What should surgeons know in cases of oncological pathology in the context of covid-19 pandemic (sars cov-2)?

RECOMMENDATIONS FROM ¨SURGEONS-AEC-COVID19¨ OF THE SPANISH ASSOCIATION OF SURGEON (AEC)

• In response to the rapid evolution that hospitals face concerning the COVID-19 pandemic, and to the doubts that arise regarding the management of cancer patients who need surgery, the Spanish Association of Surgeons (AEC) want to respond to the questions that arise in this situation.
• Given the changing environment of the pandemic, these proposals are subject to the recommendations of the Ministry of Health of each country and the available evidence.

Assessment of the situation and decision making

In the current COVID-19 pandemia that we are facing, oncologic patients are at a higher risk of infection than non-oncologic surgical patients; due to both: their baseline pathology and their immunosuppression associated with their treatments (chemotherapy and surgery)^1-4.

The objective in these patients is to minimize their risk of infection and to prevent possible surgical complications; as well as to have judicious use of resources and to protect all healthcare workers.

For the decision making process, a scale (that is pending validation) with five phases that detail the progression of the COVID-19 pandemia has been developed.  It is based on current literature⁵ and on our cumulative experience from our centers after analyzing the situation internationally.  This is a dynamic scale where it can follow an escalating expansion of the SARS-CoV-2 infection as well as its decrease when hospitals begin to recuperate normalcy.

We will discuss topics related to the treatment of oncologic patients in the current setting of a COVID-19 pandemia

1.- Is preoperative screening necessary for all oncologic patients that will undergo surgery?

The European CanCer Organization (ECCO) have indicated that its extremely important that healthcare systems quickly provide a COVID-19 test for all cancer patients who are receiving active treatment (chemotherapy, radiation or surgery)⁶.

Current recommendation on highly affected areas with COVID-19 is to test all surgical oncological patients with the objective to reduce all risk associated with operating an infected patient (Phase II-V).

Preoperative screening for SARS-CoV-2 includes: epidemiologic history (contact with infected patients within the last 14 days), presence of classic symptoms (fever, respiratory symptoms, anosmia, ageusia), testing by PCR with a nasopharyngeal swab. If there is a discrepancy between clinical findings and testing, or if PCR is indeterminate, a CT of the chest can be a quick adjunct that can aid in diagnosis for COVID-19 due to its high sensitivity^7,8.

However PCR testing is subject to hospital availability, to the priority level given at a particular moment and using judicious use of available resources. If PCR cannot be done, screening via a chest CT has been proposed, if not available then ultrasonography or a Chest Xray can be done.

Currently there are no recommendations in the literature regarding type of screening and interpretation of their results for cancer patients who require surgery in areas where the infection incidence by SARS-CoV-2 is low (Phase I).

2.- Are cancer patients more likely to develop COVID-19?

Cancer patients are more susceptible to infections than individuals without cancer due to their malignant process as well as their overall immunosuppressive state caused by employed treatments (chemotherapy or surgery). Therefore these patients are more likely to develop COVID-19 and have a worse prognosis^1-4.

Therefore, cancer patients and their family should know and apply contact protective measures and maximize precautions to prevent transmission.

3.- How can we decide whether to postpone surgery or not in a cancer patient during the COVID-19 pandemia?

Due to the current circumstances, decision whether to proceed with elective surgery for cancer should be based on:

• SARS-CoV-2 infection incidence: The phase we are currently in and a rapidly increasing infectious curve⁹.
• Hospital resources: availability of oncologic rooms/wards separate from COVID-19 patients, ICU beds, respiratory/ventilation support, Personal Protective Equipment (PPE).
• Risk/benefit assessment regarding reducing progression of disease vs developing complications from developing an infection with SARS-CoV-2 (readmission, postoperative complications, mortality).
• Individual tumor specific risk assessment for postponing the procedure 6-8 weeks when the COVID-19 infection may be less prevalent.
• Assessment of surgical morbidity and the potential need for ICU stay or the need for mechanical ventilation.

The decision to postpone or not the surgery should be made by a hospital multidisciplinary committee preferably by telematics, on a case by case basis with the goal of establishing: risk in function of local circumstances, prevalence of COVID-19, and the availability of non-surgical options if surgery is to be postponed.

Patients should be informed that their treatment decision is based on consensus by a multidisciplinary team and the factors taken into consideration are: risk of infection by coronavirus, available resources at the moment, tumor characteristics, and expected outcomes from postponing treatment.

