Management of colorectal cancer during the COVID19 pandemic: Recommendations from a statewide multidisciplinary cancer collaborative

COVID-19 has resulted in significant disruptions in cancer care. The Illinois Cancer Collaborative (ILCC), a statewide multidisciplinary cancer collaborative, has developed expert recommendations for triage and management of colorectal cancer when disruptions occur in usual care. Such recommendations would be applicable to future outbreaks of COVID-19 or other large-scale disruptions in cancer care.
of Surgeons and is led by experts representing the breadth of disciplines involved in comprehensive cancer care.
One of the ILCC's first actions was to create recommendations for cancer care during the COVID-19 pandemic. To accomplish this, diseasespecific workgroups were created, consisting of medical, surgical, and radiation oncology experts. After evidence review, guidelines were produced based on expert consensus and disseminated to participating sites.
We present here the ILCC multidisciplinary evidence-based consensus recommendations. These recommendations address colorectal cancer care during the COVID-19 pandemic and are applicable to other largescale care disruptions. pandemic cannot be based entirely on evidence. The recommendations provided here are a reasonable approach to these situations but do not replace clinical decision-making. To the extent possible, oncologic outcomes should not be compromised because of COVID-19.
In addition, when possible, treatments that patients would not normally receive should be avoided.

## | summary of evidence

## | delayed surgical treatment of colon cancer
- Up to a 120-day period from diagnosis to surgical treatment of colorectal cancer was not associated with worse survival. [bib_ref] Do moderate surgical treatment delays influence survival in colon cancer?, Wanis [/bib_ref] - A systematic review of five studies with diagnosis-to-surgery intervals up to 56 days concluded that there was no association between surgical delay and survival in colon cancer. [bib_ref] The effect of time from diagnosis to surgery on oncological outcomes in..., Hansen [/bib_ref] - Patients with stage I-III colon cancer who had primary elective surgery >40 days after diagnosis experienced reduced survival. Each 14-day increase in the interval from diagnosis to surgery was associated with a 6% increase in the hazard of death. [bib_ref] Impact of delay to surgery on survival in stage I-III colon cancer, Grass [/bib_ref] 

## | delayed surgical treatment of rectal cancer
- A delay of >60 days from symptom onset to radiation or surgical treatment was associated with lower survival. [bib_ref] Therapeutic delay reduces survival of rectal cancer but not of colonic cancer, Iversen [/bib_ref] - A review found no association between treatment delay and survival among patients with rectal cancer. [bib_ref] Relationship of diagnostic and therapeutic delay with survival in colorectal cancer: a..., Ramos [/bib_ref] - An interval of >6-8 weeks from completion of neoadjuvant therapy to surgery was associated with improved rates of complete pathologic response but not overall survival. [bib_ref] Increasing the interval between neoadjuvant chemoradiotherapy and surgery in rectal cancer: a..., Petrelli [/bib_ref] - A watch-and-wait approach for patients with rectal cancer who had a complete clinical response to neoadjuvant therapy was shown to result in worse survival than total mesorectal excision but can be considered in selected patients. [bib_ref] Assessment of a watch-andwait strategy for rectal cancer in patients with a..., Smith [/bib_ref] 

