The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

708 | Colorectal Disease. 2022;24:708–726.wileyonlinelibrary.com/journal/codi Received: 23 November 2021 | Revised: 9 February 2022 | Accepted: 6 March 2022 DOI: 10.1111/codi.16117 ORIGINAL ARTICLE The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study COVIDSurg Collaborative* This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2022 The Authors. Colorectal Disease published by John Wiley & Sons Ltd on behalf of Association of Coloproctology of Great Britain and Ireland. *Collaborating authors are listed in Appendix A. Registration number: C l i n i c a l T r i a l s . g o v identifier: NCT04384926. Correspondence Joana F. F. Simoes, NIHR Global Health Research Unit on Global Surgery, University of Birmingham, Birmingham, UK. Email: jfs94[email protected].uk Abstract Aim: The SARS- CoV- 2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus nondelayed surgery. Methods: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January– April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. Results: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90– 1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69– 1.27, P = 0.672). Longer delays were not associated with poorer outcomes. Conclusion: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID- 19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in longterm survival attributable to delays is likely to be due to micrometastatic disease. KEYWORDS colorectal cancer, coronavirus, COVID- 19, SARS- CoV- 2, surgery, surgical delay | 709 SIMOES and COVIDSURG COLLABORATIVE INTRODUCTION Globally, colorectal cancer is the third most commonly diagnosed cancer type and the second largest cause of cancer death [1]. The severe acute respiratory syndrome coronavirus 2 (SARS- CoV- 2) pandemic has affected all aspects of healthcare and has led to variable delays to the delivery of colorectal cancer surgery across the globe [2,3]. It is estimated that over 28 million operations were cancelled in the initial 3 months of disruption alone [4,5]. This creates a unique ‘natural experiment’ to explore the effects of treatment delay on outcomes of colorectal cancer surgery. Although there is no international guidance on the optimal timing for colorectal cancer resection, it is generally perceived as a time critical intervention. In the UK, the National Health Service sets a target of 4 weeks from a treatment decision to definitive treatment in cancer care, but global practice and policy varies significantly. A number of modelling studies and systematic reviews have explored the impact of delays on longterm survival in colorectal cancer, but it is unclear whether this is related to poorer initial cancer control (i.e., lower rates of complete resection) or micrometastatic disease spread [6]. Understanding the effects of surgical delay during the SARS- CoV- 2 pandemic will help inform future prioritization of surgical waiting lists during postpandemic recovery and postoperative surveillance by the multidisciplinary team. This study aimed to explore the association between delayed surgery for colorectal cancer in patients not undergoing neoadjuvant therapy and surgical resectability during the SARS- CoV- 2 pandemic. METHODS Study design and setting This was an international prospective cohort study which included consecutive patients with a decision for elective curative surgery from the multidisciplinary team meeting, tumour board or equivalent. Any hospital worldwide undertaking elective colorectal cancer surgery was eligible for inclusion in this analysis. Each participating site recruited consecutive eligible patients for a period of 3 months following the emergence of COVID- 19 in their local area (first notification of SARS- CoV- 2 ranging between January and April 2020). Each site obtained ethical approval according to local regulations, and the COVIDSurg- Cancer study (overall inclusion by cancer type available in Table S12) was preregistered with Clini calTr ials.gov (identifier NCT04384926). Patient inclusion, pathways and followup All patients with a decision for curative cancer surgery or who would normally have been offered curative surgery in the prepandemic setting but an alternative treatment was offered due to COVID- 19 were included. Patients were excluded from this study if they had (1) planned palliative surgery, (2) a suspected cancer that was later found to be benign on histopathology, (3) a suspected benign tumour that was later found to be cancerous or (4) received endoscopic treatment only (e.g., transanal endorectal microsurgery). From all the included patients, some of them did receive their planned curative surgery but some ended up not receiving it during the study period. For patients who were operated, followup data were collected at 30 days after surgery. For patients who remained nonoperated, their last known status was recorded. All followup was completed by 31 August 2020 with a minimum follow- up of 3 months for all included patients. The characteristics of nonoperated patients were described and reasons for the nonperformance of the planned surgery were reported. This allows a comprehensive understanding of the whole sample and an informed discussion on how treatment pathways that were in place during the study influenced the patient groups that we are comparing. Of all the operated patients, some required surgical resection alone and some required neoadjuvant therapy (chemotherapy and/ or radiotherapy prior to surgery). Due to differences in disease biology, and potential effects of treatment intervals in patients undergoing neoadjuvant therapy, the patients who received neoadjuvant therapy were excluded from the main analysis as their disease behaviour is expected to be fundamentally different. However, tumour location and the type of neoadjuvant treatment are reported in the supplement for completeness. Delay to surgery The main analysis on surgical delays focused on patients who received their planned surgery with curative intent, without having received neoadjuvant therapy. Delay to surgery was defined according to the number of weeks from the date of the decision for curative surgery to the date when the patient received surgery. For the primary analysis, patients who were operated more than 4 weeks after their decision for surgery were classified as delayed and those who were operated within 4 weeks were defined as nondelayed. This 4- week cutoff was informed by UK National Institute for Clinical Excellence guidance and standards for timely delivery of cancer care [7]. What does this paper add to the literature? This was a prospective cohort study of 5453 patients with a decision for curative colorectal cancer surgery. Surgical delays of up to 12 weeks were not associated with worse rates of complete resection. Any reduction in longterm survival attributable to delays is likely to be due to micrometastatic disease and should be the focus of postoperative surveillance programmes. 