Management changes for patients with endocrine-related cancers in the COVID-19 pandemic

in Endocrine-Related Cancer

Correspondence should be addressed to D Raghavan: derek.raghavan@atriumhealth.org

Substantial management changes in endocrine-related malignancies have been required as a response to the COVID-19 pandemic, including a draconian reduction in the screening of asymptomatic subjects, delay in planned surgery and radiotherapy for primary tumors deemed to be indolent, and dose reductions and/or delays in initiation of some systemic therapies. An added key factor has been a patient-initiated delay in the presentation because of the fear of viral infection. Patterns of clinical consultation have changed, including a greater level of virtual visits, physical spacing, masking, staffing changes to ensure a COVID-free population and significant changes in patterns of family involvement. While this has occurred to improve safety from COVID-19 infection, the implications for cancer outcomes have not yet been defined. Based on prior epidemics and financial recessions, it is likely that delayed presentation and treatment of high-grade malignancy will be associated with worse cancer outcomes. Cancer patients are also at increased risk from COVID-19 infection compared to the general population. Pandemic management strategies for patients with tumors of breast, prostate, thyroid, parathyroid and adrenal gland are reviewed.

Abstract

Substantial management changes in endocrine-related malignancies have been required as a response to the COVID-19 pandemic, including a draconian reduction in the screening of asymptomatic subjects, delay in planned surgery and radiotherapy for primary tumors deemed to be indolent, and dose reductions and/or delays in initiation of some systemic therapies. An added key factor has been a patient-initiated delay in the presentation because of the fear of viral infection. Patterns of clinical consultation have changed, including a greater level of virtual visits, physical spacing, masking, staffing changes to ensure a COVID-free population and significant changes in patterns of family involvement. While this has occurred to improve safety from COVID-19 infection, the implications for cancer outcomes have not yet been defined. Based on prior epidemics and financial recessions, it is likely that delayed presentation and treatment of high-grade malignancy will be associated with worse cancer outcomes. Cancer patients are also at increased risk from COVID-19 infection compared to the general population. Pandemic management strategies for patients with tumors of breast, prostate, thyroid, parathyroid and adrenal gland are reviewed.

Introduction

The COVID-19 pandemic has required substantial changes in the management of cancer, with decisions being predicated on a careful risk–benefit analysis. It has been necessary to balance the relative merits of speed and intensity of anti-cancer therapy vs the potential risks of viral infection, particularly for patients with reduced immune profiles or specific cardio-pulmonary toxicity from anti-cancer treatments. In all situations, the keynote of management has been to maximize the safety of patients, their caregivers and healthcare workers.

Despite important warnings about the rising risks of pandemics in the 21st century (Gates 2018), the world population at large and, in particular, its political leadership and the medical profession have been unprepared for a viral onslaught of this magnitude and intensity. This has been compounded by lack of transparency about the onset of the infection in Wuhan, China, the extraordinarily swift global pace of spread, the severity of medical management issues for around 5–15% of patients, the impact and prevalence of asymptomatic carriers, and the global inexperience in pandemic care (Zhu et al. 2020).

The initial cases were reported in Wuhan, China, in December 2019, and by March 2020 a pandemic was declared by the World Health Organization. The speed of global spread has been facilitated by transmission by contact and aerosolized droplets (with a potential dwell time of 2–4 h in the air and longer on surfaces), with symptoms that can arise 2–14 days or longer after exposure (Zhu et al. 2020), often with an asymptomatic spread. The symptoms are quite characteristic, including fever, cough, fatigue, sputum production, dyspnea, chills, loss of taste and smell, and myalgia predominating. However, there is a considerable similarity to the common cold, influenza and allergic diatheses, confounding the precision of diagnosis (Lauer et al. 2020, Zhu et al. 2020).

The specific situation of the patient with cancer in the present (COVID-19 pandemic) environment is a mixture of hyperbole and substance, with the former being drawn predominantly from the popular press and television outlets. Early reports from China and Italy have suggested that cancer patients are more likely to become infected and are at high risk for severe clinical complications, such as the need for ventilation, intensive care unit admission, or death (Liang et al. 2020, Onder et al. 2020, Yu et al. 2020). A review of patients hospitalized at Wuhan University showed that hospital-acquired viral transmission accounted for around 40% of admitted patients (Wang et al. 2020).

With this background, clinicians have moved swiftly to refine treatment paradigms for patients with a range of cancers, including approaches to screening in asymptomatic patients, the timing of surgery or radiotherapy, and the management of advanced disease. In view of the relative paucity of published information, we have assessed the strategy of treatment in our multidisciplinary tumor conferences, predicated on a review of the available literature and lessons learned from prior pandemics, and have created paradigms of treatment aimed at maximizing the safety of patients. This overview is focused on COVID-19 management of common endocrine-related cancers.

General considerations

During the HIV, SARS and Zika virus epidemics, principles of management were developed for large populations beset with these viruses, given that each one had spread relatively rapidly and without specific vaccines or active treatments being available. These approaches, crafted initially from first principles, have been applied to the current pandemic, despite relatively scant published information. The key approach has been to ensure the safety of patients, their families or caregivers, and the healthcare workers involved in their care (see Table 1).

Table 1

General parameters of pandemic management for patients with endocrine-related cancers.

ParametersPre-treatmentDuring treatmentAfter departure
Medical imperatives
Risk–benefit analysis

• Prognosis of tumor

• Intercurrent disease

• Risk factors for COVID-19

• COVID-19 positive?

• Access to testing?
Pre-screening for risk (telephone)

Careful evaluation

• General

• COVID-19

• Cancer prognosis

Establish clear aims and expectations of treatment

Choosing wisely principles

Connection with nurse navigators
Temperature check and risk questionnaire on arrival

Review approach to aims and expectations of treatment

Psychological support as unusually high-stress period compounded by COVID-19

Physical/social distancing in clinic, infusion center, radiation unit, diagnostic centers
Re-assess aims vs. toxicity vs. response vs. COVID-19 environment

Emphasis on virtual follow up visits – medical, social and psychological issues

Structured approach to safe phlebotomy and blood tests

Nurse navigators
Timing of treatment

• Surgery?

• Radiation?

• Systemic?

