Coronavirus disease 2019 (COVID-19) pandemic is accelerating in an unprecedented manner,
with 3,175,207 confirmed cases and 224,172 deaths worldwide.[1] Studies from China and Italy reported that individuals with cancer have a two-fold
higher rate of COVID-19 infection and a ten-fold higher risk of mortality as compared
to individuals patients without cancer.[2], [3], [4] Cancer caregivers are battling in the wake of a scarcity of workforce, personal
protective equipment, medications, and risk of COVID-19 infection. This catastrophic
situation warrants a relook of management of epithelial ovarian cancer adapted to
the local context. Various guidelines on ovarian cancer management and publications
of landmark trials were reviewed in this regard, and the latest literature on COVID-19
was studied.[5], [6] These are the suggestions from science and cost-care consortium for managing ovarian
cancer patients during the COVID-19 pandemic [Table 1].
Table 1
Summary of consensus opinions for managing ovarian cancer patients during the coronavirus
disease 19 pandemic
|
Clinical scenario
|
Surgery
|
Chemotherapy
|
Maintenance
|
Follow-up
|
|
PDS: Primary debulking surgery, NACT: Neoadjuvant chemotherapy
|
|
Newly diagnosed
|
PDS
|
Three weekly chemotherapy
|
None
|
Three monthly unless
|
|
Stage I/II
|
Delay 4-12 weeks
|
Delay up to 42 days post-PDS
|
|
clinically symptomatic
|
|
Newly diagnosed
|
Interval debulking
|
Three weekly NACT
|
Bevacizumab+olaparib/
|
Monthly for olaparib
|
|
Stage III/IV
|
after neoadjuvant
|
Delay adjuvant
|
bevacizumab/observation
|
Three monthly unless
|
|
Neoadjuvant
|
NACT preferred
|
chemotherapy±bevacizumab up
|
for BRCA wild
|
clinically symptomatic
|
|
candidate
|
Delay 1-4 weeks
|
to 42 days post IDS
|
Olaparib for BRCA mutant
|
|
|
Newly diagnosed
|
PDS
|
Three weekly chemotherapy
|
Bevacizumab+olaparib/
|
Monthly for olaparib
|
|
Stage III/IV
|
Delay 4-12 weeks
|
Delay adjuvant
|
bevacizumab/observation
|
Three monthly unless
|
|
Primary debulking
|
|
chemotherapy±bevacizumab up
|
for BRCA wild
|
clinically symptomatic
|
|
surgery candidate
|
|
to 42 days post-PDS
|
Olaparib for BRCA mutant
|
|
|
Platinum sensitive
|
Avoid/defer
|
Three weekly chemotherapy ±
|
Olaparib for responsive
|
Monthly for olaparib
|
|
relapse
|
secondary
|
Bevacizumab
|
disease
|
Three monthly for
|
|
cytoreductive surgery
|
Assess after 2 cycle
|
Observation
|
observation unless
|
|
|
|
|
clinically symptomatic
|
|
Platinum-resistant
|
Avoid/defer
|
Cyclophsphamide+bevacizumab/
|
Observation
|
Three monthly for
|
|
relapse
|
secondary
|
epoposide+cyclophsphamide/
|
|
observation unless
|
|
cytoreductive surgery
|
melphalan/olaparib for
|
|
clinically symptomatic
|
|
|
BRCAmutant
|
|
|
Newly Diagnosed Ovarian Cancer
Newly Diagnosed Ovarian Cancer
The intent of early-stage (I/II) ovarian cancer is curative, so it should be managed
with primary debulking surgery (PDS) and adjuvant chemotherapy for 3–6 cycles. In
view of COVID-19, the European Society of Medical Oncology prioritize newly diagnosed
ovarian cancer selected for PDS as a medium priority, and it can be deferred by 4
weeks.[7] Similarly, the Society of Gynecologic Oncology (SGO) classifies PDS for newly diagnosed
early-stage ovarian cancer as a Tier 2A/B (nonurgent) category of Modified Elective
Surgery Acuity Scale and can be delayed by 4–12 weeks.[8] There is no change in the standard surgical staging procedure for PDS. An open approach
should be considered rather than laparoscopy, as it can generate aerosols.[9]
Stage III/limited stage IV carcinoma ovary patients are managed with PDS followed
by adjuvant chemotherapy or neoadjuvant therapy (NACT) followed by interval debulking
surgery (IDS) and further adjuvant chemotherapy. The neoadjuvant treatment is employed
to achieve rapid clinical response, low operative morbidity, and optimal debulking
surgery.[10] As prior surgery is associated with significant mortality in COVID-19 patients with
cancer.[3] Hence, it is vital to start NACT rather than PDS for a newly diagnosed patient of
stage III/IV ovarian cancer. The recent COVID-19 guideline for SGO classifies IDS
as Tire 3A/B (semi-urgent). The decision for IDS after 3–4 cycles of NACT can be delayed
up to 1–4 weeks.[8], [11], [12]
The goal of adjuvant therapy after PDS or NACT is to consolidate the benefits achieved
so far. Adjuvant chemotherapy is beneficial if it is started within 3–6-week postsurgery.[13], [14] Unless compelling, it is prudent to delay adjuvant therapy until 6-week post-surgery
in the current scenario.