14631318, 2022, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/codi.16117 by Universidad De Sevilla, Wiley Online Library on [06/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 710 | SIMOES and COVIDSURG COLLABORATIVE Outcomes The primary outcome measure for the study was complete resection, defined as disease amenable to surgical removal at the time of surgery with a negative circumferential resection margin (R0, no microscopic or macroscopic disease within 1 mm of the circumferential resection margin). Patients whose disease became unresectable during the study period or whose surgical resection was achieved with positive resection margins (R1 or R2) were classified as having an incomplete resection. Secondary outcomes were also compared between patients undergoing delayed and nondelayed surgery. These included the 30- day postoperative mortality rate, 30- day major postoperative complication rate (defined as Clavien– Dindo Grade III– V complications) [8], stage change from baseline (clinical) to pathology (according to the American Joint Committee on Cancer [AJCC] 8th edition of the TNM staging system [9], defined as upstaged for any increase in stage, downstaged for any decrease in stage and no change for patients remaining at the same stage group), detection of new metastatic disease (clinically, intraoperatively or on radiological imaging that was not present at the time of decision for surgery) and the rate of emergency surgery (i.e., as all patients had an initial plan for elective surgery at study entry, emergency surgery can be interpreted as a cancerrelated complication requiring emergency intervention). The indications for emergency surgery are presented. Data variables Baseline information was collected for each patient at the point of entry to the study. This included age, sex, American Society of Anesthesiologists (ASA) physical status classification, Eastern Cooperative Oncology Group (ECOG) performance score, Revised Cardiac Risk Index (RCRI), body mass index (BMI) (defined as underweight if <18.5 kg/m2, normal if 18.5– 24.9 kg/m2, overweight if 25– 29.9 kg/m2 or obese if ≥30 kg/m2), clinical (based on imaging and clinical observation at the time of decision for surgery) and pathological TNM stage groups collected according to the AJCC 8th edition, country income (grouped as high, upper middle and low/low middle income, as per the World Bank index classification based on gross national income per capita), surgical approach (open, laparoscopic or converted), anastomotic performance (with or without defunctioning stoma) and anastomotic method (handsewn or stapled). Data handling and statistics All the data collected were nonidentifiable and uploaded to a secure online server hosted by the University of Birmingham, using the Research Electronic Data Capture (REDCap) system. Data management and analysis used RStudio version 4.0.3 with the ‘readr’, ‘tidyverse’, ‘dplyr’, ‘gmodels’, ‘Hmisc’ and ‘finalfit’ packages (R Foundation for Statistical Computing). Unadjusted categorical data were compared using the chisquared test with Fisher's exact modification where required. A P value <0.05 was considered statistically significant. Logistic regression models were used to explore the association between delay to surgery and complete resection, adjusting for clinically plausible patient and disease factors selected a priori. All missing data were recorded and are reported in the tables and figures. Reflecting differences in treatment timelines and capacity across different resource settings, we performed a sensitivity analysis exploring longer delays of 6, 8 and 12 weeks from treatment decision to surgery, and the primary outcome measure. Given that patients undergoing emergency surgery could have shown distinct clinical features at the time of decision for surgery that made them more likely to receive an urgent intervention, a preplanned subgroup analysis was performed for patients undergoing planned (elective) surgery only. Further subgroup analyses were performed looking exclusively at colon cancers, rectal cancers, early disease and advanced disease. For this purpose, early disease stage was defined as organ confined, nonnodal, nonmetastatic (T1– 3 N0 M0) and advanced disease was defined as reaching the serosa, nodal or metastatic disease (T4, N+ or M1). A sensitivity analysis of the adjusted and unadjusted results was conducted to explore the impact of longer delays in resectability: 0– 4, 5– 8, 9– 12 and more than 12 weeks from decision to surgery. RESULTS In total, 5453 patients eligible for elective curative colorectal cancer surgery were included from 304 hospitals in 47 countries. This corresponds to 24.4% of all the patients included in the COVIDSurg- Cancer study (the remaining being patients with other cancer types) [10]. Of these 66.3% (3616/5453) had colon cancer and 33.7% (1837/5453) had rectal cancer. The clinical colorectal cancer stage was advanced in 63.6% (3466/5453) of the patients and early in 36.4% (1987/5453). Around twothirds of the patients were ASA grade 1– 2 (66.7%, 3619/5453) and onethird were ASA grade 3– 5 (33.2%, 1809/5453). The majority of the patients were from high income countries (84.3%, 4599/5453), with 9.2% (500/5453) being from upper middle income countries and 6.4% (351/5453) from lower middle or low income countries. Nonoperated patients From all the included patients, 6.6% (358/5453) did not receive their planned operation during the study period (Figure 1), of whom 74.3% (266/358) were still planned to have curative surgery at the time of followup. Patients who were not operated were more likely to have rectal cancer (52.5% vs. 32.4%, P < 0.001), worse performance status (5.9% vs. 2.9% were ECOG 3– 4, P < 0.001), lower BMI (9.3% vs. 3.5% were underweight, P < 0.001), higher stage disease (14.6% vs. 10.3% had clinical Stage IV, P = 0.004) and be from a low/lower middle 14631318, 2022, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/codi.16117 by Universidad De Sevilla, Wiley Online Library on [06/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License | 711 SIMOES and COVIDSURG COLLABORATIVE income country (18.2% vs. 5.6%, P < 0.001) (Table S1). The reasons why patients did not receive their planned operation are detailed in Table S2, with the most common reasons being a multidisciplinary team decision to avoid surgery due to patient risk (72.6%, 260/358), disease progression (29.1%, 104/358) and patient being unable to travel to hospital during the pandemic (26.3%, 94/358). Operated patients Of the 5095 operated patients, 15.5% (791/5095) received neoadjuvant therapy and 85.4% (4304/5095) underwent surgery without neoadjuvant treatment. The majority of the patients receiving neoadjuvant therapy had rectal cancer (81.8%, 647/791). Neoadjuvant therapy regimens by cancer location are shown in Figure S1. From the 4304 patients who received an operation without neoadjuvant therapy, 59.5% (2559/4303) had surgery within 4 weeks of treatment decision and 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older (53.0% vs. 46.3% aged over 70 years, P < 0.001), men (58.7% vs. 54.6%, P = 0.008), more comorbid (37.7% vs. 30.9% were ASA 