The Value of Postmastectomy Radiation for Cancer Patients at Risk for Local Recurrence

abstracts & commentary

Synopsis: There remains some controversy regarding the use of postmastectomy radiation therapy. In this report from the University of Pennsylvania, the outcomes of high-risk patients (those with large primary tumors, close or involved surgical margins, or axillary nodes positive) treated between the years 1977-1992 were detailed. The data support the use of this modality for high-risk patients.

Sources: Metz JM, et al. Cancer J Sci Am 1999;5: 77-83. Pierce LJ. Cancer J Sci Am 1999;5:70-72.

There remains some controversy on the value of postmastectomy radiation therapy in the treatment of breast cancer. With regard to patients at high risk for recurrence after mastectomy, the controversy relates to the balance of increased toxicity vs. improved disease control and overall survival. In this report from the University of Pennsylvania, Metz and colleagues report their long-term experience in treating such patients.

Over a 15-year period (1977-1992), 221 patients at high risk for local-regional recurrence after mastectomy were treated with radiation therapy, with or without adjuvant hormonal or chemotherapy. The median age was 51 years. Patients were classified as high-risk because of T3 or T4 tumors, positive lymph nodes, or close or positive surgical margins. Radiation therapy consisted of 45-50.4 Gy to the chest wall in 1.8-2.0 Gy fractions. Regional lymph nodes were also treated with radiation therapy in 85% of the cases. Of the 221 cases, 151 (68%) received adjuvant chemotherapy. Patients receiving adjuvant chemotherapy were younger (median age 48, compared to a median age of 64 for those who did not receive chemotherapy) and had a greater degree of axillary node involvement (median 5 nodes vs 1). Adjuvant hormonal therapy was administered to 116 patients (53%). The median follow-up was 4.3 years.

In the overall group, the actuarial local-regional failure rate at 10 years was 11% (95% CI 6.5%-16.7%). The site of first failure was distant metastases in 75 patients (34%), local-regional recurrence in 11 patients (5%), and coincidental local-regional and distant in three patients (1%). Of the 11 patients who developed local-regional recurrence as the site of first-treatment failure, that recurrence developed at a median of 1.3 years, and nine (82%) subsequently developed systemic metastases.

Metz et al conclude that their experience supports the continued use of postmastectomy radiation therapy for patients at high-risk for local-regional recurrence.

COMMENTARY

Recommendations about the use of radiation therapy after mastectomy have varied over the years, but these days its use is common, particularly in those at high risk for local-regional recurrence. The downside, of course, is the fear of toxicity, primarily to the heart as evidenced in a number of clinical trials.1,2 Other risks include rib fractures and late second solid tumors. Patients at high risk are typically candidates for chemotherapy as well and agents commonly in use (anthracyclines, taxanes, and possibly Herceptin) may potentially enhance cardiotoxicity.

Nonetheless, enthusiasm for radiation treatment in this setting has re-emerged with the publication of two randomized trials (from Denmark and British Columbia) in recent years.3,4 In these studies, both disease-free and overall survival were enhanced by the addition of postmastectomy radiation therapy. The survival advantage was initially more evident in the Danish study and was only marginally significant in the British Columbia analysis. However, a recent update of the British Columbia study (at 15 years) now clearly demonstrates a survival advantage for those who received radiation therapy.5 A recent update of the Danish study, with a median of 10 years of follow-up, confirms the earlier results.6 Postoperative radiation therapy reduces the risk of recurrence, which leads to improved survival.

As pointed out by Dr. Pierce in her editorial review, the value of the University of Pennsylvania series (as reported by Metz et al) may lie in its comprehensive detailing of treatment technique and outcomes in a series from a single institution. Although some persisting questions, such as the necessity for treatment of the internal mammary nodes, could not be addressed satisfactorily in this series, the report did lend sufficient confidence that radiation therapy can be delivered safely with acceptable toxicity, and result in enhanced long-term survival for high-risk patients. v

References

1. Rutqvist LE, et al. Int J Radiat Oncol Biol Phys 1992;22:887-896.

2. Cuzick J, et al. J Clin Oncol 1994;12:447-453.

3. Overgaard M, et al. N Engl J Med 1997;337:949-955.

4. Ragaz J, et al. N Engl J Med 1997;337:956-962.

5. Ragaz J. American Society for Therapeutic Radiology and Oncology Consensus Meeting on Postmastectomy Radiotherapy 1998.

6. Overgaard M, et al. Lancet 1999;353:1641-1648.

Which of the following statements about post mastectomy radiation therapy for patients at high risk for recurrence is false?

a. Local-regional recurrence rates have been shown in a number of series to be reduced.

b. Disease-free survival has been shown to be enhanced in treated patients.

c. Potential cardiac toxicity precludes the adjuvant use of anthracyclines or taxanes.

d. Patients who later develop local recurrence have a high incidence of systemic disease within a short time interval.

e. Overall survival is improved by post mastectomy radiation therapy.