Background

Transanal Endoscopic Microsurgery

TEMS is a minimally invasive approach to local excision of rectal lesions. It has been used in benign conditions such as large rectal polyps (that cannot be removed through a colonoscope), retrorectal masses, rectal strictures, rectal fistulae, pelvic abscesses, and in malignant conditions (e.g., malignant polyps). Use of TEMS for resection of rectal cancers is more controversial. TEMS can avoid the morbidity and mortality associated with major rectal surgery, including the fecal incontinence related to stretching of the anal sphincter, and can be performed under general or regional anesthesia.

The TEMS system has a specialized magnifying rectoscope with ports for insufflation, instrumentation, and irrigation. This procedure has been available in Europe but has not been widely used in the U. S. Two reasons for this slow adoption are the steep learning curve for the procedure and the limited indications. For example, most rectal polyps can be removed endoscopically, and many rectal cancers need a wide excision and are thus not amenable to local resection.

Other Treatment Options

The most common treatment for rectal cancer is surgery; the technique chosen will depend on several factors. The size and location of the tumor, evidence of local or distal spread, and patient characteristics and goals are all attributes that will affect the treatment approach. Open, wide resections have the highest cure rate but may also have significant adverse events. Most patients find the potential adverse events of lifelong colostomy and/or bowel, bladder, or sexual dysfunction acceptable in the face of a terminal illness. Laparoscopic-assisted surgery, with lymph node dissection as indicated, is technically difficult in the pelvic region but is being investigated as a less invasive alternative to open resection.

Local excision alone does not offer the opportunity for lymph node biopsy and therefore has been reserved for patients in whom the likelihood of cancerous extension is small, local excision can occur under direct visualization in rectal tumors within 10 cm of the anal verge. TEMS extends local excision ability to the proximal rectosigmoid junction. Adenomas, small carcinoid tumors, and nonmalignant conditions (e.g., strictures, abscesses) are amenable to local excision by either method.

The use of local excision in rectal adenocarcinoma is an area of much interest and may be most appropriate in small tumors (<4 cm) confined to the submucosa (T1, as defined by the tumor, node, and metastasis staging system). Presurgical clinical staging, however, may miss up to 15% of regional lymph node spread. During local excision, the excised specimen should be examined by a pathologist; if adverse features such as high-grade pathology or unclear margins are observed, the procedure can be converted to a wider resection. Despite this increased risk of local recurrence, local excision may be an informed alternative for patients. TEMS permits local excision beyond the reach of direct visualization equipment.

Regulatory Status

In 2001, the Transanal Endoscopic Microsurgery (TEMS) Combination System and Instrument Set (Richard Wolf Medical Instruments) was cleared for marketing by the U.S. Food and Drug Administration (FDA) through the 510(k) process. The FDA determined that this device was substantially equivalent to existing devices for use in inflating the rectal cavity, endoscopically visualizing the surgical site, and accommodating up to three surgical instruments. In 2011, the SILS™ Port (Covidien) was cleared for marketing by the FDA through the 510(k) process. The SILS™ Port is a similar instrument that can be used for rectal procedures including TEMS. Another device determined by the FDA to be substantially equivalent to these devices is the GelPOINT® Path (Applied Medical Resources). FDA product codes: HIF, GCJ, FER.

Table 1. Transanal Endoscopic Microsurgery Devices Cleared by the US Food and Drug Administration

Device	Manufacturer	Date Cleared	510(k) No.	Indication
AP50/30 Insufflator with Insuflow Port	Lexion Medical LLC	8/28/2019	K191780	For use in transanal endoscopic microsurgery
AirSeal	ConMed Corporation	3/28/2019	K190303	For use in transanal endoscopic microsurgery
GRI-Alleset Veress Needle	GRI Medical and Electronic Technology Co. Ltd.	6/11/2018	K172835	For use in transanal endoscopic microsurgery
SurgiQuest AIRSEAL iFS System	ConMed Corporation	3/16/2018	K172516	For use in transanal endoscopic microsurgery
TEMED Gas Diffuser	TEMED	2/14/2018	K173545	For use in transanal endoscopic microsurgery
AP 50/30 Insufflator with Insuflow Port	LEXION Medical LLC	11/14/2017	K170799	For use in transanal endoscopic microsurgery
Veress Needle	WickiMed (Huizhou) Medical Equipment Manufacturing Co.Ltd.	9/14/2017	K172120	For use in transanal endoscopic microsurgery
GelPOINT Path Transanal Access Platform	Applied Medical Resources Corp.	7/20/2017	K171701	For use in transanal endoscopic microsurgery
HumiGard Surgical Humidification System HumiGard Humidified Insufflation Kit	FISHER & PAYKEL HEALTHCARE	6/23/2017	K162582	For use in transanal endoscopic microsurgery
LaparoLight Veress Needle	Buffalo Filter LLC	5/18/2017	K171139	For use in transanal endoscopic microsurgery
PNEUMOCLEAR	W.O.M World Of Medicine GmbH	5/15/2017	K170784	For use in transanal endoscopic microsurgery
ENDOFLATOR 40 ENDOFLATOR 50	KARL STORZ ENDOSCOPY-AMERICA INC.	3/2/2017	K161554	For use in transanal endoscopic microsurgery
U-Blade Veress Needle	TIANJIN UWELL MEDICAL DEVICE MANUFACTURING CO.LTD.	12/12/2016	K162648	For use in transanal endoscopic microsurgery
S698 Symbioz flow	SOPRO - ACTEON GROUP	6/17/2016	K153367	For use in transanal endoscopic microsurgery
Insufflator 50L FM134	W.O.M WORLD OF MEDICINE GMBH	3/4/2016	K153513	For use in transanal endoscopic microsurgery
Unimicro Veress Needle	Unimicro Medical Systems (ShenZhen) Co.Ltd.	7/31/2015	K150068	For use in transanal endoscopic microsurgery
SurgiQuest AirSeal iFS System	SURGIQUEST INC.	3/20/2015	K143404	For use in transanal endoscopic microsurgery
GELPOINT PATH TRANSANAL ACCESS PLATFORM	APPLIED MEDICAL RESOURCES CORP.	1/2/2014	K133393	For use in transanal endoscopic microsurgery

Related Policies

• None

2. Transanal endoscopic microsurgery is considered medically necessary for treatment of clinical stage T1 rectal adenocarcinomas than cannot be removed using other means of local excision and that meet all of the following criteria:

• Located in the middle or upper part of the rectum,
• Well or moderately differentiated (G1 or G2) by biopsy,
• Without lymphadenopathy, and
• Less than one third the circumference of the rectum.

