key: cord-0981657-vf981g3b
authors: Santoro, Giulio A.; Grossi, Ugo; Murad-Regadas, Sthela; Nunoo-Mensah, Joseph W.; Mellgren, Anders; Di Tanna, Gian Luca; Gallo, Gaetano; Tsang, Charles; Wexner, Steven D.
title: DElayed COloRectal Cancer Care during COVID-19 Pandemic: Global Perspective from an International Survey (DECOR-19)
date: 2020-11-17
journal: Surgery
DOI: 10.1016/j.surg.2020.11.008
sha: 8dc7ec89aa8128dc50bc731812ce2a573e2f0fdf
doc_id: 981657
cord_uid: vf981g3b

BACKGROUND: The widespread nature of coronavirus disease 2019 (COVID-19) has been unprecedented. We sought to analyze its global impact with a survey on colorectal cancer (CRC) care during the pandemic. METHODS: The impact of COVID-19 on preoperative assessment, elective surgery, and postoperative management of CRC patients was explored by a 35-item survey, which was distributed worldwide to members of surgical societies with an interest in CRC care. Respondents were divided into two comparator groups: 1) ‘delay’ group: CRC care affected by the pandemic; 2) ‘no delay’ group: unaltered CRC practice. RESULTS: A total of 1,051 respondents from 84 countries completed the survey. No substantial differences in demographics were found between the ‘delay’ (745, 70.9%) and ‘no delay’ (306, 29.1%) groups. Suspension of multidisciplinary team meetings, staff members quarantined or relocated to COVID-19 units, units fully dedicated to COVID-19 care, personal protective equipment not readily available were factors significantly associated to delays in endoscopy, radiology, surgery, histopathology and prolonged chemoradiation therapy-to-surgery intervals. In the ‘delay’ group, 48.9% of respondents reported a change in the initial surgical plan and 26.3% reported a shift from elective to urgent operations. Recovery of CRC care was associated with the status of the outbreak. Practicing in COVID-free units, no change in operative slots and staff members not relocated to COVID-19 units were statistically associated with unaltered CRC care in the ‘no delay’ group, while the geographical distribution was not. CONCLUSIONS: Global changes in diagnostic and therapeutic CRC practices were evident. Changes were associated with differences in health-care delivery systems, hospital’s preparedness, resources availability, and local COVID-19 prevalence rather than geographical factors. Strategic planning is required to optimize CRC care.

The widespread nature and impact of the coronavirus disease 2019 (COVID- 19) pandemic has been unprecedented. 1 The global transmission of the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has been rapid because of the high infectivity and a relatively high rate of asymptomatic carriers in a highly mobile and interconnected global world. 2 As of August 20 th 2020, the World Health Organization (WHO) confirmed 22,256,220 cases of including 782, 456 deaths. 3 A lack of preparedness and a lack of appreciation of the gravity of the pandemic have led to significant strains on health care systems around the world. In the first half of 2020, most nation's health care resources were overwhelmed by the COVID-19 and many hospitals essentially became coronavirus accepting hospitals during the emergency phase. 4, 5 The impact of COVID-19 on global oncological care has been profound. [6] [7] [8] COVIDSurg Collaborative estimated that 28,404,603 elective operations were cancelled or postponed worldwide during the 12 weeks of peak disruption, with 38% being for cancer. 4 Colorectal cancer (CRC) is the third leading cause of cancer related deaths globally. The pandemic has led to major disruptions and delays in CRC practice, which may adversely affect survival outcomes for several years to come. 8 The primary aim of our survey was to analyze the global impact of the COVID-19 outbreak on both diagnosis and treatment of CRC. The secondary aim was to explore which factors were associated with changes in CRC care or with unaffected practice.

Surgical divisions treating CRC across the world were eligible to participate, including those in countries that did not currently have COVID-19 outbreaks during the study-period. Only one collaborator per surgical division was eligible to take part, although multiple divisions from the same hospital could participate in the survey. To obtain a representative sample of participants, national and international surgical societies with interest in CRC care from six geographical regions were asked to endorse the study and disseminate the survey by e-mail to their members. The societies had no role in study design, data collection, analysis and interpretation, or in the writing of the report. To overcome the temporal bias of distribution, the link to the online survey was made available for three weeks, from May 20-June 10, 2020.

