Elsevier

Gynecologic Oncology

Volume 102, Issue 3, September 2006, Pages 523-529
Gynecologic Oncology

Surgery after concurrent chemoradiotherapy and brachytherapy for the treatment of advanced cervical cancer: Morbidity and outcome: Results of a multicenter study of the GCCLCC (Groupe des Chirurgiens de Centre de Lutte Contre le Cancer)

https://doi.org/10.1016/j.ygyno.2006.01.022Get rights and content

Abstract

Objectives.

To evaluate the morbidity and therapeutic value of surgery after concurrent chemoradiotherapy and brachytherapy in a multicentric series of patients with advanced cervical cancer.

Methods.

Patients with stage IB2 to IVA cervical cancer treated with concurrent chemoradiotherapy and pelvic radiotherapy followed by brachytherapy and surgery from seven participating French comprehensive cancer centers were enrolled. The surgical treatment consisted of a hysterectomy, which ranged from radical hysterectomy to anterior pelvic exenteration, and lymph node resection. Acute toxicity, pathological response, overall, and disease-free survival were assessed for each pathological response to therapy.

Results.

One hundred seventy-five patients were enrolled from September 1987 to June 2002. The median age was 44 years [27;75]. Patients distribution according to clinical classification was as follows: 41 stage IB2, 18 IIA, 77 IIB, 12 IIIA, 14 IIIB, and 13 IVA. Forty-six patients experienced 51 postoperative complications. Thirty-three patients experienced grade 2 morbidity (18.9%, 33/175), among whom 19 experienced urinary complications (57.5%, 19/175). No post treatment mortality was observed. Grade 3 toxicity rate was 6.9% (12/175). Pathological complete response rate was 38% (67/175). After a median follow-up of 36 months, overall survival and disease-free survival were significantly better in patients who had a pathological complete response to therapy than those who achieved a partial pathological response (P < 0.0001).

Conclusion.

Surgery after concurrent chemoradiotherapy and brachytherapy for advanced cervical cancer leads to an acceptable morbidity. Furthermore, surgery allows evaluation of the pathological response to therapy and improves local control in the case of partial pathological response.

Introduction

Cervical cancer is the most frequent cause of death by cancer in women from developing countries [1]. Prognosis for patients with cervical cancer depends on the stage of disease at diagnosis, based on the International Federation of Gynecology and Obstetrics staging system (FIGO) [2], [3]. For years, the treatment of advanced cervical cancer had experienced no major changes, with radiotherapy alone considered as the standard treatment [4]. Due to the difficulty to obtain free margins and to the high rate of associated morbidity, surgery was contra indicated for a long time and was only used as for pelvic exenterations [5]. Treatment of patients with locally advanced cervical cancer remains, however, suboptimal. In 1998, the reported five-year survival rates for stages IB, IIB, IIIB, and IVA were 72%, 64%, 42%, and 16%, respectively [6]. Based on a 10-year follow-up, pelvic failure was shown to occur in 35–50% of stage IIB–III patients treated by radiation therapy alone with a dose of 80 Gy [7]. According to a recent meta-analysis, concurrent chemoradiotherapy, the new standard treatment for locally advanced cancer, was shown to significantly improve the overall and progression-free survival rates and reduce local and distant recurrence compared to radiation therapy alone [8]. Surgery was not performed in most of the studies considered in this meta-analysis.

Interestingly, in a study by Duenas-Gonzales et al., the five-year survival rate reported after neoadjuvant chemotherapy followed by surgery was 15% higher than that obtained with radiation alone [9].

Keys et al. reported rates of complete pathological response of 41 to 52% after concurrent chemoradiotherapy in stage IB2 cervical cancer [10]. This study demonstrates that hysterectomy provides an information on the pathological response to therapy. Considering the rate of partial pathological response after concurrent chemoradiotherapy, the lack of surgery points the risk of an under-treatment especially in terms of local control. Moreover, concurrent treatment modality without surgery still failed to find a statistically significant difference for the more advanced cervical cancer stages III and IVA as compared to radiotherapy alone [11], [12].

The aim of our study was twofold. Our main objective was to evaluate the morbidity of surgery after concurrent chemoradiotherapy and brachytherapy in a multicenter series of patients with advanced cervical cancer. Our second objective was to evaluate the overall and disease-free survival rates associated with pathological responses to therapy.

Section snippets

Patients and methods

This observational retrospective multicenter study included patients with advanced cervical cancer treated with chemoradiotherapy, brachytherapy, and surgery.

Results

One hundred seventy-five patients with advanced cervical cancer treated in seven French comprehensive cancer centers from September 1987 to June 2002, were retrospectively enrolled in this study. Patients' characteristics are summarized in Table 2. Only 10 of the 175 patients received less than 25 mg/m2 of platin weekly. One hundred seventy-one patients had a pelvic lymphadenectomy, 71 also had a paraaortic lymphadenectomy, and 4 had a paraaortic lymphadenectomy only. At the time of the

Discussion

The role for surgery to evaluate the local spread and lymph node involvement in cervical cancer has been emphasized since 1978, recommending complete parametrial resection and systematic resection of pelvic and aortic lymph nodes to constitute an objective method of staging cervical cancer [15]. Whether surgical resection of the initial site of cancer spread should be omitted, when using multimodality treatments, in patients with an advanced cervical cancer, remains to be determined.

Conclusion

Surgery should be considered after concurrent platin-based chemoradiotherapy and brachytherapy in advanced cervical cancer surgery, as it allows assessment of pathological response and improves local control.

Prospective randomized studies should be conducted to determine how surgery can best benefit advanced cervical cancer patients when part of a combined treatment.

Several issues, such as the extent of surgery, which can vary based on preoperative treatment response, warrant further

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