4.- Is there a higher complication rate in cancer patients with COVID-19 infection?

Although the available literature is infrequent in this scenario, a study from China, where most of the published literature comes from, observed that cancer patients had a higher risk of serious complications, in terms of the need for admission to the intensive care unit, requiring invasive ventilation and an increase in mortality, compared to cancer-free patients, with deterioration being more rapid and severe in cancer patients ¹.

5.- How should a patient with cancer who is NOT infected with COVID-19 be treated?

In patients without known infection by COVID-19 and when the logistical situation permits, surgery could be considered in most cases, and the epidemiological situation should be assessed, as always. However, decisions must be individualized after considering the general objectives of the treatment, the tumor stage as well as the general condition of the patient.

In colorectal surgery it is recommended to avoid primary anastomosis in patients at risk (ultra-low anastomoses, diabetics, preoperative radiotherapy, fragile, elderly patients, etc.), both due to the high risk of an added complication of infection by COVID-19 for the patient and to avoid development of sepsis that may require necessary resources in the health system¹⁰.

The limited evidence available at present does not allow specific recommendations to be made for each tumor type but the attached bibliography can be consulted.

6.- How should a patient with cancer and COVID-19 infection be treated?

In patients infected with COVID-19, treatment of infection should be prioritized over cancer treatment, except in urgent situations (perforation, obstruction, bleeding). Therefore, surgical or chemotherapy treatment should be postponed. If surgery is required, it must entail the minimum necessary procedure and with less possibility of postoperative complications (assess regional anesthesia, use of stents, derivative stomata).

7.- Is an oncology patient awaiting surgery with neoadjuvant chemotherapy at an increased risk of complications? 

The main cancer treatment associated with immunosuppression is chemotherapy, so patients who receive it can be considered a population vulnerable to serious complications after COVID-19 infection. For this reason, patients undergoing chemotherapy treatment should take extreme precautions to avoid transmission and assess the risk/benefit ratio of continuing their administration during the period of virus expansion.

Regarding adjuvant treatment, there is limited evidence of the consequences of delaying or stopping chemotherapy treatment versus the benefits of potential prevention of COVID-19 infection. Clinical decisions should be individualized taking into account factors such as the risk of tumor recurrence if adjuvant chemotherapy is delayed, modified or discontinued, the number of cycles of adjuvant chemotherapy already completed, and the patient’s tolerance for treatment.

For solid tumors, adjuvant therapy with intent to cure should be given despite the risk of COVID-19 infection. Patients with metastatic disease, delaying treatment can worsen the overall state of the patient and the therapeutic window may be lost¹¹.

8.- In an oncology patient awaiting surgery with neoadjuvant chemotherapy, is it better to have surgery or another cycle of chemotherapy to postpone the surgery?

Although each case must be assessed individually, taking into account the general condition of the patient, their oncological situation and the risk of surgery (both due to the possibility of postoperative complications and the situation in each hospital), it would be advisable during the period of virus expansion to give an additional course of chemotherapy before surgery so that it can be delayed without losing the therapeutic window and expecting COVID-19 infection to be less prevalent then.

Clinical trials for colon cancer where the administration of neoadjuvant chemotherapy (FOxTROT)¹² or trials done for rectal cancer where preoperative neoadjuvant chemotherapy was used^13-15 can support this decision making. Regarding esophagogastric cancer, The Association of Upper Gastrointestinal Surgery of Great Britain and Ireland (AUGIS) recommends that in patients where a prolonged recuperation is expected, chemotherapy as neoadjuvant or as definite treatment can be considered¹⁶.

On the other hand, there are contradicting recommendations from different medical societies as to when not to start potentially immunosuppressive chemotherapy in patients where a 2-3 weeks delay does not results in an increased risk to that patient¹⁷.

9. How to handle the resection pieces?

Surgical pieces are considered infectious samples, so they must be handled as such and will be delivered to the assigned department according to the protocol established by each Hospital.

10. How should follow-up of the cancer patient be done?

During the period of greatest transmission, the number of on-site medical visits should be minimized. It may be reasonable to postpone routine follow-up visits temporarily or even until after the epidemic ends or to make those appointments by phone or telematics whenever possible. Endoscopic or radiological tests for monitoring the cancer patient without active treatment may be delayed at this time.

If you need to contact the doctor in person for a specific problem or worsening of symptoms, you should try to make the appointment at an outpatient consultation to avoid going to the hospital.