Medicare Coverage:
There is no National Coverage Determination (NCD) or Local Coverage Determination (LCD) for jurisdiction JL for this service. Therefore, Medicare Advantage Products will follow the Horizon BCBSNJ Medical Policy.


[RATIONALE: This policy was created in 2010 and has been updated regularly with searches of the MEDLINE database. The most recent literature update was performed through September 9, 2019.

Evidence reviews assess the clinical evidence to determine whether the use of technology improves the net health outcome. Broadly defined, health outcomes are the length of life, quality of life (QOL), and ability to function - including benefits and harms. Every clinical condition has specific outcomes that are important to patients and managing the course of that condition. Validated outcome measures are necessary to ascertain whether a condition improves or worsens; and whether the magnitude of that change is clinically significant. The net health outcome is a balance of benefits and harms.

To assess whether the evidence is sufficient to draw conclusions about the net health outcome of technology, two domains are examined: the relevance, and quality and credibility. To be relevant, studies must represent one or more intended clinical use of the technology in the intended population and compare an effective and appropriate alternative at a comparable intensity. For some conditions, the alternative will be supportive care or surveillance. The quality and credibility of the evidence depend on study design and conduct, minimizing bias and confounding that can generate incorrect findings. The randomized controlled trial (RCT) is preferred to assess efficacy; however, in some circumstances, nonrandomized studies may be adequate. RCTs are rarely large enough or long enough to capture less common adverse events and long-term effects. Other types of studies can be used for these purposes and to assess generalizability to broader clinical populations and settings of clinical practice

Transanal Endoscopic Microsurgery

Clinical Context and Therapy Purpose

The purpose of TEMS in patients who have rectal adenoma(s) or early rectal adenocarcinoma is to provide a treatment option that is an alternative to or an improvement on existing therapies.

The question addressed in this policy is: Does TEMS improve the net health outcome in patients with rectal adenoma(s) or with early rectal adenocarcinoma?

The following PICOs were used to select literature to inform this policy.

Patients

The relevant populations of interest are patients with rectal adenoma(s) or with early rectal adenocarcinoma.

Interventions

The therapy being considered is TEMS.

TEMS is performed in an inpatient surgical center, conducted under anesthesia with the specialized equipment needed and surgeons sufficiently experienced with the technology.

Comparators

The following practices are currently being used to treat both rectal adenoma(s) and with early rectal adenocarcinoma: standard transanal excision (TAE) and laparoscopic excision.

Outcomes

The general outcomes of interest are overall survival (OS), tumor recurrence, and treatment-related adverse events (e.g., incontinence, sexual dysfunction).

Follow-up after hospital discharge (24 to 48 hours) takes about 1 to 2 weeks.

Study Selection Criteria

• Methodologically credible studies were selected using the following principles:
• To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs;
• In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.
• To assess long-term outcomes and adverse events, single-arm studies that capture longer periods of follow-up and/or larger populations were sought.
• Studies with duplicative or overlapping populations were excluded.

The endoscopic approach to benign or premalignant lesions is similar to that throughout the colon, and studies have focused on the relative safety of the technique. The evidence presented in this section may include adenomas. However, the focus of this research is on the safety of the procedure.

Systematic Reviews

Barendse et al (2011) reported on a systematic review compared TEMS with endoscopic mucosal resection (EMR) for rectal adenomas larger than 2 cm.^1, Included in the review were 48 TEMS and 20 EMR studies; all were treated as single-arm studies. No controlled trials were identified that compared TEMS with EMR directly. Early adenoma recurrence rates, within 3 months of the procedure, were 5.4% (95% confidence interval [CI], 4.0% to 7.3%) with TEMS and 11.2% (95% CI, 6.0% to 19.9%) with EMR (p=0.04) in pooled estimates. After 3 months, late adenoma recurrence rates in pooled estimates were 3.0% (95% CI, 1.3% to 6.9%) with TEMS and 1.5% (95% CI, 0.6% to 3.9%) for EMR (p=0.29). Lengths of hospitalization and readmission rates did not differ significantly between procedures. For TEMS, the mean hospital length of stay was 4.4 days and 2.2 days for EMR (p=0.23). Hospital readmission rates were 4.2% for TEMS and 3.5% for EMR (p=0.64). Complication rates after TEMS, for rectal adenomas only, were 13.0% (95% CI, 9.8% to 17.0%) and 3.8% (95% CI, 2.8% to 5.3%) after EMR, for colorectal adenomas (p<0.001). Postoperative complications increased significantly with larger polyp size (p=0.04). However, postoperative complication rates remained higher for TEMS after adjusting for a larger mean polyp size in the TEMS studies (8.7%; 95% CI, 5.8% to 12.7%) than in EMR studies (4.2%; 95% CI, 2.9% to 6.3%; p=0.007). These results would suggest that TEMS may be associated with lower early cancer recurrence than with EMR but late cancer recurrence (after three months) may not differ significantly between procedures. Complications were significantly higher with TEMS for rectal adenomas larger than 2 cm. This systematic review was limited by the low quality of the available studies, particularly on the single-arm study evidence base.

Middleton et al (2005) conducted a systematic review of TEMS based on published results through August 2002.^2, Three comparative studies, including an RCT, and 55 case series were included. The first area of study was the safety and efficacy in the removal of adenomas. In the RCT, no difference could be detected in the rate of early complications between TEMS (10.3% of 98 patients) and direct local excision (17% of 90 patients) (relative risk, 0.61; 95% CI, 0.29 to 1.29). TEMS resulted in lower local recurrence (6% [6/98]) than direct local excision (22% [20/90]) (relative risk, 0.28; 95% CI, 0.12 to 0.66). The 6% local recurrence rate for TEMS in this trial is consistent with rates found in the TEMS case series.

