Transanal local resection is one of the commonly employed surgical approaches for early rectal cancer. It is also recommended by many clinical guidelines for the treatment of early rectal cancer. Among these therapies, transanal endoscopic microsurgery (TEM) is the most commonly performed. Currently, TEM is mainly performed on patients with T1 low-risk rectal cancer (1). Generally speaking, the following criteria are favorable for TEM (2): lesions accounting for less than 30% of the rectal circumference; largest diameter of the tumor less than 3cm; distance between the margin and the tumor greater than 3mm; mobile tumor (not fixed); less than 8cm from the anal margin; T1 tumor; no vascular, lymphatic or nerve infiltration; highly to moderately differentiated. Other criteria where TEM can be considered include: no signs of lymph node metastasis in imaging examination; polyps resected under endoscopy showed cancerous infiltration, or the pathological examination results were uncertain; additional extended local resection was required; full-thickness resection was achieved.

With its excellent oncological and surgical safety (3), TEM allows for full-thickness resection and suture under direct vision (4, 5). Compared with radical surgery, TEM has been widely used for its superior anal function protection, low operation risk and fast postoperative recovery (6–9). The technique is especially popular with elderly patients and patients requesting anus preservation (10, 11). However, the risk of local recurrence and distant metastasis after TEM is still present (4). Clinical studies indicated that the local recurrence rate of T1stage rectal cancer after TEM was about 10% (12), and the 5-year local recurrence rate of the patients with high risk or incomplete resection exceeded 30% (13). The patients with pathological high-risk factors were generally recommended to pursue additional radical surgery after TEM (14). For those high-risk patients who failed to undergo additional radical surgery, the prognosis after TEM deserved further evaluation (15). This study aimed to investigate the prognosis of the patients over 60 years old who underwent TEM in our center, regardless of the presence or absence of postoperative pathological high-risk factors.

A retrospective analysis was conducted based on the collected data of the early rectal cancer patients over 60 years old who underwent TEM at the department of colorectal surgery of Tianjin Union Medical Center from January 2011 to January 2016. Patients with a histopathological diagnosis of malignancy were enrolled. Cases of severe dysplasia and carcinoma in situ and neoadjuvant chemoradiotherapy were excluded. All patients underwent preoperative digital rectal examination and colonoscopy. The local tumor stage and lymph node status were assessed by pelvic MRI or transrectal ultrasound, and distant metastasis was assessed by chest and abdominal CT scan. There was no evidence of lymph node involvement and distant metastasis in preoperative imaging.

The operation was performed by three surgeons with extensive experience in TEM surgery. All procedures were performed under general anesthesia, as previously described (16, 17). Resection margins were marked to incorporate a 1-cm cuff of normal mucosa around the location where cancer was known or suspected. In most patients, a full-thickness resection was performed. Closure of the rectal wall defect was routinely performed.

All patients were diagnosed with early rectal cancer (pT1-T2) according to the UICC/AJCC T Staging System (Seventh Edition) for pathological staging. pT1 tumors were evaluated according to the Kikuchi submucosal staging system (Sm1-3). The resection margin was considered positive when the cancer was located within 1 mm of the specimen’s resection margin.

The collected data included demographic information, preoperative staging, intrarectal ultrasonography, MRI, adjuvant therapy, surgical details, complications, tumor histopathology, postoperative management (additional radical surgery, radiotherapy or monitoring), recurrence and metastasis. The present study was approved by the Ethics Committee of Tianjin Union Medical Center.

During the 5-year period from January 2011 to January 2016, 265 TEM procedures were recorded. 47 early rectal cancer patients over 60 years old underwent TEM, including 20 males and 27 females, with an average age of 69.9 years (ranging from 60 to 88 years old). Adenocarcinoma was confirmed by preoperative pathological biopsy in 25 patients. The mean distance between the lesion and the anal verge was 5.4cm (range 4-12cm), and the preoperative staging evaluated by transrectal ultrasound/MRI was no later than cT1N0M0 in all patients. The detailed screening workflow is shown in Figure 1 , and the demographic data and tumor characteristics are displayed in Table 1 .

