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.


 

FROM NEW ENGLAND JOURNAL OF MEDICINE


Even though the trial was initially powered on the assumption that there would be a 4.5 year follow-up for all patients, only 59.7% reached that length of follow-up. However, the trial still reached 84% power to detect noninferiority of the primary outcome (disease-free survival) with minimally invasive surgery, which was not found, they noted.

Similarly, in the population-based cohort study of 2,461 women who underwent radical hysterectomy for stage IA2 of IB1 cervical cancer between 2010 and 2013, 4-year mortality was 9.1% among 1,225 patients who underwent minimally invasive surgery vs. 5.3% among the 1,236 patients who underwent open surgery (HR, 1.65), Alexander Melamed, MD, of Harvard Medical School, Boston, and his colleagues reported (N Engl J Med. 2018 Oct 31. doi: 10.1056/NEJMoa1804923).

Of note, the 4-year relative survival rate following radical hysterectomy for cervical cancer remained stable prior to the widespread adoption of minimally invasive approaches; an interrupted time-series analysis involving women who underwent surgery during 2000-2010, which was also conducted as part of the study, showed a decline in 4-year survival of 0.8% per year after 2006, coinciding with increased use of minimally invasive surgery, the investigators said.

For the main patient-level analysis, the researchers used the National Cancer Database, and for the time-series analysis they used information from the Surveillance, Epidemiology, and End Results program database.

“Our findings suggest that minimally invasive surgery was associated with a higher risk of death than open surgery among women who underwent radical hysterectomy for early-stage cervical cancer. This association was apparent regardless of laparoscopic approach, tumor size, or histologic type,” they concluded.

The findings are unexpected, eye-opening, and should inform practice, according to Ritu Salani, MD, of the Ohio State University, Columbus.

“This is something we have to discuss with patients,” she said in an interview, noting that while these aren’t perfect studies, they “are the best information we have.

Data reported in September at a meeting of the International Gynecologic Cancer Society show that surgical complications and quality of life outcomes are similar with minimally invasive and open surgery, therefore the findings from these two new studies suggest a need to shift back toward open surgery for patients with cervical cancer, she said.

One “catch” is that survival in the open surgery group in the LACC trial was unusually high and recurrence rates unusually low, compared with what might be expected, and the explanation for this observation is unclear.

“There may be some missing pieces that they haven’t been able to explain, but it’s not clear that they would change the outcome,” she said.

Justin Chura, MD, director of gynecologic oncology and robotic surgery at Cancer Treatment Center of America’s Eastern Regional Medical Center in Philadelphia, said in an interview, “The results of the study by Ramirez et al. are certainly disappointing for those among us who are advocates of minimally invasive surgery (MIS). In my own practice, I transitioned to minimally invasive radical hysterectomy approximately 10 years ago. Now that approach has to be reconsidered. While there are likely subsets of patients who will still benefit from a MIS approach without worsening oncologic outcomes, we do not have robust data to reliably identify those patients.


“One factor that warrants further investigation is the use of a uterine manipulator. While I do not use a manipulator out of personal preference (one less step in the operating room), the idea of placing a device through the tumor or adjacent to it, has biologic plausibility in terms of displacing tumor cells into lymphatic channels,” he said. “Until we have more data, an open approach appears to be preferred.”*


Dr. Ramirez and Dr. Melamed each reported having no relevant disclosures. Dr. Salani and Dr. Chura are members of the Ob.Gyn. News editorial board, but reported having no other relevant disclosures.*

sworcester@mdedge.com

SOURCE: Ramirez P. N Engl J Med. 2018 Oct 31. doi: 10.1056/NEJMoa1806395.

*This article was updated 11/9/2018.

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