LACC Confirms the Superiority of Open Surgery in Cervical Cancer

Key Points:

• The Laparoscopic Approach to Cervical Cancer (LACC) clinical trial established that, for early-stage cervical cancer , open surgery should be the standard of care rather than minimally invasive surgery.
• At 4.5 years of follow-up, overall survival was 90.6% in the minimally invasive group and 96.2% in the open surgery group, consistent with the original LACC analysis.
• Spread into the abdominal and pelvic cavities was significantly more frequent in the minimally invasive group, suggesting that tumor exposure is a component of this surgical approach.

Contrary to Expectations...

The effectiveness of surgical approaches for early-stage cervical cancer has generated considerable debate in recent years. Minimally invasive surgery was favored for a time because it is less invasive than open surgery. LACC, however, raised important questions about its safety and effectiveness. This article examines the final LACC analysis and its implications for clinical practice.

Details of the Final Analysis

Women undergoing minimally invasive radical hysterectomy for early-stage cervical cancer face nearly 3 times the risk of death over the following 4.5 years compared with open surgery, confirming that open surgery should remain standard care.

This is the conclusion of LACC's final overall survival analysis. The findings, published in the Journal of Clinical Oncology (JCO), reaffirm the results of the 2018 New England Journal of Medicine publication of the original LACC analysis and extend its practice-changing findings.

At that time, laparoscopy and laparotomy were both considered acceptable approaches to radical hysterectomy in early-stage cervical cancer. The hypothesis entering LACC was that minimally invasive approaches would be no worse than open surgery in terms of recurrence risk.

Instead, the trial found significantly worse disease-free survival after minimally invasive surgery: 86% at 4.5 years, compared with 96.5% after open surgery. Overall survival (OS), a secondary outcome, showed a similar difference. At 3 years, OS was 93.8% in the minimally invasive group and 99% in the open surgery group.

The findings came as a genuine shock to gynecologic oncologists.

They changed the standard of care for early-stage cervical cancer. Groups such as the National Comprehensive Cancer Network (NCCN) and European Society of Gynaecological Oncology revised their recommendations to favor open radical hysterectomy as the standard approach. Across the United States, minimally invasive procedures fell from more than 75% before LACC to 41% within 2 years of publication.

Nevertheless, the original report prompted further questions. The trial had been stopped early because of excess deaths in the minimally invasive arm.

This raised the question, "What would happen if every patient were actually followed for 4.5 years?" Might the findings differ?

The new JCO analysis shows that the answer is no.

Consistent Results

The findings are based on 631 patients with FIGO 2009 stage 1A1 to 1B1 cervical cancer (92% had 1B1). Of these, 319 were randomized to minimally invasive surgery (84% conventional laparoscopy and 16% robotic surgery) and 312 to open surgery. Rates of adjuvant treatment were similar between groups.

At 4.5 years, OS was 90.6% and 96.2% in the minimally invasive and open surgery groups, respectively (HR for death from any cause = 2.71, 95% CI [1.32, 5.59]; P = 0.007). Of 28 deaths in the minimally invasive arm, 22 were from cervical cancer; in the open arm, 8 of 10 deaths were from cervical cancer.

As in the original LACC analysis, disease-free survival was significantly worse in the minimally invasive group (HR 3.91, 95% CI [2.02, 7.58]; P < 0.001). Findings were similar after adjustment for age, body mass index, disease stage, lymph node involvement, lymphovascular invasion and ECOG status.

Other Unresolved Questions

JCO also examined questions such as tumor size and the importance of previous cervical conization.

In a prespecified subgroup analysis, researchers found a disease-free survival treatment effect favoring open surgery in patients with tumors ≥ 2 cm (HR 4.25, 95% CI [1.73, 10.4]). There was no significant between-group difference among those with tumors < 2 cm.

However, recurrence risk was generally very low among patients with tumors < 2 cm, and the study was not powered to detect a difference between surgical approaches in this population.

Among patients without previous conization, minimally invasive surgery increased recurrence almost 6-fold (HR 5.85, 95% CI [2.47, 13.9]; P < 0.0001). No such difference was found among those who had undergone conization (HR 1.27, 95% CI [0.39, 4.17]; P = 0.69).

Does this mean minimally invasive surgery is oncologically safe after conization? Unfortunately, the study was not sufficiently powered to answer that question.

Conization is performed when a tumor is too small to determine its depth of invasion. In other words, patients undergoing conization have a very low recurrence risk.

In these cases, conization may remove part of the existing tumor, so radical hysterectomy may not substantially change recurrence risk. However, it was noted that no study specifically designed to answer this question is available.

Conclusion

LACC has clearly established the superiority of open surgery in early-stage cervical cancer. The findings provide important guidance for selecting a surgical approach and highlight the need for careful assessment to improve survival. Choosing open surgery in early-stage cervical cancer is therefore important for patient survival and minimizing recurrence risk.