In March 2020, the World Health Organization declared the novel COVID-19 outbreak a global pandemic [1].
In an attempt to contain the spread of the virus and preserve medical resources, including mechanical ventilators, intensive care unit beds, and health personnel, many surgical societies, institutions, and government officials recommended postponing operations that were not emergency [2-4].
Consequently, surgical care in the US was limited to urgent and emergent oncologic cases. Additionally, social distancing and other restrictions have contributed to a significant decrease in colorectal operations and screening colonoscopies around the world [5-7].
The treatment of rectal cancer has evolved significantly in recent decades with the introduction of preoperative neoadjuvant treatment, and surgical techniques designed to allow preservation of the anal sphincter, and local resection (rectal preservation surgery) for low rectal tumors.
The current paradigm of rectal cancer treatment takes into consideration not only optimal cure rates, but also functional outcomes, in addition to morbidity and mortality considerations.
Widespread implementation of neoadjuvant chemoradiotherapy (CRT) has led to tumor shrinkage, allowing a higher rate of sphincter-sparing operations, with higher rates of negative margins, and reduced lymphovascular invasion, as seen in surgical specimens [8-11].
Total neoadjuvant therapy (TNT), a promising treatment strategy that incorporates chemotherapy with CRT before surgery, was originally described for poor-risk rectal cancers [12].
It has recently been added to the National Comprehensive Cancer Network (NCCN) guidelines as an alternative treatment strategy for locally advanced rectal cancer [13].
Theoretically it offers several surgical advantages, such as increasing the possibility of performing sphincter-preserving operations and potentially decreasing the probability of requiring an ileostomy. However, none of these theoretical advantages were confirmed in a recent meta-analysis, suggesting that the benefit remains primarily in disease control, and in decreasing recurrence rates [14].
However, adequately treated rectal cancer requires extensive preoperative planning, multidisciplinary team meetings (MTE), administration of preoperative treatments, and considerable operating room and staff resources. Such evidence-based practice measures are well described in the Commission on Cancer National Accredited Program for Rectal Cancer (NAPRC) standards [15].
Since the pandemic was declared in March 2020, all those crucial resources have been limited. A major global healthcare concern was the indirect effects of changes in healthcare and social distancing caused by the pandemic, causing patients to present with advanced malignancies due to lack of adequate screening. , and access to medical services [16,17].
In patients diagnosed with rectal cancer, this could potentially manifest as a decline in the rate of sphincter-sparing operations, and a proportional increase in the prevalence of abdominoperineal resections.
The authors hypothesized that rectal cancer treatment was significantly impacted by the Covid-19 pandemic. To evaluate this impact, they retrospectively reviewed the trend in oncological operations in newly diagnosed rectal cancer patients, at the institution where they work, during the first year of the Covid-19 pandemic.
| Methods |
A retrospective review of a NAPRC-accredited, prospectively maintained, institutional review board-approved database of a referral center was performed after institutional review board approval was obtained (FLA-20-048).
Patients undergoing surgery for rectal cancer diagnosed during the period between 2016 and 2021 were included and divided into 2 groups. Patients operated on during the first year of the Covid-19 pandemic (March 2020 – February 2021) comprised the Covid-19 era study group, while patients operated on previously (March 2016 – February 2020) were placed in the pre-Covid-19 control group.
Clinical staging was determined by magnetic resonance imaging (MRI) of the pelvis, using a scanning protocol for rectal cancer. Patients with clinical stage T3 and T4, defined by MRI, were considered to have locally advanced disease. All patients were discussed at a NAPRC-accredited institutional weekly rectal cancer EMR, and all decisions were made in adherence to current NCCN clinical practice guidelines [13].
No patients were referred for longer treatment protocols, such as TNT, due to limitations or restrictions caused by the pandemic, as all decisions were based solely on oncological considerations.
Patients who presented with liver or lung metastases before surgery (synchronous presentation), detected with routine computed tomography (CT) of the chest, abdomen, and pelvis, or by positron emission tomography/CT, who were undergoing surgery for rectal cancer following a consensus decision by the REM, were also included in the study.
The time of diagnosis was defined as the date of the endoscopic procedure on which the biopsy was obtained showing histopathological evidence of rectal cancer. The primary outcome measure was the rate of sphincter-sparing operations, compared with abdominoperineal resection (APR), for rectal cancer.
Sphincter-sparing operations included transanal local resection, and low anterior resection (LAR) with restorative protectomy or coloanal anastomosis. Non-conserving sphincter surgery involved RAP with permanent colostomy. This study did not include patients with active Covid-19 infection.
> Statistical analysis
Univariate analysis was used to compare patient characteristics between the control and study groups, using c2 analysis or Fisher’s exact test, as appropriate, for categorical variables, while the t test was used . two samples for continuous variables.
To compare the results between the control and study groups, a Poisson model was performed to evaluate differences in rates, and the Wilcoxon rank sum test was performed to test the difference in time to surgery or treatment. . All data analyzes were performed using SPSS software, version 20.0 (IBM Corp, New York, NY).
| Results |
Two hundred thirty-four patients with rectal cancer were included in the study. The pre-Covid-19 control group included 180 patients (77%), and the Covid-19 era study group comprised 54 patients (23%).
