Research

JAMA | Original Investigation

Transanal vs Laparoscopic Total Mesorectal Excision

and 3-Year Disease-Free Survival in Rectal Cancer
The TaLaR Randomized Clinical Trial
Ziwei Zeng, MD; Shuangling Luo, MD; Hong Zhang, MD; Miao Wu, MD; Dan Ma, MD; Quan Wang, MD;
Ming Xie, MD; Qing Xu, MD; Jun Ouyang, MD; Yi Xiao, MD; Yongchun Song, MD; Bo Feng, MD; Qingwen Xu, MD;
Yanan Wang, MD; Yi Zhang, MD; Lishuo Shi, PhD; Li Ling, PhD; Xingwei Zhang, MD; Liang Huang, MD;
Zuli Yang, MD; Junsheng Peng, MD; Xiaojian Wu, MD; Donglin Ren, MD; Meijin Huang, MD; Ping Lan, MD;
Jianping Wang, MD; Weidong Tong, MD; Mingyang Ren, MD; Huashan Liu, MD; Liang Kang, MD;
for the Chinese Transanal Endoscopic Surgery Collaborative (CTESC) Group

Visual Abstract
IMPORTANCE Previous studies have demonstrated the advantages of short-term Supplemental content
histopathological outcomes and complications associated with transanal total mesorectal
excision (TME) compared with laparoscopic TME. However, the long-term oncological
outcomes of transanal TME remain ambiguous. This study aims to compare 3-year
disease-free survival of transanal TME with laparoscopic TME.

OBJECTIVE To evaluate 3-year disease-free survival between transanal TME and laparoscopic
TME in patients with rectal cancer.

DESIGN, SETTING, AND PARTICIPANTS This randomized, open-label, noninferiority, phase 3

clinical trial was performed in 16 different centers in China. Between April 2016 and June
2021, a total of 1115 patients with clinical stage I to III mid-low rectal cancer were enrolled. The
last date of participant follow-up was in June 2024.

INTERVENTIONS Participants were randomly assigned in a 1:1 ratio before their surgical
procedure to undergo either transanal TME (n = 558) or laparoscopic TME (n = 557).

MAIN OUTCOMES AND MEASURES The primary end point was 3-year disease-free survival, with
a noninferiority margin of −10% for the comparison between transanal TME and laparoscopic
TME. Secondary outcomes included 3-year overall survival and 3-year local recurrence.

RESULTS In the primary analysis set, the median patient age was 60 years. A total of 692 male
and 397 female patients were included in the analysis. Three-year disease-free survival was
82.1% (97.5% CI, 78.4%-85.8%) for the transanal TME group and 79.4% (97.5% CI,
75.6%-83.4%) for the laparoscopic TME group, with a difference of 2.7% (97.5% CI, −3.0% to
8.1%). The lower tail of a 2-tailed 97.5% CI for the group difference in 3-year disease-free
survival was above the noninferiority margin of −10 percentage points. Furthermore, the
3-year local recurrence was 3.6% (95% CI, 2.0%-5.1%) for transanal TME and 4.4% (95% CI,
2.6%-6.1%) for laparoscopic TME. Three-year overall survival was 92.6% (95% CI,
90.4%-94.8%) for transanal TME and 90.7% (95% CI, 88.3%-93.2%) for laparoscopic TME.

CONCLUSIONS AND RELEVANCE In patients with mid-low rectal cancer, 3-year disease-free
survival for transanal TME was noninferior to that of laparoscopic TME. Author Affiliations: Author
affiliations are listed at the end of this
TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02966483 article.
Group Information: The Chinese
Transanal Endoscopic Surgery
Collaborative (CTESC) Group
members are listed in Supplement 4.
Corresponding Author: Liang Kang,
MD, PhD, Department of General
Surgery (Colorectal Surgery),
Guangdong Provincial Key Laboratory
of Colorectal and Pelvic Floor
Diseases, Biomedical Innovation
Center, The Sixth Affiliated Hospital,
Sun Yat-sen University, No. 26
Yuancun Erheng Rd, Guangzhou,
JAMA. doi:10.1001/jama.2024.24276 Guangdong 510655, China (kangl@
Published online January 23, 2025. mail.sysu.edu.cn).

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 Research Original Investigation Transanal vs Laparoscopic TME and Disease-Free Survival in Patients With Rectal Cancer

