RCC accounts for 3% of all malignancies and 80%-85% of primary renal cancer[21]. Bone is the second most common site of metastasis in RCC patients, following lung[22, 23]. In the present study, we constructed diagnostic and prognostic nomograms to predict the risk of BM in newly diagnosed RCC patients and the OS of RCC patients with BM by analyzing a large number of data, respectively. We believe that two nomograms representing OS and distant metastasis, respectively, are complementary and can increase their clinical value in patients with RCC. The total score can be calculated by obtaining data for the corresponding variable on the nomogram for each RCC patient. The risk of BM can then be easily identified on the diagnostic nomogram, identifying patients in the high-risk group and guiding clinical practice in early intervention. Similarly, the prognosis of RCC patients with BM can be determined from the prognostic nomogram. In the validation of the two nomograms, the two nomograms showed excellent performance in BM risk assessment and OS prediction in RCC patients, respectively, which will enable more accurate personalized clinical decision-making and monitoring.
Despite the poor prognosis of RCC patients with BM, early detection of BM may be critical for patients with RCC to receive appropriate treatment. Therefore, exploring the risk factors for BM in RCC patients is important for clinical decision-making. At the molecular level, cadherin-11, transforming growth factor-β, insulin-like growth factor, and fibroblast growth factor has been reported to be associated with BM in RCC patients[24, 25]. Nevertheless, these biomarkers are difficult and impractical to apply immediately to clinical decision-making. In addition, regarding some practical clinical features, sex, T stage, N stage, grade, liver metastasis, lung metastasis, brain metastasis, and histologic type have been reported as relevant risk factors for BM in newly diagnosed RCC[18]. To date, however, predictive models have not been developed, which means that it is not possible to identify an individual's risk of BM by combining all independent predictors associated with BM. The results of the present study showed tumor size, liver metastasis, lung metastasis, brain metastasis, N stage, T stage, histologic type, and grade was a significant predictor of BM in RCC. The association between these factors and BM in RCC patients has been reported in previous studies. Previous studies have confirmed the relationship between tumor grade, TNM staging, and BM in newly diagnosed RCC patients[18]. TNM staging is widely used in the assessment of prognosis in cancer patients. Notably, a greater contribution of TNM staging was shown in both the diagnostic nomogram and the prognostic nomogram. With increasing tumor size, an increasing number of lymph node metastases, and the presence of distant organ metastases, the risk of BM in RCC and the risk of death in RCC patients with BM are significantly increased.
In addition, our study found a poor prognosis of RCC BM patients with lymph node metastasis, brain metastasis, lung metastasis, without surgery, poor tumor differentiation, and histologic type of the collecting duct. A prognostic nomogram was established based on six independent prognostic factors. The results suggested that a nomogram can be an effective tool for identifying high-risk patients. The impact of histologic type on metastatic potential and prognosis of metastatic patients is often overlooked when discussing treatment options. In this study, collecting duct RCC had a higher incidence of BM and a worse prognosis compared to other renal cancer subtypes. Collecting duct RCC is reported to be a rare entity that occurs in <2% of patients with kidney cancer, often resulting in a poor prognosis[26]. In addition, the above correlation has been confirmed in previous studies[27, 28]. The relationship between lung metastasis, brain metastasis, surgery, and prognosis in patients with RCC has also been widely reported in previous studies. Lin et al. reported a better prognosis in patients with only BM than in patients with concomitant pulmonary metastases, and a significantly better prognosis for patients with single BM than in patients with multiple bone and/or visceral metastasis[29]. Similarly, Toyoda et al. reported a shorter median survival in patients with extra-BM compared to those without (8 vs 33 months, p=0.0084)[30]. Surprisingly, contrary to previous reports, the presence of liver metastasis was not an independent prognostic factor in our study [31, 32]. However, this is consistent with what has been reported by Santoni et al.[17]. For the treatment of RCC patients with BM, recent consensus suggests the use of a multimodal treatment strategy that includes extensive resection of the lesion, radiotherapy, systemic therapy, and other local treatment options[33]. Of RCC patients with BM, the goal of surgical treatment is to improve the prognosis, local tumor control, pain relief, and preservation or reconstruction of function. Based on the results, we found that surgery was not only an independent prognostic factor, but that patients who had surgery showed a better prognosis. As reported in several studies, surgical removal of isolated or minimally metastatic lesions can improve the prognosis of patients with BM, thus providing a multidisciplinary team to support the treatment plan for these patients[34-36]. Although renal cancer is usually not sensitive to radiotherapy and chemotherapy, palliative radiotherapy has the potential to significantly relieve local symptoms and improve quality of life[37, 38]. Tyrosine kinase inhibitors (TKIs) and anti-vascular endothelial growth factor antibodies are now widely used as first- and second-line therapy for advanced RCC. Direct evidence on the effects of targeted drugs on BM is currently limited to a few studies that have shown that TKIs can prolong the mean time to progression of existing bone lesions and reduce the formation of new bone lesions[2, 39]. Unfortunately, the SEER database does not contain specific analyses of targeted therapies, chemotherapy, radiotherapy, and we are unable to analyze their influence on prognosis in further detail. In addition, further research on important prognostic factors for OS with BM in RCC is necessary.
However, some limitations of our study should be noted. First, information collected in the SEER database is about the disease at the time of the first diagnosis and does not record BM that occurred later. Secondly, the prognostic impact of the amount of BM should not be overlooked, but there is no record of this in the SEER database. Third, we did not have access to some biomarkers from the SEER database, such as transforming growth factor-β, insulin-like growth factor, and fibroblast growth factor. Fourth, this was a retrospective study in which selection bias was inevitable and information on detailed treatment was not available in the SEER database.