Is it time to change surgery for early-stage low-risk cervical cancer to simple hysterectomy?

Radical hysterectomy has long been a standard surgical procedure for early-stage cervical cancer. About 80% of early-stage cervical cancer can be treated with radical hysterectomy, and the survival rate after radical hysterectomy is approximately 80% or more [1]. However, since urinary dysfunction and defecation dysfunction occur in around 40% of patients after radical hysterectomy, a decrease in quality of life has long been a problem [2]. To complement this, a nerve-sparing radical hysterectomy procedure has been proposed, but although this is a very reasonable surgical procedure in theory, it is not yet clear whether it helps reduce morbidity and quality of life [3]. Another method is to find a low-risk group in which the risk of parametrial metastasis is negligible and sufficient tumor-free resection margin can be secured with simple hysterectomy and to omit parametrectomy [4]. Studies comparing simple hysterectomy and radical hysterectomy have been discouraged due to concerns about the decrease in survival rate that will occur if parametrectomy is omitted in cervical cancer. The SHAPE trial was the first prospective randomized controlled trial comparing simple hysterectomy and radical hysterectomy in low-risk early-stage cervical cancer, and demonstrated that simple hysterectomy was non-inferior to radical hysterectomy in terms of pelvic recurrence rate at 3 years [5].

In the SHAPE trial, pelvic relapse free survival was initially the primary endpoint, but due to insufficient event occurrence, it was changed to pelvic recurrence rate at 3 years. The pelvic recurrence rate was shown to be non-inferior, but in fact, exptrapelvic recurrence and overall recurrence were more frequent in the simple hysterectomy group, and deaths due to cervical cancer were also more frequent in the simple hysterectomy group even though positive lymph node, positive resection margin and positive parametrium were more in radical hysterectomy group. The total recurrence rate including pelvic and exprapelvic recurrence after simple hysterectomy was 4.3% in SHAPE trial. In ConCerv trial that included patients with negative resection margin after loop electrosurgical excision procedure or conization, the total recurrence rate was 3.5% after simple hysterectomy in low-risk early-stage cervical cancer [6]. The total recurrence rate was 2.9% after radical hysterectomy in SHAPE trial. It was 0.7% in all stage IB1 cervical cancer after open radical hysterectomy in LACC trial [7]. Many study groups are expected to conduct follow-up studies evaluating less radical surgery in the future, and exptrapelvic recurrence should also be included as a primary endpoint.

The definition of low-risk early-stage cervical cancer is same with the definition of low-risk disease for parametrial involvement. These criteria vary somewhat among studies, but include usual type histology (squamous cell carcinoma, adenocarcinoma, and adenosqumous carcinoma), tumor <2 cm, depth of invasion <10 mm, negative lymphovascular space invasion, and negative lymph node metastasis [4]. In the ConCerv trial, adenocarcinoma was limited to grade 1 and 2 [6]. In the SHPAE trial, cases with invasion depth of less than 50% on magnetic resonance imaging (MRI) were also included. Instead, lymphovascular space invasion was not considered in the SHPAE trial. In fact, it is inaccurate to diagnose low-risk disease using these conditions before surgery. It is difficult to accurately measure tumor size and lymphvascular space invasion before surgery, and diagnosing stromal invasion depth with MRI is also very inaccurate. In SHAPE trial, parametrial involvement was noted in 1.7% of patients after radical hysterectomy, but no one had parametrial involvement in simple hysterectomy. The parametrial involvement might be missed in simple hysterectomy group because parametrectomy was not performed. To diagnose low-risk early-stage cervical cancer, more accurate method is needed.

The SHAPE trial did not clearly specify the size and extent of parametrectomy in radical hysterectomy. In radical hysterectomy, the size and extent of parametrectomy varies greatly depending on the surgeons. Also, morbidity varies depending on the size and extent of parametrectomy. Because the size and extent of parametrectomy can be appropriately adjusted considering the size and invasion depth of the tumor, morbidity can also be reduced by performing tailored parametrectomy in radical hysterectomy [8]. Because diagnosis of low-risk early-stage cervical cancer before surgery is not very accurate, the disease may not be low-risk disease after surgery. For example, if the postoperative cervical invasion depth is close to full thickness invasion or the cervical tumor free resection margin is not sufficient on final pathology after surgery, radical hysterectomy using tailored parametrectomy might be more appropriate than simple hysterectomy in this case. So, simple hysterectomy can be a reasonable option for low-risk early-stage cervical cancer, and radical hysterectomy using tailored parametrectomy also can be a reasonable option.

In conclusion, SHAPE trial showed non-inferiority of simple hysterectomy with respect to pelvic recurrence rate in patients with low-risk early-stage cervical cancer. When deciding whether to use simple hysterectomy in low-risk early-stage cervical cancer, it should be considered that it is difficult to accurately diagnose low-risk disease before surgery, total recurrence and cervical cancer-related death are somewhat higher than radical hysterectomy, and radical hysterectomy using tailored parametrectomy can also lower morbidity.