C
olorectal cancer is a widespread disease, ranking as the
third-most common type of cancer worldwide.1 Spe- Key Points
cifically, rectal cancer accounts for more than one-
Question Is transanal total mesorectal excision (TME) noninferior
third of all colorectal cancer cases.1 The primary treatment for to laparoscopic TME in 3-year disease-free survival in patients with
rectal cancer typically involves a multidisciplinary approach, rectal cancer?
with surgical intervention as the cornerstone. Among surgi-
Findings The transanal TME group exhibited 3-year disease-free
cal techniques, total mesorectal excision (TME) is estab-
survival of 82.1%, compared with 79.4% in the laparoscopic TME
lished as the standard for mid and low rectal cancer.2,3 In re- group. The lower tail of a 2-tailed 97.5% CI for the group difference
cent years, laparoscopic TME has gained preference due to its in 3-year disease-free survival was above the noninferiority margin
advantages, such as enhanced postoperative recovery and re- of −10 percentage points.
duced complication rates. Furthermore, laparoscopic TME has
Meaning This study supports the use of transanal TME for patients
demonstrated comparable long-term oncological outcomes to preoperatively assessed with stage I to III rectal cancer in places
open TME.4-6 Nonetheless, managing obesity in male pa- where expertise in surgical robotic techniques is not available.
tients with a constricted pelvic space presents specific chal-
lenges. Laparoscopic TME may result in suboptimal resection
specimens, an increased complication rate, and a higher con- for rectal cancer from large-scale randomized clinical trials. At
version rate.7 present, trials such as COLOR III and ETAP-GRECCAR 11 are in
Robotic surgical procedures have become increasingly the enrollment phase.21,22 Consequently, this study aims to re-
popular in recent years. 8,9 The robotic system offers en- port 3-year long-term survival and locoregional recurrence in
hanced visualization of the surgical field and superior instru- patients randomly assigned to undergo either transanal TME
ment maneuverability with optimal stability. This allows for or laparoscopic TME within the framework of the TaLaR trial,
ambidextrous movements, reduces tremor, and improves dex- with a particular focus on 3-year disease-free survival.
terity, thereby enabling more precise dissection, even in con-
fined spaces. These advantages could override the daunting
challenges of laparoscopic TME. Compared with robotic sur-
gical procedures, transanal TME, which utilizes laparoscopic
Methods
instruments, has also garnered significant interest due to its Study Design and Participants
potential to enhance visualization and facilitate dissection in The TaLaR trial, a phase 3, multicenter, randomized, clinical
the distal portion of the TME procedure.10,11 Currently, trans- noninferiority study, recruited from April 2016 to June 2021
anal TME is considered an alternative method to address the to compare the long-term oncological outcomes of transanal
challenges of laparoscopic TME, particularly in regions lack- TME with laparoscopic TME in patients with rectal cancer. The
ing access to surgical robots. Several studies have reported fa- trial included 16 centers across 10 provinces in China. Institu-
vorable results with transanal TME, indicating it may yield tional review board approval was obtained from each partici-
higher-quality resected specimens and achieve similar or im- pating hospital, and written informed consent was obtained
proved short-term outcomes compared with laparoscopic from all patients. Randomization of eligible patients in a 1:1 ra-
TME.12-14 Moreover, the benefits of transanal TME for postop- tio between transanal TME and laparoscopic TME treatments
erative recovery, quality of TME, and sphincter preservation was facilitated through a web-based system at the data cen-
have contributed to its growing adoption by surgeons for the ter in Guangzhou, China. The study followed the Consoli-
management of mid-low rectal cancers.14,15 Nonetheless, 2019 dated Standards of Reporting Trials (CONSORT) reporting
data from the Norwegian Colorectal Cancer Group reported a guidelines.
local recurrence rate of 7.9% (12/152) among patients treated The eligibility criteria for this trial included patients aged
with transanal TME, with 6 patients experiencing multiple lo- 18 to 75 years with an American Society of Anesthesiologists
cal recurrences and 8 patients encountering local recurrence class I to III classification, a diagnosis of clinical stage I to III
within 1 year.16 In contrast, the local recurrence rate in co- rectal adenocarcinoma located below the peritoneal reflec-
horts from the Norwegian Colorectal Cancer Registry was 3.4%, tion confirmed by preoperative imaging, and potential candi-
leading to the suspension of transanal TME in Norway.16 Fur- dates for curative treatment using sphincter-sparing tech-
thermore, a Dutch study reported a high incidence of local re- niques following TME principles. Exclusion criteria comprised
currences (10% [12/120]) in an implementation cohort, includ- patients with T1 cancers amenable to local resection, con-
ing a significant rate of multifocal recurrences.17 These findings firmed involvement of the circumferential resection margin
have raised substantial concerns regarding the oncological by preoperative imaging, those who underwent an abdomi-
safety of transanal TME.18 noperineal resection, tumors involving the internal sphinc-
Although the Ta-LaTME study group reported undimin- ter or levator ani, and patients with contraindications for sur-
ished short-term outcomes between transanal TME and lapa- gical procedures. Patients underwent preoperative pelvic
roscopic TME,19 and the TaLaR trial demonstrated compa- magnetic resonance imaging for rectal cancer and computed
rable surgical safety of transanal TME and laparoscopic TME tomography for thoracic and abdominal conditions to ex-
with improved recovery time for patients with mid-low rec- clude distant metastases. The detailed study protocol and com-
tal cancer,20 evidence is still lacking to establish the effective- prehensive statistical analysis plan were approved and acces-
ness of long-term oncological outcomes of transanal TME sible in Supplement 1 and Supplement 2, respectively.

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 Transanal vs Laparoscopic TME and Disease-Free Survival in Patients With Rectal Cancer Original Investigation Research