3– 5, P < 0.001), have a lower performance status (46.4% vs. 53.4% were ECOG 0), be from a higher income country (90.1% vs. 83.7% were from high income countries), have a higher BMI (22.5% vs. 17.4% were obese) and have a rectal cancer (26.9% vs. 20.8%, P < 0.001) and early stage disease (41.9% vs. 32.8% were clinical Stage I). Full demographics are shown in Table 1. Outcomes of delayed surgery Delayed patients did not have lower rates of complete resection, compared to nondelayed patients. In the unadjusted analysis, delayed patients were more likely to have resectable disease (93.7% vs. 91.9%, P = 0.032) and less likely to develop new metastases (6.2% vs. 10.1%, P < 0.001) than nondelayed patients. Changes in disease stage from baseline to pathological staging were more common in delayed patients, including both upstaging and downstaging (Table 2). Delayed patients were also less likely to have had emergency surgery (4.5% vs. 22.9%, P < 0.001) whilst waiting for their planned surgery, mainly due to obstructive symptoms. Other indications for emergency surgery in this cohort are shown in Table S3. There were no significant differences in 30- day major postoperative complications (9.3% vs. 9.8%, P = 0.648) or postoperative mortality rates (1.5% vs. 2.2%, P = 0.126). After adjustment for case mix, delay was not associated with significantly lower rates of complete resection (OR = 1.18, 95% CI 0.90– 1.55, P = 0.224) (Figure 2). The full adjusted model can be found in Table S4. Subgroup analysis In the subgroup analysis of patients undergoing elective surgery only, delay was not associated with lower rates of complete resection (OR = 0.94, 95% CI 0.69– 1.27, P = 0.672) (logistic regression FIGURE 1 Flowchart of patient inclusion, with outcomes stratified by delay versus nondelay. Delay was defined as a time from decision to treat to surgery of >4 weeks All colorectal patients (n=5453) Operated 93.4% (n=5095) Neoadjuvant therapy 15.5% (n=791) Non-delayed 59.5% (n=2559) Resectable disease 91.9% (n=2261) Resectable disease 93.7% (n=1583)Resectable disease 91.9% (n=2261) New metastatic disease 10.1% (n=229) 30-day mortality 2.2% (n=56) Emergency surgery 22.9% (n=585) New metastatic disease 6.2% (n=98) 30-day mortality 1.5% (n=26) Emergency surgery 4.5% (n=78) Delayed 40.5% (n=1744) No neoadjuvant therapy 85.4% (n=4304) No neoadjuvant therapy 66.5% (n=238) Neoadjuvant therapy 33.5% (n=120) Not Operated 6.6% (n=358) 14631318, 2022, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/codi.16117 by Universidad De Sevilla, Wiley Online Library on [06/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 712 | SIMOES and COVIDSURG COLLABORATIVE model available in Figure S2). Demographic trends of delayed patients were also similar to the main analysis (Table S5). When looking at colon and rectal cancers in isolation, a delay of 4 weeks was not associated with a reduced rate of complete resection in colon (OR = 1.33, 95% CI 0.95– 1.87, P = 0.101) or rectal cancer (OR = 0.91, 95% CI 0.58– 1.44, P = 0.692). Delay was not associated with poorer TABLE 1 Demographic features of patients having delayed and nondelayed surgery Nondelayed (n =2559) Delayed (n =1744) P value Site Colon 2028 (79.2) 1274 (73.1) <0.001 Rectum 531 (20.8) 470 (26.9) Age <70 years 1374 (53.7) 819 (47.0) <0.001 ≥70 years 1185 (46.3) 925 (53.0) Sex Female 1162 (45.4) 720 (41.3) 0.008 Male 1397 (54.6) 1024 (58.7) ASA grade 1– 2 1764 (69.1) 1084 (62.3) <0.001 3 – 5 789 (30.9) 657 (37.7) Missing 6 3 ECOG score 01343 (53.1) 795 (46.4) <0.001 1– 2 1101 (43.5) 867 (50.6) 3– 4 85 (3.4) 50 (2.9) Missing 30 32 Revised Cardiac Risk Index 1– 2 2382 (93.1) 1598 (91.6) 0.086 ≥3 177 (6.9) 146 (8.4) Body mass index Underweight 92 (3.7) 45 (2.6) <0.001 Normal 1,121 (44.7) 634 (37.1) Overweight 858 (34.2) 646 (37.8) Obese 437 (17.4) 385 (22.5) Missing 51 34 Stage group Stage I 806 (32.8) 709 (41.9) <0.001 Stage II 560 (22.8) 365 (21.6) Stage III 863 (35.1) 503 (29.7) Stage IV 230 (9.4) 116 (6.9) Missing 100 51 Country income High income 2143 (83.7) 1571 (90.1) <0.001 Upper middle income 259 (10.1) 116 (6.7) Low/lower middle income 157 (6.1) 57 (3.3) Approach Open 1203 (47.1) 800 (45.9) 0.733 Minimally invasive 1216 (47.6) 850 (48.8) Converted to open 137 (5.4) 92 (5.3) Missing 3 2 Anastomosis Yes (with defunctioning stoma) 330 (13.1) 199 (11.6) 0.316 Yes (without defunctioning stoma) 1716 (68.3) 1187 (69.1) No 467 (18.6) 331 (19.3) Missing 46 27 Anastomotic method Stapled 1646 (80.5) 1125 (81.2) 0.641 Handsewn 398 (19.5) 260 (18.8) Missing 515 359 Notes: Delay was defined as a time from decision to treat to surgery of >4 weeks. Data reported as n (%). Percentages expressed of column total. P values calculated using chisquared test. Abbreviations: ASA, American Society of Anesthesiologists classification; ECOG, Eastern Cooperative Oncology Group. 14631318, 2022, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/codi.16117 by Universidad De Sevilla, Wiley Online Library on [06/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License | 713 SIMOES and COVIDSURG COLLABORATIVE resectability in patients with early disease only (OR = 1.20, 95% CI 0 . 6 7 – 2 . 1 8 , P = 0.537) or advanced disease only (OR = 1.11, 95% CI 0 . 8 1 – 1 . 5 2 , P = 0.517). Full logistic regression models for the subgroup analysis are shown in Tables S 6 – S 9 . Sensitivity analysis of longer surgical delays In a sensitivity analysis exploring the association of longer delays and complete resection, 59.5% (2559/4304) of patients were operated in 0– 4 weeks, 25.3% (1089/4304) in 5– 8 weeks, 8.9% (384/4304) in 9– 12 weeks and 6.3% (271/4304) in >12 weeks from decision to surgery (all demographics available in Table S10). Longer delays were not associated with worse resectability outcomes in unadjusted (Table S11) or adjusted analyses (Table 3). Compared to patients undergoing surgery within 4 weeks of treatment decision, the odds of complete resection were not significantly different at 5– 8 weeks from treatment decision (OR = 1.16, 95% CI 0.86– 1.59, P = 0.344), at 9– 12 weeks (OR = 1.40, 95% CI 0.85– 2.41, P = 0.206) or beyond 12 weeks (OR = 1.03, 95% CI 0.62– 1.80, P = 0.920). DISCUSSION AND CONCLUSIONS During the first wave of the SARS- CoV- 2 pandemic, one in 15 patients did not receive their planned operation for colorectal cancer. In those who did undergo surgery, delays of more than 4 weeks did not appear to be associated with reduced rates of complete resection. This was robust to several sensitivity and subgroup analyses. Although there are inherent biases in this study design, including selection bias in those that were exposed to treatment delay, this study represents a unique natural experiment to better understand the pathobiology of survival after colorectal cancer surgery. Whilst longterm oncological outcome data are not yet available for this cohort, these data provide important insight into the potential mechanism for the relationship between longterm survival and treatment delay. Although the previous studies show controversial findings on the impact of delay to oncological