Neoadjuvant chemotherapy followed by large cone resection as fertility-sparing therapy in stage IB cervical cancer

Highlights

• Pelvic lymphadenectomy should be done before starting neoadjuvant chemotherapy to rule out high risk.

• Neoadjuvant chemotherapy followed by conization has a low risk of preterm delivery.

• Fertility sparing surgery is not a standard therapy and should be reserved for patients with a high fertility wish.

Abstract

Background

Standard treatment of cervical cancer FIGO stage IB1 is a radical hysterectomy with pelvic lymphadenectomy. As the number of patients with a preserved fertility wish has increased, the need for fertility sparing surgery emerges. In this study we discuss 11 patients with cervical carcinoma stage IB treated with neoadjuvant chemotherapy followed by large cone resection.

Methods

In this retrospective study we included 10 patients with FIGO stage IB1 and 1 patient with IB2 cervical cancer, who first received a pelvic lymphadenectomy followed by neoadjuvant chemotherapy and conization. Paclitaxel–ifosfamide–carboplatin or a combination of paclitaxel–carboplatin was used as neoadjuvant chemotherapy.

Results

Complete response after chemotherapy was observed in 64%, partial response in 27% and 9% had progressive disease. All patients with response underwent a conization, with no residual disease on pathology in 80%. Patients with residual disease were treated by radical hysterectomy. In 9 patients fertility sparing surgery could be performed and 6 (67%) got pregnant. Five patients had 7 children and two patients had four missed abortions. Two premature deliveries at 32 and 33 weeks were described, both in the same patient. Recurrence was observed in one patient that was treated with simple hysterectomy followed by radiochemotherapy. Median follow up time is 58 months with all patients alive and no evidence of disease until now.

Conclusions

Neoadjuvant chemotherapy followed by conization seems to be a promising new fertility sparing treatment modality in patients with cervical carcinoma stage IB1, but further studies with larger populations should confirm these data.

Introduction

Cervical cancer is the fourth most common cancer in women and the leading gynecological malignancy worldwide [1]. Age distribution shows three peaks at the age of 35, 50 and 70 years. The most frequently used standard treatment for FIGO stage IB1 has been radical hysterectomy with pelvic lymphadenectomy.

As the mean age of first delivery has increased over the last decades, the number of patients wishing to preserve fertility at the time of diagnosis has increased. Fertility-sparing surgical options, such as laparoscopic (LRT), abdominal (ART) and vaginal radical trachelectomy (VRT) or simple trachelectomies with or without pelvic lymphadenectomy, have been reported [2], [3], [4], [5]. A study of Schmeler et al. showed that 60% of trachelectomy specimens did not contain residual invasive malignant disease, [6], [7], [8], [9], [10] which raises the question if less radical surgery is possible in some cases. Furthermore, trachelectomies have been associated with preterm deliveries (before 31 weeks) in about one third of the patients [11].

The option of neoadjuvant chemotherapy (NACT) has been described for the above performed surgery [12], [13]. Another option is conization which can be performed in a selected group of patients in the low-risk group FIGO stage IA2 to IB1 disease [10]. Tumor size smaller than 2 cm, negative lymphovascular space invasion (LVSI), stromal invasion less than 10 mm and low risk histological types (squamous, adeno- and adenosquamous carcinoma) are prognostic factors that have been proposed as criteria to perform conservative surgery. Several studies have shown that the risk of parametrial involvement and parametrial node involvement in this group is as low as 1% [14], [15], [16].

Neoadjuvant chemotherapy (NACT) followed by radical hysterectomy is mainly used in some centers in cervical cancer stages IB2–IIB [17], [18], [19]. These studies showed that neoadjuvant chemotherapy results in a high number of responses [20]. The EORTC 55994 trial has recently closed accrual and is comparing NACT followed by radical hysterectomy versus concomitant chemoradiotherapy (CCRT).

In the current study we report on 11 patients with cervical cancer IB1 or IB2 who received first a pelvic lymphadenectomy followed, in case of negative pelvic lymph nodes, by NACT and conization. The goal of the NACT is to reduce the resection of the cervix as much as possible in the hope of reducing the incidence of preterm labor [21]. Literature shows that pregnancy loss or delivery before 32 weeks is reported in 44% for vaginal radical trachelectomy and 38% for abdominal radical trachelectomy. For the patients treated with NACT followed by fertility sparing surgery (including our series) the incidence is estimated on 30% [22]. Furthermore, radical trachelectomy has been associated with autonomic nerve damage resulting in possible sexual and lower urinary tract dysfunction or colorectal motility disorders [11].