It is of great importance for rare disorders such as PB to identify the prognostic factors affecting the survival of patients and evaluate the effectiveness of current treatment regimens. Thus, acquiring abundant clinical materials of PB cases is critical to achieving this goal. However, to conduct prospective clinical trials seem an exceedingly challenging issue owing to limited PB cases. In this study, we conducted a retrospective analysis based on enormous clinical data of PB which was collected by the SEER database from 1976 to 2017. To the best of our knowledge, this study was the largest series analysis concerning PB. Notably, the results from this analysis confirmed that age, year of diagnosis, treatment options, the extent of tumor extension, and tumor size were the dependent prognosis of patients with PB. Interestingly, the results of this analysis indicated that the overall survival rate of patients with PB has little to do with the application of radiotherapy. However, the combination of RT and CT was found to be an independent prognostic factor for survival.
Hitherto, there is no defining the optimal management strategies for PB, owing to extremely limited data. Furthermore, clinical risk factors associated with prognosis were still less clear in groups with PB. Thus the aim of the study was to clear the ideal treatment regimen and identify the independent prognostic factors for PB. Given a higher precision of nomogram developed previously than the classical stage system for prognosis in some cancers (29, 30), a prognostic nomogram for PB, consequently, was developed based on the data of 243 PB cases. Finally, the clinical utility of the nomogram was assessed by the DCA.
The aggressiveness, the major characteristic of malignancy, is the chief cause of most cancer patients with a poor prognosis. The results of this study revealed, almost without exception, that the overriding risk factor of PB was the continuous extension of disease, which was in line with those studies (31, 32). Detailed, the HR for groups with tumor extension extended to adjacent connective tissues versus those with tumors confined to the gland of origin was 3.37, while that for tumor extension extended to adjacent organs or structures versus those with tumors confined to the gland of origin was 5.25. The finding indicated that the death risk of groups with tumor extension extended to adjacent organs or structures was roughly four-fold of those with tumors confined to the gland of origin. As well, survival analysis demonstrated that overall survival was, compared with those whom tumors confined to the gland of origin, much reduced in groups whose tumor extension exceeded the gland of origin.
Thus far, the impact of tumor size on prognosis is still an intensely controversial issue. The results of a study conducted by Tirada and her colleagues found that increased tumor size often portended a poor prognosis for patients with cancers (33). Consistent with this, a study from Dittmar et al. showed that one of the high-risk factors for mortality was the larger tumor size (34). Besides, it has been reported that the risk of death and recurrence was increased as enlargement of tumor size (35). Yet there is evidence that tumor patients trended to a more poor survival when tumor size was smaller (36, 37). In conformity with this, the results of this analysis revealed that smaller tumor size was an independent prognostic factor of poor survival (HR = 0.95, P˂0.01), which indicated that increased risk of death by 5% for every 1 mm decrease in tumor size.
Multiple lines of evidence illustrated that PB, comparing to infratentorial primitive neuro-ectodermal tumors, carried more poor outcomes irrespective of treatment regimens (38–40). But the aggressive surgical resection is still recommended in the management of PB, and surgical treatment was regarded as the first-line therapy strategy (9, 20). In this analysis, the effect of varied treatment regimens on the prognosis of patients with PB was analyzed, and found that those treatment options presented different influences on clinical outcomes. It is important to note that the risk of death was diminished considerably in patients who received the RT combined with CT, RT after surgical treatment as well as RT after surgery combined with CT. Precisely, the HR for the RT combined with CT versus RT was 0.17, while that for RT after surgical treatment and RT after surgery combined with CT versus CT was 0.38 and 0.30, respectively. Those results indicated that the risk of death is reduced by 62% and 70% in patients who underwent RT after surgery and in patients who underwent RT after surgery combined CT, respectively, compared with those who underwent CT alone. Unsurprisingly, survival analysis in this study draws a conclusion that was in line with those findings. Though surgical resection was known as the first-line therapeutic option and strongly recommended (21), of note, the results of this study could not yet support that surgical treatment alone could significantly improve the prognosis of patients with PB. Interestingly, the results from a survey conducted by Mallick and his colleagues revealed that the clinical outcome was markedly improved in patients who received surgical resection and adjuvant radiotherapy (41). The findings of this study found that the RT after surgical resection and RT after surgery combined with CT were independent prognostic factors which could improve remarkably clinical survival outcome.
About the function of CT in PB is a contentious issue. It seems that PB was responsive to CT as reported by Schild et al. (42) and Ghim et al. (43). However, the findings of this study found that CT failed to improve the overall survival of patients, which was not in harmony with that. It is interesting to note that a study conducted by Mynarek et al. (6) draws a similar conclusion with us, which could not support the effectiveness of CT in PB. Likewise, there is also no consensus regarding the role of RT against PB. A study by Clark and his colleagues (44) demonstrated that PB was resistant to the RT. However, several studies believed that PB was sensitive to the ratio therapy (39, 45, 46). But the findings of this analysis could not determine that patients only received RT was benefitting from the RT treatment. The limited number of PB cases may be the primary reason why the discrepancy occurred on the effectiveness of RT and CT. Hence, high-quality clinical studies are crucial to clarify those disagreements about RT and CT.
Age is typically regarded as risk factors of many disorders, such as neurodegenerative disease.
It was of interest that age was also a key risk factor of PB, which was identified in this analysis. Our findings revealed that overall survival improved significantly with the increase of age (HR = 0.73), which was in agreement with studies (47–49). In great detail, the risk of death was reduced by 27% for every 5-year increase in patient age. It may perhaps be the fact that the biological behaviors of PB vary with increasing age, but it is essential that plenty of studies were conducted to confirm this conclusion.
There was no doubt that this study also has some limitations. Firstly, a long span of a few decades’ years consumed patient data collection leads to heterogeneity in an examination, diagnosis, and treatment modalities. Additionally, part of the information on some critical items of tumor size and extension was not available in the primary data in which multiple imputation was performed. Although multiple imputation adopted widely in some studies was conducted in this analysis, there is inevitably an existing difference between the primary data and imputation data. Thirdly, the sequence of various treatment options was unknown, which might lead to an unrealized evaluation for the effect of the sequence on patients’ prognosis. Despite the shortcomings of this study, its advantages were also considerable and conspicuous. Compared with previous studies, more abundant information about prognostic factors of PB was supplied in this study. Also, the inherent bias and heterogeneity were limited through the regression analysis, and the statistical power was improved significantly on account of enlargement in the number of PB cases. More importantly, the risk factors in the model were more accessible to achieve than those realized by a high-priced technique and a great deal of time.