Simple hysterectomy SHAPE-ing up to be the treatment of choice for early cervical cancer under 2 cm

Cervical cancer is the fourth most common cancer in women [1]. While we hope global human papillomavirus vaccination efforts will change this reality, as a result of screening programs 42% of women in North America present with localized disease [2]. Radical hysterectomy has been recommended for most patients, presenting with stage IA2 to 4 cm IB3 cancers [3]. Overall survival is excellent, however there are significant adverse effects associated with parametrial and vaginal resection [4].

We congratulate Plante et al. on completing this randomized non-inferiority trial of 700 patients with stage 1A2 and 1B1 cervical cancer comparing simple hysterectomy and pelvic node dissection to radical hysterectomy and pelvic node dissection (recently published in the New England Journal of Medicine) [5]. The primary endpoint was designed to detect non-inferiority of pelvic-relapse free survival at 3 years, with secondary outcomes including overall survival, parametrial involvement, quality of life and treatment-related toxicity. The 3-year pelvic-recurrence rate was 2.5% in the simple hysterectomy group and 2.2% in the radical hysterectomy group per intention to treat analysis (2.8% and 2.3% per protocol analysis) and the upper 95% confidence limit did not meet the pre-defined threshold of inferiority. The 3-year extra pelvic relapse-free survival and overall survival were 98.1% vs. 99.7% and 99.1% vs. 99.4%, respectively. Surgical margins were similar (2.4% SH vs. 2.7% RH).

Patient reported outcomes of sexual health were measured by the Female Sexual Function Index and the Female Sexual Distress Scale-Revised, and bowel, bladder and non-sexual vaginal symptoms were measured by EORTC QLQ-C30 with QLQ-CX24. Simple hysterectomy was associated with decreased pain experience and favorable sexual health. Patients who underwent simple hysterectomy reported less sexual worrying and increased sexual enjoyment at 3 months, less sexual pain and improved sexual lubrication for the first 12 months, and improved sexual vaginal functioning for the first 24 months. Overall better body image and increased sexual activity was reported for up to 36 months. Decreased urinary retention and incontinence also favored simple hysterectomy (0.6% vs. 9.9% and 4.7% vs. 11%, respectively). These findings of decreased sexual health and increased bladder symptoms in patients undergoing radical hysterectomy are consistent with the literature [6,7,8,9].

The ConCerv trial prospectively evaluated patients with cervical cancer up to 2 cm, treated with conization or simple hysterectomy, and concluded conservative surgery may be offered based on a cumulative recurrence of 3.5% over a median follow up of 36.3 months [10].

A systematic review of the literature including 2,662 women demonstrated no significant association between mortality and simple vs. radical hysterectomy in patients with microscopic disease, and the recent SCCAN retrospective trial of 1,257 patients comparing type B, C1 and C2 radical hysterectomy techniques found no survival difference for tumors up to 2 cm with increased radicality of surgery [11,12].

What can we conclude from all this? The evidence from these studies is congruent; non radical surgery for small cervical cancers is safe, not associated with increased relapse rates, and improves quality of life, measured through patient reported outcomes. Rarely do we find a therapy, that relative to standard of care, is as effective yet less complex, less costly and better tolerated by patients. While it is unlikely this study will be replicated, these findings stimulate additional questions. With no reason to suspect otherwise, will the 5-year overall survival be consistent with these 3-year findings? Given that the majority of patients in the ConCerv trial (96%) and the SHAPE trial (75%) underwent minimally invasive surgery for their hysterectomy, what is the optimal surgical approach for these patients [10,13]? Can sentinel node biopsy replace full pelvic lymphadenectomy for cervical cancer staging? (Hopefully answered in the SENTICOL3 study [14].) What is the optimal vaginal/tumour free resection margin? In patients wishing for fertility preservation can an analogous evidence base be used to support treatment with cone biopsy or simple trachelectomy and pelvic lymph node assessment (as proposed in the ConCerv trial [10])?

While we eagerly await the GOG 278 trial results to provide further prospective evidence of quality of life measures and relapse-free survival in women with early cervical cancer treated with simple hysterectomy, it would seem obvious to most clinicians that patients meeting the inclusion criteria of the SHAPE study, can (and should) now be treated with simple hysterectomy rather than radical hysterectomy.