Primary Tumor Resection Ups Survival in Stage IV Breast Ca

CHICAGO—The use of surgical resection of local disease in women presenting with metastatic breast cancer results in a statistically significant survival advantage, Seema Khan, MD, said at the Lynn Sage Breast Cancer Symposium.

The intact primary tumor can be considered as a resectable metastatic site, particularly in women with limited metastatic disease, she said. This finding is significant because about 6,000 women present annually in the United States with stage IV disease and an intact primary tumor.

"The usual approach to this problem is systemic therapy, and local treatment is recommended only if the primary tumor is symptomatic. But today I hope to convince you that perhaps surgery can play a role in patients with stage IV disease," said Dr. Khan, associate professor of surgical oncology, Northwestern University Medical School.

Pros and Cons

Dr. Khan described some of the reasons for leaving the tumor alone in stage IV disease. The intact primary aids in diagnosis and can influence the selection of therapy. The primary also provides an indication of measurable disease and can be followed over time, and also followed to assess response. There is some morbidity associated with resection of the primary tumor, which affects some patients more than others. Finally, there is the intriguing possibility that the primary tumor may provide a source of cytokines and angiostatin, which restrain metastases.

The arguments against resecting the primary tumor were challenged in a study conducted by the Southwestern Oncology Group (SWOG 8949) in patients with metastatic renal cell cancer (N Engl J Med 345:1655-1659, 2001). This study was difficult to perform—it took 6 years to recruit 240 patients. "In the end, the study showed that surgical resection of the primary tumor did, in fact, increase survival," Dr. Khan said. "These findings are very provocative and should lead us to reconsider our attitude towards the primary tumor in patients with metastatic disease from other organ sites."

Current Study

Dr. Khan presented findings from an analysis of data from the National Cancer Data Base (NCDB) of the American College of Surgeons of 16,023 women presenting with stage IV breast cancer disease and an intact primary between 1990 and 1993. Among these women, 43% received no surgical resection of the primary tumor and only palliative care, and 57% underwent surgical resection of the primary tumor (38% partial and 62% total mastectomy). The mean age was 62.5 years. Tumor size data was available for all of the patients; 40% had large tumors (T3 and T4).

"We also looked at the use of surgery by metastatic burden because that is one of the selection factors when offering surgical resection," Dr. Khan said. With more than three sites involved, the use of surgical therapy was somewhat infrequent; when only one site was involved, more than 60% of the women had surgical therapy for the primary site, she said.

The 3-year observed survival rate for the entire group was 24.9%. The mean survival duration was 19.3 months for the no-surgery group, 26.9 months for the partial mastectomy group, and 31.9 months for the total mastectomy group.

Three-year survival rates for women in each of these treatment groups were 17.3%, 27.7%, and 31.8%, respectively. Surgical patients with clear margins did even better, with 3-year survival rates of 34.7% and 35.7% for those patients with partial and total mastectomy, respectively, vs 26.4% and 26.1%, respectively, for those patients with involved margins.

A multivariate Cox proportional hazards model identified surgical resection of the primary tumor as being independently and significantly associated with patient outcomes. The overall finding was a hazard ratio for death of 1.0 in the no-surgery group, 0.88 in women undergoing partial mastectomy, and 0.74 in those undergoing total mastectomy. "So surgical resection actually is providing some benefit for these women," Dr. Khan said.

She cautioned that the study was a retrospective analysis and that selection bias may have been a factor in the results, since patients with fewer metastatic sites were more likely to have surgery for the primary tumor. A randomized trial is needed to determine the true value of surgical resection of the primary tumor in this setting, she said. The full report of Dr. Khan’s study can be found in the journal Surgery (132:620-627, 2002).