• Adjuvant?b

• Neoadjuvant?b

• Observation?
Delay visits/Rx if safe

Clear communication of reasons for plan

Discussion of options

Consent document including COVID-19 rationale
Review the use of repeated Rx (radiation, systemic Rx) if COVID-19 phase changesAssess for symptoms of progressive CA if Rx delayed

Careful assessment and documentation of treatment toxicity vs. symptoms of COVID-19 – important for timing of next Rx
TriagingTiming/delay of treatment

Use of virtual consultation
Virtual follow-up increased

Thoughtful planning re follow-up scans and their timing
Staffng considerationsStaffing rotations – on/off

Reduce patient facing by increased virtual visits
Masking/social distancing of staff

Personal protection equipment
Virtual follow-up increased
Patient-focused issues
Education and communication

• Cancer-focused

• COVID-focused

• Treatment impact and complications

• Reason for no visitors policya
Standard pre-arrival operating procedures and telephone pre-check

Access to nurse navigators

Printed and electronic materials
Reinforcement of principlesFollow-up education

Nurse navigators

Virtual follow-up visits to cover COVID-19 safety protections
Importance of masking and social distancingEducational materials

Web access to information
Staff education and standard operating procedures

Signage

Reinforcement
Follow-up education

Role of nurse navigators

aExcept specific indications – end of life, ICU, physical assistance needed, and children – visitors must be screened for symptoms/exposures/travel.

bFor example, use of adjuvant rather than neoadjuvant chemotherapy if there is no significant difference in cancer outcome (=delay chemo).

Rx, treatment.

Early in the current pandemic, the leadership of the Levine Cancer Institute, a 25-site academic-hybrid, multidisciplinary cancer institute in three states, which sees more than 17,000 new cases per year and has more than 200,000 patient encounters annually, developed a strategy of cancer management with this key criterion in mind. The available literature was reviewed, tumor-specific teams considered each tumor type and modified their standard approaches where appropriate, and a series of conference calls and webinars were held internationally to gain experience from those with earlier exposure to the COVID-19 virus. The intent was to minimize the risks of viral exposure, predicated on social/physical distancing, delay or reduction of the intensity of treatment where possible, with aggressive testing for viral antigens while attempting not to impair cancer treatment outcomes. Our general approach to pandemic cancer care has been documented in detail (Raghavan et al. 2020).

Viral testing parameters

‘Patient under investigation’ (PUI) testing parameters have been defined for our overall healthcare system, which includes around 40 hospitals that are responsible for 12 million encounters annually. These include influenza-like illness (ILI) (fever >38°C (100.4°F), subjective fever, plus chills, cough or dyspnea), a domicile in long-term care or prison, plus one added risk factor (immunocompromised, lung disease (including asthma or COPD), or major vascular episode or inability to give a history). Recently, it has been shown that loss of the sensation of taste and/or smell is strongly associated with COVID-19, although this is less reliable in patients receiving radiotherapy to the oropharynx or chemotherapy. The implementation of COVID-19 testing is predicated on the availability of testing kits, and this continues to cause widespread variation internationally of measured new case rates.

Standardized management procedures

As previously reported, keystones of overall cancer management, focused on risk–benefit analysis with an emphasis on safety from viral infection and optimal survival from cancer, have included (Raghavan et al. 2020):

  • virus-adapted consideration of risk/benefit ratio of diagnostic and treatment options;
  • emphasis on clear, proactive communication for patients, families and staff regarding virus-adapted changes in management, rules regarding social and physical distancing policies, reduction of visitors for inpatients and outpatients, and so on;
  • assurance of symmetrical and instant communication of COVID-19-specific alterations in standard treatment algorithms, using a system of computerized pathways (Electronically Accessible or EA Pathways), predicated on whatever evidence is available and/or first principles in the context of COVID-19 (Fig. 1); for systems without this level of electronic sophistication, white-board or paper modifications of standard operating procedures and protocols can be distributed to all staff and provide a reasonable alternative as long as they are current and accurate (Table 2);
    Figure 1
    Figure 1

    Electronically accessible pathway for breast cancer in COVID-19 pandemic.

    Citation: Endocrine-Related Cancer 27, 9; 10.1530/ERC-20-0229

    Table 2

    Suggested triage of newly diagnosed well-differentiated thyroid cancer during COVID-19 pandemic (white-board model).

    ATA risk categoryClinical featuresSurgeryRadioactive iodineInitial follow up when routine care delayed
    LowConfined to gland, central neck low-volume metastasesMay delay with increased surveillanceNot indicated6–12 weeks
    IntermediateMinor extrathyroidal extension, larger volume metastasesDelay not recommendedMay possibly be delayed up to 3–6 months6–12 weeks
    HighGross extrathyroidal extension, distant metastasesDelay not recommendedDelay not recommended4–6 weeks
  • restructuring of social support via nurse navigators, social workers and ancillary staff;
  • physical/social distancing via reduced non-urgent clinic visits and with increased physical spacing in clinics; physical spacing is supported by structured data (Chu et al. 2020);
  • increased use of virtual consultation when consistent with patient safety and need;
  • alterations to staffing with 14-day rotations of mixed teams of physicians and advanced practice professionals to ensure a reservoir of non-COVID-infected staff at all times;
  • universal masking of patients and staff, with patient-facing staff wearing scrubs whenever possible, and added Personal Protective Equipment (PPE) for high-risk situations; N95 or equivalent masks appear to provide added protection compared to routine surgical masks (Chu et al. 2020);
  • application of a conceptual framework (Hanna et al. 2020, Raghavan et al. 2020) addressing goals and likely success of treatment, risks of cancer and its treatment vs COVID-19, and effectiveness of available treatment;
  • delay of surgery or radiotherapy for lower risk, indolent malignancies;
  • replacement of intravenous by oral medications where possible;
  • use of hormonally active medications in preference to cytotoxics where feasible and appropriate;
  • tumor-specific approaches have been applied to the use of adjuvant and neoadjuvant treatment strategies, usually predicated on likelihood of response and potential patterns of toxicity, as outlined subsequently;
  • careful review of potential COVID-19 issues relating to targeted therapies and immunoactive agents;
  • maintenance of all aspects of supportive oncology, including careful attention to pain management, psychosocial support, cancer rehabilitation, much of which can be achieved by virtual visits, depending on the acuity of the service being provided;
  • consideration of establishing a separate ‘COVID-19 positive’ unit for large volume clinical practices when numbers of infected cancer patients increase dramatically; for smaller clinical teams, physical separation, masking, and so on of infected patients are reasonable alternatives;
  • explicit discussion of new COVID-19-related risks of procedures (or of associated delay) with documentation of consent.

As our mission at Levine Cancer Institute is to be a cancer center ‘without walls’, our standard operations prior to the pandemic, across 25 sites, has involved extensive use of electronic communication (including tumor conferences, grand rounds, meetings of tumor-specific teams), with linked and standardized treatment programs predicated on our Electronically Accessible Pathways. In retrospect, it appears that this has facilitated considerable agility during the early phases of the pandemic, which may explain the relatively low volumes of COVID-19 infected cancer patients at our institution to date.