Case Series

Numerous case series of TEMS have evaluated the treatment of rectal adenomas; many included mixed populations of patients with benign and malignant lesions.^{3,4,5,6,7,8,9,10,11,12,13,14,15,} Most were retrospective, and a few compared outcomes with other case series of standard excision. These case series offer useful information on the completeness of resection, local recurrence, and complications, but do not provide definitive evidence on the comparative efficacy of this procedure because the comparisons were limited by potential selection bias leading to differences in the patient populations.

Al-Najami et al (2016) reported on longer-term follow-up for a prospective cohort study of 280 patients with advanced polyps and early rectal cancer treated with TEMS.^16, Most patients (n=163 [63%]) had benign disease. Postoperative complications were more frequent in malignant cases (24.0%) than in benign cases (10.8%; p=0.03). A standard follow-up protocol was followed by 83% and 85% of benign and malignant cases, respectively. Over a mean follow-up of 16.4 and 15.2 months in the benign and malignant groups, recurrence rates were 8.3% and 13.5%, respectively.

Section Summary: Rectal Adenoma(s)

There is a lack of high-quality trials comparing TEMS with standard surgical approaches for the removal of rectal adenomas. The available evidence is primarily from single-arm studies and has reported that TEMS can be performed with relatively low complication rates and low recurrence rates. It is not possible to determine the comparative efficacy of TEMS and other surgical approaches with certainty based on the available evidence. Systematic reviews of nonrandomized comparative studies have concluded that the local recurrence rate with TEMS may be lower than for other procedures, but that short-term complication rates may be higher. These conclusions are limited by potential selection bias, leading to differences in the patient populations; in particular, it is possible that patients undergoing TEMS had lower disease severity than patients undergoing standard excision. Therefore, it is not possible to form conclusions about the comparative efficacy of TEMS and alternative approaches.

Rectal Adenocarcinoma

Clinical Context and Therapy Purpose

The purpose of TEMS in patients who have early rectal adenocarcinoma is to provide a treatment option that is an alternative to or an improvement on existing therapies.

The question addressed in this policy is: Does TEMS improve the net health outcome in patients with early rectal adenocarcinoma?

The following PICOs were used to select literature to inform this policy.

Patients

The relevant populations of interest are patients with early rectal adenocarcinoma.

Interventions

The therapy being considered is TEMS. TEMS is performed in an inpatient surgical center, conducted under anesthesia with the specialized equipment needed and surgeons sufficiently experienced with the technology.

Comparators

The following practices are currently being used to treat early rectal adenocarcinoma: standard TAE and laparoscopic excision, which are performed in an inpatient surgical center, conducted under anesthesia by a surgeon.

Outcomes

The general outcomes of interest are OS, functional outcomes, health status, QOL, tumor recurrence, and treatment-related adverse events (e.g., incontinence, sexual dysfunction).

Follow-up after hospital discharge (24 to 48 hours) takes about 1 to 2 weeks.

Study Selection Criteria

Methodologically credible studies were selected using the principles described in the first indication.

Systematic Reviews

A meta-analysis by Lu et al (2015) compared TEMS with total mesorectal excision for T1 rectal cancer.^17, Studies selected included 1 RCT and 6 non-RCTs (303 treated with TEMS; 557 treated with total mesorectal excision). For the outcome of postoperative recurrence, the rate of local recurrence was higher after TEMS (odds ratio [OR], 4.63; 95% CI, 2.03 to 10.53; p<0.001, I²=0%). For the 6 studies reporting on OS, there were no significant differences between the TEMS and total mesorectal excision groups (OR=0.87; 95% CI, 0.55 to 1.38; p=0.55, I²=0%).

Clancy et al (2015) published a systematic review of the comparative efficacy of TEMS and standard TAE for early rectal cancer.^18, Six studies including outcomes for 927 excisions were selected, all of which were nonrandomized. On combined analysis, TEMS had a higher rate of negative surgical margins (OR=5.3; 95% CI 3.2 to 8.7) and a lower rate of recurrence (OR=0.25; 95% CI, 0.15 to 0.40) compared with standard excision. Complication rates did not differ significantly between techniques (OR=1.018; 95% CI, 0.658 to 1.575).

Sajid et al (2014) reported on a systematic review and meta-analysis of TEMS and radical resection for stage T1 and T2 rectal cancers.^19, Included in the review were 5 RCTs and 5 cohort studies (445 TEMS patients, 438 radical resection patients). In random-effects models, there was a greater risk of local recurrence with TEMS than with radical resection (OR=2.78; 95% CI, 1.42 to 5.44; p<0.003) and a greater risk of overall recurrence (OR=2.01; 95% CI, 1.18 to 3.42; p<0.01). The risk of distant recurrence did not differ significantly between procedures (OR=0.87; 95% CI, 0.41 to 1.83; p=0.71) nor did OS rates (OR=0.90; 95% CI, 0.49 to 1.66; p=0.74). In a subgroup analysis of the 5 RCTs, the risk of overall recurrence remained higher with TEMS (OR=2.21; 95% CI, 1.10 to 4.41; p<0.03). OS rates, however, did not differ significantly between TEMS and radical resection (OR=0.80; 95% CI 0.43 to 1.47; p=0.47), and postoperative complications were significantly lower with TEMS (OR=0.19; 95% CI, 0.08 to 0.44; p<0.001).

Wu et al (2011) published a meta-analysis on TEMS and conventional surgery for stage T1 rectal cancers.^20, Five studies were selected, including a prospective RCT and 4 retrospective, nonrandomized studies for a total of 397 (216 TEMS, 181 conventional rectal surgery) patients. Combined analyses were performed for mortality, postoperative complications, recurrence rates, and five-year survival. No deaths were reported from either procedure, and TEMS had fewer postoperative complications (16/196) than conventional surgery (77/163). On combined analysis, the odds for complications was 0.10 (95% CI, 0.05 to 0.18). There was a higher rate of local recurrence or distant metastasis at a 40-month follow-up for TEMS (12% [26/216]) than for conventional radical surgery (0.5% [1/181]). On combined analysis, the odds for recurrence in the conventional surgery group was 8.64 (95% CI, 2.63 to 28.39). The 5-year survival (not specified as disease-specific or overall), as reported in 4 studies, did not differ significantly between groups (80.1% [157/196] for TEMS vs 81% [132/163] for conventional surgery). These results supported the conclusion that TEMS is associated with fewer early complications but higher rates of recurrence than standard resection, with no demonstrable differences in OS.