outcomes [11– 14], a systematic review looking at longterm survival for patients undergoing colorectal cancer surgery 1 month and 3 months after the diagnosis showed a reduction in overall and diseasefree survival with surgical delays [15]. Another multispecialty review of delays TABLE 2 Unadjusted outcomes compared between delayed and nondelayed patients Nondelayed (n =2559) Delayed (n =1744) P value Resectability Complete resection 2261 (91.9) 1583 (93.7) 0.032 Incomplete resection 199 (8.1) 106 (6.3) Missing 99 55 Resection margins Positive 107 (4.4) 74 (4.4) 1 Negative 2310 (95.6) 1599 (95.6) Missing 142 71 Progression to unresectable disease Yes 127 (5.0) 40 (2.3) <0.001 No 2432 (95.0) 1703 (97.7) Missing 0 1 New metastatic disease Yes 229 (10.1) 98 (6.2) <0.001 No 2036 (89.9) 1472 (93.8) Missing 294 174 Stage change (from baseline to pathology) Downstaged 393 (18.1) 335 (22.0) 0.001 No change 1236 (56.9) 775 (50.8) Upstaged 543 (25.0) 416 (27.3) Missing 387 218 30- day mortality Died 56 (2.2) 26 (1.5) 0.126 Alive 2502 (97.8) 1718 (98.5) Missing 1 0 30- day major postoperative complications Yes 251 (9.8) 163 (9.3) 0.648 No 2307 (90.2) 1581 (90.7) Missing 1 0 Urgency Emergency 585 (22.9) 78 (4.5) <0.001 Elective 1973 (77.1) 1663 (95.5) Missing 1 3 Notes: Delay was defined as a time from decision to treat to surgery of >4 weeks. Data reported as n (%). Percentages expressed of column total. P values calculated using chisquared test. 14631318, 2022, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/codi.16117 by Universidad De Sevilla, Wiley Online Library on [06/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 714 | SIMOES and COVIDSURG COLLABORATIVE in multimodal cancer treatment showed a negative impact on longterm oncological outcomes [6]. This study suggests that a delay to surgery does not affect shortterm pathooncological outcomes. It raises the hypothesis that any decrease in longterm survival observed is unlikely to be due to initial cancer control and may be related to micrometastatic disease spread. Patients whose surgery is delayed might therefore benefit from closer followup strategies for early detection of relapse and metastatic disease. Further research is required to understand the effectiveness of enhanced followup pathways on longterm survival, alongside their performance in different tumour biology patterns (not captured in this study). The clinical features of nonoperated patients suggest clinical selection based on a perceived high risk of surgical complications, given that these patients had worse performance status, were more likely to be underweight and had more advanced disease. Although these decisions probably aimed to protect frail patients from the additional risk conveyed by perioperative SARS- CoV- 2 infection, they might have exposed some patients with advanced disease to a risk of progression to palliative disease. Changes in the management of colorectal cancer during the COVID- 19 pandemic have been described by several research groups, including reduction of the number of patients receiving surgery and shorter treatment regimens [16– 18]. This study provides further insight on the drivers of these clinical decisions and on which patients might have been more impacted by them. Advanced (nonorgan confined) and rectal cancers were also more likely to be operated promptly, as opposed to early and colon cancers which were more likely to be delayed. This suggests that additional features of the disease were perceived by surgical teams as justifying early surgery, which might explain why nondelayed patients had higher nonadjusted rates of progression to unresectable disease and new metastasis. Changes in disease stage observed in this study include higher rates of both upstage and downstage with increased delay. As delayed patients were more likely to have advanced disease, this might reflect lower reliability of clinical staging and imaging studies in advanced cancers, particularly when nodal disease is present [19]. The performance of elective colorectal cancer surgery within 4 weeks of treatment decision might not be feasible in many settings worldwide, even in a prepandemic setting [20,21]. Additionally, there might be variation in the usual timeframes from decision to surgery across settings, depending on local practices and pathways (e.g., preoperative assessment efficiency, existence of routine prehabilitation programmes). This study looked at longer delays of 8 and 12 weeks which showed no association with resectability impairment either, ensuring the generalizability of the findings. Symptoms of obstruction, perforation or bleeding in patients awaiting elective surgery might have prompted earlier surgery, explaining why emergency surgery was more common in nondelayed patients (undergoing surgery within 4 weeks of treatment decision). FIGURE 2 Multivariate logistic regression model exploring the association between delay to surgery and resectability, adjusting for patient and disease factors. Number in dataframe 3966, number in model 3966, missing 0, Akaike information criterion 1786.9, C statistic 0.776. Full model presented in Table S4. Delay was defined as a time from decision to treat to surgery of >4 weeks. Data reported as odds ratio (95% confidence interval, P value). OR >1 means higher odds of resectability for delayed patients, OR <1 means lower odds of resectability for delayed patients. ASA, American Society of Anesthesiologists classification; ECOG, Eastern Cooperative Oncology Group; RCRI. Revised Cardiac Risk Index Resectability: OR (95% CI, p-value) Delay Delayed Colon Rectum <70 >=70 Female Male Grades 1-2 Grades 3-5 0 1-2 1-2 3-4 >=3 Stage I Stage II Stage III Stage IV Non-delayed - - - - - - - - 1.18 (0.90-1.55, p=0.224) 0.51 (0.38-0.67, p<0.001) 1.03 (0.78-1.36, p=0.833) 0.92 (0.71-1.19, p=0.510) 0.99 (0.73-1.36, p=0.972) 0.74 (0.55-0.99, p=0.041) 0.29 (0.17-0.53, p<0.001) 1.17 (0.70-2.07, p=0.558) 0.65 (0.40-1.03, p=0.066) 0.33 (0.23-0.49, p<0.001) 0.05 (0.03-0.07, p<0.001) Odds ratio (95% CI, log scale) 0.5 1.0 1.5 2.0 2.5 Site Age Sex ASA grade ECOG score RCRI score Stage group 14631318, 2022, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/codi.16117 by Universidad De Sevilla, Wiley Online Library on [06/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License | 715 SIMOES and COVIDSURG COLLABORATIVE Although we presented the reasons for emergency surgery in this cohort of patients awaiting planned resection, some could have had symptoms of obstruction or other acute complication at the time of treatment decision, to whom a delay beyond 4 weeks would not be clinically acceptable. To address the selection bias that these clinical findings might have had in the length of delay from decision to surgery, we performed a subgroup analysis of patients undergoing elective surgery only, that again showed no difference in resectability with surgical delays. This study has several important limitations. Longerterm follow- up of this cohort will be required to explore the true clinical impact of treatment delay for these patients. The second is