Cancer surgery

In most cancer centers, surgical departments have adhered to a universal overall strategy for cancer surgery, defined by the projected urgency of need compared to the safety of the patient and surgical staff (Bartlett et al. 2020, Francis et al. 2020; https://www.asge.org/home/joint-gi-society-message-covid-19). ‘Non-essential surgery’ is generally delayed, both to prevent unnecessary exposure and to conserve surgical and PPE resources, as well as ICU and surgical beds in case of need for pandemic management. The American College of Surgeons and Society of Surgical Oncology have defined three phases of COVID-19 acuity, reflecting the extent of community-wide medical resource utilization (and inverse availability of resources, such as PPE and hospital/ICU beds). In phase I, the least intensive with the least intrusion into standard availability of resources, a lower bar is set for cases eligible for surgery (as discussed below in tumor-specific sections) (Bartlett et al. 2020). Phase II reflects intermediate levels of acuity. Conversely, in phase III, where all resources are routed to urgent management of COVID-19 cases and ventilator and ICU capacity have been exhausted, only extremely urgent, immediately life-threatening cases are considered (Bartlett et al. 2020).

The route of surgery (open vs laparoscopic) and COVID-19 antigen status are important determinants and have been reviewed in various position papers, such as the joint statements from specialty surgical societies (Bartlett et al. 2020, Francis et al. 2020). A particular source of debate has been the strengths and drawbacks of open vs laparoscopic surgery. For example, in normal circumstances, the surgical approach to prostatectomy has shifted largely to minimally invasive/robotic-assisted laparoscopic approaches (Alemozaffar et al. 2015). Several studies have demonstrated viral particles in surgical smoke, and such particles may be more prevalent and aerosolized within the pneumoperitoneum required for laparoscopic surgery (Johnson & Robinson 1991, Capizzi et al. 1998, Hensman et al. 1998, Kwak et al. 2016, Zheng et al. 2020), leading to the controversy. The absence of data specific to coronavirus particles has meant the American College of Surgeons and other surgical societies have generally left the decision to individual surgeons to choose the appropriate surgical approach to any given case, with recommendations on how to minimize the release of aerosolizing particles and appropriate use of PPE (https://www.facs.org/covid-19/clinical-guidance/elective-case).

Clinical trials

Clinical trials have been severely impacted by the COVID-19 pandemic, specifically with regard to activation, enrollment and ongoing conduct. The safety of patients and clinical trials staff remains crucially important, and thus accrual to many trials has been suspended, with the use of virtual technology wherever feasible for follow-up and for patients who remain on active treatment trials. At our institution, each disease section reviewed their respective clinical trial portfolios, maintaining in ‘active status’ studies for which alternative treatment options were unavailable (and with a reasonable likelihood of therapeutic response). Registry, specimen collection, and non-urgent patient treatment studies have been temporarily suspended to avoid added patient and staff exposure. Similarly, during the crisis, new cancer trials have not been opened because of risk–benefit considerations and, most particularly, the uncertainty of patient benefit in early phase trials. Most tumor types have standards of care in place, and the default position has predominantly been to adhere to those.

Wherever possible, adherence to active and ongoing clinical trial protocols has been maintained, especially for responding patients, but when patient safety has dictated variation from protocol, the deviation is reported accordingly. Where patients have continued treatment on cancer trials, data management and research nursing staff and the trial monitors from many sponsoring organizations have leveraged virtual visits and electronic documentation wherever possible.

Breast cancer

The management of breast cancer is at the forefront of modern oncology, with very carefully defined pathways of treatment that are stage-specific,and which represent a detailed understanding of the biology of this disease, including the interplay of hormone receptors, genetic mutations, a well-defined range of biological characteristics and prognostic and predictive determinants (Harbeck & Gnant 2017, Waks & Winer 2019). One of the defining features of breast cancer management is the very well developed and interactive communication systems and advocacy networks that have been developed by and for breast cancer patients and survivors, and these have provided extensive accurate (and sometimes inaccurate) information for their constituents. This constitutes a relatively unique added demand for informed decision making in the COVID-19 era, as compared with the populations dealing with many other tumor types.

In line with the risk–benefit analyses that have characterized medical management during the pandemic, all routine screening (mammography, CT scans, ultrasounds) of asymptomatic women have been discontinued (Dietz et al. 2020, Tasoulis et al. 2020, Viale et al. 2020), reasoning that the increased risks of exposure to COVID-19 are greater than the likely benefit of immediate, early diagnosis. However, for patients presenting with symptoms (breast mass, new dimpling, cutaneous inflammation of the breast, etc), appropriate medical management is routinely initiated, with either face-to-face or virtual consultation, followed by diagnostic tests if indicated.

For patients with clinically localized breast masses and a positive core needle biopsy, most surgical practices have moved to achieve early complete resection, especially in the early phases of the pandemic, as defined by specialty surgical societies. This has not been practicable in crisis centers, such as Wuhan, New York City and Venice at the peak of the pandemic, again because of risk–benefit considerations and lack of availability of resources. Much of this type of surgery is completed at ambulatory surgical centers rather than in the inpatient operative setting.

Analogous to the treatment of other cancers during the pandemic, the rationale for modifications in the multidisciplinary management of breast cancer is extensive. The goals include an assurance that the long-term clinical outcomes are optimized, the risk of exposure among patients and staff is minimized, protecting patients from significant immunosuppression, and preserving vital resources within a healthcare system. Although minimal definitive evidence is available on how to best treat breast cancer patients during the COVID-19 pandemic, several organizations including the COVID-19 Pandemic Breast Cancer Consortium and European Society for Medical Oncology (ESMO) have issued position papers to assist healthcare providers (Dietz et al. 2020, De Azambuja et al. 2020).

Surgery

Recommendations have been published by several organizations including the Society of Surgical Oncology and the American College of Surgeons regarding the management of breast cancer surgeries (Bartlett et al. 2020, Curigliano et al. 2020; https://www.facs.org/-/media/files/covid19/guidance_for_triage_of_nonemergent_surgical_procedures_breast_cancer.ashx). The underlying principle during the COVID-19 crisis as with surgical approaches with other cancers is to perform surgery in patients likely to have ‘survivorship compromised’ if surgery is not performed within the ensuing 3 months. These are highlighted as follows. For ductal carcinoma in situ (DCIS), it is recommended that surgery be deferred for 3–5 months. For ER-positive DCIS, endocrine treatment can be given during the delay, until surgery can be performed. For stage I and II hormone-receptor (HR) positive, HER2-negative breast cancer, surgery can be deferred for several months and neoadjuvant endocrine therapy can be given until surgery is possible.

For larger, stage III HR-positive and HER2-negative breast cancer, this strategy can also be applied to downstage the tumor and improve the possibility of breast conservation (Spring et al. 2016). For triple-negative breast cancer and HER2+ breast cancer, presenting with clinical ≥T2 and/or ≥N1 disease, the standard approach is neoadjuvant chemotherapy and should continue to be utilized. Upfront surgery for these two breast cancer subtypes could be considered if the patient is unable to undergo chemotherapy (because of COVID-19 risk) or if the tumor is small and the pathologic information is able to inform decisions about the type of chemotherapy to be given. Breast re-excision is deferred until completion of adjuvant chemotherapy. With regards to reconstructive surgery, it is recommended that autologous reconstructions be postponed during the pandemic. Implant-based reconstruction at the time of mastectomy could still be reasonable to perform depending on resources and the severity of the COVID-19 threat. Prophylactic surgery for asymptomatic high-risk patients is currently viewed as being of low priority.