Sgourakis et al (2011) conducted a meta-analysis of stage T1 and T2 rectal cancer treatment that compared TEMS with standard resection and TAE.^21, Eleven studies were selected for analysis and included 3 randomized controlled, 1 prospective, and 7 retrospective trials (total n=1191 patients; 514 TEMS, 291 standard resections, 386 TAE). Numerous combined analyses were performed to measure mortality, complications, and recurrence rates. For postoperative complication rates, the combined analysis showed a significantly lower rate of major complications for TEMS than for standard resection (OR=0.24; 95% CI, 0.07 to 0.91). Minor complications did not differ significantly between groups. Overall postoperative complications did not differ significantly between TEMS and TAE when stage T1 and T2 tumor data were pooled. Follow-up for all studies was a mean or median of more than 30 months (except for follow-up >20 months in 1 treatment arm in 2 studies). For T1 tumors, local recurrence was significantly higher for the TEMS group than for the standard resection group (OR=4.92; 95% CI, 1.81 to 13.41), as was overall recurrence (OR=2.03; 95% CI, 1.15 to 3.57). Distant metastasis (OR=1.05; 95% CI, 0.47 to 2.39) and OS (OR=1.14; 95% CI, 0.55 to 2.34) did not differ significantly between groups. Results were similar when data were analyzed for T1 and T2 tumors, except that disease-free survival was significantly longer with TEMS than with TAE. There was less evidence for T2 tumors, and conclusions for that group of patients were less clear. The results of this review also supported conclusions that TEMS is associated with fewer postoperative complications than standard resection, higher local and distant recurrence rates, and no differences in the long-term OS.

Doornebosch et al (2009) discussed weaknesses in the evidence and unresolved issues about the role of TEMS.^22, Reviewers posed three questions: “First, is there enough evidence to propagate LE [local excision] as a curative option in selected (T1) rectal carcinomas? Second, if LE is justified, which technique should be the method of choice? Third, can we adequately identify, pre- and postoperatively, tumors suitable for LE?” They noted that selection bias in studies complicated answering the first question; and a significant portion of tumors recurred in all studies using various techniques for LE(including TEMS), although it seemed not to influence survival rates. Reviewers noted that the published case series reporting outcomes after TEMS for T1 rectal carcinomas used inclusion criteria that were not always clear and used salvage procedures that could introduce bias. TEMS was demonstrated to be a safe procedure in all series; complication rates varied between 5% and 26%, and complications were generally minor. Local recurrence rates for TEMS varied between 4% and 33% in the studies reviewed. On the third question, reviewers assessed whether high recurrence rates could be improved by better tumor selection. They noted that TEMS had been incorporated into surgical practice based largely on retrospective case series, and noted that, despite the lack of level I evidence, its use seemed justified in well-selected T1 rectal cancers. They also indicated that some view TEMS as an alternative for patients with T1 lesions who are currently undergoing other methods of LE (e.g., using the Parks technique instead of radical surgery).

Table 2. Comparison of Trials/Studies Included in SR & M-As for Adenocarcinoma

Study	Clancy (2015)18,	Sajid (2014)19,	Sgourakis (2011)21,
Han (2012)	âš«
De Graaf (2011)	âš«	âš«
Christoforidis (2009)	âš«		âš«
Lebedyev (2009)	âš«		âš«
Moore (2008)	âš«		âš«
Langer (2003)	âš«
Allaix (2012)		âš«
Chen (2013)		âš«
Heintz (1997)		âš«
Langer (2002)		âš«
Lee (2002)		âš«
Lezoche (2007)		âš«
Lezoche (2012)		âš«
Palma (2009)		âš«	âš«
Winde (1996)		âš«	âš«
Lezoche (2008)			âš«
Langer (2003)			âš«
Heintz (1998)			âš«
Lee (2003)			âš«
De Graaf (2009)			âš«
Dixon (2006)			âš«

MA: meta-analysis; SR: systematic reviews.

Table 3. SR & M-A Characteristics for Adenocarcinoma

Study	Dates	Trials	Participants1	N (Range)	Design	Duration
Clancy (2015)18,	2003-2012	6	Patients with rectal lesions treated with TEM or transanal excision	927 excisions (NR)	Retrospective and prospective	NR
Sajid (2014)19,	1996-2013	10	Patients with rectal cancer undergoing TEM with RR	883 (NR)	RCT	NR
Sgourakis (2011)21,	1996-2009	11	Patients with stage I rectal cancer	1191 (NR)	RCT	NR

MA: meta-analysis; NR: not reported; RCT: randomized controlled trial; RR: radical resection; SR: systematic reviews; TEM: transanal endoscopic microsurgery.

Table 4. SR & M-A Results for Adenocarcinoma

Study	Post-Operative Complication Rate	Recurrence Rate
Clancy (2015)18,
OR	1.018	0.248
95% CI	0.658–1.575	0.154–0.401
P-value	0.937	<0.001
Sajid (2014)19,
OR	0.19	2.78
95% CI	0.08–0.44	1.42–5.44
P-value	<0.001	<0.003
Sgourakis (2011)21,
OR	0.16	2.03
95% CI	0.06–0.38	1.15–3.57

CI: confidence interval; MA: meta-analysis;OR: odds ratio; SR: systematic review.

Randomized Controlled Trials

E. Lezoche et al (2012) published an RCT of 100 patients with T2 rectal cancers without evidence of lymph node or distant metastasis randomized to TEMS or laparoscopic total mesorectal excision.^23, All patients also received neoadjuvant chemoradiation before surgery. All patients in the TEMS group completed the procedure. With laparoscopic resection, 5 (10%) patients required conversion to open surgery (p=0.028), and 23 patients required a stoma. Postoperative complications did not differ significantly between groups. Disease-free survival also did not differ significantly between groups (p=0.686) at a median follow-up of 9.6 years (range, 4.7-12.3 years for laparoscopic resection; range, 5.5-12.4 years for TEMS). Local recurrence or metastases occurred in six TEMS patients and five laparoscopic patients.

