The Impact of COVID-19 on the Oncologic Outcomes of 3236 Patients Undergoing
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medRxiv preprint doi: https://doi.org/10.1101/2021.04.19.21255730; this version posted April 20, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . The impact of COVID-19 on the oncologic outcomes of 3236 patients undergoing ColoRectal Cancer surgery in Northern Italy in 2019 and 2020 (COVID-CRC): results of a multicentric comparative cohort study. Matteo Rottoli,1,2 Gianluca Pellino,3 Antonino Spinelli,4,5 Maria Elena Flacco,6 Lamberto Manzoli,6 Mario Morino,7 Salvatore Pucciarelli, 8 Elio Jovine,2,9 Moh’d Abu Hilal,10 Riccardo Rosati,11 Alessandro Ferrero,12 Andrea Pietrabissa,13 Marcello Guaglio,14 Nicolò de Manzini,15 Pierluigi Pilati,16 Elisa Cassinotti,17 Giusto Pignata,18 Orlando Goletti,19 Enrico Opocher,20 Piergiorgio Danelli,21 Gianluca Sampietro,22 Stefano Olmi,23 Nazario Portolani,24 Gilberto Poggioli,1,2 and the COVID-CRC Collaborative* * Collaborating authors are listed in the Supplementary File 2. 1 IRCCS Azienda Ospedaliero Universitaria di Bologna, Bologna, Italy 2 Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy 3 Department of Advanced Medical and Surgical Sciences, Università degli Studi della Campania "Luigi Vanvitelli", Naples, Italy 4 Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy 5 IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy 6 Department of Medical Sciences, University of Ferrara, Ferrara, Italy 7 AOU Città della Salute e della Scienza, Turin, Italy 1 NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice. medRxiv preprint doi: https://doi.org/10.1101/2021.04.19.21255730; this version posted April 20, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . 8 First Surgical Clinic, Department of Surgical, Oncological, and Gastroenterological Sciences, University of Padua, Padua, Italy 9 Division of General and Emergency Surgery, IRCCS Azienda Ospedaliero- Universitaria di Bologna, Bologna, Italy 10 Fondazione Poliambulanza Hospital, Brescia, Italy 11 Department of Gastrointestinal Surgery, IRCCS San Raffaele Scientific Institute and San Raffaele Vita-Salute University, Milan, Italy 12 Ospedale Mauriziano Umberto I, Turin, Italy 13 Department of Surgery, University of Pavia and Fondazione IRCCS Policlinico San Matteo, Pavia, Italy 14 Department of Surgery, Colorectal Surgery Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy 15 Surgical Clinic Unit, University Hospital of Trieste, Trieste, Italy 16 UOC Chirurgia Oncologica Esofago e vie digestive, Istituto Oncologico Veneto (IOV-IRCCS), Padua, Italy 17 Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano - Università degli Studi di Milano, Milan, Italy 18 ASST Spedali Civili di Brescia, Brescia, Italy 19 Chirurgia Generale Humanitas Gavazzeni Bergamo, Italy 20 ASST Santi Paolo e Carlo, Dipartimento di scienze della salute - Università degli Studi di Milano, Milan, Italy 21 ASST Fatebenefratelli Sacco, Milano; Dipartimento di Scienze Biomediche e Cliniche, Università degli Studi di Milano, Milan, Italy 22 Divisione di Chirurgia Generale ed Epato-Bilio-Pancreatica. ASST Rhodense. Ospedale di Rho, Monumento ai Caduti, Rho, Milan, Italy 2 medRxiv preprint doi: https://doi.org/10.1101/2021.04.19.21255730; this version posted April 20, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . 23 Chirurgia Generale ed Oncologica, Policlinico San Marco GSD, Zingonia, Bergamo, Italy 24 Department of Clinical and Experimental Sciences, Surgical Clinic, University of Brescia, Italy Corresponding author (and requests for reprints): Matteo Rottoli Surgery of the Alimentary Tract IRCCS Azienda Ospedaliero Universitaria di Bologna, Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna Via Massarenti 9 40138 Bologna, Italy ORCID ID: 0000-0003-0278-4139 Telephone number: +390512145262 Email: [email protected] Manuscript word count: 2831 Key words: colorectal cancer; oncologic outcome; COVID-19; SARS-CoV-2, screening; FIT. 3 medRxiv preprint doi: