Clinical Factors Associated with Treatment Outcomes Following Whole-brain Irradiation in Patients with Prostate Cancer

Discussion

Since prostate cancer is the most common type of cancer in men, considerable research is performed in order to improve the outcomes of these patients, including preclinical studies and clinical investigations of new systemic treatments, surgical approaches and radiation techniques (8-13). In contrast to metastatic spread to the bone, metastases to the brain are very rare. Although prostate cancer is one of the most common types of cancer, patients with brain metastases from this tumor entity account for fewer than 1% of patients presenting with metastases to the brain (1-3). Therefore, little is known about this particular patent group in this regard. In order to provide additional information, the present study was carried out. It investigated potential associations between clinical factors and outcomes in terms of local control and survival in order to identify independent prognostic factors.

According to the results of this study, the time interval from prostate cancer diagnosis to WBI was an important prognostic factor. On multivariate analysis, an interval of more than 28 months showed a trend towards association with improved local control and a significant association with improved survival. In addition, a KPS of 80% (when compared to ≤70%) was an independent predictor of better survival. The performance status has been identified as an independent predictor of survival in previous studies including patients with brain metastases from different tumor entities (6, 14-16). The most widely used tool for estimating the survival of patients with metastases to the brain is the RPA classification, published in 1997 (6). This classification includes three prognostic groups with median survival times of 7.1 months (RPA class 1), 4.2 months (RPA class 2) and 2.3 moths (RPA class 3), respectively. It was mainly based on the KPS (<70% vs. ≥70%) but additionally on age (<65 vs. ≥65 years) and extracranial disease. The prognostic value of the RPA classification for patients with brain metastases from prostate cancer was investigated in the present study. However, the RPA classification did not achieve significance on univariate analysis. This may be explained by the fact that the vast majority of patients with prostate cancer are 65 years or older, which means that discrimination by age will not be important for these patients. Furthermore, the RPA classification does not consider the time interval from prostate cancer diagnosis to WBI, which proved to be an important prognostic factor in the present study particularly focusing on prostate cancer (6). Similar limitations could be expected for the graded prognostic assessment tool, another commonly used survival score for patients with brain metastases (16). This tool was based on four factors, including age (>60 vs. 50-59 vs. <50 years), but not on the interval from prostate cancer diagnosis to WBI. These considerations demonstrate the importance of looking separately at different tumor entities, as performed in the current study. Bearing in mind its limitations due to the retrospective design and the small number of patients included, one may suggest choosing a WBI program for an individual patient based on the two independent predictors of survival identified in this study. Patients with an interval from prostate cancer diagnosis to WBI of ≤28 months and a KPS of ≤70% have a very poor prognosis and might be considered for a short WBI program, or even best supportive care alone. A previous study suggested that 4 Gy × 5 was not inferior to 3 Gy × 10 in a large cohort of patients with metastases to the brain from different tumor entities (4). The survival rates at 6 months were 24% and 27%, respectively (p=0.29). In contrast, those patients with an interval from prostate cancer diagnosis to WBI of >28 months and a KPS of >70%, who have a more favorable prognosis, would likely benefit from WBI with higher total doses and lower doses per fraction such as 2.5 Gy ×14 or 2 Gy × 20. A previous study of long-term surviving patients with brain metastases from various tumor entities suggested that WBI with 2 Gy × 20 led to significantly better local control and survival than 3 Gy × 10 (5); the survival rates at 12 months were 61% and 50%, respectively (p=0.008).

In conclusion, this study identified two independent predictors of survival. These two clinical factors should be considered when assigning personalized treatment regimens for individual patients and when designing prospective clinical trials.