of recurrence | (CC)RT can be deferred up to 8 weeks after surgery in consideration of risk of Sedlis criteria |
| B | Postoperative status - high risk of recurrence | It is preferable to perform CCRT on schedule |
| B | Stage IB3, and IIA2 | It is appropriate to perform EBRT using hypofractionation to reduce the number of visit to clinic. Radical hysterectomy can be chosen on the decision of physician. |
| B | Locally advanced cervical cancer (IIB- IVA) | CCRT is recommended on schedule, and could consider hypofractionation to reduce the number of visit to clinic. Brachytherapy should be done on time unless there is COVID-19 symptom. |
| B | Stage IVB cervical cancer | It is preferable to perform chemotherapy consisting of cisplatin and paclitaxel, (+/−) bevacizumab on schedule. |
| Recurrent cervical cancer | ||
| B | Cervical stump recurrence | Surgical resection or radiation therapy can be considered according to the level of institutional resources on schedule |
| B | Vaginal recurrence with bleeding | It is recommended to perform brachytherapy or EBRT on schedule |
| B | Local recurrence within pelvis | (CC)RT is recommended on schedule, and could consider hypofractionation to reduce the number of visit to clinic. Brachytherapy should be done on time unless there is COVID-19 symptom. |
| B | Distant recurrence - chest only | Chemotherapy is recommended on schedule, but it can be deferred for several week in case of no adverse effect caused by the delay of treatment |
| B | Distant multiple recurrence | Chemotherapy is recommended on schedule, but it can be deferred for several week in case of no adverse effect caused by the delay of treatment |
| B | Pelvic side wall recurrence | Ultra-radical surgery or radiation could be recommended according to the level of institution resources |
| Follow-up | ||
| C | Follow-up after curative operation | Surveillance can be deferred based on the level of risk for recurrence |
| C | Follow-up after curative radiation | Surveillance can be deferred based on the level of risk for recurrence |
| Special situation | ||
| B | Occult cervical cancer after simple hysterectomy | The treatment can be chosen among observation, surgery, or radiation after pathologic review. It can be deferred for several week in case of no adverse effect caused by delay of treatment |
| C | Condition requiring palliative treatment | The treatment can be postponed after consultation with multidisciplinary team |
| A | Serious toxicity (i.e. fever, pain, dyspnea, bowel perforation, and unstable vital sign) | Immediate management of toxicity should be required as soon as possible even in the circumstances of COVID-19 pandemic |
| B | Neutropenia | Administration of hematologic growth factor is recommended as quickly as possible |
COVID-19, coronavirus disease 2019; CCRT, concurrent chemo-radiation treatment; EBRT, external beam radiation therapy; LLETZ, large loop excision of the transformation zone.
Table 3. Recommendations for endometrial cancer care during the COVID-19 pandemic.
| Priority | Patient's status | Management |
|---|---|---|
| Diagnostic approach | ||
| A | Vaginal bleeding, suspicious uterine pathology | In case of clinically significant AUB, office-based endometrial biopsy should be performed in outpatient setting based on the level of institution resources or regional circumstances of COVID-19 |
| Premalignant disease | ||
| B | EIN, wants preserving fertility | Start conservative treatment such as oral progestin and LNG-IUD |
| B | EIN, not wants preserving fertility | Simple hysterectomy might be postponed up to 8 weeks. |
| Conservative treatment such as oral progestin and LNG-IUD can be applied alternatively until the pandemic is over. | ||
| Surgical staging | MIS approach with SLN mapping is recommended because it confers fast recovery and less complication, and accurate nodal staging | |
| A | Surgical staging in patients with active bleeding | Staging operation with hysterectomy should be performed as soon as possible. |
| B | Surgical staging in patients without active bleeding | Staging operation can be delayed up to 8 weeks. |
| B | Clinical stage IA, grade I | Conservative treatment such as oral progestin and LNG-IUD can be applied alternatively until the pandemic is over. |
| Adjuvant treatment | Adjuvant treatment can be deferred up to 9 weeks after surgery. | |
| C | Surgical stage I, II with low risk factor | Adjuvant therapy might be discontinued during the crisis of COVID-19 |
