Dr. Indu Bansal Aggarwal:
Time to re-evaluate, re-strategize & review the management and treatment of common gynaecological cancers like Cervical, Ovarian and Endometrial cancer during COVID-19 pandemic.
In February 2020, COVID-19, caused by the novel SARS-CoV2 (severe acute respiratory syndrome coronavirus-2) was declared as a public health emergency of international concern and subsequently a ‘Pandemic’ by the World Health Organization (WHO) on 11th March, 2020. It seemed to have a very unprecedented course (1). Cancer patients are at a higher risk of serious illness from COVID-19 as their immune systems are often compromised either because of their tumors or due to the treatments they receive. If you or your loved ones are diagnosed or are being treated for cancer, here are some recommendations discussed in this article to help prevent infection.
Cancer Risk and COVID-19: As per scientific evidence, cancer patients admitted in Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, it was observed that the infection rate in cancer patients was double that of general population (2). Unfortunately, cancer patients were at high risk of developing serious complications following COVID infection and at an increased risk of death and/or intensive care unit admission (3). The fatality rates were also markedly higher among patients with comorbidities: 11% for cardiovascular disease, 7% for diabetes, 6% for chronic respiratory disease, and 6% for cancer (4). It is recommended that routine follow up visits to hospital should be avoided and tele-consultation or video conferences should be arranged whenever appropriate for these high-risk groups.
Risk and Benefit Assessment for a Cancer Patient Treatment During COVID-19 Crisis: The patient maybe newly diagnosed, currently on treatment, a routine follow-up case, a case with recurrence post treatment or someone in need of routine cancer screening tests. Therefore, it is important to triage all cancer patients into high, medium or low risk priority groups and then decide appropriate treatment. The probable adverse effects caused by a delay in standard cancer therapy and the risks of increased complications associated with chemotherapy and surgeries should be explained to the patients in detail. It is also very important to discuss the risk/benefit of each treatment decision and/or any modification in treatment plan as well as its implications on future cancer outcomes with the family of the patient. An informed documented consent should be taken for every case. Most importantly, all patients should get a preoperative COVID test and COVID testing should also be done before chemotherapy and radiotherapy as per institutional protocols.
The treatment regimen in different gynaecological cancers are discussed here as per standard guidelines. However, the treating physician should follow his/her institutional protocols, guidelines laid out by multidisciplinary tumour boards and personal judgement for individual cases.
Cervical Cancer: The diagnostic assessment of low-grade cervical cancer via screening tests might be postponed for 6-12 months but screening for high-grade cervical cases should be further investigated within 12 weeks (5). Patients with persistent vaginal bleeding, abdominal pain, anuria, ureteral obstruction, renal obstruction, deep venous thrombosis (DVT), post-surgical complications, neurological symptoms and newly diagnosed patients need immediate treatment (6).
Patients with low-risk or microscopic disease (< 2cm, low risk histology) could be considered for conization or simple trachelectomy (removal of the cervix, upper vagina and parametrium- tissue surrounding the cervix). Sentinel lymph nodes (SLN) +/- for stage IA may be postponed for up to 2 months (5). It is recommended that for stages 1A2, 1B1-IIA, radical hysterectomy with bilateral salpingo-oophorectomy (BSO) and lymphadenectomy should be a medium priority (7). Further, patients with high operative risks or co-morbidities should be deferred by 4-6 weeks.
For locally advanced cases, chemoradiation for 1B3-IVA should not be delayed (8) and hypofractionation (more doses of radiation are delivered per treatment, so that patients can complete their course of radiation therapy in a much shorter time than the conventional treatment) may be tried in certain cases. Brachytherapy which is a form of radiotherapy where a sealed radiation source is placed inside or next to the area requiring treatment should form an essential part of treatment and should be done as per standard guidelines. In rare situations, when brachytherapy can’t be performed, the cases should be considered for Intensity-modulated radiotherapy (IMRT) boost which uses linear accelerators to deliver precise radiation to a tumor and minimize the radiation dose to surrounding normal tissue (5,9).
However, in case of metastatic/recurrent disease, radiation for brain metastasis, spinal cord compression should be offered. Chemotherapy with paclitaxel/platinum and carboplatin/ cisplatin may be offered in a 3 weeks interval regimen with liberal growth factor support. Bevacizumab may be used with a watch on hypertension and proteinuria and immune checkpoint inhibitors should be used only in clinical studies.
