Reply to L.B. Marks Et Al.

We thank Marks, Kaidar-Person, and Poortmans for their comments in a letter to the editor in response to our recent article in Journal of Clinical Oncology titled “Postmastectomy Radiotherapy: An American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology Focused Guideline Update.” We agree that the risk of localregional failure (LRF) by itself is not sufficient to determine the full value of postmastectomy radiotherapy (PMRT). As they demonstrate, even reducing LRF by a substantial amount will not lead to improved survival unless systemic therapy is effective enough to prevent a substantial proportion of patients from experiencing systemic relapse that could result from residual disease in irradiated areas. This was also shown in an analysis of the Danish trials with regard to receptor phenotype. The impact of PMRTon LRF was substantial in all patient subgroups, but PMRT did not change overall survival rates in patients with estrogen receptor–negative, progesterone receptor–negative, or human epidermal growth factor receptor 2–positive cancers. Systemic therapy has changed considerably since that used in the Danish trials (tamoxifen given for only 1 year for postmenopausal women and nine cycles of intravenous cyclophosphamide, methotrexate, and fluorouracil given every 4 weeks for premenopausal patients). Hence, the value of PMRT in the subgroup labeled as good (patients whose 5-year LRF rate was 11% in the Danish trials) is uncertain. However, its value may well be less with current systemic treatment regimens, because long-term LRF rates in patients receiving such therapies are considerably , 10% in many more recent series. We hope that the results from the SUPREMO trial and further analysis of prospective and retrospective studies will allow for a much more selective, tailored use of PMRT than in the past, to maximize its benefits at the least possible price in toxicity. And we greatly appreciate the writers’ endorsement of our call for shared decision making between all oncologic specialists and the patient about the benefits of PMRT for each individual.