key: cord-0944742-u6g8eu9s
authors: Sarfaty, Michal; Feldman, Darren R.; Morris, Michael J.; Motzer, Robert J.; Rathkopf, Dana E.; Regazzi, Ashley M.; Iyer, Gopa; Voss, Martin H.; Bajorin, Dean F.; Rosenberg, Jonathan E.
title: Genitourinary medical oncology expert opinion survey regarding treatment management in COVID-19 pandemic
date: 2021-01-07
journal: Clin Genitourin Cancer
DOI: 10.1016/j.clgc.2020.12.002
sha: b155d6d8aeac3a3b51f20fad2afe96c8d6a4b8e8
doc_id: 944742
cord_uid: u6g8eu9s

BACKGROUND: The worldwide COVID-19 public health pandemic has restructured clinical care of cancer patients throughout the world. The specific changes in the management of genitourinary (GU) cancers in different cancer centers due to COVID-19 are not known and some clinical scenarios remain controversial. We conducted an opinion survey to determine what changes in cancer treatment strategies are occurring due to the COVID-19 pandemic. METHODS: A 20-item online survey was sent on 05/25/20 to 170 expert GU medical oncologists from Europe and North America. The survey solicited responses to changes in GU cancer management in the setting of the COVID-19 pandemic. Data was collected and managed via a secure REDCap Database. RESULTS: Surveys were completed by 78 (45.8%) of 170 GU oncologists between 05/25/20 and 06/25/20. Clinical practice changes due to COVID-19 in at least one scenario were reported by 79.1% of responders, most pronounced in prostate cancer (71.8%) and least in urothelial cancer (23%). Preferences for change in management varied by country with 78% of US oncologists indicating a change in their practice (37/47), 57% for Canadian oncologists (4/7) and 79% in Europe (19/24). CONCLUSIONS: This study suggests international practice changes are occurring in GU cancer care during the COVID-19 pandemic. The variability in practice changes between countries may reflect differences in COVID-19 case load during the timepoint of data collection. These results, based on expert opinion during this rapidly changing crisis, may inform the oncologic community regarding the effects of COVID-19 on genitourinary cancer care.

The public health crisis of the worldwide Coronavirus disease 2019 (COVID-19) pandemic has restructured clinical activity of hospitalized and outpatient care throughout the world 1 .

Experience from the world's pandemic epicenters suggests that cancer patients are at a higher risk for complications and death from COVID-19 [2] [3] [4] .

Cancer centers across the world have changed their daily clinical practice to accommodate rapidly changing conditions, such as protecting patients and staff from transmission and infection, prioritizing treatments at a time of healthcare constraints and adjusting treatment strategies due to a dearth of hospital resources 5, 6 . Another consideration in clinical decision making is the change in the patient's risk/benefit ratio for any given treatment; treatments providing only a small benefit may not be recommended during the pandemic.

These practice changes have not been standardized, as each center follows internal guidelines reflecting its regional affliction from COVID-19, the percentage of health care workers transferred to COVID-19 care and the change in surgical capacity.

The specific effects of COVID-19 on the management of genitourinary cancers in different cancer centers are not well known. Recommendations published from Canada 7 and Europe 8, 9 differ and some clinical scenarios remain controversial. There is an urgent need to understand what real-world practice changes are occurring within the oncologic community, share data and experience during this rapidly changing crisis, and provide practical information to help guide decision making.

We conducted a genitourinary medical oncology expert opinion survey to determine the current treatment management of genitourinary cancers during the COVID-19 pandemic.

A structured 20-item questionnaire was developed by the investigators (see supplement). The questionnaire consisted of five domains: prostate cancer (PC), urothelial cancer (UC), renal cell carcinoma (RCC), testicular cancer (TC) and general issues.

The survey link was sent on 05/25/20 by email to a list of 170 GU genitourinary medical oncology experts. The list was compiled by investigators by reviewing first and last authors of key trials conducted in the field published in 2010-2020, practicing in academic centers in North America and Europe, with available email addresses. Demographic data collected included cancer center's name and state of practice. All other personal information was de-identified.

Study data were collected and managed using Research Electronic Data Capture (REDCap) electronic data capture tools hosted at MSKCC 10, 11 . REDCap is a secure, web-based software platform designed to support data capture for research studies, providing 1) an intuitive interface for validated data capture; 2) audit trails for tracking data manipulation and export procedures; 3) automated export procedures for seamless data downloads to common statistical packages; and 4) procedures for data integration and interoperability with external sources. When multiple treatment options were provided, a comment stating there were no contraindications to any treatment option was included.

