Advances in the Treatment of Gynecologic Malignancies

In their review, Drs. Kim, Alvarez, and Omura have outlined a diverse group of clinical trials in a very limited space. Their summary highlights some of the most important insights gained from these trials, placing particular emphasis on the role and perspective of the Gynecologic Oncology Group (GOG). Although their review appropriately divides these studies into three major groups (early cervical cancer, locally advanced cervical cancer, and vulvar cancer), the results also reveal common themes that can be used to guide the overall management of women with carcinomas of the female lower genital tract.

Postoperative Adjuvant Treatment

Several studies demonstrate the potential value of postoperative radiation for patients with regional metastases or other high-risk features, but also suggest that selecting patients to avoid the need for both radical surgery and radiation might reduce the overall morbidity of treatment. Although the authors suggest that postoperative radiation therapy does not affect survival in patients who have regional metastases from early cervical cancers, I would contend that the question has never been adequately studied—retrospective comparisons are rife with selection bias, and a randomized trial initiated in the early 1990s closed when it failed to accrue more than a handful of patients.

Homesley et al[1] demonstrated that the improved regional control rate achieved with postoperative therapy for vulvar cancer does lead to a better survival rate. Sedlis et al[2] reported a significant improvement in pelvic disease control and an encouraging (although preliminary) comparison of survival rates with postoperative radiation for node-negative intermediate-risk cervical cancer. It would be surprising if survival rates did not improve with better local control of node-positive patients. However, the Southwest Oncology Group (SWOG) trial published by Peters et al[3] clearly demonstrates an unacceptably high pelvic recurrence rate of more than 20% with pelvic irradiation alone and convincingly demonstrates the improvement achievable with the addition of concurrent chemotherapy.

Although the postoperative cervical cancer trials demonstrated important improvements with adjuvant treatment, patients who received the most aggressive treatment in each trial continued to fail locally at a rate of about 10%. The Homesley trial showed few regional recurrences, but the preliminary report was made with short follow-up and was never updated.

One wonders whether selected patients would benefit from even more aggressive therapy—eg, concurrent chemotherapy for certain intermediate-risk patients or higher-dose, conformal radiation therapy (or brachytherapy) for selected node-positive patients. However, as Kim et al point out, these treatments are not without harm—each modality increases the risk of major treatment-related morbidity, and indiscriminate use of trimodality therapy cannot be condoned.

The tools at our disposal should be carefully used to avoid radical surgery in patients who require postoperative radiation therapy and to accurately select patients who will benefit from adjuvant radiation or chemoradiation. Advanced imaging with magnetic resonance imaging and positron-emission tomography may help make some of these selections. Ultimately, we need much more sensitive indicators of the risk of recurrence than the currently used histologic and morphologic prognostic factors. Early studies of biochemical, immunohistochemical, and molecular tests suggest that the future might provide us with better ways of selecting these treatments.