Surgical Delays Linked With Higher Risk in Some Gastrointestinal Cancers

Scott C. Fligor, MD

In light of the COVID-19 pandemic, many elective surgical procedures had been cancelled or rescheduled to maximize hospital capacity and prevent unnecessary exposure for patients, but surgical delays might lead to worse outcomes for certain patients with gastrointestinal cancers, according to results from a study conducted by investigators from Beth Israel Deaconess Medical Center (BIDMC) and published in the Journal of Gastrointestinal Surgery.¹

Results showed that the delayed resection of colorectal cancer (CRC) could result in poorer survival outcomes; the consequences of delaying surgical procedures in pancreatic and gastric cancers are more uncertain.

For colorectal cancer (CRC), investigators identified a total of 1066 abstracts. After undergoing additional screening, 62 full papers were reviewed, and 43 studies were included in the analysis. Several large studies from the National Cancer Database and the Surveillance, Epidemiology, and End Results–Medicare database showed that delaying surgery by 30 to 40 days in patients with CRC was linked with lower survival. Thus, the data support rapid resection of this disease when possible in accordance with available resources.

A total of 394 abstracts were identified with regard to pancreatic cancer; after analyzing 21 full papers, 9 were included in the study. Results from 2 of these studies showed that patients who had surgical delays of more than 30 days had increased disease progression. Notably, 1 study demonstrated that patients with resectable pancreatic ductal adenocarcinoma who were operated on within 32 days of imaging experienced a 50% reduction in the risk of tumor progression to unresectable disease.

Of the 633 abstracts screened for gastric cancer, 6 full papers were included in the study. Investigators found that time to surgery was not an independent prognosis factor in this tumor type; none of the studies examined indicated worse survival with prolonged time to surgery.

“When we started this research, little knowledge existed about how long we could safely delay surgery for these cancers or how to prioritize which operations should occur first,” first author Scott C. Fligor, MD, a general surgery resident at Beth Israel Deaconess Medical Center, said in a recent press release.² “In the context of the coronavirus pandemic, we were concerned that both surgeons and patients were forced to make decisions without a clear understanding of the risks of surgical delay.”

In response to the pandemic, the healthcare community as a whole had to adapt treatment strategies and care plans. The Centers for Disease Control and Prevention recommended rescheduling elective surgeries,³ and the American College of Surgeons (ACS) and the Society of Surgical Oncology (SSO) issued guidance for triage of nonemergent surgical procedures.^4,5 Despite these guidelines, the impact of time to surgery for patients with cancer has not been well characterized and it is unclear just how long surgical cases can be delayed without impacting outcomes.

To this end, investigators conducted a systematic review identifying literature that was published from 2005 to 2020 that focused on the impact of time to surgery on outcomes in different gastrointestinal malignancies, including CRC, pancreatic cancer, and gastric cancer. Investigators also reviewed available guidance from ACS and SSO to identify an evidence-based approach to surgical prioritization during this time.

Colorectal Cancer

Among the studies that were analyzed, the majority focused on rectal cancer (n = 33), while 7 focused on colon cancer and 3 were on both colon and rectal cancer. “To our knowledge, there have been no consensus guidelines published on the timing of surgical resection in CRC,” the authors noted. They added that triage guidelines issued by ASC recommend resection as soon as feasible for primary resection of the disease. ASC also recommends to consider delaying resection of locally advanced resectable colon cancer by giving 2 to 3 months of neoadjuvant chemotherapy followed by surgery.

“Delayed resection of colon cancer leads to delayed staging, which in the setting of positive nodes would delay administration of chemotherapy,” the authors wrote. “If resection must be delayed, strong consideration should be given to administration of neoadjuvant chemotherapy to all colon cancers.”

For rectal cancer, ACS guidelines also call for resection as soon as feasible after neoadjuvant therapy, according to the authors. For rectal cancer cases that have clear and early evidence of downstaging from neoadjuvant chemoradiation, delay for resection should be considered. Delay could constitute additional wait time or more rounds of chemotherapy.