A newsletter with a reminder was sent every week. Informed consent was obtained by voluntary participation and no compensation was offered. The study was registered at ClinicalTrials.gov (NCT 04488549).

A 35-item survey on DElayed COloRectal cancer care during (Appendix 2) was designed by the steering committees formed by the principal investigators.

Meetings were conducted via teleconference to define the appropriateness, feasibility and preliminary validity of the questions to include. Further validation of the survey was achieved by pilot testing on 10 surgery residents to ensure adequate sentence construction and correct interpretation of the questions. We elected not to delay the survey process by performing a formal full validation to glean insights from the results in an expeditious manner in this critical period.

J o u r n a l P r e -p r o o f 8 The platform 'Online surveys' (formerly BOS -Bristol Online Survey), developed by the University of Bristol, in accordance with the COnsolidated criteria for Reporting Qualitative Research (COREQ) and the CHEcklist for Reporting Results of Internet E-Surveys (CHERRIES statement) 9 (Appendix 3) was used. Proprietary survey software and local servers were used to ensure data protection. The fully de-identified dataset was kept on password protected computers. Responses were single or multiple choice, numeric, and open text. All questions were set as mandatory fields with real-time validation and automated skip logic to prevent missing data and avoid illogical or incompatible responses. No randomization of items was used. Quantitative data were automatically collected by the software and exported to a tabulated format. Estimated mean time to complete the survey was 10-15 minutes.

The survey was structured in the following four sections:

1. Demographics and personal practice (Q. 1-Q.13) : including respondents' gender, country, hospital-level, total number of hospital beds, specialty-specific (Q.8: general surgery/ colorectal surgery) division, annual volume of CRC surgery and laparoscopic CRC resections in the division, and average long-course chemoradiation therapy (CRT)-to-surgery interval in for rectal cancer.

After demographics, respondents were asked if they experienced any delay in CRC care (Q.14).

There were two comparator groups: 1) 'no delay': respondents were redirected to a single question (Q.35) investigating the reasons of unaffected practice; 2) 'delay': respondents continued the survey with the following sections: 2. Hospital response to COVID-19 emergency (Q. 15-Q.22 

Continuous variables were summarized by means and standard deviations (SD), and categorical variables by proportions. Comparisons of categorical variables across groups were made by Pearson's chi-square tests. A series of hierarchical binary and ordinal logistic regression models were performed to assess the association between respondents' preferences and their characteristics, with geographical area as random effect. The Brant test was performed to assess the proportional odds assumption in the ordinal logistic model. Uniand multivariable hierarchical logistic models were fitted to explore the association between delay and a pre-defined set of covariates (demographics, hospital characteristics and respondents' personal practice in CRC care). To assess the factors associated with the J o u r n a l P r e -p r o o f recovery of practice, it was first calculated the time interval in days between the date of achievement of the 100 th COVID-19 positive case in the respondent's country and the date of recovery (fully recovered or improved) or the date of persistently limited CRC care and then fitted a zero inflated negative binomial regression. 10 Adjustments to the P-values for multiple testing were not performed, and statistical significance was assessed using alpha=0.05. All analyses were performed using Stata 16 (StataCorp LLC, College Station, TX, USA).

Twenty national and international surgical societies from six geographical regions endorsed the study and disseminated the survey to their members in the time frame (May 20-June 10, 2020) ( Figure 1 ).

A total of 1,051 respondents, representing 1,051 colorectal or surgical divisions, from 84 countries ( Figure 1 ) completed the survey and were included in the final analysis: Europe 603 respondents (57.4%), Asia 218 (20.7%), North America 120 (11.4%), South America 68 (6.5%), Africa 27 (2.6%) and Oceania 15 (1.4%) . The mean interval between the achievement of the 100 th COVID-19 case in each respondent's country and the date of survey completion was higher for respondents from North America (70 days) and Europe (64 days) ( Figure 2 J o u r n a l P r e -p r o o f reporting this case volume for rectal cancer. Thirty-five percent of respondents reported regular use of laparoscopy in >75% of cases in CRC surgery (Table 1) . Most respondents (70.7%) indicated 8-12 weeks as the optimal long-course CRT-to-surgery interval in rectal cancer. Demographics and personal practice were consistent across the geographical regions and the only difference in this proportional distribution was found in the annual number of surgeries for rectal cancer more frequent in Asia (Table 1) .