the risk of selection bias in the comparison of delayed and nondelayed patients. We attempted to overcome this through multivariable modelling and several subgroup and sensitivity analyses, but the analysis may still be subject to residual bias from unmeasured confounders. Third, patients who remained nonoperated may have had a poorer prognosis at baseline and/or may have been subject to disease progression and other cancerrelated sequelae which could lead to underestimation of the impact of delay (7% of the cohort overall). Fourth, we were unable to explore the impact of treatment delay in patients with prior neoadjuvant therapy, who pose a biologically distinct treatment group. Finally, histological data were not collected and therefore we were unable to explore whether molecular subtypes or mutational status differed between the groups, and whether this impacted resection. SARS- CoV- 2 waves are not the only pressure that health systems face, and many factors can cause delays in the delivery of surgical care. These findings can inform clinical decision making, management of surgical waiting lists and patient informed consent before surgery. Guidance on management of colorectal cancer should also take these findings into account when designing followup strategies for patients who are operated for colorectal cancer. The possibility of performing cancer resection with a few weeks of delay without a negative impact on local control could be important for patients who may benefit from longer periods of prehabilitation and preconditioning before surgery, in order to achieve a better fitness status and optimize perioperative outcomes. TABLE3 Multivariate logistic regression model exploring the association between stratified delay to surgery and resectability, adjusting for patient and disease factors Nonresectable (n =297) Resectable (n =3669) OR(univariable) OR(multivariable) Delay 0– 4 weeks 193 (8.2) 2154 (91.8) – – 5– 8 weeks 66 (6.5) 955 (93.5) 1.30 (0.98– 1.74, P = 0.079) 1.16 (0.86– 1.59, P = 0.344) 9– 12 weeks 19 (5.3) 338 (94.7) 1.59 (1.01– 2.67, P = 0.060) 1.40 (0.85– 2.41, P = 0.206) >12 weeks 19 (7.9) 222 (92.1) 1.05 (0.66– 1.76, P = 0.855) 1.03 (0.62– 1.80, P = 0.920) Site Colon 200 (6.6) 2846 (93.4) – – Rectum 97 (10.5) 823 (89.5) 0.60 (0.46– 0.77, P < 0.001) 0.51 (0.38– 0.68, P < 0.001) Age <70 158 (7.9) 1850 (92.1) – – ≥70 139 (7.1) 1819 (92.9) 1.12 (0.88– 1.42, P = 0.358) 1.03 (0.78– 1.36, P = 0.828) Sex Female 127 (7.3) 1604 (92.7) – – Male 170 (7.6) 2065 (92.4) 0.96 (0.76– 1.22, P = 0.749) 0.91 (0.70– 1.18, P = 0.491) ASA grade 1– 2 187 (7.1) 2437 (92.9) – – 3 – 5 110 (8.2) 1232 (91.8) 0.86 (0.67– 1.10, P = 0.226) 0.99 (0.73– 1.36, P = 0.964) ECOG grade 0129 (6.4) 1874 (93.6) – – 1– 2 144 (7.9) 1690 (92.1) 0.81 (0.63– 1.03, P = 0.090) 0.74 (0.55– 0.98, P = 0.039) 3– 4 24 (18.6) 105 (81.4) 0.30 (0.19– 0.50, P < 0.001) 0.29 (0.17– 0.53, P < 0.001) RCRI grade 1– 2 278 (7.6) 3387 (92.4) – – ≥3 19 (6.3) 282 (93.7) 1.22 (0.77– 2.03, P = 0.421) 1.18 (0.71– 2.08, P = 0.544) Stage group Stage I 39 (2.7) 1418 (97.3) – – Stage II 35 (4.0) 838 (96.0) 0.66 (0.41– 1.05, P = 0.078) 0.65 (0.40– 1.03, P = 0.066) Stage III 102 (7.8) 1205 (92.2) 0.32 (0.22– 0.47, P < 0.001) 0.34 (0.23– 0.49, P < 0.001) Stage IV 121 (36.8) 208 (63.2) 0.05 (0.03– 0.07, P < 0.001) 0.05 (0.03– 0.07, P < 0.001) Notes: Number in dataframe 3966, number in model 3966, missing 0, Akaike information criterion 1790.1, C statistic 0.776. Delay was measured from decision to treat to surgery. Data reported as odds ratio (95% confidence interval, P value). OR >1 means higher odds of resectability for delayed patients, OR <1 means lower odds of resectability for delayed patients. Abbreviations: ASA, American Society of Anesthesiologists classification; ECOG, Eastern Cooperative Oncology Group; RCRI, Revised Cardiac Risk Index. 14631318, 2022, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/codi.16117 by Universidad De Sevilla, Wiley Online Library on [06/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 716 | SIMOES and COVIDSURG COLLABORATIVE FUNDING INFORMATION This study was funded and supported by the National Institute for Health Research Global Health Research Unit on Global Surgery, Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, Medtronic, Sarcoma UK, the Urology Foundation, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research. The funders did not interfere with the data collection or presentation of results. AUTHOR CONTRIBUTION Individual contributions to this paper are listed in the appendix. The writing group and statistical analysis group have analysed, interpreted and drawn conclusions from the data. The COVIDSurg operations team, international cancer leads and dissemination committees led the conduct of the study and contributed to data curation. The listed collaborators have contributed with patient level data from their sites. CONFLICT OF INTEREST There are no conflicts of interest to declare. ETHICAL STATEMENT This study was approved in every participating country and hospital as per local requirements. National and hospital leads were responsible and guaranteed the necessary approvals ahead of data upload. DATA AVAILABILITY STATEMENT Datasharing requests will be considered by the management group upon written request to the corresponding author. If agreed, deidentified participant data will be available, subject to a datasharing agreement. TWITTER @CovidSurg REFERENCES 1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. 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See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License | 723 SIMOES and COVIDSURG COLLABORATIVE Tébar Zamora A* (Complejo Hospitalario De Toledo, Toledo); Palma P, Cayetano Paniagua L, Gomez Fernandez L* (Consorci Sanitari De Terrassa, Barcelona); Collera Ormazabal P, Diaz del Gobbo R, Farre Font R, Flores Clotet R, Gómez Díaz CJ*, Guàrdia N, Guariglia CA, Osorio Ramos A, Sanchez Jimenez R, Sanchon L, Soto Montesinos C (Fundació Althaia— Xarxa Assistencial Universitària de Manresa, Manresa); Alonso- Lamberti L, García- Quijada J, Jimenez Miramón J, Jimenez V*, Jover JM, Leon R, Rodriguez JL, Salazar A, Valle Rubio A (Getafe University Hospital, Getafe); Aguado López H* (Hellín Hospital, Albacete); Bravo Infante R, De Lacy FB, Lacy AM*, Otero A, Turrado- Rodriguez V*, Valverde S (Hospital Clinic Barcelona, Barcelona); Anula R, Avellana R, Camarero Rodríguez E, Catalán Garza V, Dziakova J, García Alonso M, Lasses Martínez B, López Antoñanzas L, Muguerza JM*, Ochagavía S, Peña Soria MJ, Rivera- Alonso D, Saez Carlin P, Sánchez del Pueblo C, Sanz Ortega G, Sanz- López R, Torres A (Hospital Clínico De Madrid, Madrid); Martín- Arévalo J, Moro- Valdezate D*, Pla- Marti V (Hospital Clínico Universitario De Valencia, Valencia); Beltrán de Heredia J, De Andrés- Asenjo B*, Gómez Sanz T, Jezieniecki C, Nuñez Del Barrio H, Ortiz de Solórzano Aurusa FJ, Romero de Diego A, Ruiz Soriano M, Trujillo Díaz J, Vázquez Fernández A (Hospital Clínico Universitario De Valladolid, Valladolid); Lora- Cumplido P, Sosa- Rodríguez MV* (Hospital De