Rectal cancer is one of the most common malignancies in clinic and associated with inferior oncological outcomes in terms of DFS and OS[7]. According to the authoritative guideline of colorectal cancer in China published in 2020, radical surgery is accepted as the standardized procedure for T2N0M0 rectal cancer. Low anterior resection (LAR) is recommended for high-mid rectal cancer, while abdominoperineal resection (APR) or anus-preserving curative surgery is recommended for low rectal cancer[8]. Based on the guidelines of the National Comprehensive Cancer Network (NCCN), transanal surgery is recommended for T1N0M0 tumors without myometrial invasion of rectum wall. However, with the evolving surgical techniques and organ-preserving demands, LE has been increasingly used in rectal cancer upstaged to T2. Anus-preserving surgery has been a research hotspot in the field of surgical treatment of rectal cancer in recent years. It is worth mentioning that thorough preoperative tests, precise clinical stages, exquisite surgical skills, and close follow-up are required for anus-preserving surgery[9].
Preoperative Evaluation
In the management of rectal cancer, clinical examinations have been proved to be good indicators in clinical staging, which plays significant roles in identifying the type of operation and avoiding improper treatment[10]. Although pelvic MRI has limitations in differentiating T1/T2 tumors, it exhibits high accuracy in preoperative assessment of T/N stage of rectal cancer[11-12]. Researchers illustrate the accuracy of MRI for T staging ranged from 67% to 83%[13],and for N staging about 56.8%[14]. EUS has advantages in identifying intratumoral vascularization, measuring tumor size, and finding tumor microvasculature[15-17]. In addition, the possible relationships of regional tumors and distant metastasis can be noted based on CT or PET-CT.
Therefore, the clinicians carefully refer to auxiliary tests of all patients before proceedings and determine the surgical methods in this research. Radical resection is usually recommended for high-risk patients with lymph node metastasis. LE along with adjuvant CRT (aCRT) is performed for these cases who cannot tolerate radical surgeries and have strong willingness to preserve the anal. This study attempts to confirm whether LE can yield better oncological outcomes and fewer complications in the treatment of T2N0M0 mid-low rectal cancer.
Surgical Method
Whether LE can achieve the radical cure and gain better clinical benefits or not are significant concerns for physicians and patients. Clinical findings show that operations for mid-low rectal cancer are performed in relatively narrow spaces of pelvic[18]. However, the narrow surgical field makes traditional LE hard and may have an adverse impact on the anal preservation. Actually, LE can be accomplished by several ways, including transanal excision (TAE), transanal endoscopic microsurgery (TEM), and excision with Endo-GIA. TAE is one of the most widely used surgical methods, but is difficult to manipulate because of the narrow pelvic spaces. And,TEM not only requires a specialized operation platform but also has the disadvantages of a longer learning curve and an insufficient resection range[19]. In these senses, LE with Endo-GIA is implemented after patients signed the informed consents, but it is rarely performed across other institutions in China.
During the operation, closure, cutting and anastomosis around the tumor can be competed in one time, resulting in decreased tissue retraction. Full thickness excision, complete tumor removal and negative margins can be guaranteed because the thickness of Endo-GIA nails is more than 1 cm. Endo-GIA is featured with convenient processes, clear removal-suture effects, and rapid healings. This novel surgical design can largely prevent the anus from being excised. However,there are a few caveats in this technique that are worth mentioning. For example, we shall confirm the integrity of posterior vaginal wall and no peri-rectal tissue embedded into Endo-GIA before firing the stapling devices, so that staples will not transfix the vaginal wall to prevent the postoperative rectovaginal fistula. The adequate blood supply, free tension and patency of anastomotic stoma should be examined after the anastomosis is completed.
Major Findings
It is found that LE surgery with Endo-GIA is associated with decreased surgical duration, decreased intraoperative hemorrhage, reduced hospital stay and dramatically reduced postoperative complications compared with TME. Surprisingly, the recurrence rate and mortality rate in the LE group are no worse than those in the TME group. Despite older patients with a poorer physical function in the LE group, OS, 1-year DFS and 3-year DFS are not significantly different from those in the TME group. These findings clearly illustrate that LE exhibits non-inferiority in outcomes and achieve less trauma than TME.