Randomization and Masking Outcomes

Eligible patients were randomized preoperatively in a 1:1 ra- In this analysis, the primary outcome measure focused spe-
tio to undergo either transanal TME or laparoscopic TME cifically on 3-year disease-free survival, while secondary out-
through a web-based randomization system utilizing central comes included 3-year overall survival and 3-year local recur-
allocation and stratification by center. Participating centers sub- rence. As of June 2024, this trial had a minimum follow-up
mitted patient information to the data center at the Sixth period of 36 months postprocedure. Disease-free survival was
Affiliated Hospital of Sun Yat-sen University in Guangzhou, defined as the time from intervention to disease or death from
China, where central randomization was conducted. Informa- any cause, censored at the last day the patient was alive with-
tion regarding treatment assignments was subsequently com- out evidence of disease. If there were no follow-up data on
municated to each participating center. After completing ran- death or tumor recurrence, the final date of no relapse was con-
domization, neither surgeons nor patients were masked to the firmed as the termination point. A detailed definition of the
treatment assignment. Detailed randomization information is outcomes is presented in Supplement 1.
available in Supplement 1.
Statistical Analysis
Surgical Quality Control and Procedure The sample size was calculated using PASS software. The
Surgeons were selected from the membership of the Chinese estimated sample size for this trial was 1114 participants.
Transanal Endoscopic Surgery Collaborative (CTESC) Group, The assumptions underlying the sample size calculation
with eligibility criteria defined as follows: (1) completion of at were based on 3-year disease-free survival or 5-year overall
least 100 laparoscopic TME and 50 transanal TME procedures survival among patients with clinical stage I to III rectal can-
by each surgical team; (2) an anticipated annual caseload of cer treated with laparoscopic TME. Based on trials comparing
at least 50 laparoscopic TME and 30 transanal TME proce- laparoscopic and open surgical procedures, which have used
dures; and (3) confirmation of qualification by the CTESC a noninferiority margin ranging from 5% to 15% for 3-year
Research Committee, which required the evaluation of uned- oncological outcomes, 5,23,24 a noninferiority margin of
ited videos from 2 laparoscopic TME and 2 transanal TME 10% for 3-year disease-free survival was selected for the cur-
procedures performed on obese male patients (body mass rent study. The anticipated 3-year disease-free survival and
index [BMI; calculated as weight in kilograms divided by 5-year overall survival were set at 74.6% and 77.4%, respec-
height in meters squared] ≥28) with rectal cancer below the tively. An α error rate of 2.5% was allocated to each of the
peritoneal reflection. disease-free survival and overall survival end points, based
Surgical quality control was ensured through the re- on a Bonferroni correction, and a 2-tailed 97.5% CI was calcu-
view of unedited videos by the CTESC Research Committee, lated to evaluate each of the 2 end points. If the lower 1.25%
which provided regular feedback to the investigators. Both tail of the CI of difference in 3-year disease-free survival
transanal TME and laparoscopic TME procedures were per- between the 2 groups was larger than the noninferiority mar-
formed in accordance with TME principles. The key distinc- gin of −10% difference, then transanal TME would be demon-
tion was that transanal TME was performed from a transanal strated to be noninferior to laparoscopic TME. The sample
bottom-up approach. The methods of anastomosis were not size was based on a designed power of 80% for both 3-year
uniform, allowing for either handsewn or stapled anastomo- disease-free survival and 5-year overall survival. This rela-
sis. Detailed information on the procedure is available in tively wide noninferiority margin was considered acceptable
Supplement 1. to clinicians and patients, given the expectation that trans-
anal TME might be superior to laparoscopic TME in terms
Follow-Up of less surgical trauma, quicker recovery, and higher rates of
The follow-up process was rigorously managed by special- sphincter preservation.14,20
ized teams at each participating research center, which were By June 2024, this trial had a minimum follow-up of 36
responsible for scheduling and conducting regular assess- months for patients after the surgical procedure, which
ments at predetermined intervals. In the first year after the would achieve sufficient power to test a noninferiority mar-
surgical procedure, follow-up evaluations were conducted gin of −10% for the comparison of the 2 groups in 3-year
every 3 months, followed by every 6 months in the second disease-free survival. Consequently, the primary outcome
year, and annually thereafter. Tumor marker examinations reported in this study centered on 3-year disease-free sur-
were performed at each designated time point. Colonosco- vival. The evaluation of 3-year disease-free survival was con-
pies, chest and abdominal computed tomographic scans, ducted in the primary analysis set, excluding patients who
and pelvic magnetic resonance imaging were scheduled at were later discovered not to have met the inclusion criteria at
3, 12, 24, 36, 48, and 60 months postprocedure. Additional baseline. In the transanal TME group, no patients underwent
imaging examinations were recommended if symptoms or laparoscopic TME and no patients in the laparoscopic TME
examination results indicated potential local recurrence or group underwent transanal TME. For this analysis, the
metastasis. Patients who refused follow-up according to the primary analysis set and per-protocol populations were iden-
protocol were recorded as lost to follow-up and analyzed tical. Noninferiority of transanal TME to laparoscopic
with the cases meeting the study criteria at the end of the TME would be accepted if the lower tail of the estimated dif-
study. The detailed follow-up outline is presented in ference in 3-year disease-free survival, represented by the
Supplement 1. 97.5% CI, was above −10%.

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 Research Original Investigation Transanal vs Laparoscopic TME and Disease-Free Survival in Patients With Rectal Cancer

Figure 1. Flow of Patient Enrollment and Randomization

1479 Assessed for eligibility

364 Excluded
246 Declined enrollment
98 Enrollment in other trials
13 Emergency surgical procedure
7 Other

1115 Randomized

558 Randomized to undergo transanal TME 557 Randomized to undergo laparoscopic TME

14 Excluded 12 Excluded
6 Withdrew consent 4 Withdrew consent
3 Underwent Miles operationa 2 Found distant metastases
3 Postoperative pathology was not rectal intraoperativelyc
adenocarcinoma 4 Underwent Miles operationa
2 Underwent procedure as randomized, 1 Postoperative pathology was not rectal
but did not provide proper consentb adenocarcinoma
1 Underwent procedure as randomized,
but later refused consentd

544 Underwent transanal TME and 545 Underwent laparoscopic TME and
included in the primary analysis sete included in the primary analysis sete

c
TME indicates total mesorectal excision. Patients were found to have peritoneal metastasis (n = 1) or liver metastasis
a
Surgeons decided to perform the abdominoperineal resection (Miles (n = 1) intraoperatively.
d
operation) procedure, according to the specific intraoperative circumstances. After the procedure, the patient refused to participate and have their data
The Miles operation is used for the treatment of rectal cancers, involving the used in any analysis.
removal of the distal colon, rectum, and anal sphincter complex, resulting in e
The primary analysis set excluded patients who were later discovered not to
a permanent colostomy. have met the inclusion criteria at baseline.
b
Two patients randomized to undergo transanal TME did not provide proper
consent; hence, their data could not be used in any analysis.