Radiation

Several groups have published guidelines on radiation therapy for breast cancer during the COVID-19 pandemic (Coles et al. 2020, De Azambuja et al. 2020, Dietz et al. 2020). Radiation is commonly delivered after surgery and chemotherapy. Depending on the circumstances, the sequencing of surgery, systemic therapy, and radiation may be modified during the pandemic. For example, in patients with HR-positive, HER2-negative breast cancer who need both adjuvant chemotherapy and radiation, consideration could be given to giving radiation before chemotherapy without resulting in the compromised outcome (Bellon et al. 2005). This could be helpful if immunosuppressive chemotherapy is to be avoided but then has to be balanced with the frequency of facility visits and the risk of exposure this would impose. For adjuvant therapy, hypofractionated, shorter regimens (42.6 Gy in 16 fractions or 40 Gy in 15 fractions) in the adjuvant setting should be considered when feasible and this approach results in similar safety and efficacy to conventional fractionation (Whelan et al. 2010, Haviland et al. 2013). In order to reduce exposure of patients and staff, the boost can be omitted in patients >50 years of age with HR+ and/or small HER2+ breast cancers. If necessary, radiation can be postponed up to 3 months for high-risk patients and up to 6 months for low-risk patients (Van Maaren et al. 2017). Typical settings in which to consider the omission of radiation therapy (in which survival is not affected) could include (1) patients aged ≥ 65 with an early stage, HR+, HER2-negative, node-negative, grade 1–2 breast cancer, provided that the patient agrees to take endocrine therapy (Hughes et al. 2013, Kunkler et al. 2015) and (2) after excision of a low-to-intermediate grade ER-positive DCIS.

Systemic therapy

A major principle in the administration of systemic treatment for patients with breast cancer during the pandemic is the implementation of alternative dosing schedules to limit the number of in-person visits to the cancer center, reducing the risk of immunosuppression when possible, and switching therapy to oral agents, if an equivalent formulation is available. For example, the backbone chemotherapy regimen given in the adjuvant and neoadjuvant setting is composed of an anthracycline and taxane. If a patient is receiving weekly intravenous paclitaxel, consideration can be given to dose-dense (every 2 weeks) intravenous paclitaxel so that fewer visits are needed. This regimen does require an injectable growth factor agent to be given more than 24 h after the administration of chemotherapy. If feasible, we have encouraged self-injection of pegfilgrastim or biosimilar, at home. Another example is the modification of monthly leuprolide acetate in premenopausal women receiving adjuvant endocrine therapy to 3-monthly formulation of the LHRH analogue, in order to reduce the frequency of visits (Kendzierski et al. 2018). If patients have not had previous ovarian function breakthrough on an every 3-month suppression schedule, then these patients can be switched to every 3-month leuprolide acetate injections. At our institution, we have opted to check hormone levels at the second injection point and if not suppressed, then switch patients to a monthly injection.

Early stage disease

For a patient with an early stage hormone receptor (HR)-positive, HER2-negative breast cancer, a common approach is proceeding to upfront surgery. During the pandemic, consideration has been given to offer neoadjuvant endocrine therapy to a clinical stage I or II HR-positive, HER2-negative breast cancer if there will be a deferral of definitive surgery by 3 months or more (Dietz et al. 2020). This approach can be reasonably applied to tumors with low genomic assay scores, low-grade tumors, and invasive lobular disease. However, several factors should be weighed in this scenario of upfront NET vs upfront surgery, including the risk of the tumor enlarging with a delay in surgery, potential added burden on hospital resources, and the risk of exposure to SARS-CoV-2. Genomic evaluation of a HR-positive, HER2-negative invasive breast cancer can be obtained to help guide initial decisions regarding neoadjuvant systemic therapy during the pandemic. An Oncotype DX Breast Recurrence Score is traditionally sent on the resected breast cancer. The Society of Surgical Oncology suggests that, if a clinician desires genomic testing such as Oncotype DX to decide between endocrine therapy and chemotherapy, testing can be sent on the core biopsy. It is important to emphasize that sending a core biopsy represents untreated breast tissue and is optimal to send this type of tissue for Oncotype Dx testing; this avoids the concern that endocrine treatment alters mRNA expression levels used to calculate the Recurrence Score. Core biopsy specimens have been shown to produce Recurrence Score results highly concordant with resection specimens (Anderson et al. 2009). If endocrine therapy is deemed appropriate, the patient can be treated with neoadjuvant agents for at least 3–6 months and then proceed to surgery. For postmenopausal patients with HR-positive, HER2-negative early breast cancer who may have just had surgery during the height of the pandemic and need chemotherapy, it may be safe to delay chemotherapy for more than 3 months and to administer endocrine therapy as a bridge in such patients.

In patients with low-risk HER2-positive breast cancer, consideration can be given to shorten the duration of adjuvant trastuzumab to less than 12 months, based on data from the Phare and Persephone prospective randomized trials, both of which showed that 6 months of adjuvant trastuzumab was not inferior to 12 months of trastuzumab (Earl et al. 2019, Pivot et al. 2019). In patients who have been receiving ongoing adjuvant anti-HER2 targeted therapy, an infusion can be postponed by 6–8 weeks (De Azambuja et al. 2020). For ejection fraction monitoring in patients receiving anti-HER2-treatment, follow-up echocardiogram can be performed at 4-month intervals and then deferred in the absence of symptoms. Patients with triple-negative breast cancer can only be effectively treated with chemotherapy, and for those with a higher risk of relapse, their adjuvant and neoadjuvant treatment should not be delayed. In patients who are receiving adjuvant zoledronic acid every 6 months, this can be deferred during the height of the pandemic.

Patients presenting with locally advanced breast cancer are at greater risk of local progression, with ulceration or cutaneous involvement, or early dissemination, and this situation requires greater urgency of management. In these situations, treatment results in substantial benefit, in all breast tumor types, namely triple-negative, HER2-positive, and high-risk HR-positive, Her2-negative, and should not be postponed.

Advanced disease

For patients with metastatic disease, the sites of involvement, symptoms and pace of the disease should govern management. In general, the modifications in metastatic breast cancer treatment during the COVID-19 crisis include using less myelosuppressive regimens when feasible, increasing the interval between staging scans especially without symptoms of progressive disease, and lengthening the interval between other monitoring assessments such as ejection fraction on anti-HER2 therapy. Based on risks and preferences, thoughtful consideration could be given to decreasing regimen intensity, moving away from weekly dosing schedules, and delaying the timing of infusions, when appropriate. Patients who are symptomatic or who are in early line treatment, where published data show improved clinical outcomes in the metastatic setting, should proceed. For example, there should be early use of first-line treatment of a HER2-positive metastatic breast cancer with a taxane, trastuzumab and pertuzumab, as this clearly provides improved overall survival (Swain et al. 2013). For patients receiving later lines of salvage treatment, it may be reasonable to discuss drug holidays or best supportive care.