Ovarian Cancer: Intestinal obstruction, bowel perforation, massive ascites, acute abdominal pain, pleural effusion, rupture of mass, torsion, post-surgical complications as anastomotic leak should be considered as the high priority situations. Symptomatic patients with intestinal obstruction or pain should be considered as a high priority group while newly diagnosed patients should be taken as medium priority. In patients who are on regular follow up or on maintenance therapy, routine imaging studies might be postponed (6).
For the early stages, wait and watch strategy should be followed. Staging laparotomy can be deferred for up to 4 weeks and it is preferable to avoid para-aortic dissection (10). Adjuvant chemotherapy with a combination of paclitaxel or carboplatin for up to 4 cycles should be sufficient and if patient is not medically fit, single agent chemotherapy with carboplatin may be given for 6 cycles (11).
For low grade serous ovarian cancers, oral hormone therapy should be preferred (12). Neoadjuvant chemotherapy (preferably 3 weekly regimens) can be offered to patients for 3-4 cycles or even up to 6 cycles to delay surgery and use of growth factor support is recommended. Intra-peritoneal chemotherapy should be avoided (6, 13). Interval cytoreduction can be deferred up to 4-6 weeks of chemotherapy and ultra-radical resection, extensive resection, para-aortic dissection or HIPEC should be avoided (6). Adjuvant chemotherapy should be administered on time for high grade serous, endometroid histology as the OS decreases by 4% for each week of delay (13). Non-platinum based chemotherapy should be a low priority option and should be discussed case to case. Risk reducing surgeries for genetic predisposition, surgery for benign masses, palliative resections for recurrent tumors or for oligometastatic disease should be deferred (6). Maintenance therapy options should include oral PARP inhibitors for BRCA positive patients for high grade serous/endometroid cancers and maintenance therapy with Bevacizumab may be continued with a close watch on hypertension and urinalysis. In case of recurrent tumors, delayed treatment in asymptomatic recurrences or only CA-125 elevation should be opted and if there is a symptomatic recurrence, less intensive regimens such as single-agent carboplatin (platinum-sensitive disease), single-agent paclitaxel, metronomic combination or poly (ADP-ribose) polymerase inhibitor with growth factor support can be considered.
Endometrial Cancer: Immediate treatment should be given to symptomatic patients with bleeding, pain, intestinal obstruction, anuria, Deep vein thrombosis (DVT), pulmonary embolism should be considered as high priority (6). Deferred treatment should be given to the patients who need fertility preserving surgery, who have a slow growing central recurrence and patients on follow up should be considered as low priority (6). Imaging should not be delayed in patients with intestinal obstruction, peritonitis, anastomotic leak, ureteral compression, hydronephrosis, DVT and in those recently diagnosed with high grade histology (6).
For surgical point of view, total abdominal hysterectomy (TAH) and bilateral salpingo-oophorectomy (BSO) with/without sentinel lymph node biopsy (SLNB) may be considered for grade 2/3 histology in patients with no morbidities. Laparoscopic surgeries should be avoided because of aerosol generation. Time to wait for surgery should be limited to 6 weeks and the time to adjuvant therapy should be limited to 9 weeks. A delay in surgery of more than 6 weeks was associated with the worst overall survival (OS) in type I endometrial cancers, with stages I and II only. However, in type II cancers of any stage, time to surgery (TTS) had no significant impact on the OS (14). Hormone responsive Type I endometrial cancers can be treated with hormone therapy such as megestrol acetate or medroxyprogesteone acetate and surgery can be delayed up to 6 weeks. Levonorgestrol- releasing Intrauterine Devices (LNG-IUS) or Mirena can be used for treatment of complex atypical hyperplasia or low-grade endometrial cancer (15). Adjuvant treatment for high grade with aggressive histology, residual disease, symptomatic unresectable cases or resection margin positive cases should not be delayed by more than 9 weeks.
COVID-19 has affected the treatment of gynaecologic cancer patients both in terms of prioritization and identification of strategies to reduce hospital access and length of stay (16). The important thing cancer patients can follow to keep COVID-19 at distance is to wash hands frequently and maintain social distancing. As cancer patients are more prone, they should ensure thorough and frequent hand-washing using soap or alcohol-based hand sanitizer. Make sure to avoid crowds, group meetings, social and public gatherings and stock your medicines. A few routine follow-up visits can be delayed safely or conducted through tele-calling. For patients undergoing chemotherapy or radiation therapy, unless they are exposed or showing symptoms of COVID-19 or tested positive, they should continue treatment and follow the guidelines with proper isolation protocols to mitigate the risk of SARS-CoV-2 infection. Further, if you experience any COVID-19 symptoms, call your treating doctor or contact nearest COVID treatment designated healthcare centre immediately.
