Surgery or chemoradiation for stage IB cervical cancer? How cost effectiveness impacts a complex decision

See accompanying article by Katanyoo and colleagues on page 97.

The decision regarding options for treatment for stage IB cervical cancer is complex. Competing factors that arise from the perspective of cancer control (survival), treatment toxicity, quality of life, and geographic location of the patient (related to access to specific healthcare resources) all play a role in the ultimate decision to pursue primary chemoradiation versus primary radical surgery. In the mind of most patients and their healthcare providers, the most important outcome is that of cancer survival. In stage IB cervical carcinoma, it appears that two treatments, albeit with a very different toxicity profile, have identical survival.

In a landmark study, Landoni et al. [1] randomized patients to radical surgery versus radiotherapy (without concurrent chemotherapy) for early stage cervical cancer. Amongst these 237 women, survival was identical in the surgical and the radiation arms. However, severe morbidity (requiring surgical or medical treatment) was experienced by 28% of those undergoing radical surgery and by 12% in those undergoing radiation therapy. Thus, and partially as a result of this randomized controlled clinical trial, the decision to treat a patient with cervical cancer with radical hysterectomy or with radiation therapy is based on an assessment of the patient and her expected tolerance of the different rates and categories of toxicities associated with the treatments. For example, a young, sexually active woman with stage IB cervical cancer is often recommended to undergo primary radical surgery (to preserve her ovarian and vaginal function), whereas an elderly patient with comorbid medical conditions is often recommended to have undergo radiation therapy (to minimize the short and long-term surgical risks). While this study provides a starting point for the discussion about the comparative outcomes in the treatment of early-stage cervical cancer, it is important to note that its relevance to the modern day use of concurrent platinum-based chemotherapy with radiation may make generalization of the results to our patients today challenging. However, there have been no randomized comparisons of primary radical surgery to primary chemoradiation that would help in assessing the outcomes of these treatments. Thus, more information to help inform treatment decisions is critical.

In this edition of the Journal of Gynecologic Oncology, Katanyoo et al. [2] present a cost-utility analysis of the primary treatment of stage IB cervical cancer, and provide us with this additional information to help inform a decision regarding radical surgery versus chemoradiation for this disease. For those readers not familiar with cost-utility, a little background is necessary to help in interpreting their manuscript. In the simplest sense, one can think of a cost-utility analysis as a balance; on one side is the "cost," made up of the actual money it costs for a treatment, the money it costs to treat a complication, and the "cost" to a patient who experiences a decrement to their quality of life (this is known as a negative "utility score"). On the other side of the balance is the "effectiveness," which is usually made up of the cancer survival, and occasionally an improvement in quality of life (a positive "utility score"). The balance between the cost and the effectiveness is used to calculate a statistic comparing the cost effectiveness of one strategy to another. When one treatment is both more effective and less costly than another, it is considered to be superior; whether the cost of that treatment is "reasonable," however, is based on many additional factors, including a societal "willingness to pay" threshold. The current trial looks at cost effectiveness from two different perspectives: one from that of the provider, and the other from that of society. These two perspectives comprise different inputs, and importantly the societal perspective includes the costs of transportation, food, lost income and other non-traditional medical expenses. The authors used an interview-based system to query previously treated patients regarding their costs incurred, the toxicities experienced, and the impact of treatment on their quality of life. Compared with chemoradiation, the authors found that radical surgery was more cost effective, but only when no adjuvant chemoradiation was prescribed following surgery. The model was found to be most sensitive to the cost of chemoradiation; when its cost was decreased by 25%, the authors noted that radical surgery became less cost effective relative to chemoradiation.

This cost utility model is powerful in that it brings up more questions than it answers. While it may seem intuitive that radical hysterectomy is more cost effective only when adjuvant radiation is not prescribed, this finding shows the importance of such a modeling study. If one were to be able to predict before starting a surgery which patient would be most likely to require postoperative chemoradiation, then surgery might not be pursued. However, there is neither a biomarker nor an imaging modality that has the ability to reliably predict which patients would require adjuvant chemoradiation. If one were to exist, then only those patients expected to maximally benefit would be prescribed a treatment, thereby maximizing its effectiveness (and improving its cost effectiveness). Since primary surgery was found to be less cost effective when postoperative adjuvant chemoradiation was prescribed, continued investigation of a biomarker or imaging modality that predicts which patients might require postoperative therapy is an important goal to improve both clinical and cost outcomes of treatment of stage IB cervical cancer. The authors are to be commended for their investigation of the impact of treatment from a societal perspective. Given the difference between a single visit to the hospital (with postoperative recovery) for radical hysterectomy and 25 fractions of external beam radiation, four fractions of brachytherapy and weekly cisplatin chemotherapy for chemoradiation, the impact to the patient in terms of indirect treatment-related costs (transportation, for example) would be expected to impact cost effectiveness and deserves consideration.

There are some limitations to this study, however. Importantly (and fortunately), the absolute difference in the cost (and cost effectiveness) of radical hysterectomy versus chemoradiation are very small, and fall beneath the willingness to pay thresholds of most societies. Thus, it could be argued that in a woman with a stage IB cervical cancer, treatment with either modality is reasonable. It would be interesting to have been given a sense for the general clinical characteristics of the 100 women studied. In particular, it would be helpful to know the potential impact of radiation therapy on ovarian and vaginal function (which would be expected to be greater in younger women), and to determine the effect this had on quality of life (which impacts the utility score and thus cost effectiveness). Additionally, newer cervical cancer treatment strategies, such as the use of combination platinum-based chemotherapy [3] or the use of adjuvant chemotherapy following chemoradiation [4] (both of which have been reported to improve outcome of women receiving primary chemoradiation) were not evaluated. While these strategies may not be feasible in geographic locations in which healthcare resources are limited, their use would certainly increase cost as well as possibly increase effectiveness.

Does this manuscript by Katanyoo et al. [2] answer the question as to whether a patient with a stage IB cervical cancer should undergo a radical hysterectomy or chemoradiation? It does not. However, the information from a modeled cost utility analysis is critical in helping patients, providers, insurers, and governments make informed decisions. Continued investigation of what contributes to the cost effectiveness of cancer therapy is critical in improving the outcomes for our patients while reigning in increasing healthcare costs.