Would more aggressive adjuvant therapy following minimally invasive surgery help close the survival gap with open surgery?

Click here to read the Cover Story, “Minimally invasive cervical cancer surgery may promote disease recurrence; professionals urge patience.”

Yes, but the issue may surround compliance with recommended adjuvant therapy.

We recently presented our findings at the Society of Gynecologic Oncology Annual Winter Meeting from a retrospective analysis of cases performed at Levine Cancer Institute between 2007 and 2018. We showed a slight difference between minimally invasive and open approaches favoring the open approach, but this may be explained by a significant difference in compliance with recommendations for adjuvant therapy. Fewer minimally invasive patients followed through on recommendations for adjuvant therapy.

So, the issue really is not about more aggressive adjuvant therapy, but about compliance with recommendations for adjuvant therapy for patients with risk factors for recurrence.

Another important finding of our study was that we may be able to select better candidates for minimally invasive surgery using the updated 2018 Fédération Internationale de Gynécologie et d’Obstétrique (FIGO) staging system. The new stage IB1 includes patients with tumors confined to the cervix that are less than 2 cm in greatest dimension. Previously, it included tumors up to 4 cm in size. When we looked at outcomes for patients who had minimally invasive radical hysterectomy with tumors smaller than 2 cm, the outcomes no longer favored an open approach. Therefore, 2018 FIGO staging may be useful to define a low-risk group of women for whom minimally invasive radical hysterectomy is appropriate.

We look forward to a clinical trial to further examine these important concepts.

Reference:

Dandapani M, et al. Outcomes of minimally invasive versus open radical hysterectomy for early-stage cervical cancer incorporating 2018 FIGO staging. Presented at: Society of Gynecologic Oncology Annual Winter Meeting; Jan. 17-19, 2019; Lake Tahoe, Calif.

Monica Dandapani Levine, MD, is a resident in obstetrics and gynecology at Atrium Health. She can be reached at 1021 Morehead Medical Drive, Charlotte, NC 28204; email: monica.levine@atriumhealth.org. Disclosure: Levine reports no relevant financial disclosures.

No.

The recent phase 3 multi-institutional randomized controlled Laparoscopic Approach to Cervical Cancer study showed that minimally invasive radical hysterectomy for early-stage cervical cancer is associated with lower rates of DFS and OS compared with open abdominal radical hysterectomy. Another epidemiologic study using the National Cancer Database showed similar outcomes.

Given these compelling results, many gynecologic oncologists began transitioning their practices from minimally invasive surgery to open techniques for this unique patient population.

Some explanations for worse outcomes include the use of a uterine manipulator in close proximity to the cervical tumors, which may cause local tumor spread. Also, a high learning curve for surgeons using laparoscopic techniques for this technically challenging procedure may have resulted in close margins of resection compared with the open technique. Most patients in the minimally invasive surgery group had laparoscopic surgery, whereas in the United States, the majority of radical hysterectomies are done using a robotic approach, which often allows for better visualization and improved radical pelvic dissection.

It is also important to take into account the increased morbidity of the open approach compared with minimally invasive techniques, which allow for quicker recovery and fewer perioperative complications. Before generalizing recommendations for an open approach for all women with early-stage cervical cancer, the gynecologic community is looking to further evaluate manipulator use, surgical techniques and procedural radicality of the minimally invasive approach.

Addition of adjuvant therapy, such as radiotherapy or chemotherapy, to try to close the gap between the OS and DFS rates has been suggested for patients undergoing minimally invasive radical hysterectomy. These adjuvant therapies are usually reserved for patients who have high-risk features for recurrence — deep stromal invasion, lymphovascular space invasion and large tumor size — in an attempt to further decrease recurrence rates.

Patients who undergo these dual-modality treatments are at high risk for early and late complications, including fistula formation, bowel obstruction, necrosis and infections, decreased sexual function and decreased ovarian function. Due to these morbidities, gynecologic oncologists try to avoid radical hysterectomy on a patient who will subsequently need radiation. Introduction of radiation therapy to patients who do not have these high-risk factors, simply because they had minimally invasive surgery, is not warranted at this time, as it introduces significant toxicities without any clear benefit.

Randomized controlled trials would be needed to justify increase in morbidity in this group of patients.

References:

Melamed A, et al. N Engl J Med. 2018;doi:10.1056/NEJMoa1804923.

Ramirez PT, et al. N Engl J Med. 2018;doi:10.1056/NEJMoa1806395.

Eugenia Girda, MD, FACOG, is a gynecologic oncologist at Rutgers Cancer Institute of New Jersey and an attending physician at Robert Wood Johnson University Hospital New Brunswick, an RWJBarnabas Health facility. She can be reached at Rutgers Cancer Institute of New Jersey, 195 Little Albany St., New Brunswick, NJ 08903. Disclosure: Girda reports no relevant financial disclosures.