The primary analysis was performed using a Cox propor-

tional hazards model to calculate hazard ratios (HRs) with Results
97.5% CIs for 3-year disease-free survival and 95% CIs for
3-year overall survival and local recurrence, applying the log- Patient Characteristics
rank test to calculate the P value. Three-year disease-free sur- The detailed short-term results were previously reported.20
vival, overall survival, and local recurrence were estimated From April 2016 to June 2021, a total of 1115 patients were en-
by Kaplan-Meier survival curves, along with corresponding rolled from 16 medical centers in China. As shown in Figure 1,
97.5% CIs for 3-year disease-free survival and 95% CIs for the primary analysis set included 544 in the transanal TME
overall survival and local recurrence. Prior to analysis, the group and 545 in the laparoscopic TME group. Baseline char-
proportional hazards assumption was evaluated using the acteristics and pathological outcomes are shown in Table 1
Schoenfeld residuals test. Univariate and multivariable Cox (eTable 1 in Supplement 3), and the overall missing rate was
regression analyses were performed to estimate mean and 1.3% (14/1089). In this study, there were 359 and 333 male pa-
secondary survival outcomes for 3-year disease-free survival tients and 150 and 121 obese patients in the transanal TME and
and overall survival, with 95% CIs and P values between laparoscopic TME groups, respectively.
groups according to the HR accompanied by their 95% CI.
Participants who refused follow-up according to the protocol Primary Outcome
after treatment were considered missing, and all values col- The incidence of recurrence within 3 years postprocedure
lected during the follow-up period were censored to assess was reported in 86 patients in the transanal TME group and
the potential effect of any missing data. All statistical tests 96 patients in the laparoscopic TME group (Table 2). Overall
were 2-sided and, while specific P values are presented, 3-year disease-free survival was 80.7% (97.5% CI, 78.1%-
those less than .05 were considered statistically significant. 83.5%), with 82.1% (97.5% CI, 78.4%-85.8%) in the transanal
All statistical analyses were performed using SAS version 9.3 TME group and 79.4% (97.5% CI, 75.6%-83.4%) in the laparo-
(SAS Institute). This trial utilized a data monitoring commit- scopic TME group (Figure 2) (eTable 2 in Supplement 3). The
tee and is registered with ClinicalTrials.gov (NCT02966483). difference in 3-year disease-free survival between the 2

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 Transanal vs Laparoscopic TME and Disease-Free Survival in Patients With Rectal Cancer Original Investigation Research

Table 1. Patient Clinical and Histopathological Characteristics

Transanal total Laparoscopic total
mesorectal excision, No. (%) mesorectal excision, No. (%)
Characteristic (n = 544) (n = 545)
Sex
Male 359 (66.0) 333 (61.1)
Female 185 (34.0) 212 (38.9)
Age, median (IQR), y 58 (50-67) 60 (52-67)
BMI, median (IQR) 22.9 (20.7-24.9) 22.8 (20.9-24.8)
ASA classificationa
I (Normal) 228 (41.9) 219 (40.2)
II 279 (51.3) 270 (49.5)
III 37 (6.8) 56 (10.3) Abbreviations: ASA, American
Society of Anesthesiologists;
Tumor distance from anal verge, median (IQR), cm 5.0 (3.9-6.0) 5.5 (4.4-6.6)
BMI, body mass index (calculated as
Preoperative clinical stageb weight in kilograms divided by height
I (Less advanced) 105 (19.3) 89 (16.3) in meters squared).
a
II 220 (40.4) 243 (44.6) ASA categorizes patients into 5
levels: I, normal, healthy;
III (More advanced) 219 (40.3) 213 (39.1)
II, mild systemic disease; III, severe
Preoperative therapy 211 (38.8) 179 (32.8) systemic disease; IV, severe
Chemotherapy plus radiation 93 (17.1) 59 (10.8) systemic disease that is a constant
threat to life; V, moribund
Chemotherapy alone 116 (21.3) 120 (22.0)
undergoing surgical procedures or
Radiation alone 2 (0.4) 0 not, with little chance for survival.
Pathological stagec b
According to 7th edition of
I (Less advanced) 174 (32.0) 165 (30.3) American Joint Committee on
Cancer Staging System, clinical
II 179 (32.9) 183 (33.6) stage I includes T1 or T2 with N0M0;
III (More advanced) 164 (30.1) 173 (31.7) II, T3 or T4 with N0M0; III, any T
Pathologic complete response 27 (5.0) 24 (4.4) with N1M0 or N2M0; IV, any T or N
with M1. Clinical stage evaluated by
Macroscopic completeness of resection preoperative imaging.
Complete 487 (89.5) 469 (86.1) c
Pathological stage I includes T1 or T2
Nearly complete 57 (10.5) 76 (13.9) with N0M0; II, T3 or T4 with N0M0;
Circumferential resection margind III, any T with N1M0 or N2M0; IV,
any T or N with M1. Pathologic
Positive (≤1 mm) 5 (0.9) 5 (0.9) complete response defined as
Distal resection margine absence of malignant cells on
Positive (≤1 mm) 2 (0.4) 4 (0.7) specimen of rectal resection in
patients previously treated with
No. of harvested lymph nodes, median (IQR) 14 (10-19) 15 (11-20) preoperative therapy. Pathological
Tumor differentiation stage evaluated by rectal resection
Well 45 (8.3) 34 (6.2) specimen.
d
Involvement of the circumferential
Moderate 430 (79.0) 443 (81.3)
resection margin considered if
Poor 42 (7.7) 44 (8.1) distance ⱕ1 mm from tumor to
Lymphovascular invasion 71 (13.1) 84 (15.4) mesorectal fascia.
e
Nerve invasion 63 (11.6) 56 (10.3) Positive distal resection margin
defined if distance between closest
Adjuvant chemotherapy 297 (54.6) 301 (55.2)
tumor to cut edge of tissue ⱕ1 mm.

groups was 2.7% (97.5% CI, −3.0% to 8.1%), with an HR of (stage I: HR, 1.29 [95% CI, 0.61-2.73]; stage II: HR, 0.68 [95% CI,
0.86 (97.5% CI, 0.63-1.18). The lower tail of a 2-tailed 97.5% 0.41-1.11]; stage III: HR, 0.97 [95% CI, 0.67-1.40]).
CI for the group difference in 3-year disease-free survival was
above the noninferiority margin of −10 percentage points Secondary Outcomes
(Figure 3) (eTable 2 in Supplement 3). A similar HR was A total of 19 patients in the transanal TME group and 23 pa-
observed after adjusting for age, sex, pathological stage, neo- tients in the laparoscopic TME group experienced a local re-
adjuvant treatment, tumor differentiation, lymphovascular currence within 3 years postprocedure. No patients experi-
invasion, and nerve invasion (HR, 0.83 [95% CI, 0.63-1.10]) enced multifocal local recurrence. Three-year local recurrence
(eTable 3 in Supplement 3). for all patients was 4.0% (95% CI, 2.8%-5.2%), with the trans-
As shown in Figure 2 and eTable 4 in Supplement 3, there anal TME group at 3.6% (95% CI, 2.0%-5.1%) and the laparo-
were no significant differences between the transanal TME and scopic TME group at 4.4% (95% CI, 2.6%-6.1%), demonstrat-
laparoscopic TME groups across different pathological stages ing similar rates (HR, 0.81 [95% CI, 0.44-1.49]) (eFigure 1 in