Pancreatic Cancer

In the pancreatic cancer setting, investigators felt that the data on time to surgery and survival outcomes were unclear. While some evidence suggests that resection within 30 days reduces unexpected progression and potentially improves survival for patients with pancreatic adenocarcinomas under 2 cm, other studies evaluated did not find an association between longer time to surgery and worse survival outcomes. In fact, many large, retrospective cohort studies showed better outcomes when surgery was delayed for at least 6 weeks, although there was a concern for selection bias in the patient population.

Guidelines issued from the National Comprehensive Cancer Network recommend that surgical procedures are done 4 to 8 weeks following neoadjuvant therapy. No guidelines are available on timing for patients undergoing primary surgery, according to the authors of the analysis. “Minimal evidence exists to provide a recommendation for acceptable delay in time to surgery in pancreatic cancer,” the authors noted.

The SSO’s COVID-19 guidance called for neoadjuvant therapy in all patients with resectable disease as a way to delay surgery in this population; this recommendation is supported by available data that have indicated no difference in mortality between those with resected stage I pancreatic adenocarcinoma who were given neoadjuvant treatment versus adjuvant therapy. “This suggests that this is an acceptable strategy to delay surgery,” the authors noted.

Gastric Cancer

Investigators did not find any studies that showed an association between delayed surgery and worse survival in patients with gastric cancer. Again, no guidelines are available for understanding the appropriate time to surgery in this patient population, according to the authors. The SSO COVID-19 guidelines call for endoscopic resection of amenable cT1a lesions, primary resection of cT1b lesions, as well as neoadjuvant treatment for cT2 or higher lesions. Additionally, for patients who are on neoadjuvant therapy and are responding to the treatment and tolerating it well, extended treatment should be considered.

For stage 1 disease, no evidence of worse survival was noted, even when time to surgical procedure was over 90 days. Given some available data, delaying surgery for up to 3 months compared with neoadjuvant therapy should be considered, when resources are constrained. For more advanced diseases, there is not enough evidence available to inform guidance on time to surgery after neoadjuvant therapy. However, 1 study that evaluated this further did not find that delaying surgery for over 6 weeks impacted survival in patients with advanced gastric cancers. As such, delaying surgery up to 6 weeks in the neoadjuvant setting despite if additional therapy can be given, might be a reasonable option, according to the authors.

“Providers should consider whether alternative therapies can help to minimize the risk of delay, such as extending a course of chemotherapy before surgery or initiating chemotherapy when surgery would normally occur first,” Fligor further explained in the press release. “It is critical for patients to work with their health care team to create a safe plan for treatment during the pandemic. The right decision for each patient depends on several factors, including the type of cancer, treatments available, and the local burden of COVID-19.”

References

1. Fligor SC, Wang S, Allar BG, et al. Gastrointestinal malignancies and the COVID-19 pandemic: Evidence-based triage to surgery [published online ahead of print June 22, 2020]. J Gastr Surg. doi:10.1007/s11605-020-04712-5
2. Study: surgical delay associated with increased risk in some gastrointestinal malignancies. News release. Beth Israel Lahey Health. July 7, 2020. Accessed July 13, 2020. https://bit.ly/2CyFh3h.
3. Healthcare facilities: managing operations during the COVID-19 pandemic. Centers for Disease Control and Prevention. Updated June 28, 2020. https://bit.ly/3fJ4OWp. Accessed July 13, 2020.
4. COVID-19: elective case triage guidelines for surgical care. American College of Surgeons. March 24, 2020. https://bit.ly/2Cd8nFD. Accessed July 13, 2020.
5. COVID-19 resources. Society of Surgical Oncology. Updated June 23, 2020. https://bit.ly/3j4JInh. Accessed June 28, 2020