Complicating issues in complication reporting.

In the July 30, 1994 issue of the journal, there were several important papers dealing with the subject of reporting complications of radiotherapy. Pedersen et al. (4) make the valid argument that a truly successful therapeutic outcome requires that the patient be alive, cured, and free of significant treatment-related morbidity. To illustrate their point, they analyzed the database of 442 patients with cancer of the uterine cervix treated by radiotherapy in the Department of Oncology, Aarhus University Hospital, Aarhus, Denmark between 1974 and 1983. Using Kaplan-Meier methodology, the authors calculated the 5-year actuarial probability of late complications in five different organ systems (recta-sigmoid, bladder, small bowel, ureters, and vagina), along with the overall probability of being alive and free of both recurrent disease and treatment-related complications. Because of the relatively poor survival rate of the population under study, the actuarial estimates of probability of late treatment complications exceeded the crude incidences (i.e., proportion of treated patients who developed each type of complication) by factors of up to 3. As would be expected, the magnitude of the discrepancy increased with disease stage, because survival is inversely related to stage. Nonetheless, even in patients with Stage IIB disease, they calculated the probability of disease-free survival with no severe complication in any of the five organ systems to be only 36 + 4%, implying that radiotherapy was a rather poor treatment option for these patients. Without going into discussion of the possible reasons for the high absolute rate of complications observed in this series compared with other reports, for example, Horiot et al. (3), it is of interest to consider the appropriateness of the method of outcome reporting used by Pederson et al. (4). The Kaplan-Meier procedure they used estimates the cumulative probability of late complications if death were eliminated. This is not the same as the probability of complications in patients who survive: if the propensity to complications either increases or decreases the probability of death, the Kaplan-Meier estimate is incorrect. In this context, the article by Caplan et al. (1) is highly relevant. These authors point out that the KaplanMeier method overestimates the probability of late complications when there is a high mortality rate, and suggest that the parameters of cumulative incidence and cumulative conditional probability be used to define the probability and risk of complications. However, regardless of the statistical tools used for time-adjusted methods of reporting late complications, we believe that it is crucial to make the notional distinction between experiencing a complication at some point in time and having a complication at a subsequent point in time. None of the commonly used methods of results repotting makes this distinction: complications are scored as “events” that, having occurred, are irreversible. In point of fact, however, not all treatment complications are permanent-some resolve spontaneously and others are amenable to correction. From the vantage point of the cancer patient, the essential issue is not so much whether a complication occurs, but to what extent his/her quality of life is diminished by the event. In the case of a complication that spontaneously resolves or is corrected, the decrement in quality of life exists only for the finite period during which the patient has the complication. Admittedly, most late effects of radiation therapy are chronic and sometimes progressive, but many are not. For example, after treatment for head and neck cancer, patients frequently develop transient bone exposure or mucosal ulceration (scored as a Grade 3 -4 complication according to the RTOG/EORTC scales), which heals spontaneously, causing no further problems. Such complications should not be represented as permanent injuries in outcome reporting. Yet, this is inevitably what happens when current reporting methods are used. Another example of a reversible complication is a small bowel obstruction that is surgically corrected without further morbidity.