G. Lezoche et al (2008) reported on a similar RCT evaluating of 70 subjects with stage T2 rectal cancer without evidence of lymph node or distant metastasis on imaging.^24, Patients were randomized to TEMS or laparoscopic resection via total mesorectal excision. All patients received chemoradiation before surgery. Median follow-up was 84 months (range, 72-96 months). Two (5.7%) local recurrences were observed after TEMS and 1 (2.8%) after laparoscopic resection. Distant metastases occurred in one patient in each group. The probability of survival from rectal cancer was 94% for both groups. Overlap of patients studied in the 2008 and 2012 trials could not be determined.

Table 5. Summary of Key RCT Characteristics for Adenocarcinoma

Study; Trial	Countries	Sites	Dates	Participants	Interventions
					Active	Comparator
Lezoche 23,(2012)	Italy	1	1997-2004	Patients with T2 rectal cancers	TEM (n=50)	Laparoscopic total mesorectal excision (n=50)
Lezoche (2008)24,	Italy	1	NR	Patients with T2 rectal cancers	TEM (n=35)	Laparoscopic resection via total mesorectal excision (n=35)

NR: not reported; RCT: randomized controlled trial; TEM: transanal endoscopic microsurgery.

Table 6. Summary of Key RCT Results for Adenocarcinoma

Study	Local Recurrence	Distant Metastases	Probability of Survival	Disease-Free Survival
Lezoche (2012)23,				No significant difference between groups (p=0.686)
TEM	4 (8%)	2 (4%)
LR	3 (6%)	2 (4%)
Lezoche (2008)24,
TEM	2 (5.7%)	1 (2.8%)	94%
LR	1 (2.8%)	1 (2.8%)	94%

LR: laparoscopic resection; RCT: randomized controlled trial.

The purpose of the limitations tables (see Tables 7 and 8) is to display notable limitations identified in each study. This information is synthesized as a summary of the body of evidence following each table and provides the conclusions on the sufficiency of the evidence supporting the position statement.

Table 7. Relevance Limitations

Study	Populationa	Interventionb	Comparatorc	Outcomesd	Follow-Upe
Lezoche (2012)23,				3. No CONSORT reporting of harms
Lezoche (2008)24,				3. No CONSORT reporting of harms

The study limitations stated in this table are those notable in the current review; this is not a comprehensive limitations assessment.

^a Population key: 1. Intended use population unclear; 2. Clinical context is unclear; 3. Study population is unclear; 4. Study population not representative of intended use.

^b Intervention key: 1. Not clearly defined; 2. Version used unclear; 3. Delivery not similar intensity as comparator; 4. Not the intervention of interest.

^c Comparator key: 1. Not clearly defined; 2. Not standard or optimal; 3. Delivery not similar intensity as intervention; 4. Not delivered effectively.

^d Outcomes key: 1. Key health outcomes not addressed; 2. Physiologic measures, not validated surrogates; 3. No CONSORT reporting of harms; 4. Not establish and validated measurements; 5. Clinical significant difference not prespecified; 6. Clinical significant difference not supported.

^e Follow-Up key: 1. Not sufficient duration for benefit; 2. Not sufficient duration for harms.

Study	Allocationa	Blindingb	Selective Reportingc	Follow-Upd	Powere	Statisticalf
Lezoche (2012)		1,2,3. Blinding unclear			1. Some power calculations not reported
Lezoche (2008)24,	3. Allocation concealment unclear	1,2,3. Blinding unclear			1. Some power calculations not reported

^a Allocation key: 1. Participants not randomly allocated; 2. Allocation not concealed; 3. Allocation concealment unclear; 4. Inadequate control for selection bias.

^b Blinding key: 1. Not blinded to treatment assignment; 2. Not blinded outcome assessment; 3. Outcome assessed by treating physician.

^c Selective Reporting key: 1. Not registered; 2. Evidence of selective reporting; 3. Evidence of selective publication.

^d Follow-Up key: 1. High loss to follow-up or missing data; 2. Inadequate handling of missing data; 3. High number of crossovers; 4. Inadequate handling of crossovers; 5. Inappropriate exclusions; 6. Not intent to treat analysis (per protocol for noninferiority trials).

^e Power key: 1. Power calculations not reported; 2. Power not calculated for primary outcome; 3. Power not based on clinically important difference.

^f Statistical key: 1. Intervention is not appropriate for outcome type: (a) continuous; (b) binary; (c) time to event; 2. Intervention is not appropriate for multiple observations per patient; 3. Confidence intervals and/or p values not reported; 4. Comparative treatment effects not calculated.

A large number of case series and retrospective nonrandomized comparative reviews have been published.^{3,4,5,6,7,8,9,10,11,12,13,} The case series offers useful information on the completeness of resection, local recurrence, and complications, but does not provide definitive evidence on the comparative efficacy of TEMS because the comparisons were limited by potential selection bias leading to differences in patient characteristics.

Much of the research has focused on the technical aspects of TEMS and on other, non-neoplastic applications. Other studies have investigated the use of TEMS with adjuvant therapy or additional techniques. For example, Walega et al (2010) reported on a small study that added endoscopic mesorectum resection to TEMS.^25,

