Oncologic and Reproductive Outcomes Following Fertility-Sparing Surgery for Early Cervical Cancer

Cervical cancer is the fourth most common cancer in women, nearly half of whom are diagnosed at an early stage. In early stages, cervical cancer carries an excellent prognosis. Upwards of 40% of these patients are of reproductive age, making preservation of their fertility a key concern. As a result, multiple fertility sparing procedures have been developed.

The case for these newer surgical options is presented in a systematic review by researchers from Cleveland Clinic, published in The Journal of Minimally Invasive Gynecology. Using the highest-quality available data, the authors extensively outline the data on oncologic and reproductive outcomes for vaginal radical trachelectomy (VRT), abdominal radical trachelectomy (ART), minimally invasive radical trachelectomy (MIS-RT), and conization or simple trachelectomy (ST).

“There are few studies directly comparing the different approaches to radical trachelectomy or other less radical fertility sparing procedures, so we pooled the available data to provide a best comparison of recurrence rates and reproductive outcomes,” says Michelle L. Kuznicki, MD, first author of the study. “We also looked at studies using neoadjuvant chemotherapy in conjunction with these procedures to see if that influenced the outcomes.” The authors found that in carefully selected patients, oncologic outcomes with VRT, ART, MIS-RT and ST were comparable, with recurrence risks of approximately 4% and cancer death rates of less than 2%. Live birth rates, however, seem to favor less radical surgery: 71.9% for ST, compared with 65%, 57.1% and 44.0% for VRT, MIS-RT and ART, respectively.

Oncologic outcomes

The minimum median follow-up for the included studies was 12 months and early cervical cancer was defined as FIGO stages IA, IB or IIA. The authors screened more than 2,400 studies, of which 53 were included, each of which enrolled at least 10 patients. Half of the studies were purely retrospective and there were no randomized prospective studies identified.

“One thing we learned is that further prospective studies are needed to investigate whether the less radical surgeries are adequate treatment and potentially as good compared with the standard-of-care options we offer patients with early-stage cervical cancer,” says Peter Rose, MD, Section Head of Gynecologic Oncology at Cleveland Clinic and senior author on the study.

To arrive at their conclusions, the authors calculated combined recurrence rates, cancer death rates, pregnancy rates and live birth rates per procedure on the basis of all included studies that reported outcomes on that procedure.

“This was an inter-trial pooled comparison and the evidence suggests that patients with tumors < 2 cm are ideal candidates for the fertility-sparing procedures,” says Dr. Rose. “It’s important, however, to ensure that there are no positive lymph nodes. Any evidence of metastasis would preclude a woman from these surgical options.”

Besides tumor size and presence of lymphovascular space invasion, other factors noted by the authors that limit the use of the fertility-sparing procedures include higher risk histology such as high-grade neuroendocrine carcinomas. They recommend evaluation by an infertility specialist before such surgery for any patient with a history of infertility.

Commenting on the evidence for the individual procedures, the researchers underscored that the combined recurrence rate after ART was comparable to that for radical hysterectomy. Patients should be counseled about the possible higher risk of recurrence with an MIS approach extrapolating from radical hysterectomy data. However, these trials were not powered to look at tumors < 2 cm. Therefore, the data remain unclear in this fertility sparing population with small tumor size. The surgical risks of an open versus MIS approach to RT, they say, should be considered on an individual basis and discussed with patients during the shared decision-making process.

Response rates to neoadjuvant chemotherapy, which is not yet standard of care, appeared to be high—84% to 100%—but the researchers say those data must be interpreted with caution, given the small number of patients represented in the studies.

Reproductive outcomes

Reproductive outcomes following any of the included fertility sparing procedures were favorable, with live birth rates between 44–71.9% depending on procedure. In patients who were able to become pregnant, the preterm delivery rates following radical trachelectomy ranged from 20% to 100%, making these gestations high risk. They advise prenatal monitoring by a maternal-fetal medicine specialist and a planned cesarean section for these patients. In terms of postsurgical follow-up, the National Comprehensive Cancer Network recommends interval surveillance every three to six months for the first two to three years and every six to 12 months thereafter. Says Dr. Kuznicki, “We follow patients very closely after fertility-sparing surgery for early-stage cervical cancer to ensure that they have no evidence of recurrence, and that is generally done with at least a patient history, physical examination and Pap smear.”