| B | Surgical stage I, II with intermediate to high risk factors | Brachytherapy is preferred considering fewer visit and less complication risk |
| B | Surgical stage III | Depending on the discretion of the physician, adjuvant chemotherapy or radiotherapy is considered. |
| Use chemotherapy regimens that will avoid frequent patient visits (e.g. paclitaxel + carboplatin). | ||
| In case of pelvic RT, consider hypofractionation to reduce the number of visit to clinic. | ||
| B | Surgical stage IVA | Depending on the discretion of the physician, adjuvant chemotherapy or radiotherapy is considered. |
| Use chemotherapy regimens that will avoid frequent patient visits (e.g. paclitaxel + carboplatin). | ||
| In case of pelvic RT, consider hypofractionation to reduce the number of visit to clinic. | ||
| Inoperable condition | ||
| B | Inoperable clinical stage III | Chemotherapy is recommended on schedule. |
| Use chemotherapy regimens that will avoid frequent patient visits (e.g. paclitaxel + carboplatin) | ||
| B | Inoperable clinical stage IV | Chemotherapy is recommended on schedule. |
| Use chemotherapy regimens that will avoid frequent patient visits (e.g. paclitaxel + carboplatin) | ||
| B | Stage IVB | Chemotherapy is recommended on schedule. |
| Use chemotherapy regimens that will avoid frequent patient visits (e.g. paclitaxel + carboplatin) | ||
| Follow-up | Routine imaging study is not recommended until the pandemic is over | |
| C | Follow-up after primary treatment | Surveillance can be deferred based on the level of risk for recurrence |
| Recurrent disease | Choice of therapy should minimize exposure to other contacts, risk from therapy, and prognosis. | |
| B | Isolated vaginal recurrence | Brachytherapy is recommended on schedule, but it can be deferred for several week in case of no adverse effect caused by delay of treatment |
| B | Pelvic recurrence | RT is recommended on schedule, and consider hypofractionation to reduce the number of visit to clinic. |
| B | Distant recurrence with symptom | Chemotherapy is recommended on schedule. |
| Use chemotherapy regimens that will avoid frequent patient visits | ||
| C | Distant recurrence without symptom | Consider hormonal treatment |
| Use chemotherapy regimens that will avoid frequent patient visits | ||
| B | Second or more line chemotherapy after recurrence | Consider hormonal treatment |
| Use chemotherapy regimens that will avoid frequent patient visits |
COVID-19, coronavirus disease 2019; AUB, abnormal uterine bleeding; EIN, endometrial intraepithelial neoplasia; LNG-IUD, levonorgestrel intrauterine device; MIS, minimally invasive surgery; RT, radiotherapy; SLN, sentinel lymph node.
Table 4. Recommendations for epithelial ovarian cancer care during the COVID-19 pandemic.
| Priority | Patient's status | Management |
|---|---|---|
| Newly diagnosed ovarian cancer | ||
| A | Suspected ovarian cancer with symptoms indicating bowel obstruction/perforation, massive ascites, or peritonitis | Assessment should be performed as soon as possible. |
| B | Suspected ovarian cancer with no symptom and looks confined to pelvis | For presumed early stage ovarian cancer according to salpingo-oophorectomy, restaging surgery can be deferred from 6–8 weeks. |
| B | Suspected ovarian cancer with no symptom and looks spread beyond pelvis | Delaying interval debulking surgery beyond 3–4 cycles of neoadjuvant chemotherapy should be considered. |
| Choose regimens scheduled with the fewest infusion visits. | ||
| Consider lower dosing intensity and less myelosuppressive regimens to reduce neutropenia. | ||
| Avoid the prescription of dose-dense, intraperitoneal, and HIPEC regimens. | ||
| B | After 3 cycles neoadjuvant chemotherapy in suspected advanced stage ovarian cancer | Consider extending the chemotherapy plan to 6 cycles before the interval cytoreductive surgery in women who have already started neoadjuvant chemotherapy. |
| A | Suspected postoperative complications (e.g. anastomotic leak) | Assessment should be performed as soon as possible. |
| B | Incidentally found ovarian cancer | For presumed early stage ovarian cancer according to salpingo-oophorectomy, restaging surgery can be deferred from 6–8 weeks. |
| If residual suspected, reoperation should be performed. | ||
| Early stage (I–IIA) ovarian cancer requiring postoperative adjuvant chemotherapy | ||
| A | High-grade serous/endometrioid | Adjuvant chemotherapy should be performed as soon as possible. |
| B | Non-high-grade serous/endometrioid | Adjuvant chemotherapy can be an option, but should be considered less essential and discussed with the patient about minimizing the infusion visits. |
