Many patients with early-stage, low-risk cervical cancer may be spared the side effects associated with radical hysterectomy and undergo simple hysterectomy with pelvic lymph node dissection instead, according to results of the international phase III SHAPE study presented at the 2023 ASCO Annual Meeting.¹ SHAPE found that simple hysterectomy plus lymph node assessment was noninferior to radical hysterectomy plus lymph node assessment in carefully selected women with early-stage, low-risk cervical cancer. The 3-year rate of pelvic recurrence was 2.52% with simple hysterectomy compared with 2.17% with radical hysterectomy.

“In patients with low-risk cervical cancer, the risk of recurrence is quite low, suggesting that de-escalation of surgery is possible. The recurrence rate at 3 years is not inferior with simple hysterectomy, and there were fewer urologic surgical complications plus improved quality of life and sexual health [with simple hysterectomy],” said lead author Marie Plante, MD, of Laval University, Quebec. “However, careful evaluation of patients is essential to make sure they meet the selection criteria for the trial,” she cautioned.

Marie Plante, MD

“Following adequate/rigorous preoperative assessment, simple hysterectomy can now be considered the new standard of care for patients with low-risk, early-stage cervical cancer,” she added.

Cervical cancer is a global problem and the second leading cause of cancer death worldwide. As a result of effective screening in developed countries, more women in these countries present at a younger age with low-risk, early-stage disease. Radical hysterectomy is highly effective for the treatment of low-risk disease, but many women experience acute and long-term side effects that can include compromised bladder, bowel, and sexual function. A simple hysterectomy—if equally effective—would be preferable for both patients and physicians.

Study Details and Results

SHAPE was a noninferiority, phase III, randomized trial that included 700 patients in 12 countries treated at 130 centers. Patients were randomly assigned 1:1 to radical hysterectomy vs simple hysterectomy. Surgery for both arms included pelvic lymph node dissection and optional sentinel node mapping.Originally, the primary endpoint was pelvic relapse–free survival, but during the trial, it was changed to pelvic recurrence rate at 3 years.

The primary analysis was an intention-to-treat study in all randomly assigned patients, and a secondary per protocol analysis was conducted in 317 patients in the radical hysterectomy arm and 312 patients in the simple hysterectomy arm. At baseline, the median patient age was 44 years, and about 96% had an Eastern Cooperative Oncology Group performance score of 0. Median body mass index was 24.8 kg/m2. Approximately 91% of patients had stage IB1 disease, and 61.7% had squamous histology. About 50% of hysterectomies were done laparoscopically; 25%, robotically; and 23%, abdominally.

For the study, low risk was defined as squamous cell, adenocarcinoma, or adenosquamous histology; stage IA2 and IB2 with lesions of a maximum dimension of ≤ 20 mm; < 10 mm stromal invasion on preoperative LEEP or cone biopsy and < 50% stromal invasion on preoperative pelvic magnetic resonance imaging. On final pathology, about 45% of patients had residual cervical cancer detected in the hysterectomy specimen, 13% had lymphovascular space invasion, and 2.5% had positive vaginal margins. Indications for adjuvant therapy postoperatively were found in 9.2% of the simple hysterectomy group and 8.4% of those who had radical surgery.

At 3 years, the rate of pelvic recurrence was 2.52% for simple hysterectomy and 2.17% for radical hysterectomy, showing the noninferiority of simple hysterectomy in this selected group of patients. Similarly, simple hysterectomy was also found to be noninferior to radical hysterectomy in all subgroups analyzed, including stage, grade, hystology and per-protocol analysis.

There were fewer acute surgical events within 4 weeks with simple hysterectomy: 42.6% vs 50.6%, respectively (P = .04). Urinary incontinence and urinary retention were significantly worse at 4 weeks after surgery with radical hysterectomy. The rates of urinary incontinence were 2.4% and 5.5% (P = .048), and the rates of urinary retention were 0.6% and 11% (P < .0001); they were also statistically worse beyond 4 weeks of surgery, suggesting that the urinary problems persisted over time.

