麻豆传媒

SAN DIEGO -- The safety of non-radical approaches to surgery in early, low-risk cervical cancer gained additional support from a new prospective study, though fertility preservation with cone biopsy also came with some cases of disease recurrence.

In patients with stage IA1 (with lymphovascular invasion) to stage IB1 disease, extrafascial hysterectomy or cone biopsy with lymphadenectomy led to no changes in bowel function, while declines in sexual function and bladder function at 4 to 6 weeks postsurgery generally recovered to baseline levels by 6 months, reported Allan Covens, MD, of the University of Toronto and Sunnybrook Health Sciences Center.

Meanwhile, 7% of patients had a lymphedema diagnosis, according to findings of the Gynecologic Oncology Group (GOG)-278 trial presented at the Society of Gynecologic Oncology annual meeting.

"Importantly, this study identified a small risk of recurrence in the remaining cervix after cone biopsy despite negative margins," said Covens. "Thus, diligent surveillance of the cervix post-treatment is recommended to maintain a high cure rate through early surgical intervention."

Of the 203 patients in GOG-278 eligible for survival analysis, three patients -- all in the cone-biopsy group (n=68) -- had a cancer recurrence over a median follow-up of 37 months, and two deaths occurred from unrelated causes.

Of the 31 patients who wanted to become pregnant during the prospective study, 15 conceived after the cone biopsy plus lymphadenectomy procedure: three delivered preterm at a median 33 weeks, nine went to term (median 39 weeks), and four had a spontaneous abortion.

"Patient quality of life was improved after surgery in both groups, and patients' worry on cancer recurrence decreased after surgery in both groups -- more so for those undergoing simple hysterectomy," said Covens. "The cone biopsy patients reported less concerns on reproductive fertility after surgery and over time compared to pre-op assessments."

Radical surgery for early cervical cancer has high cure rates but can result in major complications. For example, one of the most challenging parts of the radical approach -- removal of the fat and connective tissue that surrounds the uterus -- can lead to blood loss, fistula formation, and bladder, bowel, and sexual dysfunction.

At the same time, Covens said in his presentation, "multiple case series have indicated that non-radical surgery is associated with less morbidity and improved quality of life." He also highlighted the recent and SHAPE trials, which supported non-radical strategies in certain patients.

In regard to perioperative morbidity in the GOG trial, Covens said "it would be important to follow these patients longer to see if this holds up. We have no reason to suspect it will not."

'Impressive' Results

The study "certainly adds to a growing body of data that less-radical surgery is safe and effective for early-stage, low-risk cervical cancer, and highlights the potential for reproductive success," commented study discussant Kristin Bixel, MD, of the Ohio State University in Columbus.

Bixel described the effects of the cone biopsies on bladder and bowel function as "minimal," which she called "impressive" compared with the SHAPE trial, in which 11% of radical hysterectomy patients had incontinence and 10% had urinary retention at 4 weeks.

The 7% incidence of lymphedema was "quite comparable to that in SHAPE as well, and honestly significantly lower than what I typically counsel patients about," she added. "I do wonder if the percentage of patients with lymphedema will increase over time, however."

She also highlighted improvement in quality of life and cancer worry scores after surgery. "This is important, as patients who are having less-radical surgery may fear that that may come with an increased risk of recurrence. But obviously, this is very subject to selection bias."

And, said Bixel, "with respect to cancer outcomes, approximately 10% of patients received adjuvant radiation therapy, and the recurrence rate was 1.5%, which is very comparable to the SHAPE and ConCerv trials as well."

She noted that nearly all patients (96% in both groups) underwent minimally-invasive surgery (MIS) rather than open surgery (4%). Most procedures in SHAPE and ConCerv were performed via MIS as well.

The landmark Laparoscopic Approach to Cervical Cancer (LACC) trial in 2018 showed that open surgery led to better disease-free survival compared with MIS in early cervical cancer. However, said Bixel, LACC was "not powered to evaluate oncologic outcomes for patients with low-risk cervical cancer and [cannot] necessarily be generalized to this patient population."

She added: "I wonder if sentinel lymph node mapping will further improve the complication rates and quality of life."

Study Details

The trial enrolled 224 women in the U.S., South Korea, and Canada with stage IA1 (with lymphovascular invasion) to stage IB1 disease, 152 of whom received extrafascial (simple) hysterectomy and 72 cone biopsy with lymphadenectomy, determined by their desire to maintain fertility.

In the simple hysterectomy group, patients had a median age of 45 years, 50% were white, 46% Asian, and 4% were Black. A majority of patients (55%) in this group had stage IB1 disease, and 68% had squamous cell histology.

Median age in the cone-biopsy group was 33 years. This cohort was 63% white, 27% Asian, and 10% Black, while 52% had stage IB1 disease and 58% had squamous cell cancer.

Adverse events of grade 3 or higher occurred in 5% of the hysterectomy patients and none of the cone-biopsy patients.