Advanced cervical cancer.

Several large, prospectively randomized clinical trials run by multi-institutional cooperative groups have established that the best treatment for advanced cancer of the cervix is primary radiotherapy with concurrent, cisplatin-based chemotherapy. In fact, patients with earlier stage cervix cancer with poor prognostic indicators (large, bulky tumors, positive pelvic lymph nodes, or unexpected parametrial disease at the time of surgery) also show a survival benefit with this approach. Adequate radiation dosing (both external beam and intracavitary) is essential. The additional benefit of periaortic lymph node irradiation is debated, but generally accepted, for patients with locally advanced disease or pelvic lymph node involvement.

Primary radiation, cisplatin, and 5-fluorouracil for advanced squamous carcinoma of the vulva.

OBJECTIVE: To evaluate a regimen of radiation and chemotherapy as an alternative for those patients in whom the location and extent of advanced vulvar carcinoma make pelvic exenteration the only surgical option. METHODS: Between December 1988 and March 1995, 14 patients with primary squamous carcinoma of the vulva who were not candidates for standard radical vulvectomy were treated with radiation therapy in combination with cisplatin and 5-fluorouracil (5-FU) chemotherapy at the Albany Medical Center. Patients ranged in age from 40 to 90 years, mean 68. Tumors were stage III in 9 patients and stage IV in 5 patients. Treatment included two cycles of chemotherapy with cisplatin (50 mg/m2) and 5-FU (1000 mg/m2/24 x 96 hr) in addition to radiation therapy. Total radiation doses to the vulva and groins ranged from 50 to 65 Gray (Gy), with pelvic doses of 45 to 50 Gy. Surgical excision of the primary site was not performed in patients who had complete clinical response. RESULTS: Acute complications included desquamation requiring treatment interruptions in 5 patients and deep venous thrombosis in 1 patient. Delayed complications were limited to small bowel obstruction and colonic stricture in one patient. There was a 92% response rate with complete responses in 9 patients (64%). Among patients with complete clinical response, there has been only one recurrence with follow-up of 7-81 months, mean 36.5. All patients with partial responses died, with survival of 8-25 months, mean 15.7. CONCLUSIONS: This combination of chemoradiation was found to be effective therapy for locally advanced vulvar carcinoma, with acceptable morbidity even in an elderly population. Surgical excision of the primary site is not necessary in patients with complete response.

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)