Overall, 745 respondents (70.9%) experienced some delays in CRC care ('delay' group) and 306 respondents (29.1%) did not ('no delay' group). These two groups were substantially homogeneous for all demographics, and personal practices ( Table 2 ). The geographical distribution between the two groups was also similar and proportionally consistent with the overall population of 1,051 respondents.

Among 745 respondents in the 'delay group', 694 (93.2%) reported that their hospitals had participated in the emergency with by either providing fully dedicated support (16.8%) or partially dedicating (76.4%) clinical activities to the management of SARS-CoV-2 patients ( 

Multivariable hierarchical logistic regression model ( Overall, 26.3% (196/745) of respondents reported that CRC patients scheduled for elective surgery needed urgent surgery due to (multiple alternatives): bowel obstruction (73%), bowel perforation (28%) or bleeding (18%) (Suppl. Fig. 1 ).

One hundred and ninety-six of 745 respondents (26.3%) reported that neoadjuvant CRT was postponed for rectal cancer patients ( 

Recovery of CRC care at the date of the survey completion (May 20-June 10, 2020) (Appendices 4-5) mirrors the status of the outbreak throughout the geographical regions.

Overall, CRC care was 'improved but not fully recovered' to pre-COVID status for 56.4%

(420/745) of respondents. The highest prevalence was in Europe (65.9%, 278/422) and North America (58.5%, 48/82). At the time of survey, in these two regions there were nations both at the peak and at the transition phase of the emergency. CRC care status was 'persistently limited' for 26% (194/745) of respondents. The highest prevalence was in Africa (75%, 12/16) and South America (72%, 41/57), two regions where most nations were at the initial phase of the emergency at the time of the study. A 'fully recovered' CRC practice was reported by 17.6% (131/745) of respondents. The highest prevalence was in Asia (25.3%, 40/158), where some nations were at the end of the emergency phase at the time of the survey. These data are consistent with the zero-inflated negative binomial regression model ( 

The 'no delay' group included 29% (306/1,051) of respondents. The reasons reported for unaltered CRC practice were (more than one factor could be reported): 1) preservation of Three main statistically significant reasons for unaltered CRC care comparing the 'no delay' to the 'delay' group were identified: 1) practicing in COVID-free divisions (16% vs. 7%, P<0.001);

2) no change in operative slots (47% vs. 3%, P<0.001) and 3) staff members not redeployed from surgical divisions to COVID-19 units (59% vs.45%, P=0.037) (Suppl. Fig. 2 ).

COVID-19 introduced a global challenge for the management of CRC. In our survey, changes in both diagnostic and therapeutic practices were reported by 71% (745/1,051: 'delay' group) of respondents. Endoscopic and radiologic procedures were highly affected by the COVID-19 J o u r n a l P r e -p r o o f emergency. Elective CRC surgery was impacted for almost all respondents (97.3%), with planned procedures being temporarily suspended (46.8%) or capacity reduced (50.5%). Our results are consistent with an earlier survey on the global impact of COVID-19 in CRC patients, completed by 289 surgeons in April 2020 during the emergency phase. 11 This study showed that outpatients services, cancer screening, diagnostics and treatment were all transiently suspended. Another study on elective oncological surgery in Italy during the COVID-19 emergency phase, demonstrated that 70% of surgical divisions had a reduction of hospital beds with an associated 76% reduction of surgical activity due to the relocation of resources. 12 Evidence is limited regarding the effect of diagnostic or surgical delays on CRC specific outcomes. [12] [13] Maringe et al. 8 Kingdom. In a retrospective cohort study, Lee et al. 14 reported that the diagnosis-to-treatment interval (DTI) for all CRC, regardless of cancer staging, should not exceed 30 days. In another cohort study, Kucejko et al. 15 reported that the ideal timing of definitive resection in colon cancer is between 3 and 6 weeks after initial diagnosis to achieve a modest but significant improvement in overall survival. The COVID-19 pandemic has increased the DTI for CRC.