Cabueñes, Gijón); Galvan Perez A, Gonzalez- Gonzalez E, Minaya Bravo AM*, San Miguel C (Hospital Del Henares, Madrid); Alonso de la Fuente N, Jimenez Toscano M* (Hospital Del Mar, Barcelona); Grau- Talens EJ, Martin- Perez B* (Hospital Don Benito- Villanueva, Don Benito (Badajoz)); Benavides Buleje JA, Carrasco Prats M*, Giménez Francés C*, Muñoz Camarena JM, Parra Baños PA, Peña Ros E, Ramirez Faraco M, Ruiz- Marín M*, Valero Soriano M (Hospital General Reina Sofía, Murcia); Allue M, Colsa P, García Domínguez M, Gimenez Maurel T, Martín Anoro LF, Ponchietti L, Rodriguez Artigas JM, Roldón Golet M*, Utrilla Fornals A (Hospital General San Jorge, Huesca); Estaire Gómez M*, Fernández Camuñas Á, Garcia Santos EP, Jimenez Higuera E, Martínez- Pinedo C, Muñoz- Atienza V, Padilla- Valverde D*, Picón Rodríguez R, Sánchez- García S, Sanchez- Pelaez D (Hospital General Universitario De Ciudad Real, Ciudad Real); Curtis Martínez C, Sánchez- Guillén L* (Hospital General Universitario De Elche, Elche); Colombari RC, Del valle E, Fernández M, Lozano Lominchar P*, Martín L, Rey Valcarcel C, Zorrilla Ortúzar J (Hospital General Universitario Gregorio Marañón, Madrid); Alcaide Matas F, García Pérez JM, Troncoso Pereira P* (Hospital Mateu Orfila, Mahon); Blas Laina JL, Cros B, Escartin J*, Garcia Egea J, Nogués A, Talal El- Abur I, Yánez C (Hospital Royo Villanova, Zaragoza); Mora- Guzmán I* (Hospital Santa Bárbara, Puertollano); Achalandabaso Boira M*, Sales Mallafré R (Hospital Universitari De Tarragona Joan XXIII, Tarragona); Marín H, Prieto Calvo M, Villalabeitia Ateca I* (Hospital Universitario Cruces, Barakaldo); De Andres Olabarria U, Durán Ballesteros M, Fernández Pablos FJ, Ibáñez- Aguirre FJ, Sanz Larrainzar A, Ugarte- Sierra B* (Hospital Universitario De Galdakao, Galdakao- Usansolo); Acosta Mérida MA*, Ortiz López D, Yepes Cano AF (Hospital Universitario De Gran Canaria Doctor Negrín, Las Palmas De Gran Canaria); Correa Bonito A, Delgado Búrdalo L, Di Martino M*, García Septiem J*, Maqueda González R, Martin- Perez E (Hospital Universitario De La Princesa, Madrid); Calvo Espino P*, Guillamot Ruano P (Hospital Universitario De Móstoles, Móstoles); Colao García L, Díaz Pérez D*, Esteban Agustí E, Galindo Jara P, Gutierrez Samaniego M*, Hernandez Bartolome MA*, Serrano González J (Hospital Universitario De Torrejón De Ardoz, Madrid); Alonso Poza A, Diéguez B, García- Conde M, Hernández- García M, Losada M* (Hospital Universitario Del Sureste, Madrid); Alvarez E, Chavarrias N, Gegúndez Simón A, Gortázar de las Casas S, Guevara- Martínez J, Prieto Nieto MI, Ramos- Martín P, Rubio- Perez I*, Saavedra J, Urbieta A (Hospital Universitario La Paz, Madrid); Aparicio- López D, Cantalejo diaz M, De Miguel Ardevines MDC, Dobón Rascón MÁ, Duque- Mallén V*, Gascon Ferrer I, González- Nicolás Trébol MT, Gracia- Roche C, Herrero Lopez M, Kälviäinen H, Martinez German A, Matute M, Sánchez Fuentes N, Santero- Ramirez MS, Saudí S (Hospital Universitario Miguel Servet, Zaragoza); Blazquez Martin A, Diez Alonso M*, Hernandez P, Mendoza- Moreno F, Ovejero Merino E, Vera Mansilla C, Matías- García B, Quiroga- Valcárcel A (Hospital Universitario Principe De Asturias, Madrid); Barranquero AG, Cerro Zaballos C, Núñez J, Ocaña J, Ramos D* (Hospital Universitario Ramón Y Cajal, Madrid); Acebes García F, Bailon- Cuadrado M, Bueno Cañones AD, Choolani Bhojwani E, Marcos- Santos P, Miguel T, Pacheco Sánchez D, Pérez- Saborido B, Sanchez Gonzalez J, Tejero- Pintor FJ* (Hospital Universitario Río Hortega, Valladolid); Alconchel F*, Conesa A, Gil Martínez J*, Gutiérrez Fernández AI, Lopez Abad A, Nicolás- López T*, Ramirez Romero P, Roca Calvo MJ, Rodrigues K*, Ruiz Manzanera JJ, Soriano AI (Hospital Universitario Virgen De La Arrixaca, Murcia); Cano A, Capitan- Morales L, Cintas Catena J, Gomez- Rosado J*, Oliva Mompean F, Pérez Sánchez MA, Río Lafuente FD, Torres Arcos C, Valdes- Hernandez J (Hospital Universitario Virgen Macarena, Seville); Cholewa H, Frasson M, Martínez Chicote C, Sancho- Muriel J* (Hospital Universitario Y Politécnico La Fe, Valencia); Estraviz B, Fernández Gómez Cruzado L, González de Miguel M, Landaluceolavarria A* (Hospital Urduliz, Bizkaia); Abad- Gurumeta A, Abad- Motos A, Martínez- Hurtado E, Ripollés- Melchor J*, Ruiz- Escobar A (Infanta Leonor University Hospital, Madrid); Cuadrado- García A*, Garcia- Sancho Tellez L*, Heras Aznar J*, Maté Mate P, Ortega Vázquez I*, Picardo AL, Rojo López JA, Sanchez Cabezudo Noguera F*, Serralta de Colsa D* (Infanta Sofía University Hospital, San Sebastian De Los Reyes); Cagigas Fernandez C, Caiña Ruiz R, Gomez Ruiz M, Martínez- Pérez P, Santarrufina Martinez S*, Valbuena Jabares V (Marqués De Valdecilla University Hospital, Santander); Cagigal Ortega EP, Cervera I, Díaz Peña P, Gonzalez J, Marqueta De Salas M, Perez Gonzalez M*, Ramos Bonilla A, Rodríguez Gómez L (Severo Ochoa University Hospital, Leganés); Alfonso Garcia M, Craus- Miguel A, Fernández Vega L, Ferrer- Inaebnit E, Gil Catalán A, González Argente FX, Jeri S, Oseira A, Pujol Cano N, Segura- Sampedro JJ*, Soldevila Verdeguer C, Villalonga B (Son Espases University Hospital, Palma De Mallorca); Blanco- Colino R, Espin- Basany E*, Pellino G (Vall D’Hebron University Hospital, Barcelona). Sri Lanka: Srishankar S, Thalgaspitiya SPB (Teaching Hospital, Anuradhapura)Arulanantham A, Bandara GBKD, Jayarajah U*, Ravindrakumar S, Rodrigo VSD (District General Hospital Chilaw, Chilaw). 14631318, 2022, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/codi.16117 by Universidad De Sevilla, Wiley Online Library on [06/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 724 | SIMOES and COVIDSURG COLLABORATIVE Sudan: Ali karar AA (Al- Rajhi, Omdurman); Elhafiz MHY* (Best Care Hospital, Khartoum); Adam Essa Adam ME*, Ahmed A (Omdurman Teaching Hospital, Khartoum); Saleh M (University of Gezira Hospital, Wad Madani). Sweden: Arkani S*, Freedman J* (Danderyds Hospital, Stockholm); Angenete E*, Park J (Sahlgrenska University Hospital, Gothenburg); Älgå A*, Heinius G, Nordberg M, Pieniowski E (South General Hospital, Stockholm); Löfgren N, Rutegård M* (Umea University Hospital, Umea). Switzerland: Arigoni M, Bernasconi M, Christoforidis D*, Di Giuseppe M, La Regina D, Mongelli F (Ente Ospedaliero Cantonale, Ticino (Lugano, Bellinzona, Locarno, Mendrisio)); Chevallay M, Dwidar O, Gialamas E, Sauvain M* (Hopital De Pourtales, Neuchatel); Adamina M*, Crugnale AS, Guglielmetti L, Peros G (Kantonsspital Winterthur, Winterthur); Gass M*, Metzger J, Scheiwiller A (Luzerner Kantonsspital, Luzern); Turina M* (Universitätsspital, Zürich). Syrian Arab Republic: Al Asadi T, Alkhateb S, Altom R, Bakkar B, Maa Albared S*, Melhem S (Damascus Hospital, Damascus); Hammed A*, Hammed S (Tishreen University Hospital, Latakia). Tunisia: Kacem MJ, Maghrebi H, Sebai A* (La Rabta Hospital, Tunis). Turkey: Aghayeva A*, Hamzaoglu I, Sahin I (Acibadem Altunizade Hospital, Istanbul; Department of General Surgery, Acibadem Mehmet Ali Aydinlar University School of Medicine, Istanbul); Akaydin E, Aliyeva Z, Aytac E, Baca B, Ozben V*, Ozmen BB (Acibadem Atakent