From the Journals

Cervical cancer survival higher with open surgery in LACC trial

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Proceed with caution

The findings by Ramirez et al. and Melamed et al. are striking in part because previous studies focused more on surgical than clinical outcomes.

They are powerful, but scientific scrutiny demands consideration of potential study-design or study-conduct issues. For example, all cancer recurrences in the LACC trial were clustered at 14 of 33 participating centers, raising questions about factors that contributed to recurrence at those centers .

Still, the findings are alarming and deal a blow to the use of minimally invasive surgical approaches in cervical cancer patients. They don’t necessarily “signal the death knell” of such approaches.

Select patients may still benefit from a less invasive approach; none of the patients with stage lA2 disease, and only one with stage lB1, grade 1 disease had a recurrence in the LACC trial.

Further, patients with tumors smaller than 2 cm also did not have worse outcomes with minimally invasive surgery in either study. However, until further details are known, surgeons should proceed cautiously and counsel patients regarding these study results.

Amanda N. Fader, MD , made her comments in an accompanying editorial (N Engl J Med. 2018 Oct 31. doi: 10.1056/NEJMoa1806395 ). Dr. Fader is with the Johns Hopkins University, Baltimore. She reported having no relevant disclosures.



Cervical cancer was more likely to recur and overall survival was lower among patients who underwent minimally invasive vs. open abdominal radical hysterectomy, based on findings from the randomized, controlled phase 3 Laparoscopic Approach to Cervical Cancer (LACC) trial of more than 600 women.

U.S. Air Force Maj. Arthur Greenwood and Capt. Stuart Winkler, 633rd Surgical Operations Squadron obstetricians, stitch up an incision after performing a laparoscopic hysterectomy at Langley Air Force Bae, Va., June 14, 2016. U.S. Air Force photo by Staff Sgt. Ciara Gosier

The alarming findings, which led to early study termination, also were supported by results from a second population-based study. Both studies were published concurrently in the Oct. 31 issue of the New England Journal of Medicine.

The disease-free survival at 4.5 years among 319 patients who underwent minimally invasive surgery in the LACC trial was 86.0% vs. 96.5% in 312 patients who underwent open surgery, Pedro T. Ramirez, MD, of the University of Texas MD Anderson Cancer Center, Houston, and his colleagues reported (N Engl J Med. 2018 Oct 31. doi: 10.1056/NEJMoa1806395).

At 3 years, the disease-free survival rates were 91.2% in the minimally invasive surgery group and 97.1% in open surgery group (hazard ratio for disease recurrence or death from cervical cancer, 3.74).

The differences between the groups persisted after adjustment for age, body mass index, disease stage, lymphovascular invasion, and lymph-node involvement. In the minimally invasive surgery group, the findings were comparable for those who underwent laparoscopic vs. robot-assisted surgery, the investigators found.

Further, at 3 years, overall survival was 93.8% vs. 99.0% (HR for death from any cause, 6.00), death from cervical cancer was 4.4% vs. 0.6% (HR, 6.56), and the rate of locoregional recurrence-free survival was 94.3 vs. 98.3 (HR, 4.26) in the minimally invasive and open surgery groups, respectively.

Study participants were women with a mean age of 46 years with stage IA1, IA2, or IB1 cervical cancer, with most (91.9%) having IB1 disease, and either squamous-cell carcinoma, adenocarcinoma, or adenosquamous carcinoma. They were recruited from 33 centers worldwide between June 2008 and June 2017. Most of those assigned to minimally invasive surgery underwent laparoscopic surgery (84.4%), and the remaining patients underwent robot-assisted surgery.

The treatment groups were balanced with respect to baseline characteristics, they noted.

The minimally invasive approach is widely used given that guidelines from the National Comprehensive Cancer Network and European Society of Gynecological Oncology consider both surgical approaches acceptable, and since retrospective studies suggest laparoscopic radical hysterectomy is associated with lower complication rates and comparable outcomes. However, there are limited prospective data regarding survival outcomes in early stage disease with the two approaches, the researchers said.

“Our results call into question the findings in the literature suggesting that minimally invasive radical hysterectomy is associated with no difference in oncologic outcomes as compared with the open approach,” they wrote, noting that a number of factors may explain the differences, such as concurrent vs. sequential analyses in the current studies vs. prior studies (in sequential analyses, earlier procedures may have been performed under broader indications and less clearly defined radiotherapy guidelines), and the possibility that “routine use of a uterine manipulator might increase the propensity for tumor spillage” in minimally invasive surgery.

Strengths of the study include its prospective, randomized, international multicenter design and inclusion of a per-protocol analysis that was consistent with the intention-to-treat analysis, and limitations include the fact that intended enrollment wasn’t reached because of the “safety alert raised by the data and safety monitoring committee on the basis of the higher recurrence and death in the minimally invasive surgery groups,” as well as the inability to generalize the results to patients with low-risk disease as there was lack of power to evaluate outcomes in that context.


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