Uterine-Preserving Surgery Achieves Same Oncologic Outcomes as Hysterectomy in Early-Stage Cervical Cancer

By Nadeem Abu-Rustum, MD, FACOG, FACS Mario Leitao, Jr., MD, FACOG, FACS Monday, January 14, 2019

Uterine-preserving surgery results in excellent and similar five-year disease-specific survival compared to hysterectomy in young women with stage IB1 cervical cancer, especially in women with smaller tumors, according to our recent research.

The retrospective study is one of the largest reported for this patient population and presents the longest follow-up. Using data from the Surveillance, Epidemiology, and End Results 18 database, which includes 18 geographic areas located in 13 states, we compared outcomes for a total of 2,717 patients with stage IB1 cervical cancer who underwent primary surgery between 1998 and 2012. A total of 125 patients had uterine-preserving surgery (UPS), and the remaining 2,592 had non-UPS, defined as a hysterectomy of any type. ⁽¹⁾

Overall, we found no difference in the five-year disease-specific survival (DSS) between the UPS and non-UPS groups (93 percent versus 94 percent, respectively, p = 0.755). DSS was significantly higher for women with tumors two centimeters (cm) or smaller. ⁽¹⁾

The findings suggest that UPS is a viable option for young women with stage IB1 tumors who wish to preserve their future fertility options, especially for those with tumors two cm or smaller. The insights are particularly valuable given that cervical cancer is most common among women between the ages of 35 and 44, ⁽²⁾ and the trend of more women delaying pregnancy toward the later years in their fertile window.

Uterine-Preserving Surgery for Cervical Cancer

In the United States, there are about 13,240 new cases of cervical cancer diagnosed annually. ⁽²⁾ The majority of cervical cancer patients under the age of 45 have stage I disease, which is associated with excellent survival. ⁽³⁾

Uterine preservation is a significant issue among younger cancer patients, especially as more of them are choosing to delay childbearing. Loss of fertility has a significantly negative psychosocial impact that persists years after diagnosis. ⁽⁴⁾^, ⁽⁵⁾

There are two types of UPS: trachelectomy, which removes the entire cervix; and conization, which removes a cone-shaped wedge of tissue from the cervix. More than two decades of data from small retrospective studies have shown that radical trachelectomy is both feasible and safe. ⁽⁶⁾^, ⁽⁷⁾ The National Comprehensive Cancer Network guidelines for cervical cancer now include radical trachelectomy with either pelvic lymph node dissection or sentinel lymph node mapping as acceptable options for treating women with International Federation of Gynecology and Obstetrics (FIGO) stage IB1 cervical cancer who wish to maintain their fertility. ⁽⁸⁾

While there has been increasing interest in reducing the morbidities associated with radical trachelectomy by performing simple conization alone, there are only minimal data available on the approach. ⁽⁹⁾^, ⁽¹⁰⁾ Further, clinicians are less likely to offer uterine preservation to women with tumors two cm or larger because it is associated with a higher risk of recurrence and lower overall survival. ⁽¹¹⁾^, ⁽¹²⁾^,(13),(14)

Study Results

For our study, we analyzed outcomes for 2,717 women under the age of 45 with FIGO stage IB1 squamous cell, adenocarcinoma, or adenosquamous cervical cancer who were treated with UPS or non-UPS primary surgery at Memorial Sloan Kettering from 1998 to 2012. A total of 125 patients had UPS: 36 were treated with conization and 89 with trachelectomy. The remaining 2,592 had non-UPS: 682 underwent a simple hysterectomy, 1,764 had a modified hysterectomy, and 146 had a hysterectomy not otherwise specified. In our analysis, we only included patients who received lymph node assessment. The median follow-up time was 79 months, with a range of zero to 179 months. ⁽¹⁾

Overall, we found no significant difference in five-year DSS between the UPS group and the non-UPS group: 93 percent versus 94 percent, respectively (p = 0.755). Factors independently associated with decreased survival included adenosquamous histology (hazard ratio [HR] 2.29, 95 percent confidence interval [CI] = 1.51–3.47), grade 3 disease (HR 2.44, 95 percent CI = 1.01–5.89), tumor size greater than two cm (HR 1.93, 95 percent CI = 1.36–2.75), and lymph node positivity (HR 2.29, 95 percent CI = 1.6–3.22). UPS was not associated with a higher risk of death. ⁽¹⁾

For women with tumors two cm or less, results showed that the five-year DSS for the UPS group was excellent and similar to the non-UPS group: 96.8 percent versus 96.3 percent, respectively (p = 0.683). But for tumors two cm or larger, the five-year DSS for the UPS group was much lower, at 82.4 percent versus 90.4 percent for the non-UPS group, respectively (p = 0.112). As expected, patients with negative lymph nodes had a better five-year DSS of 95.3 percent compared to 85.5 percent for those with positive lymph nodes (p < 0.001). ⁽¹⁾

We also analyzed survival outcomes for patients based on the type of UPS. The five-year DSS for the conization group was 90 percent compared with 94.1 percent for the trachelectomy group (p = 0.43). However, 72.7 percent of patients undergoing conization received adjuvant radiotherapy (RT) compared to the only 27.3 percent in the trachelectomy group who had RT. A separate examination of data for only those patients who did not receive RT showed no significant difference in the five-year DSS rate (100 percent for conization compared to 93.6 percent for trachelectomy, p = 0.33). ⁽¹⁾

In conclusion, UPS does not compromise DSS in this select group of young women with stage IB1 cervical cancer. UPS for treating tumors greater than two cm should be performed with caution and only in carefully selected patients until further studies clarify acceptable oncologic outcomes. Conization alone appears to be feasible and safe and confers favorable risk factors. Lymph node assessment should be performed in all patients undergoing cervical cancer surgery and is mandatory for those undergoing UPS.

We look forward to results from three prospective trials underway that are evaluating quality of life and oncologic outcomes in women with early-stage cervical cancer undergoing less versus more radical surgery: the SHAPE trial, the GOG278 trial, and the LESSER trial. While only GOG278 offers a fertility-preservation option, these three studies may provide insights on the degree of surgical intervention required to maximize outcomes in the treatment of early-stage cervical cancer.

Advancing Cervical Cancer Care

At Memorial Sloan Kettering Cancer Center, we are dedicated to improving oncologic outcomes while minimizing morbidities associated with treatment through evidence-based research.

Our cervical cancer care team of surgeons, medical oncologists, radiation therapists, radiologists, pathologists, sexual health experts, and social workers consult and collaborate on each case to develop individualized treatment plans for every patient. Fertility preservation options are available for patients with early-stage cervical cancer who would like to consider becoming pregnant in the future.

We are currently recruiting for three clinical trials for new experimental treatment approaches in cervical cancer as follows: a phase I study of an immunotherapy combination for patients with metastatic solid tumors, including cervical cancer; a phase I/II study of an experimental topical treatment for cutaneous metastases; and a study assessing a new imaging tool for measuring the amount of estrogen receptors in estrogen-sensitive cancers during treatment.

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