Clinical trials of radiation therapy for DCIS have not been powered to detect survival differences between the treatment arms and their length of follow up is insufficient to evaluate lifetime breast preservation. Therefore, we used a decision analysis to model the downstream implications of recurrence after DCIS to gain insights into the tradeoffs associated with radiation. Our model suggests that the addition of radiation therapy after excision for DCIS results in modest improvements in invasive disease-free and overall survival, with declining benefits as age at diagnosis increases. However, the likelihood of long-term breast conservation is lower with radiation, since women who receive it are generally committed to mastectomy after any local recurrence or new cancer diagnosis in the treated breast.
In the model, the survival benefit with radiation therapy is a consequence of the reduced risk of an invasive local recurrence, and is a credible finding given the proven effects of radiation on the subsequent development of invasive recurrence, and of invasive cancer recurrence on survival.17
Our analysis shows that the magnitude of this benefit is very small, a finding consistent with the lack of difference observed in the randomized trials that have assessed radiation for DCIS22
and with prior DCIS modeling efforts.23
The key question raised by our results is whether an invasive disease-free and overall survival benefit is sufficient to justify the routine recommendation of radiation therapy for all women with DCIS. An improvement in invasive disease-free survival translates into a lower probability of a new cancer diagnosis, and the resulting need for further surgery and possibly adjuvant chemotherapy. And an overall survival advantage is an even more compelling potential benefit. But these benefits must be weighed against not only the inconvenience and potential side-effects of radiation, but also the reduced probability of maintaining intact breasts over a lifetime. The magnitude of the likely survival advantage is a critical consideration in weighing these risks and benefits. A prior modeling analysis estimated that prophylactic mastectomy among 30 to 60-year-old women without elevated breast cancer risk added approximately 6 months of additional life expectancy, a more substantial benefit than we found in any age group.24
Yet we do not routinely recommend prophylactic mastectomy to women with even markedly elevated breast cancer risk, and certainly not to average risk women. Instead, prophylactic mastectomy is uniformly considered to be a preference-sensitive decision. Our results suggest that the decision about whether to include radiation after excision of DCIS is also most appropriately considered a preference-sensitive decision. Women should be fully informed about the expected outcomes of the alternative treatment strategies, including the risks of both death from breast cancer and eventual mastectomy, and encouraged to choose the strategy that is most consistent with their own values and preferences.
Our analysis has limitations inherent to all modeling analyses. It was necessary to make a limited number of assumptions about the natural history and treatment of disease in order to specify a finite number of clinical states. However, most assumptions we used applied to both treatment arms, excision alone and excision plus radiation therapy, and were therefore unlikely to bias the analysis. We used estimates derived from the literature or databases to inform our baseline analysis, and found model results to be robust across a wide-range of values for key parameters in sensitivity analyses.
No population-based data are available on the proportion of women who choose mastectomy for recurrence or new cancer after prior DCIS treatment that did not include radiation. Therefore, we extrapolated the likelihood of mastectomy by stage from treatment patterns among patients newly diagnosed with cancer in a previously non-irradiated breast (average 32%). This average was close to that reported by a prospective study of excision alone for DCIS where the likelihood of mastectomy at time of recurrence was 31%.12
Our likelihood could actually overestimate the probability of mastectomy, if one of the primary reasons a woman would opt to forego radiation for DCIS is the desire to maximize the likelihood of breast preservation. In our sensitivity analysis, we included the 48% likelihood of mastectomy observed in an early report of treatment patterns for local recurrence in the excision-alone arm of the NSABP B-17 DCIS trial,25
and found that even at this rate, the radiation strategy decreased the likelihood of breast preservation. In fact, even if the probability were much higher than in our baseline analysis, as long is it did not exceed 66%, our sensitivity analysis indicates that the no radiation strategy would result in a higher rate of breast preservation.
However, if local control rates with radiation therapy in the setting of recurrent DCIS after excision alone are inferior to those achieved with new diagnosis of DCIS or if breast-preserving surgery is possible after new diagnosis in a previously irradiated breast,26, 27
the decrement in breast preservation with radiation therapy for DCIS would be mitigated. Moreover, if a patient is ineligible for repeat breast-conserving surgery due to anatomic constraints at time of new diagnosis in a previously non-radiated breast or if she would not elect breast preservation even if it were possible, then the radiation therapy arm would maximize her likelihood of breast preservation. However, our model also indicates, that for those patients who would not have experienced a local recurrence after breast-conserving surgery alone, radiation therapy comes at a cost – they are at risk of having a second primary breast cancer, and their history of prior radiation most often precludes breast conserving options.
We also did not study the effect of adding tamoxifen to radiation therapy.9, 19
However, unless tamoxifen eliminated all recurrences, it would not change the fundamental nature of the tradeoffs we describe. Finally, we did not model outcomes after mastectomy for DCIS, as our objective was to compare alternative breast-conserving surgical strategies. It is easy to extrapolate from our findings however, since mastectomy would result in even lower local recurrence rates, with resulting improvement in invasive-free survival, while reducing the likelihood of breast-preservation to zero.
Currently, about one-half of patients receive radiation after excision for DCIS with evidence of wide regional variation in practice patterns, suggesting the lack of consensus regarding use of radiation therapy.2, 15
Much of the debate surrounding the decision to add radiation for DCIS has focused on the absolute risk of recurrence without radiation. Our results suggest that this decision should be determined by patient preferences for women at average risk of recurrence. Our model also provides some insight into the role of radiation therapy in women whose constellation of clinical and biological factors places them at highest risk of recurrence.22, 28, 29
Our sensitivity analyses reveal that among the highest recurrence-risk group the survival benefits with radiation do indeed increase, while the harms of radiation therapy, in terms of lower rates of long-term breast preservation, remain relatively stable. However, even in this group, the magnitude of the benefit conferred by radiation remains quite modest, suggesting that a decision-making paradigm that emphasizes patient preferences is appropriate in all risk groups.
Our analysis demonstrates that the decision to add radiation therapy is essentially a toss-up, and suggests that more trials with longer follow-up will not change what can be learned from a relatively simple and transparent analysis of existing data. Radiation for DCIS is prophylactic; it reduces the risk of invasive recurrence, the only lethal form of breast cancer, while increasing the probability of eventual mastectomy. The absolute magnitude of both effects is modest, such that personal patient preferences should drive decision-making. Express delineation of the tradeoffs associated with radiation therapy may help guide treatment decisions that are consonant with patient preferences, with the result that variation in care reflects those individual preferences rather than the biases of treating physicians.