Moore et al (2008) retrospectively reviewed patients who underwent TAE for rectal neoplasms and compared results for traditional transanal resection with TEMS.^26, Of 296 patients identified, 76 were excluded because of surgery due to abscesses, fistulas, inflammatory bowel disease, or multiple lesions. Forty-nine patients were excluded because of incomplete or missing charts. Records of 171 patients were analyzed; 82 patients who underwent TEMS and 89 who had a transanal resection. For patients who received TEMS, those with stage T1 lesions without adverse histologic features (poor differentiation, lymphovascular invasion) received local excision alone. Patients with T1 lesions with adverse features or T2 lesions received postoperative chemoradiation. local excision was performed for T3 lesions only in high-risk patients or those who refused radical resection. In the TEMS group, there were 40 polyps, 5 carcinoma in situ, 21 T1 lesions, 7 T2 lesions, 8 T3 lesions, no indeterminate lesions, and 1 carcinoid lesion; in the transanal resection group, there were: 38 polyps, 4 carcinoma in situ, 20 T1 lesions, 19 T2 lesions, 6 T3 lesions, 1 indeterminate lesion, and 1 carcinoid lesion. There were 12 (15%) postoperative complications (4 major) in the TEMS group and 15 (17%) complications in the transanal resection group (6 major). In the TEMS group, 90% had negative tumor margins, and none had indeterminate margins vs 71% negative and 15% indeterminate margins in the transanal resection patients. Local recurrence was less frequent after TEMS (4%) than after transanal resection (24%; p=0.004). The difference between groups in distant recurrence was not statistically significant. Three TEMS patients with malignant lesions underwent radical resection and were excluded from recurrence analyses. The recurrence rate among cancer patients did not differ statistically between groups. For patients with adenomas, the overall recurrence rate after TEMS was 3% and 32% for transanal resection. In patients with polyps, clear margins were achieved more frequently after TEMS (83%) than after transanal resection (61%).

A number of studies identified have raised questions about disease recurrence after TEMS for stage T1 rectal cancer.^27,28,29, For example, Doornebosch et al (2010) reported on TEMS for 88 patients, 18 (20.5%) of whom had a local recurrence.^27, Of them, 16 patients had salvage surgery. At the 3-year follow-up, the OS rate was 31%, and the cancer-related survival rate was 58%. Authors concluded that further tailoring patient and tumor selection before a decision for LE might improve survival.

In an editorial accompanying this study, Friel (2010) commented on the use of LE in the treatment of T1 rectal lesions.^30, He noted that the reported recurrence rate should raise concerns and calls for additional studies of recurrence with LE to verify the Doornebosch et al (2010) findings. Friel (2010) also noted that LE must still be considered as an oncologic compromise between lower surgical morbidity but higher disease recurrence and that, once fully informed, patients may find this compromise acceptable.

Section Summary: Rectal Adenocarcinoma

The evidence on the use of TEMS for rectal adenocarcinoma consists of a limited number of RCTs, nonrandomized studies, and numerous case series. Two RCTs have compared TEMS with laparoscopic excision, rather than to standard TAE, and might have included overlapping populations. This evidence generally supports the conclusion that TEMS may be associated with lower complication rates than other surgical approaches but that local recurrence rates may be higher with TEMS. However, at least one RCT has reported that the complication rates with TEMS did not differ from those for laparoscopic resection. No differences in OS rates have been reported for TEMS vs other approaches. Overall, this evidence has demonstrated that TEMS has efficacy in treating early rectal cancer, but the evidence base is not sufficient to determine the comparative efficacy of TEMS and alternative techniques.

Summary of Evidence

For individuals who have rectal adenoma(s) who receive TEMS, the evidence includes a few nonrandomized comparative studies and numerous single-arm case series. The relevant outcomes are OS, functional outcomes, health status measures, QOL, and treatment-related morbidity. The evidence supports conclusions that the removal of polyps by TEMS is associated with low postoperative complication rates and low-risk of recurrence. However, due to the low quality of the evidence base, no conclusions can be made on the comparative efficacy of TEMS and standard procedures. The evidence is insufficient to determine the effects of the technology on health outcomes.

For individuals who have early rectal adenocarcinoma who receive TEMS, the evidence includes two small RCTs, a few nonrandomized comparative studies, and numerous single-arm case series. The relevant outcomes are OS, functional outcomes, health status measures, QOL, and treatment-related morbidity. The evidence supports conclusions that TEMS is associated with fewer postoperative complications but higher local recurrence rates and possibly higher rates of metastatic disease. There is no demonstrated difference in long-term OS with TEMS in available studies. However, due to the low quality of the evidence base, these conclusions lack certainty. The evidence is insufficient to determine the effects of the technology on health outcomes.

SUPPLEMENTAL INFORMATION

Clinical Input From Physician Specialty Societies and Academic Medical Centers

While the various physician specialty societies and academic medical centers may collaborate with and make recommendations during this process, through the provision of appropriate reviewers, input received does not represent an endorsement or position statement by the physician specialty societies or academic medical centers, unless otherwise noted.

In response to requests, input was received from 2 academic medical centers while this policy was under review in 2009. Input supported the policy statements adopted in 2009. One reviewer commented specifically that this technique should be limited to select T1 rectal cancers.

Practice Guidelines and Position Statements

National Comprehensive Cancer Network

The National Comprehensive Cancer Network (v.2.2019) in its updated guidelines on the treatment of rectal cancer, altered a statement on transanal local excision to exclude transanal endoscopic microsurgery (TEM).^31, It now states, “When the lesion can be adequately localized to the rectum, local excision of more proximal lesions may be technically feasible using advanced techniques, such as transanal microscopic surgery or transanal minimally invasive surgery (TAMIS).”

However, under discussion is the statement, “TEM can facilitate excision of small tumors through the anus when lesions can be adequately identified in the rectum. TEM may be technically feasible for more proximal lesions.”

National Cancer Institute

The CI(2019) guidelines on treatment of rectal cancer indicate the management of rectal cancer is multimodal and involves a multidisciplinary team of cancer specialists with expertise in gastroenterology, medical oncology, surgical oncology, radiation oncology, and radiology.^32, Based on the increased risk of local recurrence and poor overall prognosis, management of rectal cancer diverges from colon cancer. The differences include surgical technique, use of radiotherapy, and method of chemotherapy administration. Additional issues are maintenance or restoration of the normal anal sphincter and genitourinary function. The NCI recommends as a primary treatment for patients with rectal cancer surgical resection of the primary tumor. The NCI guidance specific to this policy includes “…Transanal local excision and transanal endoscopic microsurgery for select clinically staged T1/T2 N0 rectal cancers.

