Elsevier

Gynecologic Oncology

Volume 119, Issue 3, December 2010, Pages 404-410
Gynecologic Oncology

Long-term analysis of clinical outcome and complications in locally advanced cervical cancer patients administered concomitant chemoradiation followed by radical surgery

https://doi.org/10.1016/j.ygyno.2010.08.004Get rights and content

Abstract

Objective

Preoperative chemoradiation (CT/RT) has been shown to achieve encouraging results in terms of clinical outcome in locally advanced cervical cancer (LACC). The study aims at analyzing the long-term results of this multimodal approach in a single institution series of 184 cases.

Methods

Patients underwent whole pelvic irradiation combined with cisplatin and 5-fluorouracil. After evaluation of clinical response, patients were triaged to surgery. Surgical morbidity was classified according to Chassagne grading system. Univariate and multivariate analyses were used to assess the prognostic and predictive role of clinicopathological parameters.

Results

Clinical response was observed in 96.1% of cases. A total of 174 cases were submitted to radical surgery: 124 patients (71.3%) showed complete/microscopic pathological response. In multivariate analysis, clinical response, stage of disease, and histotype predicted response to CT/RT. With a median follow-up of 58 months, recurrence and death of disease were observed in 42 and 40 patients, respectively. The 5-year DFS was 75.5%, while the 5-year OS was 77.4%.

Patients with no residual disease showed a significant longer DFS than patients with microscopic (p value = 0.0128), and macroscopic (p value = 0.0001) residual tumor after treatment. In multivariate analysis, residual tumor and stage of disease were the two most relevant prognostic factors for DFS and OS. As far as long-term toxicity is concerned, 8 out of 22 complications were grade 3/4.

Conclusion

Preoperative CT/RT is worth further investigation in LACC patients, providing encouraging survival outcomes and a favourable long-term toxicity profile.

Introduction

Since the 1999 NCI Clinical Announcement, exclusive concomitant chemoradiotherapy (CT/RT) has been representing the standard treatment for locally advanced cervical cancer (LACC) patients based on results from 5 randomized phase III studies that demonstrated an advantage in terms of disease-free (DFS) and overall survival (OS) for CT/RT compared to exclusive radiotherapy [1], [2], [3], [4], [5], [6]. However, investigational strategies employing completion surgery after chemotherapy or CT/RT have been also explored with the aim to remove potentially chemo- and radioresistant tumor foci and improve local control and possibly overall survival [2], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16]. Indeed, preoperative CT/RT has been reported to achieve very encouraging results in terms of extent of local control and overall survival [11], [12], [13], [14], although concerns remain about the potential increase of rate and severity of treatment-related complications [2], [9], [11], [14].

Previously reported long-term analyses of clinical outcome and toxicity profile of CT/RT plus completion surgery refer to relatively small sample series [9], [15], [16] which are hardly comparable because of the differences in the distribution of patients according to stage of disease [15] or use of additional treatments such as preoperative aortic irradiation, or intraoperative radiotherapy [9]. On the other hand, the reliability of more recent series, which otherwise have presented a quite acceptable sample size is heavily impaired by the heterogeneity of surgical approaches including extrafascial versus radical hysterectomy as well as pelvic lymphadenectomy versus only aortic lymph node dissection [13], [14].

The aim of this study was to analyze the long-term clinical outcome and complication profile of a strategy employing radical surgery after CT/RT in a large, prospectively collected, single-institution series of LACC patients.

Section snippets

Patients and methods

The study prospectively included 184 consecutive LACC patients accrued between March 1996 and June 2007 at the Gynecologic Oncology Units of the Catholic University of Campobasso and Rome. Inclusion criteria were the following: biopsy-proven carcinoma of the cervix (stage IB2–IVA), no evidence of disease outside the pelvis, age < 80 years, Eastern Cooperative Oncology Group performance status < 2, adequate bone marrow function (WBC > 3000, platelets > 120,000/mm3), adequate renal function (blood urea

Results

The clinicopathological characteristics and surgery details of patients in the overall series are summarized in Table 1. Overall, median age was 52.5 years (range = 25–79 years); 136 patients (73.9%) were FIGO stage IIB, while 38 cases (20.6%) had stage III–IVA disease. Seventy patients (38.0%) had positive pelvic lymph nodes at staging work up.

Fig. 1 shows the flowchart of our patients' population: 2 patients died during/after chemoradiation as a result of causes unrelated to treatment, leaving

Discussion

Even with the advent of exclusive chemoradiation, which has been recognized since 1999 as the standard treatment for LACC, the 5-year OS in this subset of patients still remains around 70%, so that the encouraging results from strategies which have revisited the role of completion surgery after CT/RT seem worthwhile [9], [16]. In this scenario, results of our study could represent a contribution to the literature since they are based on a large, prospectively collected sample population endowed

Conflict of interest statement

The authors have no conflict of interest to report.

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