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Advances in the Treatment of Gynecologic Malignancies

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.

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