Key messages
We are uncertain if local excision (LE) (removal through the anus of an early rectal cancer that has not grown beyond the muscle layer of the rectum, or stage I) may shorten the period of being cancer-free after surgery compared to radical resection (RR) (removing the entire rectum and its surrounding tissues through a major surgery). It is also unclear if LE affects cancer-related survival related compared with RR.
There is probably a large reduction in minor complications after surgery (only necessitating medications or supportive measures) with LE compared with RR for the treatment of early rectal cancer. It is unclear if LE lowers the rate of major complications.
Based on only one study, LE results in better quality of life and anal sphincter function.
What is early rectal cancer?
Rectal cancer presents at an early stage in one-third of patients and does not invade beyond the muscle layer of bowel wall; this is classified as stage I, or early rectal cancer. People with early rectal cancer may experience bleeding or pain, or only get diagnosed on screening colonoscopy. We undertook this review to compare standard surgery for rectal cancer to a new, smaller surgery that has been increasingly adopted in recent decades.
How is early rectal cancer treated?
The currently recommended treatment for stage I rectal cancer is a major surgery for removal of the rectum with all its surrounding supporting tissues, known as radical resection (RR). This extensive surgery carries significant risks of surgical and functional complications. Recently, an alternative treatment using advanced instruments through the anus has been popularized. This has enabled precise removal, or local excision (LE), of only the tumor safely through the anus with fewer complications and faster recovery. Sometimes additional therapies such as chemotherapy or radiotherapy may be used in conjunction before or after the surgery.
What did we want to find out?
We compared RR to LE to find out whether LE is as effective as or better than RR with regard to:
1. disease recurrence and survival;
2. functional and quality of life outcomes;
3. side effects and complications after undergoing surgery.
What did we do?
We looked for studies that compared RR with LE in people with early rectal cancer with or without the use of any additional treatments. We compared, summarized, and combined the results across studies and rated our confidence in the evidence.
What did we find?
We found four studies that involved 266 participants with early rectal cancer with a median age of 60 years undergoing RR or LE. Participants were studied from 17.5 months in the shortest study to up to 9.6 years in the longest study. Three studies were carried out in European countries and one in China. One study did not use any additional therapy; two studies used chemotherapy or radiotherapy before the surgery; and one study used chemotherapy after the surgery for select patients. Three of the four studies were funded by government agencies.
Main results
Results suggest that RR may decrease the chance of disease coming back locally or in other organs of the body. This means for every 100 patients undergoing LE, up to 27 may develop recurrence at 3 years compared with 15 patients per 100 after RR.
Only one study looked at anal sphincter function, including the ability to control stool or flatulence, number of leakage episodes, and the need to use diapers. RR was associated with short-term deterioration in stool frequency, flatulence, incontinence, abdominal pain, and embarrassment about bowel leakage. At 36 months after surgery, participants in the LE group had better overall stool frequency, stool frequency at night, and less embarrassment about leakage and diarrhea.
It is unclear if LE affects cancer-related survival. Additionally, studies did not present the results in a way that could help us answer if LE affects the chance of disease coming back in the pelvis.
We are uncertain if LE results in a lower rate of major complications after surgery, but we found that LE probably causes a large reduction in minor complications.
The only study that evaluated quality of life or urinary and sexual function after surgery reported a 90% or greater probability that LE results in a better overall quality of life, various role/social/emotional functions, body image, health anxiety, and urinary incontinence. The same study reported similar sexual function after both surgeries.
What are the limitations of the evidence?
We have low confidence in the evidence mainly because it was based only on a few studies, and due to the way the studies were conducted. In addition, it is possible that the results of the studies could have been affected by the fact that participants and investigators were aware of which treatment participants had received.
How up-to-date is this evidence?
This review is current to February 2022.
Based on low-certainty evidence, LE may decrease disease-free survival in early rectal cancer. Very low-certainty evidence suggests that LE may have little to no effect on cancer-related survival compared to RR for the treatment of stage I rectal cancer. Based on low-certainty evidence, it is unclear if LE may have a lower major complication rate, but probably causes a large reduction in minor complication rate. Limited data based on one study suggest better sphincter function, quality of life, or genitourinary function after LE. Limitations exist with respect to the applicability of these findings. We identified only four eligible studies with a low number of total participants, subjecting the results to imprecision. Risk of bias had a serious impact on the quality of evidence. More RCTs are needed to answer our review question with greater certainty and to compare local and distant metastasis rates. Data on important patient outcomes such as sphincter function and quality of life are very limited. Results of currently ongoing trials will likely impact the results of this review. Future trials should accurately report and compare outcomes according to the stage and high-risk features of rectal tumors, and evaluate quality of life, sphincter, and genitourinary outcomes. The role of neoadjuvant or adjuvant therapy as an emerging co-intervention for improving oncologic outcomes after LE needs to be further defined.