T1 rectal cancers without pathological risk factors may be effectively treated with TEM without jeopardizing long-term oncologic outcomes (19). In contrast, radical surgery is recommended in high-risk pathological stage T1 (pT1) or pT2 rectal cancer. However, older patients with significant comorbidity may not be viable candidates for radical surgery (20). The patients in this group were generally older (the average age was 69.9 years) and some elderly patients could not tolerate radical surgery or refused to undergo combined abdominal and perineal radical surgery, even in the presence of pathological risk factors. Therefore, some patients with larger tumors (the maximum diameter was 6.0cm) opted for TEM. Through follow-up, it was found that the 5-year OS of the patients reached 90.2%, with a favorable overall prognosis, demonstrating that TEM is a worthwhile option for elderly patients with early rectal cancer.

Significant differences in the recurrence rate between T1 and T2 patients after TEM surgery have been reported. The 5-year local recurrence rate of T2 patients was as high as 29.3 ~ 47% (21), and the lymph node involvement rate of T2 tumors was also about twice higher than that of the T1 stage (22, 23). Therefore, T2 patients should receive more active surgical treatment (24). This was also consistent with our findings. Although the results were not statistically significant, the 5-year recurrence and metastasis rate in T2 patients (28.6%) higher than that in T1 patients (16.1%) (25). Meanwhile, T1 rectal cancer also carries the risk of lymph node metastasis (26, 27). Signs of lymph node metastasis before surgery would also directly affect the treatment program (19, 28, 29). In the present study, all patients underwent preoperative MRI or intrarectal ultrasound, chest and abdominal CT scan, and no evidence of lymph node involvement and distant metastasis was found.

A detailed pathological examination should be conducted for the tissue specimens resected by TEM. For the patients with poor differentiation, large tumors, vascular invasion and other risk factors (30), an increased local recurrence rate was observed, ranging from 20% to 30% (31). Therefore, if the postoperative pathological examination showed poor histological differentiation, positive margins, lymphatic and vascular invasion, T2 and above stages, etc., additional radical surgery is recommended (32). For patients with the above-mentioned high-risk factors who refused to undergo secondary surgical resection and had unclear lymph node status, the subsequent treatment plan should be determined after multidisciplinary discussion (33).

Complete tumor resection greatly reduces the risk of local recurrence (13). Previous studies indicated that the low risk of local recurrence of rectal cancer after TEM was mostly caused by the tumor residues from the previous resection rather than from undetermined lymph node metastasis (34). Therefore, full-thickness resection, adequate resection margins and en-bloc resection are performed to achieve adequate oncological safety (35). When the tumor cannot be completely removed, such as positive margins, additional radical surgery is currently recommended (36). Studies have shown no difference in outcomes with primary TME surgery (37). Considering the relationship between the depth of invasion and lymph node metastasis and local recurrence, most scholars recommend radical surgery for patients with stage T1 rectal cancer with deep submucosal invasion (Sm3 or > 1 mm) (30), despite other studies reporting Sm3 was not related to lymph node metastasis and survival (38). In this study, Sm3 was not included in the treatment guidelines at the time of treatment for some patients. We performed a retrospective analysis and found that the DFS and OS of Sm3 patients in T1 patients were similar to those of other T1 patients. However, this finding may be related to the small sample size.

Currently, the optimal treatment measures for patients with pathological high-risk factors are controversial (15, 24, 39). Most experts still recommend additional radical surgery, but other treatment measures are also worth exploring, such as adjuvant radiotherapy (40, 41)or extended local resection for patients with a high risk of recurrence (42). However, the previous studies pointed out that even if the patients were treated with total mesorectal excision (TME), the efficacy of the radical surgery would be lower than that of direct TME due to the effects of the initial TEM (43). Nevertheless, it is not associated with increased morbidity or mortality. Immediate laparoscopic TME after TEM for rectal cancer may result in a significantly increased risk of APR (44). Furthermore, the fibrotic scar caused by full-thickness TEM hinders the maintenance of proper surgical planes during TME surgery (45). Therefore, some researchers suggest that TME surgery following TEM excision is best delayed for 6 to 12 weeks in order to reduce postsurgical inflammation (29).

In this data group, the 5-year OS of the patients with recurrence after TEM and additional radical surgery were not inferior to those of low-risk patients without recurrence. The results indicated that the additional radical surgery after the recurrence with TEM surgery could improve the prognosis of the patients. This is consistent with some other observations and conclusions (37, 46, 47). Consequently, TEM can be used in exceptional cases with high-risk factors when the patient is not fit for radical surgery (45).

