Optimal management of locally advanced cervical carcinoma

Locally advanced or recurrent cervical cancer is highly responsive to treatment and at least moderately curable with effective aggressive treatment. Radiation therapy is the mainstay of treatment for patients with this cancer. The roles for surgery and chemotherapy are as yet unproved, and both modalities are currently under investigation for their potential roles in the management of these conditions. Exenterative surgery clearly has an established utility for central pelvic failures after prior radiation therapy. Postsurgical pelvic recurrences are rarely successfully treated for cure, but considerable palliative effect is possible. The roles of intraoperative irradiation, sensitizing chemotherapy, and radical resection with interstitial irradiation are all under investigation at this time. Much has been learned over the past several decades about what parameters are important for successful radiation therapy for cervical cancers of stages IIB-IVA. While the traditional staging work-up for these patients included excretory urography, barium enema, examination under anesthesia, cystoscopy, and proctoscopy, there is now good evidence that computed tomography scan with intravenous contrast and office examination and biopsy are sufficient, with cystoscopy reserved for those few patients in whom clinical or imaging data suggest a higher risk of involvement. Surgical lymph node staging, especially of para-aortic lymph nodes, may be worthwhile in certain settings (e.g., for entry into research protocols), but it has no demonstrated role in routine clinical practice. Evidence is clear and convincing that effective treatment for these disease stages requires the inclusion of intracavitary brachytherapy. The role of interstitial brachytherapy is less clear, although there are some fervent advocates of this procedure. The debate continues about the use of low-dose-rate versus high-dose-rate brachytherapy. Treatment dose, volume, and length of treatment course are all important variables with outcome implications. The central disease requires a total dose of 8000-9000 cGy for maximal control probability, with larger tumors requiring the higher doses. The three-dimensional treatment volume must adequately surround the cancer and its likely routes of spread. Overall treatment time should be kept as short as possible, within the limits of conventional, tolerable fractionation. The potential theoretical advantage of hyperfractionated external-beam irradiation has yet to be verified in this disease but is of interest. It will be tested in an upcoming Gynecologic Oncology Group clinical trial. The negative prognostic significance of hypoxia in cervical cancers in general has been reported recently. While tumor cell hypoxia is almost certainly a problem in this disease, hypoxic cell sensitizers have not yet been found to improve treatment results. In clinical practice, reoxygenation probably occurs in these tumors. The role of paraaortic lymph node elective irradiation has been of interest for more than 20 years and was the subject of two randomized trials with quite different results. The Radiation Therapy Oncology Group trial found significantly improved survival in the treatment group assigned to receive paraaortic irradiation, when compared with the pelvic treatment group. However, a similar study by the European Organization for Research and Treatment of Cancer found no difference. The results of treatment today are substantially improved from those seen two decades ago. About 75% of patients with stage IIB disease and fully 50% of patients with stage IIIB disease are now cured with conventional irradiation alone. Clearly, there is still a need for further improvement. Of patients with urinary bladder involvement, 10%-20% are long-term survivors, as are 25%-30% of patients with para-aortic lymph node metastases. While these improvements are significant, there is clearly room for further progress. (ABSTRACT TRUNCATED)