The clinical and demographic data of the patients showed no significant differences between the 2 groups, in terms of mean age (60.0 ± 12.7 vs 60.6 ± 12.7; P = 0.7648), sex ( P = 0.3170), or body mass index (26.6 ± 4.8 vs 27.4 ± 4.6 kg/m2; P = 0.2580).
Furthermore, the ASA ( American Society of Anesthesiologists ) grade was compatible between the 2 groups. However, a significant difference ( P = 0.02) was observed in T stage at presentation: patients in the Covid-19 era group presented at a significantly higher rate of 79% (41 patients ), for stages T3/T4, compared to the pre-Covid-19 group, which occurred with a rate of 58% (103 patients).
Likewise, more patients in the Covid-19 era group presented with metastatic disease (9% vs 3%; P = 0.05).
These findings also carried over to a higher percentage of patients who presented with more advanced tumor findings on MRI, including sphincter involvement (25% vs 13%; P = 0.04) and positive circumferential resection margins. although this last difference did not reach statistical significance. In the pre-Covid-19 group, 35% of patients underwent surgery without receiving any neoadjuvant therapy, compared to only 24% in the Covid-19 era study group (35% vs 24%; P = 0.14).
Significant differences were found in relation to the type of neoadjuvant therapy, with 50% of patients in the pre-Covid-19 group receiving CRT only, and only 15% treated with TNT. That was compared to the Coviud-19 era study group, where only 24% of patients underwent conventional neoadjuvant CRT, with 52% of patients receiving TNT ( P = 0.0001).
In the pre-Covid-19 group, 155 patients underwent sphincter-sparing operations (including 141 RAB, and 14 transanal local resections), and 25 patients underwent APR. In the Covid-19 era group, 38 patients underwent sphincter-sparing operations (36 RAB, and 2 transanal local resections), and 14 patients underwent APR. When comparing results between the 2 groups, patients in the Covid-19 era group had a significantly lower rate of sphincter-sparing surgery (73% vs 86%; P = 0.028).
Time to treatment (from diagnosis to initiation of any therapeutic modality) was significantly prolonged in the Covid-19 era group (11.1 vs 8.7 weeks; P = 0.006). Furthermore, the median time from diagnosis to surgery in the Covid-19 era group was significantly longer, compared to the pre-Covid-19 group (9.5 vs 4 months; P < 0.0001).
After stratifying patients who underwent a TNT treatment protocol, the median time from diagnosis to surgery for patients treated with TNT in the Covid-19 era group was also significantly longer compared to patients in the pre-Covid-19 group (10.5 vs 9 months; P = 0.0118), while the time from diagnosis to surgery for patients without TNT, in the Covid-19 era group, It was also longer, but not statistically significant (median months: 5.5 vs 4.5; P = 0.3614).
Surprisingly, no significant differences were seen in the abdominal surgical approach techniques used between the 2 groups, or in the rate of patients who underwent transanal total mesorectal resection surgery. Pathologic review of the specimens demonstrated no significant differences in pathologic TNM staging, in the number of lymph nodes harvested, or in the quality of mesorectal resection.
| Discussion |
Colorectal cancer is the second leading cause of cancer death in the US. In 2021, it was estimated that there would be 149,500 new cases of colorectal cancer, with more than 50,000 related deaths [18].
The current treatment of colorectal cancer is characterized by a multidisciplinary approach; The successful management of this malignant disease depends greatly on early detection and diagnosis, because this directly affects the prognosis. These unprecedented times, brought on by the COVID-19 pandemic, have had a dramatic effect on healthcare.
Resources have been reduced, and social distancing has been widely implemented to try to minimize exposure to both patients and surgeons, resulting in a delay in surgery, and a massive decrease in case volume [19, twenty].
It appears that the comprehensive multidisciplinary care network for rectal cancer has been substantially negatively affected by the COVID-19 pandemic, as evidenced by the statistically significant decrease in sphincter-sparing operations during the first year of the pandemic.
The authors of this work believe that this is a sensitive parameter of the delay in diagnosis and treatment. These findings are further supported by the fact that patients operated on during the pandemic had more advanced disease, and worse findings on their initial imaging evaluation.
This can be attributed to the failure to perform timely screening colonoscopies during the pandemic.
On the other hand, these findings cannot be explained solely by delayed diagnosis, given that patients operated on during the year of the pandemic had a significantly longer duration of time from diagnosis to treatment, compared to those in the pre-Covid-19 group. .
Although this fact can possibly be attributed to the prolonged time to initiation of any form of treatment seen in the Covid-19 group (11.1 vs 8.7 weeks; P = 0.006), and although this 2-week difference represents a True delay in starting treatment is unlikely to fully explain the significant difference observed in sphincter-sparing operations between the 2 groups.
Likewise, a recently published multicenter study reviewing more than 1000 patients with rectal cancer has shown that delaying the initiation of treatment beyond 60 days from diagnosis, recommended by the NAPRC, does not significantly affect oncological outcomes [15, 22].
