Marie Plante, MD
As reported in The New England Journal of Medicine by Marie Plante, MD, of Centre Hospitalier Universitaire de Quebec, and colleagues, the phase III CX.5 SHAPE trial has shown noninferiority of simple vs radical hysterectomy in the frequency of pelvic recurrence in women with low-risk cervical cancer.1 Simple hysterectomy was associated with a reduced risk of urinary complications.
As stated by the investigators: “Retrospective data suggest that the incidence of parametrial infiltration is low in patients with early-stage low-risk cervical cancer, which raises questions regarding the need for radical hysterectomy in these patients. However, data from large, randomized trials comparing outcomes of radical and simple hysterectomy are lacking.”
Study Details
In the trial, 700 women with low-risk disease (lesions of ≤ 2 cm with limited stromal invasion) recruited from sites in 12 countries between December 2012 and November 2019 were randomly assigned to undergo simple hysterectomy (n = 350) or radical hysterectomy (n = 350). Most patients (91.7%) had stage IB1 tumors on 2009 International Federation of Gynecology and Obstetrics (FIGO) criteria (91.7%), squamous cell histologic features (61.7%), and tumor grade 1 or 2 (59.3%). The primary outcome measure was recurrence in the pelvic area (pelvic recurrence) at 3 years in the intention-to-treat population; the prespecified noninferiority margin for the between-group difference was an upper 90% confidence interval of 4%.
Pelvic Recurrence
Median follow-up was 4.5 years. At 3 years, the incidence of pelvic recurrence was 2.5% in the simple hysterectomy group vs 2.2% in the radical hysterectomy group. The difference was 0.35% (90% confidence interval [CI] = −1.6% to 2.3%), with the upper limit of the confidence interval meeting the criterion for noninferiority. In a per-protocol analysis including 317 patients in the simple hysterectomy group and 312 patients in the radical hysterectomy group, pelvic recurrence occurred in 3.2% vs 3.2% of patients (hazard ratio = 1.01, 95% CI = 0.4–2.4).
Secondary surgical outcomes in the 336 patients who had simple hysterectomy vs 337 patients who had radical hysterectomy underwent surgery as assigned, including invasion of the lymphovascular space in 13.4% vs 12.5% (difference = 0.9%, 95% CI = −4.1% to 6.0%), margins positive for disease on final pathology specimen in 2.4% vs 2.7% (difference =−0.3% (95% CI = −2.7% to 2.1%), positive nodes on final pathology specimen in 3.3% vs 4.2% (difference = −0.9%, 95% CI = −3.7% to 2.0%), residual disease in hysterectomy specimen in 45.8% vs 47.2% (difference = −1.3%, 95% CI = −8.9% to 6.2%), lesions > 2 cm on final pathology specimen in 4.2% vs 4.2% (difference = 0.0%, 95% CI = −3.0% to 3.0%), and parametrial involvement in 0% vs 1.8% (difference = −1.8%, 95% CI = −3.2% to −0.4%).
Complications and Adverse Events
Intraoperative surgical injuries occurred in 7.1% of 338 patients who underwent simple hysterectomy vs 6.4% of 344 patients who underwent radical hysterectomy; they included nerve injury in 1.5% vs 0.6%, vein injury in 1.2% vs 0.3%, bladder injury in 0.9% vs 2.6%, ureter injury in 0.9% vs 1.5%, and bowel injury in 0.6% vs 0.6%.
Surgery-related adverse events within 4 weeks after surgery occurred in 42.6% vs 50.6% of patients (P = .04), including abdominal pain in 9.8% vs 12.2%, fatigue in 5.6% vs 6.7%, pelvic pain in 5.6% vs 2.6%, constipation in 4.7% vs 6.4%, and paresthesia in 4.1% vs 6.4%. The incidence of urinary incontinence was lower in the simple hysterectomy group vs the radical hysterectomy group within 4 weeks after surgery (2.4% vs 5.5%, P = .048) and after 4 weeks (4.7% vs 11.0%, P = .003). The incidence of urinary retention was also lower in the simple hysterectomy group within 4 weeks after surgery (0.6% vs 11.0%, P < .001) and after 4 weeks (0.6% vs 9.9%, P < .001).
The investigators concluded: “In patients with low-risk cervical cancer, simple hysterectomy was not inferior to radical hysterectomy with respect to the 3-year incidence of pelvic recurrence and was associated with a lower risk of urinary incontinence or retention.”
DISCLOSURE: The study was funded by the Canadian Cancer Society and others. Dr. Plante reported no conflicts of interest. For full disclosures of the study authors, visit nejm.org.
REFERENCE
1. Plante M, Kwon JS, Ferguson S, et al: Simple versus radical hysterectomy in women with low-risk cervical cancer. N Engl J Med 390:819-829, 2024.