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 Research Original Investigation Transanal vs Laparoscopic TME and Disease-Free Survival in Patients With Rectal Cancer

Table 2. Frequency of Causes of First Recurrence and Death Within 3 Years After Surgical Procedure in Patients Who Underwent Transanal
Total Mesorectal Excision (TME) or Laparoscopic TME

No. of events
Transanal TME Laparoscopic TME Difference Hazard ratio
Event (n = 544) (n = 545) (95% CI), %a (95% CI)b P valuec
d
Recurrence 86 96 −1.8 (−6.4 to 2.8) 0.88 (0.66 to 1.18) .41
Locale 14 18 −0.7 (−2.9 to 1.5) 0.77 (0.38 to 1.54) .46
Liver 9 11 −0.4 (−2.1 to 1.4) 0.81 (0.34 to 1.95) .64
Lung 17 25 −1.5 (−3.9 to 1.0) 0.67 (0.36 to 1.24) .20
Multiple sitesf 28 27 0.2 (−2.6 to 3.0) 1.02 (0.60 to 1.74) .93
Other or uncertain sitesg 18 15 0.6 (−1.7 to 2.8) 1.18 (0.60 to 2.35) .63
Deathh 40 50 −1.8 (−5.3 to 1.6) 0.79 (0.52 to 1.20) .27
Rectal cancer 29 37 −1.5 (−5.3 to 1.6) 0.78 (0.48 to 1.26) .31
Other causei 11 13 −0.4 (−2.3 to 1.6) 0.83 (0.37 to 1.86) .66
a d
For outcomes other than all-cause death, the risk difference was calculated by Refers solely to first-time recurrence, even though patients may have
subtracting the cumulative incidence over the first 3 years in the transanal experienced multiple recurrences.
TME group from that of the laparoscopic TME group, considering competing e
Includes patients with local recurrence.
events. For all-cause death, the risk difference was determined by subtracting f
Includes patients with simultaneous recurrences at 2 or more sites, such as
the 3-year overall survival rate of the transanal TME group from that of the
local, peritoneum, liver, lung, bone, brain, distant lymph node, or other
laparoscopic TME group.
hematogenous metastatic site.
b
For outcomes other than all-cause death, competing risks survival regression g
Encompasses hematogenous recurrences at sites other than local recurrence,
was used to derive the hazard ratio, 95% CI, and P value. For total recurrence,
liver, and lung, such as recurrences at distant lymph nodes, brain, bone,
all-cause death was treated as a competing event. For specific types of
peritoneum, and unspecified sites.
recurrence, other types of recurrence and death were treated as competing
h
events. For deaths due to rectal cancer, other causes of death were treated as Post hoc exploratory outcomes.
competing events and vice versa. Mixed-effects Cox regression was used for i
Encompasses deaths from other cancers, noncancer diseases, unintentional
all-cause death. injuries, and unknown causes.
c
P values correspond to the hazard ratios.

Supplement 3). eFigure 1 and eTable 4 in Supplement 3 indi- TME groups, respectively (HR, 0.74 [95% CI, 0.42-1.31]). Among
cate no significant difference in 3-year local recurrence be- patients who received preoperative therapy, the rates were
tween the 2 groups across different pathological stages (stage 76.2% in the transanal TME group and 77.6% in the laparo-
I: HR, 0.96 [95% CI, 0.24-3.84]; stage II: HR, 0.49 [95% CI, 0.17- scopic TME group (HR, 1.08 [95% CI, 0.71-1.63]). For tumors
1.45]; stage III: HR, 1.28 [95% CI, 0.50-3.24]). larger than 3 cm, the rates were 78.7% for transanal TME and
At 3 years postprocedure, 90 patients had died (Table 2), 76.4% for laparoscopic TME (HR, 0.89 [95% CI, 0.60-1.32]).
yielding a 3-year overall survival of 92.6% (95% CI, 90.4%-
94.8%) in the transanal TME group and 90.7% (95% CI, 88.3%- Three-Year Overall Survival
93.2%) in the laparoscopic TME group (HR, 0.78 [95% CI, 0.52- In subgroup analysis (eFigure 4 in Supplement 3), 3-year over-
1.19]) (eFigure 2 in Supplement 3). The cumulative incidence all survival for male patients was 93.0% in the transanal TME
of cause-specific death did not significantly differ between the group compared with 89.3% in the laparoscopic TME group
2 groups (Table 2). As shown in eFigure 2 and eTable 4 in (HR, 0.64 [95% CI, 0.38-1.06]). For patients with a BMI of
Supplement 3, when analyzed by pathological stage, 3-year greater than 25, the rates were 92.5% in the transanal TME
overall survival was comparable between groups in patients group and 89.8% in the laparoscopic TME group (HR, 0.72
with stages I and II rectal cancer (stage I: HR, 3.40 [95% CI, 0.71- [95% CI, 0.49-1.64]). Among patients with tumors larger than
16.36]; stage II: HR, 1.36 [95% CI, 0.63-2.97]), but in stage III 3 cm, the rates were 91.9% for transanal TME and 86.6% for
patients, the transanal TME group had better overall survival laparoscopic TME (HR, 0.58 [95% CI, 0.32-1.05]).
compared with the laparoscopic TME group (stage III: HR, 0.51
[95% CI, 0.29-0.89]). A similar HR was observed after adjust-
ing for age, sex, neoadjuvant treatment, pathological stage, tu-
mor differentiation, lymphovascular invasion, and nerve in-
Discussion
vasion (HR, 0.77 [95% CI, 0.50-1.17]) (eTable 3 in Supplement 3). This study previously demonstrated that circumferential re-
section margin positivity, macroscopic quality of the TME
Subgroup Analysis specimen, the number of harvested lymph nodes, and peri-
Three-Year Disease-Free Survival operative morbidity were comparable between the transanal
Three-year disease-free survival for male patients was 81.4% TME and laparoscopic TME groups. Additionally, patients who
in the transanal TME group and 76.2% in the laparoscopic TME underwent transanal TME exhibited faster postoperative
group (HR, 0.75 [95% CI, 0.54-1.05]) (eFigure 3 in Supple- recovery.20 This study aimed to report 3-year disease-free sur-
ment 3). For patients with a BMI of greater than 25, the rates vival in patients with rectal cancer treated with either trans-
were 84.4% and 78.7% in the transanal TME and laparoscopic anal TME or laparoscopic TME. The findings indicate that 3-year