## | neoadjuvant therapy
- The feasibility phase of the FOxTROT trial suggested that neoadjuvant chemotherapy is safe for locally advanced, operable (T3-T4a, N0-2) colon cancer. [bib_ref] Feasibility of preoperative chemotherapy for locally advanced, operable colon cancer: the pilot..., Foxtrot Collaborative Group [/bib_ref] The preliminary results of the multicenter trial showed that neoadjuvant therapy reduced surgical complications but did not affect survival at 2 years. [bib_ref] FOxTROT: an international randomised controlled trial in 1052 patients (pts) evaluating neoadjuvant..., Seymour [/bib_ref] - Neoadjuvant chemoradiation is the standard of care for high-risk clinical stage II-III rectal cancer. 14 - In select cases, particularly T3-T4a disease, neoadjuvant chemotherapy may be considered. Therapy duration should be tailored to the clinical stage and anticipated ability to offer surgical resection.
The total length of therapy can be modified based on the pathologic stage. A capecitabine/oxaliplatin (CAPOX) regimen is preferable to 5-fluorouracil/leucovorin/oxaliplatin (FOLFOX) due to shorter duration, fewer clinical encounters, and improved outcomes. [bib_ref] Duration of adjuvant chemotherapy for stage III colon cancer, Grothey [/bib_ref] [bib_ref] FOLFOX or CAPOX in stage II to III colon cancer: efficacy results..., Sobrero [/bib_ref] Clinical stage III - Consider transanal excision for amenable T1 tumors.
- In select cases, consider neoadjuvant chemoradiation.
- Chemotherapy duration should be tailored to the clinical stage and anticipated ability to offer surgical resection. Total therapy duration can be modified based on the pathologic stage, and CAPOX is preferable to FOLFOX.
- Consider short course radiation (five doses of 5 Gy) to minimize hospital exposure.
- At experienced centers, consider a watch-and-wait approach for select patients with complete clinical response to neoadjuvant chemoradiation.

## Clinical stage ii-iii
- Neoadjuvant chemoradiation should be administered before surgical resection for stage II-III rectal cancers.
- Therapy duration should be tailored to the clinical stage and anticipated ability to offer surgical resection. Total therapy duration can be modified based on the pathologic stage.
- CAPOX is preferable to FOLFOX and should be administered before radiation.
- Consider short course radiation (five doses of 5 Gy) to minimize hospital exposure.
- At experienced centers, consider a watch-and-wait approach for select patients with complete clinical response to neoadjuvant chemoradiation.

## | symptomatic primary
- If hospital resources are severely limited, consider alternatives to definitive resection in patients at high risk of complications, need for intensive care, or prolonged hospitalization. Alternatives should be determined on a case-by-case basis but may include fecal diversion or resection without immediate anastomosis.
- If symptoms are not amenable to a temporizing intervention, then definitive surgery and/or radiation should be offered.
- Stenting is not recommended as a temporizing measure for rectal cancers.

## | management of metastatic colorectal cancer if surgical resources are limited
- If curative intent surgery is possible (e.g., isolated metastatic liver and/or pulmonary disease, peritoneal disease), decisions about treatment should incorporate the extent of disease, expected surgical morbidity, risk of disease progression without intervention, and availability of inpatient resources.
- If surgery is not indicated, less invasive alternative therapies including Y-90 radioembolization or stereotactic body radiation therapy should be considered.

## | patient care coordination
- Patients with colorectal cancer should have initial telehealth appointments with the following providers (if applicable) to ensure that (1) treatment can proceed quickly aftercare is resumed, and (2) patients will be known to their providers if emergent intervention is needed:
- Primary care practitioner.
- General surgeon, colorectal surgeon, or surgical oncologist
[formula] - Gastroenterologist - Medical oncologist - Radiation oncologist - Medical geneticist [/formula]
- A protocol should be developed to ensure that patients with newly diagnosed colorectal cancer are scheduled for initial appointments with these providers.
- If no immediate treatment is planned, a process should be developed to maintain contact with each patient to ensure that they are not lost to follow-up and can resume treatment when able.
- Patients should be instructed how to perform simple tasks, such as disconnecting their chemotherapy pump at home, to minimize healthcare encounters that risk exposure.

# | discussion
The need for cancer treatment guidance during the COVID-19 pandemic is imperative. The above recommendations were developed by a statewide multidisciplinary cancer collaborative consisting of a diverse group of hospitals and reflect scenarios that may be en-
[fig] |: The ILCC recommendations for the management of colon and rectal cancer during the COVID-19 pandemic Many clinical decisions regarding cancer care during the COVID-19 [/fig]
[fig] : Consider delaying therapy if inpatient resources are expected to become available within 4 weeks. [/fig]