In patients with preoperative obstruction, bleeding, perforation, or late staging, the endoscopic examination could be completed within 6 months after surgery, with subsequent follow-up once the pandemic has been controlled.

11.- What psychological support can we give to these patients?

Oncological pathology patients experience an uncertainty about the evolution of their disease and fear of getting infected with COVID-19 in this health emergency situation. Medical staff must acknowledge the psychological pressure of patients and their families and answer their questions with the best evidence available at all times. If necessary, specific psychological or psychiatric care will be recommended.

It should not be forgotten that healthcare professionals also experience symptoms of depression, insomnia, and anxiety in this situation, which must be properly addressed.

This document has been prepared with the bibliography cited below and the recommendations published by scientific societies (American College of Surgeons, American Society Clinical Oncology, Spanish Society of Medical Oncology, and Spanish Association of Coloproctology).

BIBLIOGRAPHY

1. Liang W, Guan W, Chen R, Wang W, Li J, Xu K, Li C, Ai Q, Lu W, Liang H, Li S, He J. Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China. Lancet Oncol. 2020;21:335-7.
2. Xia Y, Jin R, Zhao J, Li W, Shen H. Risk of COVID-19 for cancer patients. Lancet Oncol. 2020 Mar 3. pii: S1470-2045(20)30150-9.
3. Wang H, Zhang L. Risk of COVID-19 for patients with cancer. Lancet Oncol. 2020 Mar 3. pii: S1470-2045(20)30149-2.
4. https://www.cancerresearchuk.org/about-cancer/cancer-in-general/coronavirus-and-cancer
5. American College of Surgeons. COVID-19: Recommendations for Management of Elective Surgical Procedures 2020. https://www.facs.org/about-acs/covid-19/information-for-surgeons (accessed March 27, 2020).
6. https://www.ecco-org.eu/Global/News/Latest-News/2020/03/NEWS-Statement-on-COVID-19-from-the-European-Cancer-Organisation-Board-of-Directors
7. www.serau.org                  Indicaciones de pruebas de imagen urgentes en COVID-19
8. www.seram.es Guía básica de indicaciones de pruebas de imagen en la infección COVID-19 (V1. 21/3/2020)
9. https://doi.org/10.1016/S0140-6736(20)30753-4
10. https://aecp-es.org/index.php/recomendaciones
11. Ueda M, Martins R, Hendrie PC, McDonnell T, Crews JR, Wong TL, McCreery B, Jagels B, Crane A, Byrd DR, Pergam SA, Davidson NE, Liu C, Stewart FM. Managing Cancer Care During the COVID-19 Pandemic: Agility and Collaboration Toward a Common Goal. J Natl Compr Canc Netw. 2020 Mar 20:1-4. doi: 10.6004/jnccn.2020.7560
12. Matthew T. Seymour, Dion Morton, and on behalf of the International FOxTROT Trial Investigators. FOxTROT: an international randomised controlled trial in 1052 patients (pts) evaluating neoadjuvant chemotherapy (NAC) for colon cancer. Journal of Clinical Oncology 2019 37:15_suppl, 3504-3504
13. Marco MR, Zhou L, Patil S, Marcet JE, Varma MG, Oommen S, Cataldo PA, Hunt SR, Kumar A, Herzig DO, Fichera A, Polite BN, Hyman NH, Ternent CA, Stamos MJ, Pigazzi A, Dietz D, Yakunina Y, Pelossof R, Garcia-Aguilar J. Timing of Rectal Cancer Response to Chemoradiation Consortium.Consolidation mFOLFOX6 Chemotherapy After Chemoradiotherapy Improves Survival in Patients With Locally Advanced Rectal Cancer: Final Results of a Multicenter Phase II Trial.
14. Nasrolahi H, Mirzaei S, Mohammadianpanah M, Bananzadeh AM, Mokhtari M, Sasani MR, Mosalaei A, Omidvari S, Ansari M, Ahmadloo N, Hamedi SH, Khanjani N. Efficacy and Feasibility of Adding Induction Chemotherapy to Neoadjuvant Chemoradiation in Locally Advanced Rectal Cancer: A Phase II Clinical Trial. Ann Coloproctol. 2019 Oct;35(5):242-248. doi: 10.3393/ac.2018.09.06
15. Nilsson PJ, van Etten B, Hospers GA, Påhlman L, van de Velde CJ, Beets-Tan RG, Blomqvist L, Beukema JC, Kapiteijn E, Marijnen CA, Nagtegaal ID, Wiggers T, Glimelius B. Short-course radiotherapy followed by neo-adjuvant chemotherapy in locally advanced rectal cancer–the RAPIDO trial. BMC Cancer. 2013 Jun 7;13:279. doi: 10.1186/1471-2407-13-279
16. https://www.augis.org/wp-content/uploads/2020/03/Surgical-Priority-in-Oesophageal-and-Gastric-Cancer.pdf
17. https://seom.org/images/Recomendaciones_SEOM_COVID19_1903.pdf