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 Transanal vs Laparoscopic TME and Disease-Free Survival in Patients With Rectal Cancer Original Investigation Research

Figure 2. Cumulative Probability of Recurrence or Death for Transanal Total Mesorectal Excision (TME) vs Laparoscopic TME
Within 3 Years of Procedurea

A All stages

30

Recurrence or death, %
25

20
Laparoscopic TME
15
Transanal TME
10

0 12 24 36
Months
No. of participants at risk
Transanal TME 544 511 472 445
Laparoscopic TME 545 509 460 434
No. of recurrences
Transanal TME 0 30 40 16
Laparoscopic TME 0 31 41 24
No. of deaths
Transanal TME 0 7 9 24
Laparoscopic TME 0 9 19 22

B Pathologic complete response C Stage I

30 30
Recurrence or death, %

Recurrence or death, %
25 25

20 20

15 15

10 10
Laparoscopic TME Laparoscopic TME
5 5
Transanal TME Transanal TME
0 0

0 12 24 36 0 12 24 36
Months Months
No. of participants at risk No. of participants at risk
Transanal TME 27 27 27 27 Transanal TME 174 170 164 156
Laparoscopic TME 24 24 22 22 Laparoscopic TME 165 161 159 154
No. of recurrences No. of recurrences
Transanal TME 0 0 0 0 Transanal TME 0 2 5 5
Laparoscopic TME 0 1 1 0 Laparoscopic TME 0 4 2 4
No. of deaths No. of deaths
Transanal TME 0 0 0 0 Transanal TME 0 1 2 4
Laparoscopic TME 0 0 1 1 Laparoscopic TME 0 0 0 2

D Stage II E Stage III

30 50
Recurrence or death, %

Recurrence or death, %

25 40
Laparoscopic TME
20 Laparoscopic TME
30
15 Transanal TME
20
10
Transanal TME
5 10

0 0

0 12 24 36 0 12 24 36
Months Months
No. of participants at risk No. of participants at risk
Transanal TME 179 170 159 152 Transanal TME 164 144 122 110
Laparoscopic TME 183 173 155 145 Laparoscopic TME 173 151 124 113
No. of recurrences No. of recurrences
Transanal TME 0 9 12 2 Transanal TME 0 19 23 9
Laparoscopic TME 0 6 16 12 Laparoscopic TME 0 20 22 8
No. of deaths No. of deaths
Transanal TME 0 2 3 10 Transanal TME 0 4 4 10
Laparoscopic TME 0 2 5 4 Laparoscopic TME 0 7 13 15

a
Recurrences and deaths indicate new incidents at each time point.

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 Research Original Investigation Transanal vs Laparoscopic TME and Disease-Free Survival in Patients With Rectal Cancer