Results: 78 completed surveys (45%) were returned between 05/25/20 and 06/25/20 and were included in the analysis. Surveys were completed by medical oncologists practicing in the United States (US, n=47; from 18 states), Canada (n=7; from 2 provinces), and Europe (n=24; from 10 countries). Overall, 79.1% of oncologists stated they changed their practice compared with the pre-COVID management in at least one question. The proportion of responding oncologists reporting a management change varied by disease and by country of practice (Table 1) .

In intermediate risk localized PC, 42.9% of 63 oncologists have changed their clinical practice during the pandemic; 51.8% of them would delay treatment by 3-6 months and 48.1% would start androgen deprivation therapy (ADT) and delay definitive treatment (surgery/ radiotherapy) by 3-6 months, until the pandemic eases.

In high risk localized PC, 33.9% of 62 oncologists indicated they would change management during COVID-19. Of these, most (95%) offered to start ADT with (30%) or without (65%) next J o u r n a l P r e -p r o o f generation androgen receptor (AR) targeted therapy and to delay definitive treatment (surgery/ radiotherapy) by 3-6 months, until pandemic eases.

In metastatic hormone-sensitive PC (mHSPC) with low volume/burden disease starting 1st line treatment, 92.2% of 64 oncologists did not change their practice during COVID-19, mostly (75%) recommending ADT in combination with next generation AR targeted therapy.

In mHSPC with high volume/burden disease starting 1st line treatment, 28.1% of 64 oncologists changed their practice with most (94.4%) switching from ADT plus docetaxel to ADT plus next generation AR targeted therapy. 29 ADT plus docetaxel was still the preferred approach in 29.7% of mHSPC with high volume/burden disease.

In metastatic castrate-resistant PC (mCRPC) patients that would ordinarily start chemotherapy treatment, 68.8% of 64 oncologists indicated preferring to delay chemotherapy in patients with high COVID-19 risk; 34.4% favored delaying chemotherapy and choosing an alternative treatment in all patients, and 28.1% preferred to start chemotherapy as planned.

In patients with mCRPC treated with bone directed treatment (bisphosphonate / denosumab) and high COVID-19 risk, half (53.2%) of 64 oncologists would delay treatment by 3-6 months until the pandemic eases whereas 40% would delay treatment in all patients.

In a cisplatin-eligible patient with muscle-invasive bladder cancer, cT2-3N0M0, most oncologists (82.8%, 52/63) recommended 3-4 cycles of neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC); 10.9% preferred RC first, and considered adjuvant treatment according to pathology; and only 3.1% preferred bladder preservation with definitive chemoradiation.

Only 9.5% stated that this is different than their pre-COVID management, which changed from NAC followed by RC to either 3 instead of 4 cycles of NAC or to RC alone. 

To our knowledge, we conducted the largest global survey to date among expert medical oncologists concerning the practice patterns of genitourinary cancer patients during the COVID-19 pandemic. Practice changes during COVID-19 were noted by 79.1% of oncologists (Table 1) .

This was most pronounced in prostate cancer (71.8%) and least in urothelial cancer (23%). In testicular cancer, 52.3% stated they changed their management, which represented mostly the increased use of primary growth factor prophylaxis. The proportion of responding oncologists reporting a management change varied by country with 78% of US oncologists indicating at least one practice change (100% for oncologists practicing in NY) compared to 57% for oncologists practicing in Canada and 79% in Europe. This likely reflects differences in COVID-19 magnitude and resultant restrictions on management (e.g., surgery) and available resources between countries during the timepoint of data collection.

This survey was conducted in May-June of 2020, when it was thought that the peak of the pandemic had passed for the hardest hit areas, such as New York (NY), Spain, Italy and other European countries 12 . The number of new COVID-19 cases was also declining in Canada, which was less affected, but was still surging in the US (not including NY) 13 . One strategy commonly used as reflected in the survey was to delay certain interventions by a few months, until the J o u r n a l P r e -p r o o f pandemic eases. As the situation unfolds and number of cases continues to increase worldwide, it is clear that this strategy is not sustainable over time.

There were several limitations in our study. Our response rate was 45%, consistent with responses in published oncology-related physician surveys which vary between 31% and 61% 14 .

Although our findings may be affected by non-responder bias and recruitment methodology, we were able to collect responses capturing practices from various areas in the US, Canada and Europe. This study did not include oncologists practicing in other parts of the world, including in South America, Australia or Asia. Practice changes may have varied in different time-points of the pandemic and between different health care systems depending on available resources, possibly representing "practical" rather than "ideal" management. Cancer patients have been reported to be at increased risk of mortality from COVID-19, although it is still unclear if mortality is related to cancer type, cancer treatment or is it mainly driven by age, gender, and comorbidities 16, 17 . One recent study suggests that PC patients receiving ADT have a significantly lower risk of COVID-19 infection compared with patients not on ADT. It was hypothesized that ADT may have a protective role by suppressing TMPRSS2 levels 18 . Cancer treatment often entails intermittent or prolonged corticosteroid use, which is thought to lead to increased susceptibility to COVID-19 as a result of the immunosuppression 19 .