American Society of Colon and Rectal Surgeons

The American Society of Colon and Rectal Surgeons (2013) updated its 2010 practice parameters for the management of rectal cancer.^33, The 2013 guidelines indicated that curative local excision is an appropriate treatment modality for carefully selected, well to moderately differentiated T1 rectal cancers. Tumor size must be less than 3 cm in diameter and less than one-third of the bowel lumen circumference. Additionally, patients must not have a lymphovascular or perineural invasion. The guidelines noted that visualization with TEMS appears to be superior to the transanal approach, but randomized controlled trials are lacking. T2 lesions should be treated with radical mesenteric excision unless the patient is a poor candidate for a more extensive surgical procedure.

American College of Radiology

The ACR (2015) updated its 2010 appropriateness criteria on local excision of early-stage rectal cancer.^34,35,The ACR noted that TEMS is an appropriate operative procedure for locally complete excision of distal rectal lesions and has been “evaluated for curative treatment of invasive cancer.” ACR also noted that TEMS has “been shown to be as effective, and associated with less morbidity than conventional transanal excision” and is considered safe after treatment with chemoradiation. These ACR guidelines were based on expert consensus and analysis of current literature.

U.S. Preventive Services Task Force Recommendations

Not applicable.

Ongoing and Unpublished Clinical Trials

Some currently ongoing and unpublished trials that might influence this policy are listed in Table 9.

Table 9. Summary of Key Trials

NCT No.	Trial Name	Planned Enrollment	Completion Date
Ongoing
NCT01023984	Transanal Endoscopic Microsurgery Versus Endoscopic Submucosal Dissection For Large Rectal Adenomas (TEMENDO)	120	Dec 2019 (suspended)
NCT02885142	Early Rectal Cancer: Endoscopic Submucosal Dissection or Transanal Endoscopic Microsurgery? (MUCEM)	400	Nov 2020
NCT03718351	Randomized Controlled Trial of Endoscopic Submucosal Dissection Versus Transanal Endoscopic Microsurgery For Early Rectal Neoplasms And Large Rectal Adenomas: Comparison of Treatment Efficacy And Safety	236	Sep 2021

NCT: national clinical trial.

^a Denotes industry-sponsored or cosponsored trial.]
________________________________________________________________________________________

Horizon BCBSNJ Medical Policy Development Process:

This Horizon BCBSNJ Medical Policy (the “Medical Policy”) has been developed by Horizon BCBSNJ’s Medical Policy Committee (the “Committee”) consistent with generally accepted standards of medical practice, and reflects Horizon BCBSNJ’s view of the subject health care services, supplies or procedures, and in what circumstances they are deemed to be medically necessary or experimental/ investigational in nature. This Medical Policy also considers whether and to what degree the subject health care services, supplies or procedures are clinically appropriate, in terms of type, frequency, extent, site and duration and if they are considered effective for the illnesses, injuries or diseases discussed. Where relevant, this Medical Policy considers whether the subject health care services, supplies or procedures are being requested primarily for the convenience of the covered person or the health care provider. It may also consider whether the services, supplies or procedures are more costly than an alternative service or sequence of services, supplies or procedures that are at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of the relevant illness, injury or disease. In reaching its conclusion regarding what it considers to be the generally accepted standards of medical practice, the Committee reviews and considers the following: all credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, physician and health care provider specialty society recommendations, the views of physicians and health care providers practicing in relevant clinical areas (including, but not limited to, the prevailing opinion within the appropriate specialty) and any other relevant factor as determined by applicable State and Federal laws and regulations.

___________________________________________________________________________________________________________________________

Index:
Transanal Endoscopic Microsurgery (TEMS)
TEMS (Transanal Endoscopic Microsurgery)

References:
1. Barendse RM, van den Broek FJ, Dekker E, et al. Systematic review of endoscopic mucosal resection versus transanal endoscopic microsurgery for large rectal adenomas. Endoscopy. Nov 2011;43(11):941-949. PMID 21971923.

2. Middleton PF, Sutherland LM, Maddern GJ. Transanal endoscopic microsurgery: a systematic review. Dis Colon Rectum. Feb 2005;48(2):270-284. PMID 15711865.

3. Restivo A, Zorcolo L, D'Alia G, et al. Risk of complications and long-term functional alterations after local excision of rectal tumors with transanal endoscopic microsurgery (TEM). Int J Colorectal Dis. Feb 2016;31(2):257-266. PMID 26298182.

4. Issa N, Murninkas A, Schmilovitz-Weiss H, et al. Transanal endoscopic microsurgery after neoadjuvant chemoradiotherapy for rectal cancer. J Laparoendosc Adv Surg Tech A. Aug 2015;25(8):617-624. PMID 26258267.

5. Verseveld M, Barendse RM, Gosselink MP, et al. Transanal minimally invasive surgery: impact on quality of life and functional outcome. Surg Endosc. Mar 2016;30(3):1184-1187. PMID 26139488.

6. D'Ambrosio G, Paganini AM, Balla A, et al. Quality of life in non-early rectal cancer treated by neoadjuvant radio- chemotherapy and endoluminal loco-regional resection (ELRR) by transanal endoscopic microsurgery (TEM) versus laparoscopic total mesorectal excision. Surg Endosc. Feb 2016;30(2):504-511. PMID 26045097.

7. Verseveld M, de Graaf EJ, Verhoef C, et al. Chemoradiation therapy for rectal cancer in the distal rectum followed by organ-sparing transanal endoscopic microsurgery (CARTS study). Br J Surg. Jun 2015;102(7):853- 860. PMID 25847025.

8. Laliberte AS, Lebrun A, Drolet S, et al. Transanal endoscopic microsurgery as an outpatient procedure is feasible and safe. Surg Endosc. Dec 2015;29(12):3454-3459. PMID 25801107.

9. Samalavicius N, Ambrazevicius M, Kilius A, et al. Transanal endoscopic microsurgery for early rectal cancer: single center experience. Wideochir Inne Tech Maloinwazyjne. Dec 2014;9(4):603-607. PMID 25561999.

10. Mora Lopez L, Serra Aracil X, Hermoso Bosch J, et al. Study of anorectal function after transanal endoscopic surgery. Int J Surg. Jan 2015;13:142-147. PMID 25486265.

11. Hompes R, Ashraf SQ, Gosselink MP, et al. Evaluation of quality of life and function at 1 year after transanal endoscopic microsurgery. Colorectal Dis. Feb 2015;17(2):O54-61. PMID 25476189.