transanal TME compared with laparoscopic TME in male pa-

Figure 3. Difference in 3-Year Disease-Free Survival Between Transanal
Total Mesorectal Excision (TME) and Laparoscopic TME Groupsa
tients (disease-free survival: HR, 0.75; overall survival: HR,
0.64) and patients with a BMI greater than 25 (disease-free sur-
Favors laparoscopic TME Favors transanal TME vival: HR, 0.74; overall survival: HR, 0.72) (eFigures 3 and 4
in Supplement 3). Considering the characteristics of rectal can-
Noninferiority margin cer in European and US populations, where obese or male pa-
tients are more prevalent, this procedure may have signifi-
cant clinical application value.1 Notably, these trends not
achieving statistical significance may be due to limited sample
–15 –10 –5 0 5 10 15
sizes in the subgroup analyses. Further studies with larger
Difference in 3-year disease-free survivalb
sample sizes are needed to validate these findings.
a
Difference between transanal TME and laparoscopic TME was 2.7% (97.5% CI, Concerns regarding the long-term oncological outcomes
−3.0% to 8.1%). of transanal TME for rectal cancer are reminiscent of those
b
Transanal TME − laparoscopic TME. associated with the initial adoption of laparoscopic TME.
Studies by Larsen et al and Oostendorp et al reported local
disease-free survival for transanal TME is noninferior to that recurrence of 7.9% and 10%, respectively, in patients who
of laparoscopic TME. Furthermore, this trial demonstrated that underwent transanal TME.16,17 Inadequate purse-string clo-
3-year overall survival and 3-year local recurrence in patients sure of the rectum and intraoperative rectal injury may con-
with rectal cancer who underwent transanal TME were com- tribute to multifocal local recurrences.18 Given the learning
parable to those who underwent laparoscopic TME. curve associated with new surgical techniques, transanal
Although transanal TME was introduced more than a de- TME follows a trajectory like that of laparoscopic TME for
cade ago, several retrospective studies have found that the rectal cancer.14,27 Studies have indicated that the effective
oncological outcomes of transanal TME are comparable to learning curve for laparoscopic rectal surgical procedures
those of laparoscopic TME; the lack of high-quality random- ranges from 40 to 80 cases.4,28,29 The investigators’ previous
ized clinical trials to report these outcomes highlights an ur- study identified that the primary surgeon surpassed the
gent need for rigorous research to provide robust evidence. learning curve after 42 cases.14 Therefore, to ensure that par-
For instance, Hol et al reported a 2.0% local recurrence with a ticipating surgeons have surpassed the learning curve, the
minimum follow-up of 36 months in 159 patients, with 3-year unedited videos of 2 laparoscopic TME and 2 transanal TME
disease-free survival and overall survival of 83.6% and procedures needed to be reviewed by the CTESC group, spe-
92.0%, respectively.25 Roodbeen et al reported a 3.3% local cifically in obese male patients with rectal cancer below the
recurrence with a median follow-up of 25.5 months in 767 peritoneal reflection. Additionally, the frequency of transanal
patients with rectal cancer, with 3-year disease-free survival TME and laparoscopic TME procedures performed by the
and overall survival of 77.6% and 93.4%, respectively.26 As participating surgeons was also an important consideration
the first and largest randomized clinical trial to date compar- for the study. In this study, the local recurrence was 3.6% in
ing the long-term oncologic outcomes of transanal TME and the transanal TME group and 4.4% in the laparoscopic TME
laparoscopic TME, this study confirms that disease-free sur- group (HR, 0.81 [95% CI, 0.44-1.49]), indicating comparabil-
vival of the transanal TME group was noninferior to that of ity and acceptability. The major site of local recurrence was
the laparoscopic TME group (82.1% vs 79.4%; difference, the anastomotic area, with no multifocal local recurrence
2.7% [97.5% CI, −3.0% to 8.1%]; HR, 0.86 [97.5% CI, 0.63- reported. Thus, transanal TME can provide comparable
1.18]). Furthermore, overall survival was similar between the 3-year oncological outcomes to laparoscopic TME when per-
2 groups (92.6% vs 90.7%). Similar rates of disease-free sur- formed by experienced surgeons.
vival were observed in patients diagnosed at the same patho- The safety and feasibility of robotic procedures for rectal
logical stage. It is worth noting that the transanal TME group cancer have been well established.8,9 Peirce et al reported that
exhibited better overall survival compared with the laparo- robotic procedures offer improved urinary and erectile func-
scopic TME group in patients with stage III cancer (HR, 0.51 tion in male patients compared with conventional laparo-
[95% CI, 0.29-0.89]). These results suggest that transanal scopic procedures for rectal cancer.30 Larson et al demon-
TME is a viable option for patients with mid-low rectal can- strated that robotic rectal cancer procedures are associated with
cer, potentially offering advantages over laparoscopic TME in better short-term outcomes, including lower complication rates
3-year survival outcomes. However, further studies are nec- and reduced conversion to an open surgical procedure.31 Feng
essary to validate these findings. et al found that robotic procedures result in higher oncologi-
In patients with a relatively narrow pelvic surgical space, cal quality of resection, reduced surgical trauma, and im-
transanal TME is considered to enhance surgical quality and proved postoperative recovery compared with conventional
may improve patient outcomes.10 It is generally accepted that laparoscopic techniques.32 Compared with surgical robots,
males and obese patients have a relatively narrow surgical transanal TME also offers distinct advantages in accessing
space. In this study, according to criteria for obesity in Asian the distal rectum and operating within the narrow confines of
populations, individuals with a BMI greater than 25 were clas- the pelvis, making it a valuable approach in the management
sified as obese. Subgroup analysis indicated a trend toward im- of rectal cancer in areas where expertise in surgical robotic tech-
proved 3-year disease-free survival and overall survival with niques is not available. However, addressing the learning curve

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 Transanal vs Laparoscopic TME and Disease-Free Survival in Patients With Rectal Cancer Original Investigation Research

associated with transanal TME is crucial and it is imperative pertise in this technique. Second, all study patients included
to explore strategies to assist surgeons in overcoming this in this trial underwent sphincter-sparing surgical proce-
challenge. Based on experience, adverse outcomes associ- dures, preventing adequate assessment of the effects of trans-
ated with the learning curve can be mitigated through animal anal TME on sphincter preservation. Third, it is important to
models, comprehensive gross experiments, standardized train- note that all participating centers in this trial were in China.
ing programs, and the initial selection of patients with earlier- Given the unique demographic characteristics of the Asian
stage disease who have not undergone neoadjuvant chemo- population, caution is advised when applying the findings to
radiotherapy for transanal TME. Presently, the application of patients from other racial and ethnic backgrounds. Fourth,
single-port surgical robots exhibits notable flexibility in con- despite the large sample size of this study, it had limited
fined spaces and high compatibility with the natural anatomy power to detect small effect sizes that may nevertheless be
of the anus. This could potentially expedite the implementa- clinically important. Specifically, the lower tail of the esti-
tion of robotic transanal TME and facilitate its mastery; how- mate for 3-year disease-free survival difference was −3%, cor-
ever, further research and validation are required.33,34 Fur- responding to an upper limit of an HR of 1.18, indicating that
thermore, the application of artificial intelligence in transanal the hazard rate of adverse events could be up to 18% higher
TME procedures can assist in recognizing surgical dimen- for patients who underwent transanal TME. Fifth, given the
sions during operations and guide surgeons in real-time re- limited availability of surgical robots in China at the time this
sections. This technology may also aid surgeons in swiftly and study was conducted, it did not include a robotic surgical
accurately identifying relevant anatomical structures, thereby procedure group in the design. In future research, the investi-
enhancing their mastery of transanal TME. 35,36 Conse- gators plan to include robotic surgical procedures as an
quently, transanal TME is likely to continue being promoted experimental group.
as an alternative treatment for rectal cancer in areas where ex-
pertise in surgical robotic techniques is not available.

Conclusions
Limitations
This study has limitations. First, the participating surgeons in The TaLaR trial indicates that transanal TME is as safe and ef-
this trial were all experienced in transanal TME, which limits fective as laparoscopic TME for patients with mid-low rectal
the generalizability of results to surgeons without technical ex- cancers, measured by 3-year disease-free survival.