In one study including 33 patients who received adjuvant radiotherapy due to poor histopathological characteristics with a median follow-up of 3.2 years, the results indicated that 3 patients (9.1%) had local recurrence, and the estimated 1-year and 3-year local recurrence rates were 0% and 6.9%, respectively (40). The above protocol was also offered to the patients in the present study.

In another study, additional TEM was performed on part of the patients. It was found that the safety and radical effect of the additional TEM was nearly the same as that of the first operation (48, 49). In this study, four patients had positive margins; all of the tumors were greater than 2 cm in diameter (2.5-4 cm) and were close to the anus, increasing the risk of impaired anal function for additional surgery. The patients refused the recommended repeat TEM surgery or radical surgery and received postoperative adjuvant therapy. Although the anorectal function after repeated TEM is preserved (50), many factors including malignant lesions (51, 52), excessive circumferential mucosal defects (53), and closer proximity of the tumor to the anal verge suggest a higher risk of impaired anal function after TEM.

In addition, this study found no statistically significant differences in recurrent metastases and overall survival with or without adjuvant therapy after TEM. These findings are similar to the results of a recent study, concluding that survival after transanal local excision with or without chemoradiotherapy is comparable to that of TME, while TEM allows better bowel function and postoperative quality of life (54).

The follow-up program should be determined according to the risk of tumor recurrence and metastasis. Clinical studies indicated that the recurrence in T1 patients with local resection mostly occurred within 1 to 2 years after the surgery. Recurrence was usually located at the site of the primary lesions, and more than one-third of the patients recurred at the site outside the intestinal cavity (55). Therefore, most studies limit the duration of close follow-up to the initial 1 to 2 years (35, 56). It is generally believed that the patients should be reviewed every 3 months in the first 2 years (57). The examination included digital rectal examination, rigid sigmoidoscopy or proctoscope, ERUS and pelvic MRI, and monitoring carcinoembryonic antigen levels (58). Some scholars suggested that a CT examination of the chest and abdomen should be performed every 6 months to exclude distant metastasis (59). The postoperative follow-up of patients was performed according to guideline recommendations. Most of the patients who developed local recurrences had no obvious clinical symptoms. As a consequence, it is essential to optimize the follow-up program and closely monitor for local recurrence. The routine application of ERUS and pelvic MRI should be recommended (60).

This study has several main limitations, including the retrospective design and small sample size. Furthermore, due to various factors, some patients did not comply with the recommendations to receive postoperative adjuvant therapy, which may affect the conclusion of the study.

TEM surgery provides prominent advantages in the treatment of early rectal cancer, preserving anal function and imposing lower surgical risk and surgical pain. The results of the present study suggest a favorable overall prognosis for early rectal cancer patients over 60 years old who underwent TEM. For patients with postoperative pathological high-risk factors, additional radical surgery after local recurrence could also effectively improve the prognosis of the patients. Moreover, the stratified analysis demonstrated no difference in DFS and OS in patients above 70 years. TEM surgery may be an option for older patients with high surgical risk. With the promotion of neoadjuvant therapy, the application of TEM in patients with T2 or T3 stage tumors is being explored (21, 61–63). Further research on this topic will enable a broader application of TEM, which will play an essential role in the treatment of rectal cancer.

TEM is widely performed in early rectal cancer and also can be used in patients with high-risk factors who are not fit for radical surgery. Elderly patients tend to opt for TEM as it allows organ preservation and is a relatively safe surgery. However, these data remain to be confirmed. We report the prognosis of early rectal cancer patients over 60 years old. As an alternative for elderly rectal cancer patients with or without pathological high-risk factors, TEM is a reliable and effective therapeutic option.

The original contributions presented in this study are included in the article. Further inquiries can be directed to the corresponding author.

The studies involving human participants were reviewed and approved by the Ethics Committee of Tianjin Union Medical Center. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.

SZ, XZ and MZ conceived the idea for the study. XZ and MZ were involved in planning and supervised data collection. HJ, YZ and LZ performed data collection. MZ, YZ and LZ conducted data analysis. MZ, YZ drafted the manuscript. MX and HX contributed to writing of manuscript. All authors have discussed and decided that this manuscript is the final version and agreed to publish it.

This study was funded by Foundation of Tianjin Union Medical Center (grant number: 2016YJZD002 and 2016RMNK002). This work was funded by Tianjin Key Medical Discipline (Specialty) Construction Project.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.