Dr. Indu Bansal Aggarwal , MD (Radiotherapy), Pt. BDS PGIMS (Pandit Bhagwat Dayal Sharma Post Graduate Institute of Medical Sciences) Rohtak, Haryana, India.
Director, Department of Radiation Oncology, Narayana Superspecialty Hospital, DLF Phase 3, Gurgaon, Haryana, India.
July 31, 2020
Dr. Priyanka Samji, Ph.D (Scientific editor at Bio-Services). https://www.bio-services.org/dr-priyanka-samji-ph-d/
1. World Health Organization. Coronavirus disease 2019 (COVID-19): situation report, p. 51.
2. Yu J, Ouyang W, Chua MLK, Xie C. SARS-CoV-2 Transmission in Patients with Cancer at a Tertiary Care Hospital in Wuhan, China. JAMA Oncol. Published online March 25, 2020. doi:10.1001 jamaoncol.2020.0980.
3. Liang W, Guan W, Chen R, Wang W et al. Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China. Lancet Oncol 2020; 21: 335‑ doi: 10.1016/S1470-2045(20)30096-6.Epub 2020 Feb 14.
4. Hanna TP, Evans GA, Booth CM. Cancer, COVID‑19 and the precautionary principle: Prioritizing treatment during a global pandemic. Nat Rev Clin Oncol. 2020 Apr 2. doi: 10.1038/s41571-020-0362-6. [Epub ahead of print].
5. Ramirez PT, Chiva L, Eriksson AGZ, Frumovitz M, Fagotti A, Gonzalez A et al. COVID-19 Global Pandemic: Options for Management of Gynecologic Cancers Int J Gynecol Cancer 2020;0:1–3. doi: 10.1136/ijgc-2020-001419.Epub 2020 Mar 27.
6. ESMO management and treatment adapted recommendations during the COVID-19 Pandemic. https://www.esmo.org/guidelines/cancer-patient-management-during-the-covid-19-pandemic
7. Landoni F, Maneo A, Colombo A, et al. Randomised study of radical surgery versus radiotherapy for stage Ib-IIa cervical cancer. Lancet 350 (9077): 535-40, 1997. doi: 10.1016/S0140-6736(97)02250-2.
8. Rose PG, Bundy BN, Watkins EB, et al. Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. N Engl J Med 1999; 340(15):1144-1153. doi: 10.1056/NEJM199904153401502.
9. American Brachytherapy Society statement on coronavirus. Available from https://www.americanbrachytherapy.org/about‑abs/abs‑news/abs‑statement‑on‑coronavirus/.[Last accessed on2020 Apr 05].
10. Maggioni A, Benedetti Panici P, Dell’Anna T, Landoni F, Lissoni A, Pellegrino A, et al. Randomised study of systematic lymphadenectomy in patients with epithelial ovarian cancer macroscopically confined to the pelvis. Br J Cancer 2006; 95: 699‑
11. International Collaborative Ovarian Neoplasm Group. Paclitaxel plus carboplatin versus standard chemotherapy with either single‑agent carboplatin or cyclophosphamide, doxorubicin, and cisplatin in women with ovarian cancer: The ICON3 randomised trial. Lancet 2002; 360:505‑ Doi : 10.1016/S0140-6736(02)09738-6.
12. Fader AN, Bergstrom J, Jernigan A. Primary cyto-reductive surgery and adjuvant hormonal mono-therapy in women with advanced low-grade serous ovarian carcinoma: Reducing overtreatment without compromising survival? Gynecol Oncol 2017; 147: 85–91.
13. Dessai S, Nachankar A, Kataria P, Abyankar A. Management of patients with gynecological cancers during the COVID‑19 pandemic. Cancer Res Stat Treat 2020; 3: 40-8. doi4103/CRST.CRST_124_20
14. Pergialiotis V, Haidopoulos D, Tzortzis AS, Antonopoulos I,Thomakos N, Rodolakis A. The impact of waiting intervals on survival outcomes of patients with endometrial cancer: A systematic review of the literature. Eur J Obstet Gynecol Reprod Biol 2020; 246: 1‑
15. Pal N, Broaddus RR, Urbauer DL. Mirena IUD: Treatment of Low-Risk Endometrial Cancer and Complex Atypical Hyperplasia with the Levonorgestrel-Releasing Intrauterine Device. Obstet Gynecol 2018 Jan; 131(1):109-116. DOI: 1097/AOG.0000000000002390.
16. Martinelli F, Garbi A. Change in practice in gynecologic oncology during the COVID-19 pandemic: a social media survey, Int J Gynecol Cancer 2020;0:1–7. doi:10.1136/ijgc-2020-001585