In contrast, a recent study suggests dexamethasone treatment improves outcomes in severe COVID-19 infections 20 . Thirty percent of 69 oncologists stated they currently reduce steroid doses for emesis prevention, either upfront or in patients who previously didn't experience treatment related nausea or vomiting in prior cycles. In intermediate / poor risk metastatic RCC, 27.5% of 29 oncologists who would normally treat with ipilimumab plus nivolumab have currently changed to non-doublet CPI, to prevent the need for high-dose steroid use for immune-related toxicity. For metastatic prostate cancer treatment during the pandemic, Sommer and Powles 8 proposed that prolonged steroid treatment requires consideration. Fizazi and the GETUG group 9 recommend avoiding corticosteroid use when possible with preference for enzalutamide for first line mCRPC treatment. Only 3% of oncologists would change from abiraterone plus prednisone for metastatic prostate cancer to a different next generation AR targeted therapy, to avoid prolonged steroid use.

The ongoing COVID-19 pandemic changed how oncologists are delivering cancer care. The longterm effects of these treatment changes are yet to be determined but cancer specific mortality is expected to increase over the next several years due to delays in diagnosis and treatment of early stage disease 21, 22 . This survey describes delays and adjustments of cancer care that were being made in May-June 2020. Oncologists did not delay curative treatments for testicular cancer, MIBC and high risk PC, but were more lenient in intermediate risk PC and in some metastatic settings. The long-term effect of these "de-escalation" strategies is hard to quantify.

A recent study projected that a 4-week delay of intervention for MIBC is associated with J o u r n a l P r e -p r o o f increased mortality 23 , while another study discussed GU cancer scenarios in which a 3-6 month delay in intervention would be considered safe 24 . Interruption of clinical trial accrual is also likely to have a negative impact on research advancement and patient access to new interventions. As COVID-19 continues to pose a health threat worldwide, providing access to management strategies of expert cancer centers during this rapidly changing crisis may help inform decision making for the genitourinary oncologic community.

This research was funded in part through the NIH/NCI Cancer Center Support Grant P30 CA008748. J o u r n a l P r e -p r o o f 

Covid-19: How coronavirus will change the face of general practice forever

Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China

SARS-CoV-2 Transmission in Patients with Cancer at a Tertiary Care Hospital in Wuhan, China

Case-Fatality Rate and Characteristics of Patients Dying in Relation to COVID-19 in Italy

Fair Allocation of Scarce Medical Resources in the Time of Covid-19

Cancer, COVID-19 and the precautionary principle: prioritizing treatment during a global pandemic

Prioritizing systemic therapies for genitourinary malignancies: Canadian recommendations during the COVID-19 pandemic

Advice Regarding Systemic Therapy in Patients with Urological Cancers During the COVID-19 Pandemic

Therapeutic options for genitourinary cancers during the epidemic period of COVID-19

Research electronic data capture (REDCap)-A metadata-driven methodology and workflow process for providing translational research informatics support

The REDCap consortium: Building an international community of software platform partners

• Coronavirus deaths per million by country | Statista

Increasing response rates from physicians in oncology research: A structured literature review and data from a recent physician survey

Ethics and Resource Scarcity: ASCO Recommendations for the Oncology Community During the COVID-19 Pandemic

Patients with cancer appear more vulnerable to SARS-CoV-2: A multicenter study during the COVID-19 outbreak

COVID-19 prevalence and mortality in patients with cancer and the effect of primary tumour subtype and patient demographics: a prospective cohort study

Androgen-deprivation therapies for prostate cancer and risk of infection by SARS-CoV-2: a population-based study (N = 4532)

but not TNF Antagonists, are Associated with Adverse COVID-19 Outcomes in Patients With Inflammatory Bowel Diseases: Results from an International Registry

Dexamethasone treatment for the acute respiratory distress syndrome: a multicentre, randomised controlled trial

COVID-19 and cancer

Collateral damage: the impact on outcomes from cancer surgery of the COVID-19 pandemic

Mortality due to cancer treatment delay: systematic review and meta-analysis

Risks from Deferring Treatment for Genitourinary Cancers: A Collaborative Review to Aid Triage and Management During the COVID-19 Pandemic

* Genitourinary (GU) cancer management has been affected by COVID-19 around the world * We present an expert opinion survey to define GU cancer care changes during COVID-19 * Practice changes were reported by 79.1% of responders and differed between countries