| Adjuvant chemotherapy in advanced stage ovarian cancer | ||
| A | High-grade serous/endometrioid | Adjuvant chemotherapy should be performed as soon as possible. |
| A | High-grade serous with BRCA mutation | In patients who have a BRCA mutation and are PARP naïve, consider rucaparib monotherapy in situations where platinum therapy cannot be given. |
| B | Clear cell or mucinous tumor | Adjuvant chemotherapy can be an option, but should be considered less essential and discussed with the patient about minimizing the infusion visits. |
| C | Low-grade serous tumor | Consider deferring the adjuvant therapy as possible. |
| C | After upfront adjuvant chemotherapy | Consider deferring the maintenance chemotherapy as possible. |
| If utilizing PARPi maintenance therapy, consider the risk of the immunosuppression and exposure to COVID-19 during infusion. | ||
| Follow-up visit | Routine surveillance of asymptomatic patients should be postponed as possible. | |
| Utilize telemedicine and reduce the frequency of in-person evaluation. | ||
| C | Patients with PARPi maintenance | Most can be managed through telemedicine with scheduled blood tests and imaging done close to home. |
| C | Patients with bevacizumab maintenance | If facilities exist to continue, supervision can be performed by telemedicine, ensuring BP and urinalysis are monitored. |
| Recurrent disease | Choice of therapy should minimize exposure to other contacts, risk from therapy, and prognosis. | |
| B | Symptomatic platinum-sensitive recurrent disease | Adjuvant chemotherapy can be an option, but should be considered less essential and discussed with the patient about minimizing the infusion visits. |
| C | Symptomatic platinum-resistant recurrent disease | Non platinum-based regimen are low priority and should be used after careful review of the risk/benefit. |
| C | Symptomatic slowly growing recurrent disease | Decision should be based on clinical judgement. |
| C | Asymptomatic recurrent disease | Decision should be based on clinical judgement. |
| Special situation | ||
| C | Risk-reducing salpingo-oophorectomy for genetic predisposition to gynecological cancer | Consider deferring the surgery as possible. |
COVID-19, coronavirus disease 2019; BRCA, breast cancer gene; BP, blood pressure; HIPEC, hyperthermic intraperitoneal chemotherapy; PARPi, poly ADP ribose polymerase inhibitor.
We strongly believe that this recommendation is expected to provide clinicians with practical assistance in dealing with gynecologic cancer by prioritization and minimize potential risk of exposure to COVID-19.
Sung-Jong Lee (https://orcid.org/0000-0002-6077-2649)
Department of Obstetrics and Gynecology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
Taehun Kim (https://orcid.org/0000-0003-3198-0788)
Department of Obstetrics and Gynecology, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, Korea.
Miseon Kim (https://orcid.org/0000-0002-5118-9275)
Department of Obstetrics and Gynecology, CHA Gangnam Medical Center, CHA University School of Medicine, Seoul, Korea.
Dong Hoon Suh (https://orcid.org/0000-0002-4312-966X)
Department of Obstetrics and Gynecology, Seoul National University Bundang Hospital, Seongnam, Korea.
Jeong-Yeol Park (https://orcid.org/0000-0003-2475-7123)
Department of Obstetrics and Gynecology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
Myong-Cheol Lim (https://orcid.org/0000-0001-8964-7158)
Division of Tumor Immunology, Research Institute, and Center for Gynecologic Cancer & Center for Clinical Trial, Hospital, and Department of Cancer Control & Population Health, GSCSP, National Cancer Center, Goyang, Korea
Jung Yun Lee (https://orcid.org/0000-0001-7948-1350)
Department of Obstetrics and Gynecology, Institute of Women's Life Medical Science, Yonsei University College of Medicine, Seoul, Korea.
Jae-Weon Kim (https://orcid.org/0000-0003-1835-9436)
Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea.
Yong-Bae Kim (https://orcid.org/0000-0001-7573-6862)
Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea.
Keun-Yong Eom (https://orcid.org/0000-0003-3650-1133)
Department of Radiation Oncology, Seoul National University Bundang Hospital, Seongnam, Korea
Seung Cheol Kim (http://orcid.org/0000-0002-5000-9914)
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Ewha Womans University School of Medicine, Seoul, Korea. onco@ewha.ac.kr
Footnotes
Conflict of Interest: No potential conflict of interest relevant to this article was reported.
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