Hospital, Istanbul; Department of General Surgery, Acibadem Mehmet Ali Aydinlar University School of Medicine, Istanbul); Arikan AE*, Bilgin IA*, Kara H, Karahasanoglu T, Uras C (Acibadem Maslak Hospital, Istanbul; Department of General Surgery, Acibadem Mehmet Ali Aydinlar University School of Medicine, Istanbul); Akbas A, Altinel Y*, Calikoglu F, Ercan G, Ercetin C, Hacım NA, Meriç S, Tokocin M, Vartanoglu T, Yigitbas H (Bagcilar Research and Training Hospital, Istanbul); Doğangün M, Iflazoğlu N, Yalkın Ö* (Bursa City Hospital, Bursa); Cennet O, Dincer HA, Erol T (Hacettepe University Hospital, Ankara); Alhamed A, Ergün S*, Ozcelık MF, Sanli AN, Uludağ SS*, Velidedeoglu M*, Zengin AK (Istanbul University— Cerrahpaşa Medical Faculty, Istanbul); Kara Y*, Bozkurt MA, Kocatas A (Health Sciences University Kanuni Sultan Suleyman Training and Research Hospital, Istanbul); Eyuboglu K, Guner A*, Usta MA (Karadeniz Technical University Farabi Hospital, Trabzon); Azamat İF, Balik E*, Buğra D, Kulle CB (Koç University Medical School, Istanbul); Güler SA, Güreşin A, Tatar OC*, Utkan NZ, Yildirim A, Yüksel E (Kocaeli University Teaching Hospital, Kocaeli); Abbasov A*, Yanar H (Liv Hospital Ulus, Istanbul); Akin E, Altintoprak F*, Cakmak G, Çelebi F, Demir H, Dikicier E, Firat N, Gönüllü E, Kamburoğlu MB, Küçük IF, Mantoglu B (Sakarya University Faculty of Medicine, Sakarya); Çolak E*, Kucuk GO, Uyanik MS (University of Samsun, Samsun Training and Research Hospital, Samsun); Goksoy B* (Sehit Prof.dr. İlhan Varank Training and Research Hospital, Istanbul); Bozkurt E, Capkinoglu E, Guven O, Mihmanli M, Omeroglu S, Tanal M*, Yetkin G (Seyrantepe Hamidiye Etfal Training and Research Hospital, Istanbul); Akalin M, Arican C, Avci EK, Aydin C, Demirli Atici S*, Emiroglu M, Kaya T*, Kebabçı E, Kilinc Tuncer G, Kirmizi Y, Öğücü H, Salimoğlu S, Sert İ, Tugmen C, Tuncer K, Uslu G, Yeşilyurt D (University of Health Sciences Tepecik Training and Research Hospital, İzmir); Yildiz A*, Yildiz A (Yildirim Beyazit University Yenimahalle Training and Research Hospital, Ankara); Gultekin FA* (Zonguldak Bulent Ecevit University School of Medicine Research and Training Hospital, Zonguldak). Uganda: Lule H*, Oguttu B* (Kampala International University Teaching Hospital, Ishaka). United Kingdom: Agilinko J, Ahmeidat A, Bekheit M*, Cheung LK, Kamera BS, Mignot G, Shaikh S*, Sharma P (Aberdeen Royal Infirmary, Aberdeen); Al- Mohammad A, Ali S, Ashcroft J, Baker O, Coughlin P, Davies RJ*, Kyriacou H, Mitrofan C, Morris A, Raby- Smith W, Rooney SM, Singh AA, Tan XS, Townson A, Tweedle E (Addenbrooke’s Hospital, Cambridge); Kattakayam A, Lunevicius R, Sheel A, Sud A, Sundhu M (Aintree University Hospital, Liverpool); Angelou D, Choynowski M, McAree B*, McCanny A, Neely D (Antrim Area Hospital- Northern Health and Social Care Trust, Antrim); Kamel F, Kumar L, Madani R*, Nisar P (Ashford and St Peter’s Hospital, Chertsey); Creanga M*, Elniel M, Law J (Blackpool Victoria Hospital, Blackpool); Mosley F* (Bradford Royal Infirmary, Bradford); Arrowsmith L*, Campbell W* (Causeway Hospital, Coleraine); Grove T, Kontovounisios C, Warren O* (Chelsea and Westminster Hospital, London); Doulias T*, Li M, Martin E, Rodwell H (Colchester Hospital University, Colchester); Clifford R, Eardley N, Krishnan E, Manu N, Martin E, Roy Mahapatra S, Serevina OL, Smith C, Vimalachandran D* (Countess of Chester Hospital, Chester); Emslie K*, Labib PL*, Minto G, Natale J, Panahi P, Rogers LJ* (Derriford Hospital, Plymouth); Abubakar A*, Akhter Rahman MM, Chan E, O’Brien H, Sasapu K* (Diana Princess of Wales Hospital Grimsby, Grimsby); Ng HJ* (Dumfries and Galloway Royal Infirmary, Dumfries); Day A* (East Surrey Hospital, Redhill); Hunt A, Laskar N* (East Sussex Healthcare (Conquest Hospital and Eastbourne District General Hospital), Hastings); Gupta A*, Steinke J, Thrumurthy S (Epsom and St Helier University Hospitals NHS Trust, Epsom); Massie E, McGivern K, Rutherford D, Wilson M* (Forth Valley Royal Hospital, Larbert); Bacarese- Hamilton T, Ip M*, James A, Salerno G*, Stockdale T (Frimley Health NHS FT— Wexham Park, Slough); Handa S, Kaushal M, Kler A, Patel P*, Redfern J, Tezas S (Furness General Hospital, Barrow In Furness); Aawsaj Y, Barry C, Blackwell L, Emerson H, Fisher A*, Katory M, Mustafa A (Gateshead Health NHS Foundation Trust, Gateshead); Kretzmer L*, Lalou L, Manku B, Parwaiz I, Stafford J (George Eliot Hospital, Nuneaton); Abdelkarim M, Asqalan A, Gala T, Ibrahim S, Maw A*, Mithany R, Morgan R*, Sundaram Venkatesan G (Glan Clwyd Hospital, Rhyl); Banfield D, Boal M*, Brown O, Dean H (Gloucestershire Royal Hospital, Gloucester); Boulton AJ (Good Hope Hospital, Sutton Coldfield); Hardie CM, McNaught C* (Harrogate District Hospital, Harrogate); Karandikar S*, Naumann D (Heartlands Hospital, Birmingham); Chen F, Cheung J* (Hinchingbrooke Hospital, Huntingdon); Ayorinde J, Chase T, Cuming T, Ghanbari A, Humphreys L, Tayeh S* (Homerton University Hospital, London); Aboelkassem Ibrahim A, Evans C, Ikram H, Loubani M*, Nazir S, Robinson A, Sehgal T, Wilkins A (Hull University Teaching Hospitals NHS Trust, Hull); Dixon J*, Jha M, 14631318, 2022, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/codi.16117 by Universidad De Sevilla, Wiley Online Library on [06/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License | 725 SIMOES and COVIDSURG COLLABORATIVE Thulasiraman SV, Viswanath Y* (James Cook University Hospital, Middlesbrough); Curl- Roper T, Delimpalta C, Liao CCL*, Velchuru V, Westwood E (James Paget University NHS Foundation Trust Hospital, Great Yarmouth); Bond- Smith G*, Mastoridis S, Tebala GD, Verberne C (John Radcliffe Hospital, Oxford University Hospitals NHS Trust, Oxford); Anscomb N*, Baldwin- Smith R, Davies M, Grainger C, Haji A, Haq A, Nunoo- Mensah JW, Rizk M (King’s College Hospital, London); Bhatti MI, Boyd- Carson H, Elsey E, Gemmill E, Herrod P*, MohammedJibreel M, Lenzi E, Saafan T, Sapre D, Sian T, Watson N (King’s Mill Hospital, Sutton- In- Ashfield); Athanasiou A*, Burke J, Costigan F, Elkadi H, Johnstone J, Nahm C (Leeds Teaching Hospitals Trust, Leeds); Annamalai S, Ashmore C, Kourdouli A (Leicester Royal Infirmary, Leicester); Chean CS, Dharamavaram S, Kulkarni N, Pereira I, Shanthakunalan K, Srikumar B (Lincoln County Hospital, Lincoln); Askari A, Cirocchi N, Kudchadkar S, Patel K, Sagar J*, Talwar R* (Luton and Dunstable University Hospital, Luton); Abdalla M, Ismail O, Newton K, Stylianides N* (Manchester Royal Infirmary, Manchester); Aderombi A, Bajomo O, Beatson K, Garrett WV*, Ng V (Medway Hospital, Gillingham); Al- Habsi R, Divya GS, Dixon F, Keeler BD* (Milton Keynes University Hospital, Milton Keynes); Egan RJ*, Fabre I, Harries R*, Li Z, Parkins K, Spencer N, Thompson D (Morriston Hospital Swansea, Swansea); Gemmell C, Grieco C, Hunt L* (Musgrove Park Hospital, Taunton); Mahmoud Ali F (Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne); Seebah K, Shaikh I*, Sreedharan L, Youssef M* (Norfolk and Norwich University Hospital, Norwich); Shah J* (North Manchester General Hospital, Manchester); Baguley M, Heer B, Rogers M, Woods