Advances in the Treatment of Gynecologic Malignancies

Two things become apparent to the reader of this excellent article. First, the National Cancer Institute clearly had great foresight in 1970, when they began funding the Gynecologic Oncology Group (GOG) so that phase I, II, and III trials could be conducted in a systematic manner. Second, the authors have written a thorough review of over 3 decades of research into the biology and clinical aspects of cervical and vulvar cancer. In this short space, it would be impossible to adequately comment on the 50 studies reviewed by the authors. However, based on these studies, I would posit the rationale for a paradigm shift in the staging of cervical cancer, and would add (to paraphase Mark Twain), "the report of the complete demise of hydroxyurea as a radiation sensitizer may be an exaggeration."

Like the GOG, since 1971, we have been researching many of the same issues in cervical and vulvar carcinoma: the importance of the size of the cervical lesion and lymph node metastasis in the survival of patients with stage IB cervical cancer[1]; the importance of surgical staging by para-aortic lymphadenectomy in locally advanced stage IIB, III, or IVA cervical cancer[2]; the use of para-aortic radiation in cervical cancer patients with documented para-aortic lymph node metastasis[3]; the use of the radiation sensitizer hydroxyurea in locally advanced cervical cancer[4]; the value of pelvic lymphadenectomy in central lesions of the vulva[5]; and the rates of survival, recurrence, and inguinal lymph node metastasis in vulvar cancer.[6]

Because of the rarity of vulvar cancer in the United States—only 3,800 cases and 800 deaths are predicted for 2002[7]—new advances in the treatment of this disease will be slow and probably only result from well-designed studies conducted by cooperative groups such as the GOG. Moreover, with the 5-year survival in early-stage (IB) cervical cancer being greater than 90%, studies documenting improvement will be difficult. However, progress in the treatment of locally advanced (ie, stage IIB-IVA) cervical cancer is essential if survival is to be improved in the 21st century.

Surgical Staging

Because endometrial, ovarian, and vulvar cancer (and almost all other solid tumors) are surgically staged prior to decisions being made about postoperative therapy, it would appear that this same rationale would lead to progress in locally advanced cervical cancer if the full extent of disease is surgically documented prior to initiating radiation therapy. This is particularly germane given the lack of sensitivity and specificity of radiologic imaging studies in the diagnosis of para-aortic lymph node metastasis from cervical cancer.

In 1977, I reported on 100 consecutive patients with stage IIB, IIIB, and IVA cervical cancer who underwent preradiation para-aortic lymphadenectomy.[2] Of these, 28% had metastasis to the para-aortic lymph nodes, which are outside the field of standard pelvic radiation: 13.6% of stage IIB, 36.7% of stage IIIB, and 57.1% of stage IVA patients had para-aortic lymph node metastasis (Table 1). Looking at these percentages in another way, the highest possible cure rate for all 100 patients would be 72%, in the unlikely possibility that all such patients had their localized disease eradicated. For patients found to have para-aortic node metastasis, more uniform extended-field therapies may eventually lead to improved survival even in women with a poor prognosis.

Radioresistance