12. Stipa F, Picchio M, Burza A, et al. Long-term outcome of local excision after preoperative chemoradiation for ypT0 rectal cancer. Dis Colon Rectum. Nov 2014;57(11):1245-1252. PMID 25285690.

13. Verseveld M, Barendse RM, Dawson I, et al. Intramucosal carcinoma of the rectum can be safely treated with transanal endoscopic microsurgery; clinical support of the revised Vienna classification. Surg Endosc. Nov 2014;28(11):3210-3215. PMID 24939156.

14. Zacharakis E, Freilich S, Rekhraj S, et al. Transanal endoscopic microsurgery for rectal tumors: the St. Mary's experience. Am J Surg. Nov 2007;194(5):694-698. PMID 17936438.

15. Cataldo PA. Transanal endoscopic microsurgery. Surg Clin North Am. Aug 2006;86(4):915-925. PMID 16905416.

16. Al-Najami I, Rancinger CP, Larsen MK, et al. Transanal endoscopic microsurgery for advanced polyps and early cancers in the rectum-Long-term outcome: A STROBE compliant observational study. Medicine (Baltimore). Sep 2016;95(36):e4732. PMID 27603369.

17. Lu JY, Lin GL, Qiu HZ, et al. Comparison of transanal endoscopic microsurgery and total mesorectal excision in the treatment of T1 rectal cancer: a meta-analysis. PLoS One. Oct 2015;10(10):e0141427. PMID 26505895.

18. Clancy C, Burke JP, Albert MR, et al. Transanal endoscopic microsurgery versus standard transanal excision for the removal of rectal neoplasms: a systematic review and meta-analysis. Dis Colon Rectum. Feb 2015;58(2):254-261. PMID 25585086.

19. Sajid MS, Farag S, Leung P, et al. Systematic review and meta-analysis of published trials comparing the effectiveness of transanal endoscopic microsurgery and radical resection in the management of early rectal cancer. Colorectal Dis. Jan 2014;16(1):2-14. PMID 24330432.

20. Wu Y, Wu YY, Li S, et al. TEM and conventional rectal surgery for T1 rectal cancer: a meta-analysis. Hepatogastroenterology. Mar-Apr 2011;58(106):364-368. PMID 21661397.

21. Sgourakis G, Lanitis S, Gockel I, et al. Transanal endoscopic microsurgery for T1 and T2 rectal cancers: a meta- analysis and meta-regression analysis of outcomes. Am Surg. Jun 2011;77(6):761-772. PMID 21679648.

22. Doornebosch PG, Tollenaar RA, De Graaf EJ. Is the increasing role of Transanal Endoscopic Microsurgery in curation for T1 rectal cancer justified? A systematic review. Acta Oncol. Oct 2009;48(3):343-353. PMID 18855161.

23. Lezoche E, Baldarelli M, Lezoche G, et al. Randomized clinical trial of endoluminal locoregional resection versus laparoscopic total mesorectal excision for T2 rectal cancer after neoadjuvant therapy. Br J Surg. Sep 2012;99(9):1211-1218. PMID 22864880.

24. Lezoche G, Baldarelli M, Guerrieri M, et al. A prospective randomized study with a 5-year minimum follow-up evaluation of transanal endoscopic microsurgery versus laparoscopic total mesorectal excision after neoadjuvant therapy. Surg Endosc. Feb 2008;22(2):352-358. PMID 17943364.

25. Walega P, Kenig J, Richter P, et al. Functional and clinical results of transanal endoscopic microsurgery combined with endoscopic posterior mesorectum resection for the treatment of patients with t1 rectal cancer. World J Surg. Jul 2010;34(7):1604-1608. PMID 20174804.

26. Moore JS, Cataldo PA, Osler T, et al. Transanal endoscopic microsurgery is more effective than traditional transanal excision for resection of rectal masses. Dis Colon Rectum. Jul 2008;51(7):1026-1030; discussion 1030-1021. PMID 18481147.

27. Doornebosch PG, Ferenschild FT, de Wilt JH, et al. Treatment of recurrence after transanal endoscopic microsurgery (TEM) for T1 rectal cancer. Dis Colon Rectum. Sep 2010;53(9):1234-1239. PMID 20706065.

28. Tsai BM, Finne CO, Nordenstam JF, et al. Transanal endoscopic microsurgery resection of rectal tumors: outcomes and recommendations. Dis Colon Rectum. Jan 2010;53(1):16-23. PMID 20010345.

29. Allaix ME, Arezzo A, Caldart M, et al. Transanal endoscopic microsurgery for rectal neoplasms: experience of 300 consecutive cases. Dis Colon Rectum. Nov 2009;52(11):1831-1836. PMID 19966628.

30. Friel CM. Local excision of T1 rectal cancer: where are we now? [editorial]. Dis Colon Rectum. Sep 2010;53(9):1231-1233. PMID 20706064.

31. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Rectal Cancer. Version 2.2019. https://www.nccn.org/professionals/physician_gls/pdf/rectal.pdf. Accessed September 9, 2019.

32. National Cancer Institute (NCI). Rectal Cancer Treatment (PDQ). Healthcare Provider Version. https://www.cancer.gov/types/colorectal/hp/rectal-treatment-pdq#_43. Updated January 29, 2019. Accessed September 9, 2019.

33. Monson JR, Weiser MR, Buie WD, et al. Practice parameters for the management of rectal cancer (revised). Dis Colon Rectum. May 2013;56(5):535-550. PMID 23575392.

34. Blackstock W, Russo SM, Suh WW, et al. ACR Appropriateness Criteria: local excision in early-stage rectal cancer. Curr Probl Cancer. May-Jun 2010;34(3):193-200. PMID 20541057.

35. Russo S, Blackstock AW, Herman JM, et al. ACR Appropriateness Criteria(R) local excision in early stage rectal cancer. Am J Clin Oncol. Oct 2015;38(5):520-525. PMID 26371522.

Codes:
(The list of codes is not intended to be all-inclusive and is included below for informational purposes only. Inclusion or exclusion of a procedure, diagnosis, drug or device code(s) does not constitute or imply authorization, certification, approval, offer of coverage or guarantee of payment.)

CPT*

0184T