As noted previously, elderly patients and those with comorbidities are at higher risk for COVID-19 infection and death, and for those with low burden of HR-positive, HER2-negative metastatic disease (absence of visceral disease) receiving treatment in the first-line setting, consideration could be given to starting endocrine therapy initially and postponing the start of a cyclin-dependent kinase (CKD) 4/6 inhibitor because these agents cause myelosuppression and occasional pneumonitis. On a case-by-case basis, it may also be appropriate to avoid or delay the addition of other targeted therapy that is usually paired with aromatase inhibitors, such as everolimus (induced immune-suppression) and alpelisib (risk of diabetes). Risks and benefits of this approach should be discussed with this vulnerable population (Bartlett et al. 2020). For patients with bone metastases, it is reasonable to minimize such supportive agents as denosumab or zoledronic acid, especially if this is the only reason to enter the infusion center. However, more active management is mandated in the setting of hypercalcemia. Modifications could include delay or lengthening of treatment interval to give intravenous bisphosphonates, for example, every 3 months.

Prostate cancer

Even before the onset of COVID-19, the management of all stages of prostate cancer has been somewhat controversial, largely because of the heterogeneity of the disease and its time course, the broad availability of therapeutic options, and the impact of strong specialty-specific biases about optimal care (Raghavan 2013, Bill-Axelson et al. 2018, Raghavan 2018, Gillessen et al. 2020).

While there has been varied opinions about the utility of screening of asymptomatic subjects prior to the pandemic (Raghavan 2013), the onslaught of COVID-19 has closed down virtually all cancer screening activities, predicated on a cost–benefit analysis of risk to patients and staff vs the potential low yield of early diagnoses per number of subjects screened. This has applied to men who might otherwise have been screened for prostate cancer with measurement of prostate-specific antigen (PSA). Randomized trials have failed to show an overall survival benefit from PSA screening for asymptomatic Caucasian males (Schroder et al. 2012, Raghavan 2013), and while the urological community has continued with variants of screening (sometimes targeted at specific subpopulations), those activities have been discontinued during the pandemic and supported by recommendations from relevant professional societies (Kokorovic et al. 2020, Mejean et al. 2020; https://caunet.org/wp-content/uploads/2020/04/BAUS-Oncology-COVID-19-Prostate.pdf). In the past, substantial concern has been expressed that delays in screening lead to worse outcomes for cancers of breast, colon and lung, but the situation is much less well defined in the context of prostate cancer.

Of course, the asymptomatic screening situation is different from a specific investigation of symptoms, such as the sudden onset of dysuria, reduced urinary stream, perineal pain or features that may suggest new metastatic disease (bone pain, features of spinal cord compression and non-metastatic features of advanced malignancy). In this situation, the clinical decision process is required and would usually lead to the consultation (patient facing or virtual) and appropriate investigation and management (Kokorovic et al. 2020).

For patients with early stage prostate cancer, with a positive biopsy and negative clinical staging tests, there are no published data to drive management during the pandemic, beyond general guidance issued by professional societies, such as the Canadian Urological Oncology Group and Canadian Urological Association, the Cancer Committee of the French Association of Urology, and the British Association of Urological Surgeons (Kokorovic et al. 2020, Mejean et al. 2020; https://caunet.org/wp-content/uploads/2020/04/BAUS-Oncology-COVID-19-Prostate.pdf), and a collaborative position paper on radiotherapy for prostate cancer in the COVID-19 pandemic (Zaorsky et al. 2020). These recommendations have involved structured studies of evidence-based literature. Mostly, patients presenting with symptoms suggestive of prostate cancer are being deferred for in-person visits, diagnostic work-up and biopsies for 3–4 months, allowing the pandemic to ebb.

While active surveillance, with serial measurement of PSA and appropriate imaging protocols, has been practiced increasingly in recent years (Bill-Axelson et al. 2018), especially for good- and, perhaps, intermediate-risk tumors (i.e. well and moderately differentiated with PSA less than 10 ng/mL), most recommendations have suggested avoidance of routine clinical visits and tests, so functionally this has not been a treatment option that is in use in the COVID-19 pandemic (Kokorovic et al. 2020, Mejean et al. 2020; https://caunet.org/wp-content/uploads/2020/04/BAUS-Oncology-COVID-19-Prostate.pdf). There has been general consensus that definitive surgery should be delayed, particularly for well- and moderately differentiated tumors, provided the delay is less than around 3 to less than 6 months, for the reasons enumerated previously (Kokorovic et al. 2020, Mejean et al. 2020). A similar delay of definitive radiotherapy for good-risk tumors has been proposed by a multi-center consensus group of radiation oncologists (Zaorsky et al. 2020), based on published data on the outcomes of radiotherapy for good-risk disease.

However, the same consensus group has proposed the use of neoadjuvant androgen deprivation therapy (ADT) for patients with unfavorable intermediate-risk and poor-risk localized and locally advanced prostate cancer (Zaorsky et al. 2020). This group has provided a broader generic structure, the RADS framework (Remove visits, Avoid radiation, Defer radiation and Shorten radiation) for pandemic management. Arising from this framework, it has been specifically recommended to avoid brachytherapy during the pandemic because of its need for anesthesia, PPE and increased risk of viral spread (Zaorsky et al. 2020). There is an extensive literature that supports the use of combined modality hormones and either surgery (Messing et al. 1999) in the setting of locally extensive disease or nodal metastases or radiotherapy (Bolla et al. 2010) for high risk, clinically non-metastatic prostate cancer, and thus these recommendations seem very reasonable.

For patients with high-risk localized or locally advanced prostate cancer, several urological groups have recommended the use of radical prostatectomy if COVID-surge conditions are not current (with the hope of rapid treatment, admission and discharge prior to the onslaught), or the use of neoadjuvant ADT to delay surgery (or definitive radiotherapy) (Kokorovic et al. 2020, Mejean et al. 2020; https://caunet.org/wp-content/uploads/2020/04/BAUS-Oncology-COVID-19-Prostate.pdf). There are no defined guidelines for charting a course of treatment in the uncertain environment of a post-surge situation (i.e. after an initial surge when a second COVID-19 surge is anticipated at an uncertain future time); that decision should be made, based on population demographics, the clinical experience in the initial surge, and the predictive analytic studies that are available for that specific geographical region. In general terms, a period of ADT of 6 months or even somewhat longer would be reasonable in this clinical setting unless serial PSA measurements or the clinical findings suggested failure of ADT to achieve remission.