Over time, all quality-of-life and sexual health domains favored simple hysterectomy, including symptoms, body image, sexual worry, sexual activities, sexual enjoyment, desire, arousal, and lubrication.

Additional Commentary

“This study shows the importance of well-designed trials in surgical oncology. SHAPE shows that de-escalation of surgery can decrease morbidity and disfigurement without loss of efficacy in women with low-risk cervical cancer,” said ASCO expert Kathleen N. Moore, MD, MS, of OU Health Stephenson Cancer Center in Oklahoma City.

Kathleen N. Moore, MD, MS

“These studies are very hard to conduct, because you have to ask patients to randomize to a surgery with a known cure rate to a less radical surgery with less surgical and postoperative morbidity but an unknown cure rate. This is a big act of volunterism and selflessness on behalf of patients; the results validate their participation and are a really big deal for these patients,” she continued.

“Cervical cancer is not common in the United States, Canada, and Europe. It accounts for more than 600,000 cases and more than 350,000 deaths globally, mostly in middle- and low-income countries. The treatments there vary from standard of care [in higher-income countries],” Dr. Moore explained.

“The SHAPE trial was done among carefully selected patients,” she emphasized, “and it showed that radical hysterectomy can be converted to a simple hysterectomy [along with pelvic lymph node dissection] without loss of oncologic control but with less morbidity. Now that this study is presented, it will become a new standard of care,” Dr. Moore stated. “De-escalation of surgery may allow these women better access to curative surgical interventions.”

Julie R. Gralow, MD, FACP, FASCO

At a premeeting press conference where these data were discussed, Julie R. Gralow, MD, FACP, FASCO, Chief Medical Officer and Executive Vice President of ASCO, said: “I agree on the global implications of this study, and these results underline the importance of the [human papillomavirus] vaccine to prevent cervical cancer.” 

DISCLOSURE: Dr. Plante has had a consulting or advisory role for Merck Serono; has royalties with UpToDate; and has been reimbursed for travel, accommodations, and other expenses by AstraZeneca. Dr. Moore has served in a leadership role with GOG Partners and NRG Ovarian Committee Chair; has received honoraria from Research To Practice, Prime Oncology, Physician Education Resource, and Great Debates and Updates; has served as a consultant or advisor to AADi, Alkermes, AstraZeneca, Blueprint Pharmaceuticals, Caris Life Sciences, Clovis Oncology, Eisai, Genentech/Roche, GSK/Tesaro, Hengrui Pharmaceutical, I-Mab, Immunogen, InxMed, Iovance Biotherapeutics, Merck, Mereo BioPharma, Mersana, Myriad Genetics, Novartis, Novartis/Pfizer, Onconova Therapeutics, OncXerna Therapeutics, VBL Therapeutics, and Verastem/Pharmacyclics; has received research funding from Agenus, Amgen, Artios, AstraZeneca, Bolt Biotherapeutics, Bristol Myers Squibb, Clovis Oncology, Cyteir, Daiichi Sankyo/Lilly, Genentech, Immunocore, Immunogen, Eli Lilly, Lilly Foundation, Merck, Novartis Pharmaceuticals UK Ltd, Novogen, PTC Therapeutics, Regeneron, Takeda, Tesaro, and Verastem; has patents, royalties, or other intellectual property with UpToDate; has received travel expenses from AstraZeneca and GSK; and has reported relationships with GOG Partners. Dr. Gralow reported no conflicts of interest.

REFERENCE

1. Plante M, Kwon JS, Ferguson S, et al: An international, randomized phase III trial comparing radical hysterectomy and pelvic node dissection versus simple hysterectomy and pelvic node dissection in patients with low risk early stage cervical cancer. (LRESCC). 2023 ASCO Annual Meeting. Abstract LBA5511. Presented June 2, 2023.