A study by a multi-institutional research team, including Massachusetts General Hospital (MGH) physicians, has found evidence that patients receiving minimally invasive radical hysterectomy for early-stage cervical cancer have an increased risk of death compared to patients treated with open surgery. Their retrospective review of information from two nationwide databases will be published in the Nov. 15 New England Journal of Medicine and is receiving advance online release, along with an accompanying paper reporting a randomized clinical trial with similar results.

“This result is very surprising, since randomized trials have demonstrated the safety of minimally invasive surgery for uterine, gastric and colorectal cancers,” says Alexander Melamed, MD, MPH, of the Division of Gynecologic Oncology in the Mass General Department of Obstetrics and Gynecology, lead author of the NEJM paper. “Our own work using similar methods to investigate minimally invasive surgery for ovarian cancer found no association with increased mortality, so it seems clear that something very different may be going on in cervical cancer.”

Since it was first used to treat cervical cancer in 1992, minimally invasive radical hysterectomy – either laparoscopic or robot-assisted procedures – has become the standard of care for patients treated surgically for early-stage cervical cancer. While previous studies have suggested that outcomes for minimally invasive surgery were similar to those of open procedures, those studies were either small, confined to single institutions or followed patients for a relatively short period of time. There previously were no long-term randomized trials or large observational studies evaluating the survival of cervical cancer patients after minimally invasive radical hysterectomy.

The research team – including investigators from Brigham and Women’s Hospital, Northwestern University Feinberg School of Medicine, Columbia University/New York Presbyterian Hospital, the University of Wisconsin School of Medicine and Public Health, and the University of Texas M.D. Anderson Cancer Center – analyzed information from the National Cancer Database, which covers around 70 percent of newly diagnosed cancer cases in more than 1,500 U.S. hospitals.

Of 2,461 patients in the National Cancer Database who had radical hysterectomies for early-stage cervical cancer from 2010 through 2013, around half had minimally invasive surgery and a similar proportion had open procedures. Among those in the minimally invasive group, 94 died from any cause in the four years following surgery, compared with 70 patients in the open surgery group.  Those numbers reflect a 9.1 percent risk of death in the minimally invasive group and a 5.3 percent risk in the open surgery group. There were no differences between the groups in terms of tumor pathology or the use of radiation or chemotherapy in addition to surgery.

Since available files from the National Cancer Database only go back to 2004, the researchers also analyzed information from the Surveillance, Epidemiology and End Results (SEER) database, which includes data from 18 cancer registries covering 28 percent of the U.S. population. To track whether the increased use of minimally invasive surgery actually caused changes in the survival of patients with early-stage cervical cancer, they analyzed SEER data covering such patients treated from 2000 through 2010.

SEER database information – which reflects cancer-related deaths – showed a stable four-year survival rate prior to 2006, when minimally invasive radical hysterectomy began to be broadly adopted for treatment of early-stage cervical cancer. After that date, survival rates steadily dropped by around 0.8 percent per year, a trend that suggests that the results of the National Cancer Database analysis indicate a true cause-and-effect relationship.

“It’s important to note that our study doesn’t explain why mortality is higher among women who have minimally invasive surgery,” says Melamed, who is a clinical fellow in Obstetrics, Gynecology and Reproductive Biology at Harvard Medical School. “One possible explanation is that there could be something technical about minimally invasive radical hysterectomy that is different from the open procedure and makes a difference for long-term survival. An alternative explanation is that U.S. surgeons could have been less experienced with the minimally invasive procedure than with open surgery during the study period.

“The clinical trial that is appearing in the same issue of the Journal as our study found that patients randomly assigned to laparoscopic radical hysterectomy had higher rates of recurrence and death than those who received open radical hysterectomies,” he continues. “While we need to learn more about the reasons behind these findings, surgeons who wish to offer minimally invasive radical hysterectomy to cervical cancer patients must ensure they are informed of these risks. Personally, I will not offer minimally invasive radical hysterectomy to patients who come to me for cervical cancer treatment until compelling new research demonstrates a minimally invasive approach that does not carry these risks.”

The senior authors of the New England Journal paper are Jason Wright, MD, Columbia/New York Presbyterian Hospital; Shohreh Shahabi, MD, EMHA, and Masha Kocherginsky, PhD, Prentice Women’s Hospital/Northwestern University Feinberg School of Medicine; and J. Alejandro Rauh-Hain, MD, MPH, University of Texas M.D. Anderson Cancer Center. Marcela Del Carmen, MD, Division of Gynecologic Oncology/MGH Department of Obstetrics and Gynecology is also a co-author. The study was supported by National Cancer Institute grants P30 CA016672, 4P30 CA060553-22, and R25 CA092203; National Institute of Child Health and Human Development grant K12 HD050121-12; and by the American Association of Obstetricians and Gynecologists Foundation, the Foundation for Women’s Cancer, the Jean Donovan Estate and the Phebe Novakovic Fund.

Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH Research Institute conducts the largest hospital-based research program in the nation, with an annual research budget of more than $900 million and major research centers in HIV/AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, genomic medicine, medical imaging, neurodegenerative disorders, regenerative medicine, reproductive biology, systems biology, photomedicine and transplantation biology. The MGH topped the 2015 Nature Index list of health care organizations publishing in leading scientific journals and earned the prestigious 2015 Foster G. McGaw Prize for Excellence in Community Service. In August 2018 the MGH was once again named to the Honor Roll in the U.S. News & World Report list of "America's Best Hospitals."