Impact of hydronephrosis on outcome of stage IIIB cervical cancer patients with disease limited to the pelvis, treated with radiation and concurrent chemotherapy: A Gynecologic Oncology Group study

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Abstract

Objectives

To estimate the significance of hydronephrosis and impact of ureteral obstruction relief on outcome in patients with stage IIIB cervical cancer treated with radiation and concurrent chemotherapy.

Methods

We retrospectively studied stage IIIB cervical cancer patients treated on GOG trials 56, 85, 120 and 165 evaluating radiation and concurrent chemotherapy. Eligible patient records were reviewed to assess the presence of hydronephrosis and treatment of ureteral obstruction. Patients were classified into three groups; no hydronephrosis, hydronephrosis relieved from ureteral obstruction via stent or percutaneous nephrostomy and hydronephrosis without treatment of ureteral obstruction.

Results

539 stage IIIB patients were studied. Hydronephrosis was present in 238 (44.2%). Patient age, race, and tumor characteristics (size, histology and grade) were not significantly different between patients with or without hydronephrosis. Patients with hydronephrosis received similar doses of radiation and cisplatin-based chemotherapy. Both overall and progression-free survival were worse with hydronephrosis (log-rank test p value = 0.0189 and 0.0186, respectively). Univariable analysis identified five prognostic factors; pelvic nodal metastasis (p = 0.0001), tumor diameter (p = 0.0007), cisplatin-based concurrent chemoradiation (p = 0.0031), hydronephrosis (p = 0.0189), and performance status (p = 0.0359). Hydronephrosis was associated with worse performance status (p < 0.001). On multivariable analysis hydronephrosis was not a significant prognostic factor. Ureteral obstruction relief occurred for 88% of patients and was associated with improved survival.

Conclusion

In patients with stage IIIB cervical cancer restricted to the pelvis, hydronephrosis at presentation is a significant but not independent prognostic factor associated with poor performance status and poorer survival. Relief of ureteral obstruction is correlated with improved outcome.

Introduction

The prognosis for patients with advanced stage cervical cancer is based on both the extent of local pelvic disease and the presence of metastases. The Federation International Obstetrics and Gynecology (FIGO) staging system for cervical cancer describes various stages and substages of disease which, with the exception of the most advanced stage (stage IVB), describe the extent of local/regional pelvic disease. Despite the use of relatively standard radiation protocols, survival worsens with increasing disease stage for patients treated with or without concurrent cisplatin-based chemotherapy. Stage IIIB is defined as local extension of the cervical tumor to the pelvic sidewall or the presence of hydronephrosis. Hydronephrosis, particularly if bilateral, may result in varying degrees of renal insufficiency which may limit the ability to deliver concurrent cisplatin-based chemotherapy which has been recommended in a National Cancer Institute Clinical Alert [1]. Renal function may be improved or restored if the renal obstruction is relieved by ureteral stents or percutaneous nephrostomies. The impact of hydronephrosis and interventions to correct it has not been extensively reported in advanced stage cervical cancer patients treated with curative intent with radiation and concurrent chemotherapy [2], [3], [4], [5], [6].

The disease extent in patients with stage IIIB disease can vary depending on whether there is unilateral or bilateral parametrial disease, whether there is unilateral or bilateral sidewall involvement, whether hydronephrosis is present and if present is it unilateral or bilateral, and overall tumor size. In addition to these local factors patients with stage IIIB are at increased risk for extrapelvic metastasis. Although basic radiologic imaging with plain radiographs is allowed by the FIGO staging system, more advanced techniques including lymphangiography, computerized tomography (CT), magnetic resonance imaging (MRI) and more recently positive emission tomography (PET) which have been utilized to evaluate patients for extrapelvic nodal or distant metastases are not accepted [7]. Furthermore, the prognosis of patients with stage IIIB disease depends on how metastases to the paraaortic nodes have been excluded, i.e. radiologically or by surgical lymphadenectomy [8]. Surgical findings are not utilized in the FIGO staging system and therefore disease identified by retroperitoneal lymphadenectomy does not change the patient's disease stage.

The purpose of the current study was to estimate the significance of ureteral obstruction as a prognostic variable in stage IIIB cervical cancer with disease limited to the pelvis. Additionally, we sought to estimate the impact of relieving ureteral obstruction by ureteral stent or percutaneous nephrostomy in patients with stage IIIB cervical cancer treated with chemoradiation.

Section snippets

Materials and methods

We retrospectively reviewed patients entered on four randomized clinical trials performed by the Gynecologic Oncology Group (GOG) in locally advanced stage disease (stages IIB–IVA) conducted from June 1981 to August 2000 [9], [10], [11], [12]. These studies have all been reported previously and all utilized external and intracavitary radiation and concurrent chemotherapy. It is important to note that eligibility for these trials included a serum creatinine less than 2.0 mg/dl prior to

Results

Five hundred and thirty-nine patients with stage IIIB cervical cancer from prior GOG protocols 56 (N = 100), 85 (N = 118), 120 (N = 220) and 165 (N = 101) were studied. The demographics of these patients are presented in Table 1. Hydronephrosis was present in 238 stage IIIB patients (44.2%). Patient age, race, and tumor characteristics (size, histology and grade) were not significantly different between the groups. Patients presenting with hydronephrosis received similar cumulative doses of radiation

Discussion

The strengths of this study include the large number (539) of stage IIIB cervical cancer patients treated in four prospective randomized trials utilizing standardized radiation doses and schedules. Prognostic factors identified included pelvic nodal metastasis, tumor diameter, cisplatin-based concurrent chemoradiation, hydronephrosis, and performance status. The FIGO staging system is a clinical staging system which is widely applicable but lacks recognition of any of the above identified

Conflict of interest statement

The authors have no conflicts of interest to declare.

Acknowledgments

This study was supported by National Cancer Institute grants to the Gynecologic Oncology Group Administrative Office (CA 27469) and the Gynecologic Oncology Group Statistical Office (CA 37517). The following Gynecologic Oncology Group member institutions participated in the primary treatment studies: University of Alabama at Birmingham, Oregon Health Sciences University, Duke University Medical Center, Abington Memorial Hospital, University of Rochester Medical Center, Walter Reed Army Medical

References (19)

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