Results of the Canadian Cancer Trials Group CX.5/SHAPE trial could lead to surgical de-escalation among patients with cervical cancer.
Simple hysterectomy can now be considered “the new standard of care” for patients with low-risk, early-stage cervical cancer, according to the lead author of a new study that found simple hysterectomy to be no less effective than radical hysterectomy and pelvic node dissection among such patients.
Results of the Canadian Cancer Trials Group CX.5/SHAP
E trial presented ahead of this weekend’s 2023 ASCO Annual Meeting in Chicago.
“Although radical surgery is highly effective for the treatment of that low-risk population, women are at risk of suffering survivorship issues particularly in relation to long-term surgical side effects including compromised bladder, bowel and sexual function,” lead study author Dr. Marie Plante, professor in the department of obstetrics, gynecology and reproduction at the Université Laval in Quebec City, Canada, said in a press briefing ahead of the conference, adding that the radical approach also includes removal of the parametrium and upper vagina. “So radical surgery requires more extensive surgical skills and training and is associated with more surgical complications.”
According to the National Cancer Institute, a radical hysterectomy includes the removal of the uterus, cervix, part of the vagina and tissues and ligaments around these organs. Meanwhile, a simple hysterectomy only includes the removal of the uterus and cervix.
At a median follow-up of 4.5 years, the two groups had similar pelvic recurrence rates: 2.52% in patients who underwent a simple hysterectomy, and 2.17% in those who had a radical hysterectomy.
The overall cervical cancer incidence has decreased over the past 20 years, Plante said, though there are a higher proportion of women who present with the disease at both a younger age and with low-risk, early-stage disease.
Retrospective data have suggested that less radical surgery, which would be considered a surgical de-escalation approach, may not only be a safer option for patients, but would be associated with decreased morbidity.
The SHAPE trial, a Gynecologic Cancer Intergroup study led by the Canadian Cancer Trials Group, was comprised of 700 patients with low-risk cervical cancer (squamous cell, adenocarcinoma or adenosquamous carcinoma); stage 1A2 or 1B1 disease; less than 10 mm stromal invasion on loop electrosurgical excision/cone; less than 50% stromal invasion on MRI, a maximum dimension of 20 mm and disease that was either grade 1 to 3 or not assessable.
Half of the participating patients were randomly chosen to undergo radical hysterectomy, while the other half had a simple hysterectomy. Regardless of which arm they were enrolled onto, surgery included pelvic lymph node dissection with an optional sentinel lymph node (SN) mapping. Should SN mapping be conducted, it is preferred to use the laparoscopic approach, though the mode was optional.
Patients were stratified by Cooperative Group, SN mapping (yes vs no), stage (1A2 vs 1B1), histological type (squamous vs adenocarcinoma/adenosquamous), and grade (1-2 vs 3 vs not assessable).
The trial’s primary endpoint is three-year pelvic recurrence rate.
Additional findings showed that simple hysterectomy was noninferior to radical hysterectomy across prespecified patient subgroups, including 1B1 histologic stage, squamous histology, adenocarcinoma/adenosquamous histology, tumor grade 1 to 2, tumor grade not assessable, predefined patients and per-protocol patients whose excluded eligibility was not met following surgery.
Furthermore, data showed that pelvic recurrences were 3.1% in those who underwent a simple hysterectomy compared with 2.9% for patients who had a radical hysterectomy. Extra pelvic recurrences (recurrences happening outside of the pelvis) occurred in 2.% and .6% of patients, respectively, and the pelvic and extra pelvic recurrence rate was .9% and .6%, respectively. Extra pelvic-only recurrence rates were 1.1% in the simple hysterectomy group and 0% in the radical approach group; pelvic or extra pelvic recurrence rates were 4.3% and 2.9%, respectively.
Seven deaths occurred in both groups, and four deaths were due to cervical cancer with simple hysterectomy compared to one with radical hysterectomy.
Regarding postsurgical complications, intraoperative injuries occurred in 24 patients who underwent simple hysterectomy and 22 who had radical hysterectomy. These occurred in the bladder, ureter, nerve, bowel, vein and elsewhere.
Surgical-related side effects occurred within four weeks of surgery in 42.6% of patients on the simple hysterectomy arm and 50.6% on the radical hysterectomy arm. Four weeks after surgery, side effects occurred in 53.6% and 60.5% of patients, respectively. There were fewer acute urinary incontinence side effects in the simple hysterectomy arm than in the radical hysterectomy arm.
Quality of life and sexual health were also assessed, with sexual-vaginal functioning improved with simple hysterectomy at three, six and 12 months, and similar findings regarding sexual pain with simple hysterectomy at the same intervals. Plante added that both approaches were further assessed via sexual health scores and favor ed the simple hysterectomy group.
During the press briefing, Dr. Kathleen N. Moore, associate director of clinical research at Stephenson Cancer Center, director of the Oklahoma TSET Phase I Program and professor in the section of gynecologic oncology at the University of Oklahoma College of Medicine, commented on the global implications of the SHAPE findings following Plante’s presentation of data.
“The SHAPE trial shows that amongst those carefully selected tumors, radical hysterectomy can be converted to a simple hysterectomy, including minimally invasively. You still have to do nodes — that’s an important thing to remember,” Moore emphasized. “But you can do this without loss of oncologic control and importantly with reduction in surgical complications, postoperative morbidities — specifically, urologic morbidity. The moment this is presented, this will be the new standard of care. It represents a huge step forward in the care of women with early-stage cervical cancer. Honestly, the de-escalation may allow these women in low- and middle-income countries (…) better access to curative surgical interventions.”
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