Specific articles

• Lung Cancer Study Group, Chinese Thoracic Society, Chinese Medical Association; Chinese Respiratory Oncology Collaboration. [Expert recommendations on the management of patients with advanced non-small cell lung cancerduring epidemic of COVID-19 (Trial version)]. Zhonghua Jie He He Hu Xi Za Zhi. 2020 Mar 3;43(0):E031. Chinese.
• Zhao Z, Bai H, Duan JC, Wang J. [Individualized treatment recommendations for lung cancerpatients at different stages of treatment during the outbreak of 2019 novel coronavirus disease epidemic]. Zhonghua Zhong Liu Za Zhi. 2020 Mar 3;42(0):E007. Chinese.
• Yang L, Xu HY, Wang Y. [Diagnostic and therapeutic strategies of lung cancerpatients during the outbreak of 2019 novel coronavirus disease (COVID-19)]. Zhonghua Zhong Liu Za Zhi. 2020 Mar 2;42(0):E006. Chinese.
• Xu Y, Liu H, Hu K, Wang M. [Clinical Management of Lung CancerPatients during the Outbreak of 2019 Novel Coronavirus Disease (COVID-19)]. Zhongguo Fei Ai Za Zhi. 2020 Feb 20;23. Chinese.
• Li X, Liu M, Zhao Q, Liu R, Zhang H, Dong M, Xu S, Zhao H, Wei S, Song Z, Chen G, Chen J. [Preliminary Recommendations for Lung Surgery during 2019 Novel Coronavirus Disease (COVID-19) Epidemic Period]. Zhongguo Fei Ai Za Zhi. 2020 Feb 20;23. Chinese.
• Zhang Y, Xu JM. [Medical diagnosis and treatment strategies for malignant tumors of the digestive system during the outbreak of novel coronavirus pneumonia]. Zhonghua Zhong Liu Za Zhi. 2020 Feb 29;42(0):E005. Chinese.
• Wu F, Song Y, Zeng HY, Ye F, Rong WQ, Wang LM, Wu JX. [Discussion on diagnosis and treatment of hepatobiliary malignancies during the outbreak of novel coronavirus pneumonia]. Zhonghua Zhong Liu Za Zhi. 2020 Feb 28;42(0):E004. Chinese.
• Li Y, Qin JJ, Wang Z, Yu Y, Wen YY, Chen XK, Liu WX, Li Y. [Surgical treatment for esophageal cancerduring the outbreak of COVID-19]. Zhonghua Zhong Liu Za Zhi. 2020 Feb 27;42(0):E003. Chinese.
• Liu BL, Ma F, Wang JN, Fan Y, Mo HN, Xu BH. [Health management of breast cancerpatients outside the hospital during the outbreak of 2019 novel coronavirus disease]. Zhonghua Zhong Liu Za Zhi. 2020 Feb 26;42(0):E002. Chinese.
• Yu GY, Lou Z, Zhang W. [Several suggestion of operation for colorectal cancerunder the outbreak of Corona Virus Disease 19 in China]. Zhonghua Wei Chang Wai Ke Za Zhi. 2020 Feb 19;23(3):9-11. Chinese.
• Luo Y, Zhong M. Standardized diagnosis and treatment of colorectal cancer during the outbreak of corona virus disease 2019 in Renji hospital]. Zhonghua Wei Chang Wai Ke Za Zhi. 2020 Mar 25;23(3):211-216. doi: 10.3760/cma.j.cn.441530-20200217-00057.
• Hu XH, Niu WB, Zhang JF, Li BK, Yu B, Zhang ZY, Zhou CX, Zhang XN, Gao Y, Wang GY. [Treatment strategies for colorectal cancer patients in tumor hospitals under the background of corona virus disease 2019]. Zhonghua Wei Chang Wai Ke Za Zhi. 2020 Mar 25;23(3):201-208. doi: 10.3760/cma.j.cn.441530-20200217-00058. Chinese.