R* (Northampton General Hospital, Northampton); Mills SJ* (Northumbria Healthcare NHS Foundation Trust, Northumberland and Tyne and Wear); Sahnan K (Northwick Park Hospital, Harrow); Ahmed ME, Bukhari SI, Illingworth B, Kanthasamy S, Knights E, Ong SL, Pujari R, Tan KHM, Vanker R* (Peterborough City Hospital, Peterborough); Michel M, Patil S, Ravindran S, Sarveswaran J*, Scott L (Pinderfields Hospital, Wakefield); Khan J* (Queen Alexandra Hospital, Portsmouth); Bhangu A*, Cato LD, Kamal M, Kulkarni R, Parente A , Saeed S, Vijayan D (Queen Elizabeth Hospital Birmingham, Birmingham); English C, Evans J*, Fell A*, Halkias C, Merh R, Nikolaou S (Queen Elizabeth The Queen Mother Hospital Margate, Margate); Kaul S, Khan AH, Khan F, Mukherjee S*, Patel M, Sarigul M, Singh S (Queen’s Hospital Romford, Romford); Adiamah A, Brewer H, Chowdhury A*, Evans J, Humes D*, Jackman J, Koh A, Lewis- Lloyd C, Oyende O, Reilly J, Worku D (Queens Medical Centre, Nottingham); Bisset C, Moug S* (Royal Alexandra Hospital, Paisley); Chadha R* (Royal Berkshire Hospital, Reading); Math S, Sarantitis I, Timbrell S, Vitone L* (Royal Blackburn Hospital, Blackburn); Faulkner G* (Royal Bolton Hospital, Farnworth); Brixton G, Findlay L, Majkowska A, Manson J*, Potter R (Royal Bournemouth Hospital, Bournemouth); Bhalla A*, Chia Z, Daliya P, Grimley E, Malcolm FL, Theophilidou E (Royal Derby Hospital, Derby); Daniels IR, Fowler GE, Massey LH, McDermott FD*, Rajaretnam N (Royal Devon and Exeter Hospital, Exeter); Angamuthu N, Chowdhury S, Gilliland J, Hart C, Knowles J, Mirnezami R, Varcada M* (Royal Free Hospital, Hampstead); Beamish AJ, Magowan D, Nassa H, Price C, Smith L, Solari F, Tang AM, Williams G* (Royal Gwent Hospital, Newport); Davies E*, Hawkin P, Raymond T, Ryska O (Royal Lancaster Infirmary, Morecambe); Baron R*, Gahunia S, McNicol F*, Russ J, Szatmary P, Thomas A (Royal Liverpool University Hospital, Liverpool); Jayasinghe JD, Knowles C, Ledesma FS, Minicozzi A*, Navaratne L, Ramamoorthy R, Sohrabi C, Thaha MA*, Venn M (Royal London Hospital, London); Atherton R*, Brocklehurst M, McAleer J, Parkin E* (Royal Preston Hospital, Preston); Aladeojebi A, Ali M, Gaunt A* (Royal Stoke University Hospital, Stoke- On- Trent); Hammer C, Stebbing J (Royal Surrey County Hospital, Guildford); Coomber E, Williams O (Royal Sussex County Hospital, Brighton); Bunni J, Fairhurst K*, Mitchell S, Richards S (Royal United Hospital Bath, Bath); Hraishawi I, McIlmunn C, McIntosh S* (Royal Victoria Hospital, Belfast, Belfast); Bhasin S, Bodla AS, Burahee A, Crichton A, Fossett R, Yassin N* (Royal Wolverhampton NHS Trust, Wolverhampton); Barlow C, Ding D, Foster J, Longstaff L (Salisbury NHS Foundation Trust, Salisbury); Brown SR*, Lee M, Newman T, Steele C (Sheffield Teaching Hospital NHS Foundation Trust, Sheffield); Baker A, Konstantinou C, Ramcharan S*, Wilkin RJW (South Warwickshire NHS Foundation Trust, Warwick); Colvin HV, Shakoor Z (Southampton General Hospital, Southampton); Lawday S, Lyons A* (Southmead Hospital, Bristol); Newman S (Southport and Formby District General Hospital, Southport); Chung E, Hagger R, Hainsworth A, Karim A, Owen H, Ramwell A, Williams K* (St George’s Hospital, London); Hall J (Stepping Hill Hospital, Stockport); Harris G, Royle T*, Watson LJ (Sunderland Royal Hospital, Sunderland); Asaad P, Brown B, Duff S*, Khan A, Moura F, Wadham B (The University Hospital of South Manchester, Manchester); Mccluney S, Parmar C*, Shah S (The Whittington Hospital, London); Babar MS*, Goodrum S, Whitmore H (Torbay and South Devon NHS Trust, Torquay); Balasubramaniam D*, Jayasankar B*, Kapoor S, Ramachandran A (Tunbridge Wells Hospital, Maidstone); Beech N, Chand M*, Green L, Kiconco H, McEwen R (University College London Hospital, London); Pereca J* (University Hospital Ayr, Ayr); Arumugam S, Ibrahim B*, Khan K* (University Hospital North Durham, Durham); Gash K, Gourbault L, Maccabe TA, Newton C* (University Hospitals Bristol NHS Foundation Trust, Bristol); Baig M, Bates H, Dunne N, Khajuria A, Ng V, Sarma DR, Shortland T, Tewari N* (University Hospitals Coventry and Warwickshire NHS Trusts, Coventry); Akhtar MA*, Brunt A, McIntyre J, Milne K, Rashid MM, Sgrò A, Stewart KE, Turnbull A (Victoria Hospital Kirkcaldy, Kirkcaldy); Gossedge G*, O’Donnell S, Oldfield F (Warrington and Halton Teaching Hospitals NHS Trust, Warrington); Aguilar Gonzalez M*, Talukder S* (West Suffolk Hospital, Bury St Edmunds); Eskander P, Hanna M, Olivier J* (Weston General Hospital, Weston- Super- Mare); Basnyat P*, Davis H, Montauban P, Shrestha A (William Harvey Hospital, Ashford); Magee C*, Powell S* (Wirral University Teaching Hospital, Wirral); Flindall I, Hanson A, Mahendran V (Worcestershire Royal Hospital, Worcester); Green S, Lim M, MacDonald L, Miu V, Onos L, Sheridan K, Young R* (York Teaching Hospitals NHS Trust, York); Alam F, Griffiths O, Houlden C, Kolli VS, Lala AK, Seymour Z* (Ysbyty Gwynedd, Bangor, North Wales). 14631318, 2022, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/codi.16117 by Universidad De Sevilla, Wiley Online Library on [06/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 726 | SIMOES and COVIDSURG COLLABORATIVE United States of America: Consorti E, Gonzalez R, Kwan- Feinberg R*, Liu T (Alta Bates Summit Medical Center (Sutter Health), San Francisco); Cooper Z*, Hirji S, Mahvi D, Okafor B, Roxo V, Salim A (Brigham and Women’s Hospital, Boston); Loehrer A*, Telma K, Wilson M (Dartmouth- Hitchcock Medical Center, Lebanon, NH); Bokenkamp M, Haynes AB, Hill C, Leede E, McElhinney K, Olson KA, Riley C (Dell Seton Medical Center at the University of Texas, Austin); Bigelow B, Etchill EW*, Gabre- Kidan A*, Jenny HE, Kent A, Ladd MR, Long C, Malapati H, Margalit A, Rapaport S, Rose J, Stevens K, Tsai L, Vervoort D, Yesantharao P (Johns Hopkins Hospital, Baltimore, MD); Klaristenfeld D* (Kaiser Permanente San Diego Medical Center, San Diego); Huynh KT (Kaiser Permanente West Los Angeles, Los Angeles); Kaafarani H*, Naar L, Qadan M (Massachusetts General Hospital, Boston, MA); Cha DE, Gleeson E, Horn C, Sarpel U* (Mount Sinai, New York); Bhama A (Rush University Medical Centre, Chicago, IL); Colling K*, Najarian M (Saint Mary’s Medical Center- Essentia Health, Duluth); Azam M, Choudhry A*, Marx W (Suny Upstate University Hospital, Syracuse); Chokshi R, Glass N*, Tsui G (The University Hospital, Newark, NJ); Abel MK, Boeck M, Chern H, Kornblith LZ*, Nunez- Garcia B, Ozgediz D, Sarin A, Varma MG (University of California, San Francisco (UCSF), San Francisco); Abbott D, Acher A, Aiken T, Barrett J, Foley E, Schwartz PB, Zafar SN* (University of Wisconsin, Madison); Hawkins AT*, Maiga A (Vanderbilt University Medical Center, Nashville, TN); Ruzgar NM, Sion M, Ullrich S (Yale New Haven Hospital, New Haven, CT). Yemen: Al- Naggar H*, Al- Shehari M*, Almassaudi A, Alsayadi M, Alsayadi R, Shream S (Al- Thawra Modern General Hospital, Sana’a). 14631318, 2022, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/codi.16117 by Universidad De Sevilla, Wiley Online Library on [06/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License