Page 25 - Read Online

Murillo et al. Mini-invasive Surg. 2025;9:7 https://dx.doi.org/10.20517/2574-1225.2024.55 Page 5 of 9

[27]
resection, postoperative complications, length of stay, or 90-day mortality . The results of the REVATE
trial provide further evidence showing benefit of RAMIE over conventional MIE in performing
lymphadenectomy, particularly in the more challenging nodal basins.

Future directions and actively enrolling randomized control trials
Robot-assisted minimally invasive thoraco-laparoscopic esophagectomy vs. MIE (ROBOT-2)
The ROBOT-1 trial compared open esophagectomy to RAMIE and will now be followed by the ROBOT-2
trial comparing conventional MIE to RAMIE in resectable EA [10,28] . The ROBOT-2 trial is the first
randomized control trial comparing conventional MIE to RAMIE to be conducted outside of Asia (in
Europe) and the first to focus on EA. The primary outcome of this study is the total number of resected
abdominal and mediastinal lymph nodes specified per lymph node station. Secondary outcomes include
perioperative parameters and oncologic outcomes. The study will also include quality-of-life metrics and up
[28]
to 5-year survival . The results of the ROBOT-2 trial may clarify if prior findings are specific to squamous
cell carcinoma and the McKeown esophagectomy, or if outcomes are consistent across both histologies and
techniques. Finally, the protocol includes a cost analysis between the two modalities, a topic that requires
further examination. Though robotic surgery has been found to be less cost-effective in other types of
surgery, limited data exists on RAMIE as discussed at the end of this review. The ROBOT-2 trial has
accrued 85% of its participants and is expected to close in 2024.

Overall morbidity after total minimally invasive keyhole oesophagectomy vs. hybrid oesophagectomy (MICkey
trial)
The MICkey will also be conducted in Germany and the Netherlands, but is not specific to EA. Patients will
be enrolled in either hybrid esophagectomy (HYBRID-E) via laparoscopic or robotic abdominal phase and
open thoracic surgery or MIE including laparoscopic or robotic esophagectomy. The primary outcome will
be postoperative morbidity within 30 days. The secondary outcomes will include perioperative parameters
[29]
and patient-reported and oncologic outcomes . The MICkey trial could provide insight into outcomes of
hybrid robotic techniques compared to conventional MIE.

RAMIE vs. MIE in patients with esophageal cancer after neoadjuvant therapy (RAMIE-2)
The authors of the RAMIE trial are now actively enrolling for a second trial comparing RAMIE to
conventional MIE in patients who have received neoadjuvant therapy. The trial will occur in China and
only include squamous cell esophageal carcinoma. Neoadjuvant therapy will include chemoradiotherapy,
chemotherapy and immunotherapy. The primary endpoints will include surgical and oncological results in
[30]
patients with locally advanced ESCC after neoadjuvant therapy . The RAMIE-2 trial will further explore
the post-hoc analysis of the RAMIE trial, which demonstrated superiority of RAMIE for lymphadenectomy
in patients who underwent neoadjuvant therapy. Given current recommendations of neoadjuvant therapy
for locoregionally advanced cancer (cT2-4aN0-3M0 and T0-1 N+ M0), this study aims to provide valuable
insight for operative planning.

Summary
The results of the discussed published randomized control trials and the ongoing trials are included in
Table 1. This review included randomized control trials comparing RAMIE to MIE, but additional
randomized control trials studying RAMIE were excluded. Additional information on active clinical trials
[31]
can be found at clinicaltrials.gov .
Cost comparison
Limited data exists surrounding the cost comparison between RAMIE and conventional MIE, with no cost
analysis reported in the completed randomized control trials previously mentioned. Currently there is only