These findings suggest that TMMR may be considered a primary treatment option for both early-stage and locally advanced cervical cancer confined to the Müllerian compartment, reported lead author Henrik Falconer, MD, PhD, of Karolinska Institutet, Stockholm, Sweden, and colleagues.
What is the rationale behind TMMR?
“Current international guidelines [for cervical cancer] are primarily based on retrospective case series and a small number of outdated randomized controlled trials,” the investigators wrote in EClinicalMedicine, part of The Lancet publication platform. “The stage-dependent treatment recommendations, with surgery advised for early-stage and radiation therapy for locally advanced disease, may be considered too simplistic, suggesting that early stages of cervical cancer cannot be controlled with surgical resection alone or that locally advanced cervical cancer is inoperable.”
This mindset, they noted, overlooks the complexities of cancer spread. In contrast, TMMR and similar surgical approaches based on the cancer field model are mapped along routes of locoregional dissemination, leading to “excellent local control” in more than 600 cases at the University Hospital of Leipzig, Leipzig, Germany.
To date, however, TMMR’s adoption has been limited, and it has not been compared directly with current guideline treatments, prompting the present study.
What methods were used to compare TMMR with standard treatment?
The study compared TMMR plus therapeutic lymph node dissection (tLND) without adjuvant radiation versus standard treatment (ST) for early-stage (FIGO 2009 IB1, IIA1) and locally advanced (FIGO 2009 IB2, IIA2, IIB) cervical cancer. Standard treatment for patients with early-stage disease involved radical hysterectomy and pelvic lymphadenectomy, with adjuvant chemoradiation dependent upon final pathology. Those with locally advanced disease received definitive chemoradiation.
Data for the standard treatment group were drawn from population-based registries in Sweden, while those for the TMMR group came from the Leipzig Mesometrial Resection Study Database. The final dataset included 1,007 women treated between 2011 and 2020, with 733 undergoing standard treatment and 274 receiving TMMR.
Outcomes included RFS and OS, adjusted for clinical and tumor-related variables.
How did TMMR compare with standard treatment?
TMMR was associated with superior oncologic outcomes compared with standard treatment for early-stage cervical cancer.
Specifically, 5-year RFS was 91.2% for TMMR versus 81.8% for standard therapy (P = .002). In the adjusted analysis, TMMR was associated with a significantly lower hazard of recurrence (hazard ratio [HR], 0.39; 95% CI, 0.22–0.69) and death (HR, 0.42; 95% CI, 0.21-0.86). Also favoring TMMR, absolute difference in the risk of recurrence at 5 years was 9.4% (95% CI 3.2–15.7). In addition, 5-year OS was better in the TMMR group, at 93.3%, compared with 90.3% for standard treatment (P = .034).
Among patients with locally advanced disease, no significant differences in RFS or OS were observed.
Are these data strong enough to make TMMR the new standard treatment?
Dr. Falconer and colleagues concluded that TMMR with tLND “may replace the standard treatment approach in early-stage cervical cancer and furthermore be evaluated as an option in locally advanced cervical cancer confined to the Müllerian compartment.”
While the investigators anticipated demands for randomized controlled trials, they questioned the value of such studies, suggesting that any control arm would be “based on inconsistent or flawed concepts.”
Dr. Susan C. Modesitt
Susan C. Modesitt, MD, director of the gynecologic oncology division of Winship Cancer Institute of Emory University, Atlanta, offered a different perspective.
“They do show encouraging data in the early stage,” Dr. Modesitt said in an interview, “but I would still want to see a randomized controlled trial, because we’ve been burned before.”
She cited the LACC trial, which dispelled strong convictions about the alleged superiority of minimally invasive radical hysterectomy.
“We thought minimally invasive was so good, and we should be doing that to everybody, but we did a trial, and we found worse outcomes,” Dr. Modesitt said. “More of those early-stage women died.”
Dr. Modesitt also pointed out the lack of safety data in the present publication.
“TMMR is a bigger procedure, so I would expect more complications,” she said, noting that rates of urinary injury, nerve injury, and readmission need to be considered alongside efficacy outcomes.
How does TMMR fit into the current treatment landscape for cervical cancer?
“This is a very niche surgery that most places don’t do,” Dr. Modesitt said.
She pointed out that “multiple variations” on the standard radical hysterectomy have been proposed in the past, such as the laterally extended endopelvic resection.
“[TMMR] is not a new concept,” she said. “It’s just a question of how radical it is.”
Instead of developing new types of radical surgery, she said, the trend in the United States is toward de-escalation of surgical treatments altogether, with greater reliance upon medical options, such as immunotherapy.
“[This study] is thought provoking, and I applaud them for doing it,” Dr. Modesitt said. “But I’m not going to go out and do that on my next patient.”
This study was supported by grants from Centre for Clinical Research Sörmland (Sweden) and Region Stockholm (Sweden). Dr. Falconer is a board member of Surgical Science.