Kristine M. Conner
Medical Correspondent, OncoLink
Last Modified: November 1, 1999
In February 1999, the National Cancer Institute issued a clinical alert stating that concurrent cisplatin-based chemotherapy plus radiation therapy appears to be a superior treatment to radiation alone for women with cervix cancer. This statement was based on the results of five phase III trials that demonstrated a significant survival advantage for women with Stages IB2 through IVA cancer who received the combined treatment.
Today, three experts discussed the question of what should be considered "standard therapy" for cervix cancer. While the NCI recommendation is being adopted widely and rapidly, questions remain about what is the best treatment for each stage and for each individual patient. The panelists did not question the validity of what the five trials have shown, but they did direct audience members' attention to the many issues that remain to be resolved.
Dr. Gillian Thomas of the Toronto-Sunnybrook Regional Cancer Center started the panel discussion by mentioning the NCI statement and highlighting the fact that what has happened with the five cervix cancer trials is quite unusual. "Seldom do we have so many results from several clinical trials that seem to be pointing in the same direction," said Dr. Thomas. When she surveyed the audience as to whether they have adopted the NCI-recommended radiation therapy/chemotherapy combination as their "standard of care," most raised their hands.
Dr. Thomas went on the review the five Gynecological Oncology Group trials that led to this new standard, showing how the survival rates were higher for women who received the combined treatment-9 to 18% higher, she noted. But she also complicated the issue, emphasizing that while this practice is "being adopted pretty quickly," there is still much "we don't know" about the optimal treatment for different stages of cervix cancer. She raised a series of questions to make this point. For instance, is platinum the critical drug, or would other forms of chemotherapy produce similar results? Do women with all stages and extents of the disease benefit in the same way? What if an optimal dose and treatment schedule of radiation therapy were given alone? Would that be superior to the cisplatin/radiation combination? These questions all remain to be answered by current and future clinical trials.
Dr. Thomas also encouraged radiation oncologists to exercise their judgment on a case-by-case basis regarding whether to add cisplatin to radiation therapy. Rather than using a "blanket approach," she said, physicians should adjust to the needs of the patient. She noted that the toxicity of cisplatin can pose significant risks for patients with other conditions, such as kidney problems or diabetes.
Dr. David Moore of Indiana University and Dr. Ronald Alvarez of the University of Alabama at Birmingham, both surgeons, focused their talks on the role of surgery in treating early-stage (Stage IB to IB2) cervix cancer. Dr. Moore discussed several Gynecologic Oncology Group clinical trials to raise the question of whether hysterectomy improves outcomes for women with these stages of cervix cancer. Can hysterectomy be foregone in some cases in favor of radiation alone, or radiation with chemotherapy? Dr. Moore's answer, based on the research to date, is a qualified "yes." "More isn't necessarily better," he told the audience. "If you can achieve the same results with radiation therapy that you can with surgery and radiation therapy, then do it."
Dr. Alvarez argued that the individual patient's situation should determine whether a primary surgical approach is appropriate. "Are all patients with Stage IB2 cervical cancer identical?" he asked. "No, I don't think that's the case." Dr. Alvarez emphasized that Stage IB2 is actually a "range of cancers," with tumor size, parametrial extension, and nodal metastases varying from patient to patient. These are the factors that must be taken into account when making a decision about surgery. Thus, the improvement of imaging techniques and a clearer definition of the role of surgical staging are essential to making more informed treatment decisions for patients. Dr. Alvarez went on to consider the role of adjuvant and neoadjuvant therapies for those patients who do have surgery. Only more randomized trials of primary and adjuvant therapy will establish what is the optimal practice, he noted.
These three talks questioned the notion that there is a proven "standard" therapy for cervical cancer. While the results of the five recent clinical trials showing a benefit to combined chemotherapy and radiation are promising, uncertainties remain. Dr. Gillian Thomas captured the spirit of the panel best by advising her colleagues in the audience to "be discriminating about what you use and who you use it in."