For patients presenting with metastatic prostate cancer, initial ADT is the usual standard of care (Crawford et al. 1989). More recently, it has been shown that the novel compounds abiraterone acetate (Ryan et al. 2013) or enzalutamide (Davis et al. 2019) (or analogs) add significantly to the survival impact of ADT, both for good-risk and poor-risk metastatic disease. As abiraterone acetate is administered with corticosteroids, it would seem wise to use enzalutamide or apalutamide as the added component during the pandemic (Kokorovic et al. 2020, Mejean et al. 2020). The dose of corticosteroids is only low, but there is the variability of immunosuppression in association with these agents in the elderly. Sweeney and colleagues also reported that initial docetaxel added to ADT improves survival for poor-risk metastatic prostate cancer significantly (Sweeney et al. 2015), but during the pandemic we have focused treatment on ADT plus enzalutamide or apalutamide as initial therapy for poor-risk metastatic disease, thus avoiding extra clinic visits and the risks of myelosuppression.

One unanticipated aspect of androgen deprivation therapy has been the assertion that it may be protective against COVID-19. Glowacka et al. (2011) reported that the transmembrane serine protease 2 (TMPRSS2), one of the more frequently altered genes associated with prostate cancer, has a significant role enabling cellular invasion by the coronavirus by activating spike protein and that it reduces the antiviral antibody response. Montopoli et al. (2020), in a review of 4532 males with laboratory-confirmed COVID-19 infection, showed that patients suffering from cancer have a greater risk of COVID-19 infection than patients without cancer, but also that males being treated with androgen-deprivation therapy (ADT) had a substantially lower risk of COVID-19 infection than for patients with other cancers. Men receiving ADT also showed lower rates of infection than other non-cancer patients; furthermore, patients with prostate cancer receiving ADT had lower infection rates than prostate cancer patients not treated with ADT. Extending this theme, Stopsack et al. (2020) have recently proposed the investigation of specific inhibitors of TMPRSS2 and inhibition of the androgen signaling axis as anti-COVID-19 treatment.

For patients relapsing after standard ADT, or after salvage therapy with enzalutamide or equivalent second-line hormonal blocking therapies, the pace of the disease and clinical context should dictate the pattern of care. One of the commonest presentations is asymptomatic rising PSA levels, and this should not constitute an indication for salvage treatment during the pandemic (we would contend that treatment at this clinical-stage is palliative, and it is difficult to palliate an asymptomatic patient).

However, for symptomatic patients in whom the symptoms cannot be controlled by conventional palliative therapy, a clinical decision should be made, balancing the risks of myelosuppression vs the potential impact of COVID-19. From first principles, the use of docetaxel at a reduced dose (around 50 mg/m2, thus reducing the risk of myelosuppression) is a reasonable option, given the paucity of dose–response data supporting the use of the conventional dose of 70–75 mg/m2. For patients with the bone-dominant disease, another appropriate option is radium-223, which is highly active against bone metastases from prostate cancer without causing significant myelosuppression. This will place the Nuclear Medicine staff at some potential risk, and appropriate physical distancing and PPE should be implemented for them. We have delayed the use of bone-stabilizing agents, such as bisphosphonates, during the pandemic to reduce the frequency of clinic visits and monitoring.

The key issue is that there are many treatment options for patients with prostate cancer, some of which may even afford protection against COVID-19 per se, and management decisions should be taken based on careful risk–benefit calculation, with transparent discussion with patients and their caregivers that defines the aims and expectations of treatment. Consent documents should be modified to reflect the impact of COVID-19 on the decision process and selection of treatment and that this has been explained in detail to the patient.

Cancers of thyroid and parathyroid

The disruption of adult cancer treatment protocols during the COVID-19 pandemic has necessitated a temporary realignment of thyroid nodule and thyroid cancer care. Prior to the onset of the pandemic, there was a growing consensus that many patients were either under or over-treated for thyroid neoplasms. This culminated in the publication of guidelines formalizing risk stratification for thyroid nodule evaluation and biopsy, as well as thyroid cancer, under the auspices of the American Thyroid Association (ATA) (Haugen et al. 2016). These guidelines contain vocabulary and template readily adaptable for triage purposes during the pandemic. Several national societies also have provided guidance for physicians and reassurance for patients (Puig-Domingo et al. 2020; http://www.thyroid.org/covid-19/coronavirus-frequently-asked-questions/; https://www.aace.com/recent-news-and-updates/aace-position-statement-coronavirus-covid-19-and-people-thyroid-disease).

Most thyroid nodules are benign and malignant ones usually tend to grow slowly. Nodules without highly suspicious ultrasound characteristics (as classified by ATA or Thyroid Imaging, Reporting and Data Systems or TIRADS) generally can be observed and fine-needle aspiration biopsy for diagnosis delayed pending resolution of the pandemic. Patients not appropriate for the delay in diagnosis include those with clinical evidence of aggressiveness such as recent-onset hoarseness (indicating infiltration of the recurrent laryngeal nerve) or a rapidly enlarging mass, imaging demonstrating suspected invasion of local structures, or large suspected nodal metastases (Haugen et al. 2016, Grani et al. 2019). In cases where biopsy renders an indeterminate result (Bethesda Classes III-V), ultrasound characteristics can guide surveillance, often with repeat imaging at 3–6 months rather than immediate repeat biopsy or surgical removal (Cibas & Ali 2017, Persichetti et al. 2018). Further risk stratification of nodules by mutational analysis is a recently validated strategy, and consideration should be given to holding a sample at the initial biopsy for genetic sequencing rather than having the patient return for an additional biopsy requiring a separate encounter with the medical system (Nikiforov et al. 2019).

Preliminary data from China have listed thyroid cancer as a frequent diagnosis among patients admitted to hospitals with COVID-19 (Dai et al. 2020). If confirmed, further research would be necessary to ascertain whether this is a coincident finding due to the high prevalence of thyroid cancer or whether there are tumor-, patient-, or treatment-specific factors conveying increased vulnerability (Dai et al. 2020). In this setting, pre-treatment staging is vital, and each step must be considered in the context of comorbidities and risk of serious disease should the patient become infected. Although knowledge of genetic signatures has not been formally incorporated into published guidelines, the field is far enough along to be of clinical utility, and many centers, including ours, now routinely submit specimens for mutational testing and incorporation into treatment planning (Seib & Sosa 2019, Prete et al. 2020).