Relapsed Ovarian Cancer
Platinum-sensitive ovarian cancer should be treated aggressively, as the outcome is
better as compared to platinum-resistant/refractory cancer. It can be treated with
4-weekly regimens such as liposomal doxorubicin-carboplatin instead of 3-weekly and
weekly therapies. The 3-weekly therapies, such as carboplatin and paclitaxel, can
be continued as 4-weekly to decrease the hospital footfall.[7] Imaging should be done every two cycles to document treatment response. For chemotherapy
responders, an early switch to oral maintenance therapy is warranted.Palliative chemotherapy
for elderly or poor performance status employing weekly chemotherapy requires frequent
hospital visits. These may be converted to 3-weekly regimens of single-agent carboplatin
with an area under curve 5 (AUC-5) or carboplatin AUC-5 and paclitaxel 135 mg/m2 to
mitigate the crisis.[15], [16] Primary prophylaxis with granulocyte colony-stimulating factor can be used to prevent
leukopenia.
Platinum-resistant cancer can be managed with oral cyclophosphamide with bevacizumab
with similar benefit as compared to the standard regimens employing intravenous chemotherapy
and bevacizumab with a progression-free survival of 5 months and 6.7 months, respectively.[17], [18] For platinum-refractory carcinoma ovary, oral metronomic therapy with cyclophosphamide
and etoposide or melphalan may be considered.
Recent evidence showed higher blood vascular endothelial growth factor (VEGF) levels
in COVID-19 patients as compared to healthy controls. VEGF is a significant biomarker
of endothelial injury and a potential therapeutic target in viral acute lung injury
and acute respiratory distress syndrome (ARDS). VEGF inhibition may decrease hypoxia,
improve endothelial permeability, and clinical trials are evaluating the role of VEGF
inhibition in COVID-19.[19] Thus, anti-VEGF drugs like bevacizumab may be continued with chemotherapy subject
to patients' tolerance and treatment-emergent adverse reaction.
Low-grade serous ovarian carcinoma is usually treated with leuprolide, tamoxifen,
aromatase inhibitor, trametinib, and fulvestrant.[20] These agents are relatively safe and can be continued during the COVID-19 outbreak.
Maintenance Chemotherapy
Poly (ADP-ribose) polymerase (PARP) inhibitors such as olaparib are relatively myeloid
and platelet sparing as compare to rucaparib or niraparib. Olaparib with or without
bevacizumab can be continued as it has been associated with a minimal risk of febrile
neutropenia.[21] A higher threshold for blood product transfusions in PARP inhibitor-associated anemia
may be used, and other correctable causes of anemia should be screened, such as iron,
folate, and Vitamin B12 deficiency.
Immune Checkpoint Inhibitor in Ovarian Cancer
Immune Checkpoint Inhibitor in Ovarian Cancer
Unlike carcinoma lung, bladder, or melanoma carcinoma, epithelial ovarian cancer is
less immunogenic, and in KEYNOTE 028 Ovarian cohorts, the overall response rate of
an immune checkpoint inhibitor (ICI) is 11.5%.[22], [23] The clinico-radiologic features of an ICI-induced pneumonitis and COVID-19 pneumonia
are indistinguishable. Further, in the systemic hyperinflammation stage of COVID-19
pneumonia, cytokines storm is responsible for ARDS and organ dysfunction.[24] Patients receiving pembrolizumab (an anti-PD1 ICI) for microsatellite unstable ovarian
cancer can further accelerate the immunological injury in COVID-19. In the absence
of conclusive data to support or refute the use of ICI drugs in COVID-19, it will
be prudent to make an informed decision to continue or stop after a detailed discussion
with patients.
Follow-Up and Monitoring
Those patients, who are under follow-up, can be monitored remotely by teleconsultations.
The hospital visits for ultrasound, CA125 estimation can be deferred, and patients
should visit the hospital only if they are symptomatic from malignancy – like rapid
development of ascites and intestinal obstruction.[25]
The crux of managing ovarian cancer amidst the outbreak is the individualized approach
with informed decision-making by the patient. Trading the risk of COVID-19 with perceived
benefit from chemotherapy or immunotherapy is essential. Patient education, telephonic
consultation, and relocating to a non-COVID-19 affected hospital should be our approach
while actively treating a patient with epithelial ovarian cancer.
In summary, modifying chemotherapy regimens, minimizing hospital visits, and individualized
treatment needed for the optimal management of ovarian cancer patients during the
COVID-19 pandemic.