Total mesorectal excision is the standard of care for stage I rectal cancer. Despite major advances and increasing enthusiasm for modern endoscopic local excision (LE), uncertainty remains regarding its oncologic equivalence and safety relative to radical resection (RR).
To assess the oncologic, operative, and functional outcomes of modern endoscopic LE compared to RR surgery in adults with stage I rectal cancer.
We searched CENTRAL, Ovid MEDLINE, Ovid Embase, Web of Science - Science Citation Index Expanded (1900 to present), four trial registers (ClinicalTrials.gov, ISRCTN registry, the WHO International Clinical Trials Registry Platform, and the National Cancer Institute Clinical Trials database), two thesis and proceedings databases, and relevant scientific societies' publications in February 2022. We performed handsearching and reference checking and contacted study authors of ongoing trials to identify additional studies.
We searched for randomized controlled trials (RCTs) in people with stage I rectal cancer comparing any modern LE techniques to any RR techniques with or without the use of neo/adjuvant chemoradiotherapy (CRT).
We used standard Cochrane methodological procedures. We calculated hazard ratios (HR) and standard errors for time-to-event data and risk ratios for dichotomous outcomes, using generic inverse variance and random-effects methods. We regrouped surgical complications from the included studies into major and minor according to the standard Clavien-Dindo classification. We assessed the certainty of evidence using the GRADE framework.
Four RCTs were included in data synthesis with a combined total of 266 participants with stage I rectal cancer (T1-2N0M0), if not stated otherwise. Surgery was performed in university hospital settings. The mean age of participants was above 60, and median follow-up ranged from 17.5 months to 9.6 years. Regarding the use of co-interventions, one study used neoadjuvant CRT in all participants (T2 cancers); one study used short-course radiotherapy in the LE group (T1-T2 cancers); one study used adjuvant CRT selectively in high-risk patients undergoing RR (T1-T2 cancers); and the fourth study did not use any CRT (T1 cancers).
We assessed the overall risk of bias as high for oncologic and morbidity outcomes across studies. All studies had at least one key domain with a high risk of bias. None of the studies reported separate outcomes for T1 versus T2 or for high-risk features.
Low-certainty evidence suggests that RR may result in an improvement in disease-free survival compared to LE (3 trials, 212 participants; HR 1.96, 95% confidence interval (CI) 0.91 to 4.24). This would translate into a three-year disease-recurrence risk of 27% (95% CI 14 to 50%) versus 15% after LE and RR, respectively.
Regarding sphincter function, only one study provided objective results and reported short-term deterioration in stool frequency, flatulence, incontinence, abdominal pain, and embarrassment about bowel function in the RR group. At three years, the LE group had superiority in overall stool frequency, embarrassment about bowel function, and diarrhea.
Local excision may have little to no effect on cancer-related survival compared to RR (3 trials, 207 participants; HR 1.42, 95% CI 0.60 to 3.33; very low-certainty evidence). We did not pool studies for local recurrence, but the included studies individually reported comparable local recurrence rates for LE and RR (low-certainty evidence).
It is unclear if the risk of major postoperative complications may be lower with LE compared with RR (risk ratio 0.53, 95% CI 0.22 to 1.28; low-certainty evidence; corresponding to 5.8% (95% CI 2.4% to 14.1%) risk for LE versus 11% for RR). Moderate-certainty evidence shows that the risk of minor postoperative complications is probably lower after LE (risk ratio 0.48, 95% CI 0.27 to 0.85); corresponding to an absolute risk of 14% (95% CI 8% to 26%) for LE compared to 30.1% for RR. One study reported an 11% rate of temporary stoma after LE versus 82% in the RR group. Another study reported a 46% rate of temporary or permanent stomas after RR and none after LE.
The evidence is uncertain about the effect of LE compared with RR on quality of life. Only one study reported standard quality of life function, in favor of LE, with a 90% or greater probability of superiority in overall quality of life, role, social, and emotional functions, body image, and health anxiety. Other studies reported a significantly shorter postoperative period to oral intake, bowel movement, and off-bed activities in the LE group.