The proportion of patients receiving TNT in the Covid-19 era group was significantly higher than that in the control group. That finding may not be surprising, given the fact that these patients had a higher rate of locally advanced cancer at a time when surgical treatment was unavailable or delayed. These results are also consistent with the recent categorization of TNT as a viable treatment strategy for locally advanced rectal cancer by the NCCN [13,23].
Consequently, this practice has been adopted and increasingly employed at the authors’ institution in recent years, evidently surpassing the traditional approach of preoperative CRT, followed by preoperative adjuvant chemotherapy, in the first year of the pandemic.
Unfortunately, the much higher rate of patients undergoing TNT did not translate into a reduction in sphincter-sparing surgery. That result corresponds with the findings of a recent meta-analysis, which failed to observe an increase in sphincter-sparing surgery in patients undergoing TNT [14].
The higher proportion of patients undergoing TNT in the Covd-19 era group may be responsible – at least in part – for the longer duration of time from diagnosis to surgery in that group. However, after stratifying by TNT, the time from diagnosis to treatment in the Covid-19 era group remained significantly longer compared to TNT patients in the pre-Covid-19 group. This indicates that the time from diagnosis to surgery has become longer during the pandemic, regardless of the therapeutic strategy.
Keeping in mind that during the first year of the pandemic, at least at the authors’ institution, oncology outpatient practice remained open, and neoadjuvant treatments remained readily available, even at times when surgical management was delayed Definitely, other factors could have potentially contributed to that delay.
It remains to be determined whether surgeons’ fear of poor outcomes, complications, and anastomotic leaks has also played a role in delaying surgery [24]. However, the authors wish to emphasize, in this regard, that the decision on the appropriate oncological operation, including whether to perform a sphincter-sparing operation, or a RAP, was based solely on oncological considerations, as discussed during the presentation of each patient. with rectal cancer during institutional weekly EMR.
In any case, a longer diagnosis and treatment process is associated with a significant increase in costs and healthcare utilization [25]. Further studies are needed to determine to what extent, if any, this delay may affect oncologic outcomes.
During the pandemic outbreak, there was concern about the transmission of Covid-19 during laparoscopic surgery [26,27]. A recent study from China noted that the rate of laparoscopic surgery fell by approximately 20% in patients operated during the Covd-19 era [28]. However, the authors of the present work did not observe significant differences between the rates of minimally invasive and open surgery in their study.
It appears that initial concern about Covid-19 transmission did not translate into an increase in open surgery cases at the authors’ institution, where adherence to American College of Surgeons guidelines on restarting surgical care elective surgery, was routinely performed [29] when elective surgical activity was resumed.
Patients were routinely screened before surgery for the existence of respiratory symptoms, along with evaluation for fever, travel, occupation, and contact with individuals with suspected or present Covid-19. Additionally, all surgical patients were tested for Covid-19 before surgery, to further minimize the risk of exposure to the surgical team.
An operating room was reserved for patients with a diagnosis of active Covid-19 and, if clinically appropriate, those patients were operated on at the last minute, once the surgeries were completed in the Covid-19-free patients. However, this scenario was not a risk factor in this study.
This study has several limitations, mainly due to its non-randomized, retrospective, single-center nature, and the lack of long-term oncological follow-up. Although the cohort is relatively small, that was mainly due to the dramatic decline in case volume during the Covid-19 pandemic.
Despite those limitations, the authors believe their findings indicate a worrying trend, which should be considered when mobilizing health care resources in the future.
In conclusion, it appears that the diversion of resources towards the control of the Covid-19 pandemic was not carried out without causing other significant adverse costs. Patients with rectal cancer presented at a later and more advanced stage and paid the price with a higher rate of non-sphincter-sparing operations. This knowledge requires being more diligent in screening, and working harder to adequately reduce the time between diagnosis and surgery.
This study highlights an important lesson about continuity of care in times of uncertainty. Although future pandemics could present differently than Covid-19, it should not be forgotten that significant delays in the detection and diagnosis of malignant diseases can have a significant impact on the quality of life and survival of patients.
In future airborne pandemics, it should be remembered that continued care and patient peace of mind are feasible when appropriate safety measures are used, including personal protective equipment, pre-procedure testing, and broad promotion of vaccination, if available. [5]. Furthermore, in high-risk subgroups, the yield of a positive colonoscopy diagnosis should be doubled [30].
In relation to delaying treatment, the availability of beds and equipment should be maintained as much as possible, through the implementation of programs and the use of models to predict hospital admissions and bed occupancy, during the next waves of this or any future pandemic [31]. Furthermore, prioritizing oncological procedures and treatments over procedures performed for non-malignant indications should allow for rapid and timely surgical intervention.
Successfully accomplishing that task will become more challenging as there is a backlog of rectal cancer patients whose care will place further strain on an already overburdened healthcare system still grappling with the pandemic [32]. Long-term oncological outcomes will need to be reviewed in the future to better elucidate the impact of the Codid-19 pandemic on rectal cancer treatment.