ARTICLE INFORMATION College and Chinese Academy of Medical Sciences, Obtained funding: Kang.
Accepted for Publication: October 16, 2024. Beijing, China (Xiao); Department of Administrative, technical, or material support: Zeng,
Gastrointestinal Surgery, The First Affiliated Luo, H. Zhang, M. Wu, Ma, Q. Wang, Xie, Qing Xu,
Published Online: January 23, 2025. Hospital of Xi’an Jiaotong University, Xian, Shanxi, Ouyang, Xiao, Song, Feng, Qingwen Xu, Y. Wang,
doi:10.1001/jama.2024.24276 China (Song); Department of Gastrointestinal Y. Zhang, X. Zhang, L. Huang, Yang, Peng, X. Wu,
Author Affiliations: Department of General Surgery, Ruijin Hospital, School of Medicine, D. Ren, M. Huang, Lan, J. Wang, Tong, M. Ren,
Surgery (Colorectal Surgery), Guangdong Provincial Shanghai Jiao Tong University, Shanghai, China Liu, Kang.
Key Laboratory of Colorectal and Pelvic Floor (Feng); Department of Gastrointestinal Surgery, Supervision: Tong, M. Ren, Liu, Kang.
Diseases, Biomedical Innovation Center, The Sixth The Affiliated Hospital of Guangdong Medical Conflict of Interest Disclosures: None reported.
Affiliated Hospital, Sun Yat-sen University, University, Zhanjiang, Guangdong, China
Guangzhou, Guangdong, China (Zeng, Luo, (Qingwen Xu); Department of Gastrointestinal Funding/Support: This study was supported by
X. Zhang, L. Huang, Yang, Peng, X. Wu, D. Ren, Surgery, Nanfang Hospital, Southern Medical grants from the Sun Yat-sen University Clinical
M. Huang, Lan, J. Wang, Liu, Kang); Department of University, Guangzhou, Guangdong, China Research 5010 Program (2016005), National
Colorectal Surgery, Shengjing Hospital of China (Y. Wang); Department of Gastrointestinal Surgery, Natural Science Foundation of China
Medical University, Shenyang, Liaoning, China The Third Xiangya Hospital of Central South (82473451, 82472930, and 82200569),
(H. Zhang); Department of Gastrointestinal Surgery, University, Changsha, Hunan, China (Y. Zhang); Guangdong Provincial Clinical Research Center for
The Second People’s Hospital of Yibin, Yibin, Clinical Research Center, The Sixth Affiliated Digestive Diseases (2020B1111170004), Innovative
Sichuan, China (M. Wu); Department of Hospital, Sun Yat-sen University, Guangzhou, China Clinical Technique of Guangzhou, and National Key
Gastrointestinal Surgery, The Affiliated Nanchong (Shi); Department of Medical Statistics, School of Clinical Discipline.
Central Hospital of North Sichuan Medical College, Public Health, Sun Yat-sen University, Guangzhou, Role of the Funder/Sponsor: The funders had no
Nanchong, Sichuan, China (M. Ren); Department of China (Ling). role in the design and conduct of the study;
General Surgery, Daping Hospital, Army Medical Author Contributions: Drs Kang, Liu, M. Ren, Tong, collection, management, analysis, and
University, Chongqing, China (Tong); Department and J. Wang had full access to all of the data in the interpretation of the data; preparation, review, or
of General Surgery, Xinqiao Hospital, Army Medical study and take responsibility for the integrity of approval of the manuscript; and decision to submit
University, Chongqing, China (Ma); Department of the data and the accuracy of the data analysis. the manuscript for publication.
Gastrointestinal Surgery, The First Hospital of Jilin Drs Zeng, Luo, Zhang, and M. Wu are joint first Group Information: The Chinese Transanal
University, Changchun, Jilin, China (Q. Wang); authors. Drs J. Wang, Tong, M. Ren, Liu, and Kang Endoscopic Surgery Collaborative (CTESC) Group
Department of Gastrointestinal Surgery, Affiliated contributed equally and are co–senior authors. nonauthor collaborators appear in Supplement 4.
Hospital of Zunyi Medical University, Zunyi, Concept and design: Zeng, Luo, H. Zhang, M. Wu,
Guizhou, China (Xie); Department of Meeting Presentation: The preliminary results of
Tong, Liu, Kang. the TaLaR trial were presented at the 2024 American
Gastrointestinal Surgery, Renji Hospital, School of Acquisition, analysis, or interpretation of data: All
Medicine, Shanghai Jiao Tong University, Shanghai, Society of Clinical Oncology Annual Meeting; June 3,
authors. 2024; Chicago, IL (abstract ID: 3516).
China (Qing Xu); Department of Gastrointestinal Drafting of the manuscript: Zeng, Luo, H. Zhang,
Surgery, The First Affiliated Hospital of University of Liu, Kang. Data Sharing Statement: See Supplement 5.
South China, Hengyang, Hunan, China (Ouyang); Critical review of the manuscript for important Additional Contributions: We thank the patients
Department of General Surgery, Peking Union intellectual content: All authors. who participated in this study and their families, as
Medical College Hospital, Peking Union Medical Statistical analysis: Shi, Ling. well as the nursing and research staff at the study

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 Research Original Investigation Transanal vs Laparoscopic TME and Disease-Free Survival in Patients With Rectal Cancer

centers. We also extend our gratitude to 13. Völkel V, Schatz S, Draeger T, Gerken M, 25. Hol JC, van Oostendorp SE, Tuynman JB,
Y.X. Luo, MD (Sun Yat-sen University, Sixth Klinkhammer-Schalke M, Fürst A. Transanal total Sietses C. Long-term oncological results after
Affiliated Hospital) and Q.M. Yin, PhD (Ruprecht mesorectal excision: short- and long-term results of transanal total mesorectal excision for rectal
Karl University of Heidelberg), for their generous the first hundred cases of a certified colorectal carcinoma. Tech Coloproctol. 2019;23(9):903-911.
assistance during the revision process of this article. cancer center in Germany. Surg Endosc. 2022;36(2): doi:10.1007/s10151-019-02094-8
Drs Luo and Yin did not receive compensation. 1172-1180. doi:10.1007/s00464-021-08384-3 26. Roodbeen SX, Spinelli A, Bemelman WA, et al.
14. Zeng Z, Liu Z, Huang L, et al. Transanal total Local recurrence after transanal total mesorectal
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E10 JAMA Published online January 23, 2025 (Reprinted) jama.com

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