The primary treatment of thyroid cancer is surgical, and it is relevant that the first reported physician fatality due to COVID-19 in Wuhan, China, was that of an otolaryngologist. This has contextualized the management considerations for cancers of the thyroid and parathyroid, especially as it has been reported that head and neck surgery is associated with high COVID-19 infection rate and associated deaths (Chan et al. 2020). Patients with differentiated thyroid cancer, clinically projected by ATA classification to have low risk for recurrence pre-operatively, may safely delay the initial procedure without a negative effect on prognosis. This includes most patients with metastatic disease to local cervical nodes, found in the majority of patients with classic papillary cancer, the most frequent subtype (Haugen et al. 2016). Those considered to have ATA intermediate risk for recurrence (and possibly some with ATA high risk disease) may have a delay in surgery, after weighing of individual risk of tumor aggressiveness. Factors to consider include both patient vulnerabilities and local prevalence of COVID-19 in the community or hospital. Patients with a rapidly progressive disease by history or clinical findings, large or invasive neck metastases, distant metastatic disease, or suspected de-differentiated tumor should proceed to surgery if possible. Priority for urgent intervention is placed on the need for control of high-volume neck disease and airway protection.

An algorithm for urgent surgical intervention has been proposed at Stanford University for locally aggressive papillary, medullary and anaplastic thyroid cancer and includes parathyroidectomy when there is deteriorating renal function (Topf et al. 2020). These cases will require extra precautions in the operating room as noted previously and especially during procedures such as tracheostomy which may generate aerosolized particles. In addition, consideration has been given to the estimated transmission risk for operations on specific cancers. Thus, low risk operations (with no mucosa involved in the surgery), including thyroidectomy, parathyroidectomy, and neck dissection, have generally been given a higher priority than transoral procedures which have a higher associated risk to staff (Givi et al. 2020, Kowalski et al. 2020, Schwartz et al. 2020, Topf et al. 2020).

It is generally accepted that patients with ATA low risk disease do not benefit additionally from ablation with radioactive iodine (RAI) (Haugen et al. 2016). After surgical recovery, these patients are ideal candidates for virtual follow-up until the pandemic infection curve is favorable and routine follow-up can be resumed. Post-surgically, some patients with ATA intermediate and possibly even ATA high risk for recurrence, who are candidates for radioactive iodine for adjunctive or therapeutic treatment, may also safely delay therapy for weeks and perhaps months without significant effect on prognosis (Scheffel et al. 2016). Of particular concern, in this context, is that most RAI protocols utilize human recombinant TSH and require no fewer than four separate face-to-face encounters with medical personal, including two intramuscular injections 24 h apart followed by I-131 oral dosing 24 h later, and then whole-body scanning at 5–7 days. The need for repeated patient exposures to medical staff must, therefore, be balanced against the perceived benefits of treatment. Older protocols requiring thyroid hormone withdrawal may enable fewer staff encounters but possibly may have severe consequences if patients contract an infection while clinically hypothyroid. Our general approach to mitigating risk has been to utilize our usual protocols for RAI with human recombinant TSH in ATA intermediate- and high-risk categories while delaying therapy by up to a few weeks in patients without the clinically aggressive disease, until the risk of COVID-19 transmission is reduced (Table 2).

Pathologically aggressive subtypes, such as Tall Cell variant, which confer increased rates of residual disease and recurrence, should be promptly treated when feasible (Shi et al. 2016). Invasive neck disease with suspected residual microscopic remnants and treatable metastatic lung disease are examples of cases which also warrant proceeding directly to RAI as long as enhanced infection control protocols are in place. Myelosuppression related to I-131 is minimal, subclinical, transient, and not likely to confer additional immunosuppressive risk to the patient (Silberstein et al. 2012). However, in the period after RAI treatment, isolation protocols for radiation exposure are necessary for up to several days. Although this has yet to be reported, should the patient become infected during this time frame, the need for radiation safety precautions for health workers in the vicinity of the patient would complicate the ability to deliver care. If appropriate infection control is in place and given the relatively short period of radiation isolation, this is anticipated to be a rare, but possible, scenario (Sisson et al. 2011).

External beam radiotherapy (ERBT) is employed infrequently in thyroid cancer, with the main exceptions being recurrent invasive neck disease, typically in older patients, and localized treatment of bone metastases. Unless there is an imminent threat to the airway, consideration may be given to postponing EBRT to the neck in the setting of a rising pandemic threat, given potential radiation effects to the upper airway and esophagus (Tam et al. 2017). For patients deemed candidates for systemic therapy with FDA-approved multikinase inhibitors, with the goal to extend progression-free survival, optimal timing for initiation is often a challenge as even advanced metastatic disease tends to be slow to progress. Tyrosine kinase inhibitors exhibit varied immunomodulatory and immunosuppressive effects and substantial toxicity. In some cases, these interventions may be deferred when in a highly infectious environment. The role of immunotherapy in thyroid cancer is emerging and could be considered within research protocols, although most of these have been suspended during the pandemic (Naoum et al. 2018).

The prognosis of anaplastic thyroid carcinoma has historically been so poor that, until recently, treatment plans consisted predominantly of airway management and palliation, with a median survival of 5 months. Cytotoxic chemotherapy rarely was associated with a significant anti-tumor effect. However, a combination inhibition of the BRAF gene has recently been shown to improve substantially the response rate and progression-free survival after 1 year (Subbiah et al. 2018). Once again, the risk of serious side effects and the vulnerability of the patient to viral infection must be weighed against the likelihood of long-term remission.

The options available for patients with relapsed and metastatic cancer of the parathyroid gland are much more limited, and depending on the sites and speed of relapse, include palliative radiotherapy or cytotoxic chemotherapy, with agents such as cisplatin, the taxanes, and doxorubicin showing occasional anti-cancer effect; risk–benefit analysis will often result in referral to hospice, particularly for the elderly patient. Targeted therapeutics remain investigational and probably have a little place during the peaks or escalating phases of the COVID-19 pandemic.

In summary, dynamic, ongoing reassessment of risk through the stages of evaluation and treatment is familiar territory for those experienced in the care of differentiated thyroid cancer patients. It is not uncommon for the perceived risk of residual and/or recurrent thyroid cancer to be significantly modified by the biology of the disease as the patient advances through care. Therefore, patients assessed initially as low risk should not have their treatment postponed indefinitely. In those cases where delay is necessary, short interval follow-up can be employed, ranging from neck ultrasound performed in the office to cross-sectional imaging surveillance of suspected metastatic disease. Once again, for this pattern of care, the respective risks and benefits for patients and staff need to be factored into the decision process.

Adrenal carcinomas

In similar fashion to the malignancies discussed previously, carcinoma of the adrenal gland is a protean condition with widely variable speed of progression, which can be localized, locally extensive or occasionally metastatic. Incidentally discovered adrenal masses with low density on pre-contrast CT (Hounsfield units <10) are usually benign and can be observed if non-functional on hormonal assessment and not large (Schieda & Seigelman 2017). Biopsy of indeterminate or suspicious adrenal masses is generally contraindicated due to low diagnostic yield and risk of peritoneal seeding (Williams et al. 2014). Surgical resection is recommended when the diagnosis is not obvious by clinical presentation and imaging, the main exception being when biopsy confirmation of a metastatic focus from a non-adrenal primary would change therapeutic course. Screening for pheochromocytoma should always precede either biopsy or resection, to avoid the risk of crisis. Pheochromocytomas also require the immediate initiation of the adrenergic blockade and prompt resection, due to the unpredictable risk of life-threatening adrenergic crisis (Stewart & Story 2017).