Turaga and Girotra 16 reported that CRC surgery can be safely delayed beyond the normal wait time up to 4 weeks without having a significant impact on patient survival or cancer progression. However, in our survey, 58.3% of respondents in the 'delay group' reported that COVID-19 prolonged DTI to >5 weeks beyond normal wait time. Moreover, 43.5% of respondents reported a prolonged long-course CRT-to-surgery interval for in rectal cancer patients to ≥5 weeks beyond the optimal 8-12 weeks interval. Indeed, according to Turaga and J o u r n a l P r e -p r o o f Girotra 16 , this delay is less likely to cause harm. They reported that a postponement period of 6 weeks beyond the optimal long-course CRT-to-surgery interval for rectal cancers patients may be considered safe. Nevertheless, it remains unclear whether a prolonged time interval to surgery beyond the current recommended interval of 8 to 12 weeks results in increased morbidity or better pathological response. [17] [18] [19] [20] COVID-19 also increased the risk of urgent surgery or changing the decision-making process. 21, 22 In this survey, 26.3% (196/745) of respondents reported that CRC patients The COVID-19 pandemic changed the functioning and organization of hospitals around the world. During the surge, restrictive measures were adopted to reduce COVID-19 exposure and to preserve human and material resources. [28] [29] [30] [31] In our survey, we found that delays in CRC care were associated with differences in health care delivery systems, hospital's preparedness, resources availability, and local COVID-19 prevalence, while the geographical distribution of the respondents did not impact significantly. Important factors included hospitals dedicating their services to COVID-19 care, quarantine and/or redeployment of staff, MDT meetings suspension, and the lack of readily available PPE (Table 8) Anesthesiologists, and the Association of Perioperative Nurses. 15 ACS also provided principles for the safe resumption of elective surgery organized in two parts: core facility checklist items (general facility policies, structures and processes, outcomes reporting) and surgery-specific checklist items (policies, structures and processes, outcomes reporting) including measures to protect the patient and protocols in place for safe protection of medical first line teams. 15 In our survey, recovery of CRC care was associated to the stage of the virus outbreak at the time of study completion. Independent of the geographical region, the likelihood of reduced CRC J o u r n a l P r e -p r o o f practice was 66% higher among respondents reporting staff members quarantined (P=0.001) and 35% lower among those working in divisions with medium volume of rectal cancer surgeries (compared to low volume; P=0.036).

Our results indicate that cancer pathways need to swiftly be re-established and maintained at a near normal throughput, with attention to the backlog of patients, in order to reduce the impact of the COVID-19 pandemic. 33 Hospitals need to assume standard-of-care when the benefits exceed COVID-related mortality. 34,35 However, Caricato et al. 36 reported that oncological programs proposed in Italy to guarantee elective surgical activity were only successful in 19% of the regions. In the current study, we identified a crucial role of MDT meetings in on CRC care. Meetings suspension was associated with delays in radiology, surgery and histopathology and prolonged the CRT-to-surgery interval (Table 8 ).

In our survey, the relative homogeneity of delays seemed to reflect the lack of any absolute relation to either the geographical location or the status of the outbreak. Specifically, even within geographical regions at the same time points, some hospitals had delays while others did not. Thus, delays or lack thereof appeared to be more due to individual hospital's organization and preparedness. The plans implemented at hospitals at which no delays were experienced could be shared as 'best practices' so that other facilities could avail themselves of avoiding delays during future virus surges. Conversely, the geographical distribution was important if we consider the recovery of CRC care, because the status of the outbreak was associated with the recovery of standard clinical activities in those hospitals who were most affected by the COVID19 emergency.

