Post Mx Radiation Improves Local Control Not Overall Survival

After 10 Years, Postmastectomy Radiation Is Shown to Improve Local Control But Not Overall Survival in Women with Breast Cancer and One to Three Positive Nodes

September 28, 2016—Boston, Massachusetts--After 10 years of follow-up, postmastectomy radiotherapy improved local control but not overall survival in women with breast cancer and one to three positive lymph nodes, even after controlling for poorer prognostic features.

This outcome was reported at the 58th Annual Meeting of the American Society for Radiation Oncology (ASTRO), from September 25 – 28.

Moses M. Tam, MD, of New York University Langone Medical Center, New York, explained that the role of postmastectomy radiation in women with breast cancer and one to three positive lymph nodes in the setting of modern systemic therapy is controversial.

"I wanted clarification," Dr. Tam said, "on the controversy regarding the need for postmastectomy radiation therapy in patients with one to three positive nodes. In fact, just last week, the ASTRO/American Society of Clinical Oncology/Society of Surgical Oncology released a consensus statement on this subject. They stated that postmastectomy radiation therapy confers a clear disease control and survival benefit in patients with T1 - T2 disease and one to three positive nodes."

He continued, "Subsets of patients may be at such low risk of disease recurrence that potential toxicities may outweigh the benefit of postmastectomy radiation therapy. Our analysis evaluated one of those patient subsets, essentially, those who received modern systemic therapy."

Dr. Tam and colleagues set out to investigate the effect of postmastectomy radiotherapy on breast cancer outcomes at 10-year follow-up in women enrolled on Breast Cancer International Research Group 005, a phase 3 trial of doxorubicin/cyclophosphamide with concomitant vs sequential docetaxel.

Individual patient data at 10-year follow-up were analyzed for 1649 women treated on the control arm (sequential docetaxel). All women were node positive, HER-2 nonamplified. They underwent mastectomy or lumpectomy with negative margins followed by axillary lymph node dissection with at least six lymph nodes removed.

Postmastectomy radiotherapy was given at the investigator's discretion. Adjuvant hormonal therapy was given in hormone-positive disease. Primary analyzed outcomes included local control, locoregional control, distant metastasis, and overall survival.

Statistical analysis of categorical data was performed with Χ2 test. Survival curves were plotted using the Kaplan-Meier method, and survival estimates were obtained using log-rank test and Cox's proportional hazard model using SPSS statistical software. A propensity score analysis was performed with R statistical package.

Five hundred twenty-three women underwent mastectomy with one to three positive lymph nodes. Thirty-nine percent received postmastectomy radiotherapy, which included the chest wall, supraclavicular field (71%), and internal mammary nodes (27%). Women receiving postmastectomy radiotherapy were significantly younger, had more positive nodes, and had more advanced T stage than patients who did not receive the treatment.

Postmastectomy radiotherapy improved 10-year local control (99% vs 94%, P = .006) significantly vs patients who did not receive postmastectomy radiotherapy. The therapy did not improve 10-year distant metastases (20% vs 17%) or overall survival (86% vs 84%) vs patients who did not receive postmastectomy according to the use of propensity score analysis. A trend toward locoregional control was observed (95% vs 92%, P = .08).

Subgroup analysis including larger tumors, poorly differentiated disease, two or three positive lymph nodes, or premenopausal status did not identify a patient cohort in which postmastectomy radiotherapy predicted for improved overall survival.

Dr. Tam concluded after 10 years of follow-up, postmastectomy radiotherapy improved local control but not overall survival in women with one to three positive lymph nodes, even after controlling for poorer prognostic features.

"We found," he commented, "that patients treated with modern systemic therapy experienced excellent outcomes in local control and overall survival, regardless of whether they received radiation therapy. We also found, however, that radiation therapy provides a clear local control benefit and a trend toward improved locoregional control once we adjusted for imbalances in underlying patient characteristics."

He continued, "On multivariate analysis, we identified younger age (<40 years) and higher-grade disease were associated with higher risk of locoregional recurrence and death. These patients, therefore, may be more likely to benefit from radiation therapy"

"Future directions will involve a larger cohort of patients to help answer the question of whether radiation therapy impacts overall survival in the era of modern systemic therapy"