Ask the Experts - Concurrent Chemoradiation for Cervical Cancer?
With the recently published randomly assigned studies on concurrent chemoradiation for cervical carcinoma, should we regard this approach as a new standard for routine treatment of cervical carcinoma? In general, how widely is this approach accepted as standard among major cancer centers in the United States and Europe?

Dr. Yiu T. Fu



Overall survival from invasive cervical cancer is stage- dependent. Although early-stage disease (stage IIA or less) has, in general, a good to excellent 5-year survival, the more bulky tumors tend to do poorly. Despite novel approaches to treatment, no significant improvement in survival has occurred. Approaches included alternative radiotherapy such as the addition of hyperthermia, whereas others have investigated neoadjuvant chemotherapy with cisplatin-based treatment before radiation or surgery. These approaches have not yielded significantly improved survival. A more recent approach combines radiation therapy with concurrent chemotherapy. The theory is to inhibit the repair of sublethal cell damage from radiation, bring cancer cells into a radiosensitive phase of the cell cycle, and cause cell death with the chemotherapeutic agent(s). Thus, the potential synergistic effect is to decrease local-cell resistance to the radiation and ultimately improve survival.

In February of 1999, the National Cancer Institute (NCI) issued a clinical announcement drawing attention to the results of 5 randomly assigned phase III trials using cisplatin-based chemotherapy with radiation therapy as either initial therapy for FIGO stages IB2-IVA disease upfront or as adjuvant therapy for surgically treated high-risk FIGO stages I-IIA. Patients were randomly assigned to study arms versus a control radiation arm. The NCI summarized the data, stating that chemoradiation decreased death from cervical cancer by 30% to 50%, a significant survival benefit in each study. Given these results, the NCI recommended that strong consideration be given to treating such patients with chemoradiation.

Most major cancer centers in the United States were aware of the Gynecologic Oncology Group sponsored trials and of the preliminary data before its formal presentation and publication; thus, acceptance of such treatment is very high. The NCI announcement was targeted at nonparticipating centers and for increasing awareness of the general medical community and the public. The majority of oncology caregivers seem to agree that this method of treatment is the new standard of care for bulky cervical cancers.

Currently, there are no published results of large randomly assigned phase III trials for cervical chemoradiation from European centers. Editorial comments in response to the publication in the New England Journal of Medicine of the US studies and commentary in European journals offer some insight. These commentaries raise excellent questions: What is the role of hemoglobin concentration in these results? Were patients more commonly transfused in the chemotherapy arms; thus, was better oxygenation the real reason for increased survival? Are the projected survival benefits durable? What is the cost effectiveness of this treatment approach? Many of these questions were answered in editorial reply by the study authors. Still, such questions lead one to believe that chemoradiation is being considered by the European community, but its everyday use may not yet be the standard of care. A meta-analysis of the current data and subsequent trials will help answer these and other questions concerning the approach to bulky cervical cancer. A Markov model of cost-effectiveness would provide the necessary information that European centers need in their decision-making concerning this important treatment approach.