Our study has several limitations inherent in surveys, including voluntary participation and recall and selections bias. The respondents included a preponderance of male general surgeons from large academic centers in Europe, Asia and North America (Figure 1 ). Therefore, data from all global regions is are not equally distributed or robust. This geographic distribution mirrored the areas of highest prevalence of COVID-19 at the time of survey distribution (https://www.who.int/docs/defaultsource/coronaviruse/situationreports/20200530-covid19-sitrep131.pdf?sfvrsn=d31ba4b3_2) ( Figure 2 ). It is therefore reasonable to assume that surgeons from countries with low COVID-19 case-prevalence were less motivated to take part.

Another limitation is the lack of a formal full validation process of the survey, which was elected to obtain results in an expeditious manner in this critical period. The impact of subsequent surges is also unknown, as the long-term effect of the delays on diagnosis and/or treatment. Despite these limitations, our data provide important insights regarding the impact of COVID-19 pandemic in CRC care.

During the COVID-19 pandemic, global changes in both diagnostic and therapeutic CRC practices were evident. This problem cannot be solved by sharing best practices as the inability to render CRC care was directly related to the hospital's preparedness and availability of resources rather than to geographical factors. Future surges may again challenge human and material resources. Therefore, a solution to this disparity could potentially be addressed Comparison between "delay" and "no delay" groups in colorectal cancer care (1,051 respondents) Q14 Has your unit experienced any flaw/delay in colorectal cancer care (e.g. in undertaking surgery, oncology, radiotherapy, endoscopy, or noting a reduced number of referrals from other centers)? 1 Yes 2 No (skip to Q35) Q15

How has your hospital been preparing for the COVID-19 emergency? 1 Fully dedicated to COVID-19 patients 2 By creating dedicated pathways and wards to COVID-19 patients 3 Not involved at all in COVID-19 patients' care

Did your hospital establish external connections to COVID-free facilities in order to perform oncologic surgery? 

How did we get here? A short history of COVID-19 and other coronavirus-related epidemics

Presumed asymptomatic carrier transmission of COVID-19

Elective surgery cancellations due to the COVID-19 pandemic: global predictive modelling to inform surgical recovery plans

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

COVID-19 and the Global Impact on Colorectal Practice and Surgery

Clinical impact of COVID-19 on patients with cancer (CCC19): a cohort study

The impact of the COVID-19 pandemic on cancer deaths due to delays in diagnosis in England, UK: a national, population-based, modelling study

Improving the quality of web surveys: the checklist for reporting results of internet E-Surveys (CHERRIES)

Delay to colectomy and survival for patients diagnosed with colon cancer

A snapshot of elective oncological surgery in Italy during COVID-19 emergency: pearls, pitfalls, and perspectives

The effect of time from diagnosis to surgery on oncological outcomes in patients undergoing surgery for colon cancer: a systematic review

Effect of length of time from diagnosis to treatment on colorectal cancer survival: a population-based study

How soon should patients with colon cancer undergo definitive resection?

Are we harming cancer patients by delaying their cancer surgery during the COVID-19 pandemic?

Optimal time interval between neoadjuvant chemoradiotherapy and surgery for rectal cancer

Achieving a complete clinical response after neoadjuvant chemoradiation that does not require surgical resection: it may take longer than you think! Dis Colon Rectum

Pathological complete response due to a prolonged time interval between preoperative chemoradiation and surgery in locally advanced rectal cancer: analysis from the German StuDoQ|Rectal carcinoma registry

Does a longer waiting period after neoadjuvant radio-chemotherapy improve the oncological prognosis of rectal

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The information provided in this questionnaire will be exclusively used for research purposes. It will not be used in a manner which would allow identification of your individual responses. Since when? 1 COVID-19 did not significantly affect my geographical area 2Working at a COVID-19-free hospital 3Surgical bed capacity not reduced for COVID-19 care 4Operating slots not reduced for colorectal cancer 5Intensive care unit bed capacity not reduced for colorectal cancer surgery 6Surgical staff not redeployed to dedicated COVID- 19 units 7 No delay in diagnostic assessment of colorectal cancer 8No delay in oncologic treatment of colorectal cancer 9Other Q35_aIf you selected Other, please specify:J o u r n a l P r e -p r o o f 4 8 Fully recovered to pre-COVID status