https://doi.org/10.1101/2021.04.19.21255730; this version posted April 20, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . ABSTRACT Objective This study compared all patients undergoing surgery for colorectal cancer in 20 hospitals of Northern Italy in 2019 versus 2020, in order to evaluate whether COVID- 19-related delays in the execution of colorectal cancer screening resulted in more advanced cancers at diagnosis and worse clinical outcomes. Design A retrospective multicentric cohort analysis of patients who underwent surgery for colorectal cancer in March-December 2019 (2019) versus March-December 2020 (2020). The independent predictors of disease stage (oncologic stage, associated symptoms, clinical T4 stage, metastasis) and postoperative outcome (surgical complications, palliative surgery, 30-day death) were evaluated using logistic regression. Results The sample consisted of 1755 patients operated in 2019, and 1481 in 2020 (both mean ages 69.6 years). The proportions of cancers with symptoms, clinical T4 stage, liver and lung metastases in 2019 and 2020 were, respectively: 80.8% vs 84.5%; 6.2% vs 8.7%; 10.2% vs 10.3%; and 3.0% vs 4.4%. The proportions of surgical complications, palliative surgery, and death in 2019 and 2020 were, respectively: 34.4%vs 31.9%; 5.0% vs 7.5%; and 1.7% vs 2.4%. At multivariate analysis, as compared with 2019, cancers in 2020 were significantly more likely to be symptomatic (Odds Ratio - OR: 1.36, 95% Confidence Interval - CI: 1.09-1.69), in clinical T4 stage (OR: 1.38; 1.03- 1.85), with multiple liver metastases (OR: 2.21; 1.24-3.94), but less likely to cause surgical complications (OR: 0.79; 0.68-0.93). Conclusions 4 medRxiv preprint doi: https://doi.org/10.1101/2021.04.19.21255730; this version posted April 20, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . Colorectal cancer patients who had surgery between March and December 2020 had an increased risk of more advanced disease in terms of associated symptoms, cancer location, clinical T4 stage, and number of liver metastases. 5 medRxiv preprint doi: https://doi.org/10.1101/2021.04.19.21255730; this version posted April 20, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . SHORT SUMMARY BOX What is already known about this subject? A specific search regarding the correlation between colorectal cancer oncologic outcomes and COVID-19 showed a few modeling studies which reported the predictions of the potential impact of the diagnostic delays (due to the reduction of the screening programs) on the survival of patients affected by colorectal cancer. However, no study reported any real-life evidence regarding the correlation between the COVID-19 outbreak and the deteriorations of the oncologic outcomes of patients with colorectal cancer. What are the new findings? The present study showed that patients who had surgery for colorectal cancer between March and December 2020 had an increased risk of more advanced disease in terms of associated symptoms, cancer location, clinical T4 stage, and number of liver metastases, than patients who had surgery between March and December 2019. How might it impact on clinical practice in the foreseeable future? The present study confirmed that the backlogs of the screening programs have had, and probably will have, detrimental effects on the oncologic outcomes of patients affected by colorectal cancer. Increased resources should be placed in order to reactivate and enhance the screening programs, and to reduce the risk of colorectal cancer patients to be diagnosed with advanced cancer in the next future. 6 medRxiv preprint doi: https://doi.org/10.1101/2021.04.19.21255730; this version posted April 20, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . INTRODUCTION Coronavirus disease 19 (COVID-19), which is associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, has spread worldwide since it was first reported in China in December 2019.1,2 Italy has witnessed a rapid and uncontrolled spread of the infection since February 2020, and a number of related deaths which