This retrospective analysis of trends in post-operative survival after surgical treatment of breast cancer metastatic to the brain and spinal column suggests that a sizeable number of Medicare patients remain alive at one year's time after intervention. Unlike the majority of previous studies that included patients with multiple primary tumor types, our analyses are specific to Medicare patients with breast cancer. Furthermore, other reports generally include patients from a single clinical center, while our analysis incorporates data from a variety of clinical centers and surgeons and thus is more likely representative of the general population of Medicare patients with breast cancer. Although primarily applicable to Caucasian patients by virtue of the available data, our results may be useful for clinical decision making in Medicare patients diagnosed with metastatic breast cancer to the brain or spinal column by providing estimates of survival time after surgical intervention. Given that 10% of women in the United States will be diagnosed with breast cancer and up to 30% of these may have involvement of the brain or spinal column at some point, these data will be useful to a wide number of persons.
There were several notable findings in this analysis. First, the post-operative inpatient death rate has decreased over time. When considering cranial and spinal surgeries together, the inpatient death rate for procedures in the decade prior to 1996 was 8.4%. This decreased to 4.4% for surgeries in the decade after 1996. This finding supports previous work indicating that inpatient mortality rate following craniotomy for metastatic disease has decreased over time,30
. On the other hand, the 30 day mortality rate was almost 10% and has remained relatively constant between the two decades. The decline in in-patient mortality coupled with a constant 30 day mortality rate may suggest either a true in-patient mortality rate decrease or a move to discharge the most severely ill patients to an out-patient setting prior to their death. These post-operative death rates are generally higher that those reported from centers specializing in cancer care11, 14, 22, 23, 31
. The Sloan-Kettering surgical series of craniotomy for metastatic breast cancer reported a 30 day mortality rate of 5.7% and a rate of 1.3% following craniotomy was reported for lung cancer metastasis22, 31
. A single surgeon series of 208 craniotomies for multiple different primary tumors reported also a 1.3% 30 day mortality rate14
. Likewise, for spinal procedures, one inpatient death (1.1%) was reported in the series of 87 patients surgically treated for spinal breast cancer metastases, while a 6% 30 mortality was reported for the surgical group in the randomized clinical trial by Patchell11, 23
Additionally, the overall post-operative survival times in this study are less than what has been reported in the literature of dedicated breast cancer case series. For patients that underwent cranial surgery, the median post-operative survival was 7.7 months, while patients undergoing spinal laminectomy had a median survival of 9.4 months and patients undergoing spinal fusion had a median survival of 15.7 months. The median survival after craniotomy in the single institution case series from the Sloan-Kettering Cancer Center was 14 months22
. A median survival of 21 months after spinal surgery for metastatic breast cancer has been reported in cases series from the M.D Anderson Cancer Center and Johns Hopkins21, 23
. There are several potential explanations for these differences. First, the higher death rates in the current report may suggest an overall higher rate of peri-operative mortality and shorter overall post-operative survival time in Medicare patients. Additionally, our analysis included almost four times as many patients as contained in the prior single institution series. With this larger sample size it is likely that a wider range of patients are included and the results may be more robust. Finally, it is possible that single institution case series may have a selection bias or may actually represent a survival benefit associated with care at a dedicated cancer center. Therefore, this finding may suggest that the peri-operative mortality rates reported in centers specializing in neuro-oncology may not be widely generalizable to the entire population.
This analysis also specifically evaluated changes in overall post-operative survival over time. For cranial surgery, the median post-operative survival for patients that underwent surgery in the decade prior to 1996 was approximately 7 months. This did not significantly change for patients who underwent surgery in the decade following 1996. Survival after spinal surgery, however, did significantly increase over time for patients that underwent spinal fusion. The median survival increased over 50% from approximately 12 months for surgeries in the decade prior to 1996 to almost 20 months for surgeries in the decade after 1996. The overall survival after laminectomy without spinal fusion has not significantly increased over time. There are many possible explanations for this finding including confounding by patient selection; however, the rapid advances in spinal fusion during this time, for example the introduction of intervertebral spinal fusion cages and pedicle screw technology in the mid 1990s, may be related.
Finally, this analysis also identified clinical predictors of post-operative death and generated survival estimates. The predictors were different for cranial and spinal surgeries. It is evident that the predictors of survival after spine surgery are related to the aggressiveness of the breast cancer. The degree of histologic differentiation, the estrogen and progesterone receptor status, and the time from initial diagnosis of breast cancer to spinal surgery were significant predictors. The analysis of receptor status and the effect on survival was limited as over half of the patients had an unknown receptor status. Likewise, admission through the emergency room was predictive of survival only after spinal procedures. The implications of this type of admission are not clear; however it is reasonable to assume this is could also be a marker of an aggressive or acute disease process. Patient level information such as age and medical comorbidities were not predictive of survival. Age at the time of surgery, medical comorbidities, and presence of stage 4 cancer at initial diagnosis of breast cancer were predictive of survival after cranial surgery.
Recent interest has focused on the role of age in outcomes after the development of central nervous system metastases. In our analysis, age was a significant predictor for post-operative survival only for cranial surgery. The effect of age on survival after the development of cranial and spinal metastases has been evaluated in multiple reports with conflicting results. In several recent studies of predictive factors for survival after cranial or spinal metastases, age was not a significant predictor19, 32, 33
. In an retrospective analysis of 1292 patients with brain metastases from multiple primary tumor types, age greater than 70 was associated with a mild decrease in survival but age 60–69 was not34
. In both of the single institution surgical series of craniotomy and spine surgery for metastatic breast cancer, age was not a predictor of survival post-operatively22, 23
. A recent secondary analysis of the only randomized trial evaluating surgical treatment compared to radiation therapy of spinal metastases indicated that surgical treatment did not provide superior outcomes in patients older than 65 years of age35
These results must be interpreted in light of the limitations of a population-level study of post-operative outcomes. First, data on the clinical details of the CNS metastases treated here are not available. Therefore, patients cannot be stratified based on number, size, or surgical complexity of the CNS metastases. The number of cranial metastases has been shown to be a significant predictor of survival as well as the anatomic segment for spinal metastases33, 36
. Additionally, no information regarding additional treatments such as post-operative radiation and chemotherapy can be obtained from the inpatient records. As such, unmeasured confounders may account for differences in reported survival rates. These data do not come from a clinical trial and hence it is likely that patients with better prognosis are more likely to be offered more aggressive surgical procedures such as spinal fusion, resulting in selection bias.
This is the first report to evaluate the trends in survival after neurosurgical treatment of brain and spinal column metastases from breast cancer. Approximately one third and one half of cranial and spinal patients, respectively, are alive at 1 year after surgery. We demonstrate that inpatient death rates following neurosurgical treatment of metastatic disease have decreased in the past decade. The long-term post-operative survival, however, for cranial surgery has remained relatively constant. For spinal surgery, survival after spinal fusion, but not laminectomy alone, has increased in the past decade.