Therapeutic Regimen
A large 10-year retrospective study involving 4822 patients with T2N0M0 rectal cancer suggests that 5-year OS of radical surgery (77.4%), LE with neoadjuvant (76.1%), and LE with additional CRT (79.7%) have no statistically significant difference (P=0.786)[20]. Wang XJ et al conclude that adjuvant radiotherapy can achieve the same 5-year specific survival rate and 5-year OS as LE[21]. The above researches provide a basis for the use of LE with additional CRT as a viable treatment modality [22-23].The National Institute for Health and Clinical Excellence (NICE) guidelines (version 2021) also points out that preoperative radiotherapy is not required for early rectal cancer (cT1-T2,cN0,M0), and preoperative radiotherapy or CRT is offered to patients in cT1-T2, cN1-N2, M0 or cT3-T4, any cN, M0. In this study, LE along with aCRT is implemented to reduce the opportunity of LR and distant metastasis. In the LE group, there are only 2 deaths due to LR, while 1 case of LR recovered after TME.
On the other hand, it has also been shown that LE following neoadjuvant CRT (nCRT) can achieve encouraging oncological outcomes for T2N0 rectal cancer and may serve as an option for organ preservation[24]. Li YH et al[25] perform a study on the prognosis and complications of LE, and find that the postoperative complete tumor regression rate is 42.5%, moderate remission rate is 32.5%, the 5-year DFS is 84.3%, and no deaths occur. LE after nCRT can be an effective therapy to increase the anus preservation rate and avoid TME, and benefit mid-low rectal cancer more than high rectal cancer[26]. However, the treatment which must be mentioned here has certain limitations.Wound dehiscence, wound pain, and readmission rate may be relatively high in the context of LE combined with nCRT.
Our view contained in this paper is that preoperative CRT for T2N0M0 mid-low rectal cancer may achieve clinical remission. However, clinical remission is not equivalent to pathological remission. Taken together, nCRT influences accurate clinical staging before the operation, thus changing oncological outcomes.
Local Recurrence
LR of rectal cancer is grim because it may lead to pelvic pain, tenesmus and incontinence of feces[27-28]. LR after local resection plays a pivotal role in evaluating the efficacy on T2N0M0 mid-low rectal cancer. Taylor RH et al[29] report that the LR rate after LE varies from 0 to 37% in T2 stage patients. Halverson AL et al[30] suggest that the LR rate after LE increases among patients with T2 tumors compared with T1 tumors. Van Oostendorp SE et al[31] find that the LR rate is 4% for LE followed by TME and 14.7% followed by aCRT among T2 tumors. However, the recurrence rate is 3.45% in the LE group and 3.03% in the TME group, which has no significant difference in this study. These results prove that LE combined with CRT may show no disadvantage on LR of T2N0M0 rectal cancer. Therefore, meticulous surveillance protocol after surgery, including detailed inquires and normative examinations, should be scheduled for high-risk T2N0M0 rectal caner. Failing that, the prognosis and efficacy may be negatively affected.
Strengths and Limitations
LE combined with CRT can provide parallel oncological outcomes with radical surgery in early rectal cancer[32]. The former shows low risks of dysuria, abnormal defecation, sexual dysfunction, and stoma-induced physical and psychological trauma. Some sphincter-preserving surgeries of low rectal cancer result in anal dysfunction with poor defecation control and frequent defecation. Due to the lack of large-scale prospective research, however, this study is limited to patients with strong organ-preserving willingness and underlying medical conditions. It is believed that with the development of TNM staging and oncological CRT,transanal local resection combined with CRT for early rectal cancer tends to be a viable and effective strategy with the advances in TNM staging system and oncologic CRT.
However, a main shortcoming in this study is the relatively short of follow-up time. Only 1-year and 3-year follow-up are presented, but 5-year follow-up is absent. Long-term managements need to be emphasized by surgeons in each patient's treatment regimen[33]. Our recommendation allows for diligent preoperative planning and informed discussion with patients so that they are fully aware of the risks and benefits of each procedure.