The success of strategies for risk mitigation during the pandemic for patients with adrenal lesions remain poorly defined, but a strategy can be determined using experience from other solid tumors combined with an understanding of the unique features of adrenocortical carcinoma (ACC). In areas of low viral prevalence or as epidemiologic concerns abate with public health measures, decision-making favors standard protocols (Jozaghi et al. 2020). During periods of rising or peak incidence, a more conservative approach is taken, with key determinants including the age and physical state of the patient, extent of intercurrent disorders, and features of the tumor.

Pre-treatment staging is routinely employed based on initial indications of tumor aggressiveness on imaging and by the presence of hormonal secretory syndromes. Excess secretion of cortisol and steroid precursors (resulting in Cushing’s syndrome or subclinical hypercortisolism), characteristic of the majority of these tumors, results in a state of immunosuppression and patient vulnerability to overwhelming infection. The mortality in these patients can be presumed to be high in the setting of concurrent infection with COVID-19 (Dekkers et al. 2013).

Because resection is the only chance for cure in ACC, surgery should not be delayed at the stages when complete resection is possible (stage I and II), although this approach may have to be delayed during an escalating or crisis phase of the pandemic. For the best chance at complete R0 resection, open adrenalectomy is considered standard when ACC is suspected (https://www.nccn.org/professionals/physician_gls/pdf/neuroendocrine.pdf). However, the effect of the choice of surgical procedure on disease clearance and long-term prognosis has become controversial as laparoscopic procedures have increased in recent years. Uncertainty regarding the role of laparoscopic adrenalectomy in ACC has arisen due to the possible risk of peritoneal seeding (Autorino et al. 2016). Additional concerns have arisen during the pandemic in this context (see previous discussion), therefore, open resection remains the preferred option for patients with high suspicion of ACC during the COVID-19 pandemic.

For patients with completely resected tumors, the benefit of adjuvant treatment with radiation to the adrenal bed and/or mitotane has not been defined and is the subject of ongoing trials (Bedrose et al. 2020). In the setting of the COVID-19 pandemic, there seems little place for adjuvant therapies without proven substantial survival benefit. For patients suffering from hypercortisolism who are not candidates for surgery, cortisol blockers and inhibitors of steroidogenesis are the mainstays of therapy. Mitotane is also employed therapeutically for its adrenolytic activity with the goal of stabilization of progressed, recurrent, or metastatic disease. It is not generally associated with myelosuppression. Due to its long half-life, mitotane can be dose escalated without the immediate need for measurement of blood levels if reasonably tolerated. Patients experiencing significant symptoms such as nausea, fatigue, and central nervous system effects may still benefit from reduced dosing, which results in blood levels considered to be sub-therapeutic. Therefore, temporary dose-reduction with less frequent in-person visits and laboratory work is a reasonable option during periods of impaired access to routine care, with telemedical support. Patients on long-term mitotane therapy are almost universally adrenally insufficient as a consequence. The required block-and-replace strategy with oral steroids is complex even under normal circumstances. In a pandemic setting, it is a challenge to keep follow-up visits at a minimum while avoiding the risk of adrenal insufficiency on the one hand and iatrogenic Cushing’s syndrome with immunosuppression on the other (Terzolo et al. 2014). It is noteworthy that COVID-19 infection may disrupt the hypothalamic–pituitary–adrenal axis, causing functional hypoadrenalism, and it is known that COVID-19 may localize to the adrenals (Pal 2020).

When metastatic adrenal carcinoma has progressed despite mitotane, cytotoxics only have modest additional utility. For the COVID-19 pandemic, cisplatin is probably the most appropriate single agent, given an objective response rate of 20–30%, of which about half are sustained for more than 6–12 months, and only modest dose-dependent myelosuppression. Other options, such as paclitaxel, gemcitabine and etoposide are all associated with significant myelosuppression, although one benefit of etoposide is its availability as an oral medication. Although multi-agent chemotherapy may have a small response benefit, its use is not recommended during the COVID-19 pandemic due to greater myelosuppression and lack of overall survival benefit compared to single-agent cytotoxic therapy (Fassnacht et al. 2012). In this setting, risk–benefit analysis is crucial, and we do not use cytotoxics for metastatic adrenal cancer that is stable or only slowly progressive. These recommendations are made from first principles, as we are unaware of any published data to guide the management of metastatic adrenal tumors in the COVID-19 pandemic (Megerle et al. 2018).

During this uncertain time, compounded by the relative infrequency of these tumors, patient and family engagement in decision-making regarding goals of care should be especially emphasized. Frequent video or phone contact when office visits are reduced can be immensely reassuring and should be considered a vital part of the palliative strategy. Individualizing care for patients with rare and complex tumors is imperative, and therefore some forum for review of these cases is encouraged, even if not within an academic setting. Access to a tumor board is required, and at our institution, the Endocrine Tumor Board has been able to conduct its case reviews without interruption by transitioning to virtual meetings. Especially when circumstances change on an almost daily basis, our experience during the COVID-19 pandemic has demonstrated the value of an integrated, multidisciplinary approach with all the support that brings, not only for our vulnerable patients but for the physicians who care for them.

Summary

The COVID-19 pandemic has created a complicated set of issues for patients with endocrine-related cancers, wherein patients, families and healthcare workers are potentially placed at increased risk. Protection for all participants is crucial, both by reducing risks of virus exposure and by maintaining active treatment algorithms commensurate with optimal cancer survival. Physical/social distancing, extensive use of virtual consultation, a careful review of the risk–benefit of treatment (and its urgency), and modification of therapeutic approaches to reduce patient-facing contact whenever feasible and safe are important elements of the strategy of pandemic cancer care. Meticulous strategies of communication to patients, families and staff are essential to make these changes as palatable as possible. In addition, modifications of Tumor Board functions must be implemented, leveraging electronic technology to allow the virtual presentation of pathology and radiology and discussion of complex cases, a particularly important aspect of cancer center function given the uncertainties that surround the interface of COVID-19 and cancer. We have summarized the strategies employed to maintain the quality and safety of care for patients with early, locally advanced and metastatic cancers of breast, prostate, thyroid and adrenal, in each case focusing on maintaining the best outcomes with least morbidity and risk.

Author contribution statement

Each author has contributed equally to the manuscript, including accumulation of data and literature review, writing, editing, and review of the manuscript. Dr Raghavan acted as editor of the entire work in addition to the roles aformentioned.

Declaration of interest

The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of this review.

Funding

The preparation of this article was supported by a generous grant from the Leon Levine Foundation – LLF-1. This was awarded in 2011 and provides continuous funding for the academic activities of staff of the Levine Cancer Institute.

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