Clinical benefit of early treatment with bone‐modifying agents for preventing skeletal‐related events in patients with genitourinary cancer with bone metastasis: A multi‐institutional retrospective study

Abstract

Objectives To evaluate the clinical benefit of bone‐modifying agents and identify the risk factors of skeletal‐related events in patients with genitourinary cancer with newly diagnosed bone metastasis. Methods This was a multicenter retrospective study including a total of 650 patients with bone metastasis of the following cancer types: hormone‐sensitive prostate cancer (n = 443), castration‐resistant prostate cancer (n = 50), renal cell carcinoma (n = 80) and urothelial carcinoma (n = 77). Clinical factors at the time of diagnosis of bone metastasis were analyzed. Early treatment with bone‐modifying agents was defined as follows: administration of bone‐modifying agents before the development of skeletal‐related events and within 6 months from the diagnosis of bone metastasis. Results During the follow‐up period (median 19.0 months, interquartile range 6.0–43.8 months), skeletal‐related events were reported in 88 (20%) patients with hormone‐sensitive prostate cancer, 17 (34%) patients with castration‐resistant prostate cancer, 58 (73%) patients with renal cell carcinoma and 34 (44%) patients with urothelial carcinoma. Early treatment with bone‐modifying agents significantly prolonged the time to the first skeletal‐related event in castration‐resistant prostate cancer, renal cell carcinoma and urothelial carcinoma, but not in hormone‐sensitive prostate cancer. Bone pain and elevated alkaline phosphatase levels were independent predictive risk factors of the first skeletal‐related event. The subgroup analysis showed that early treatment with bone‐modifying agents was associated with prolonged time to the first skeletal‐related events in patients with bone pain or elevated alkaline phosphatase levels. Conclusions Early treatment with bone‐modifying agents should be considered, especially for patients with bone pain and elevated alkaline phosphatase levels, to prevent skeletal‐related events in patients with genitourinary cancer with bone metastasis.

Female sex is associated with a lower risk of bone metastases and favourable prognosis in non-sex-specific cancers

“…The latest study showed that the 1-year survival rate of cancer patients with BM ranged from 10% in lung cancer patients to 51% in breast cancer patients [2]. Bone-modifying agents were accepted to significantly retard the first occurrence of SRE [6, 9]. Bisphosphonate was reported to be correlated with the better outcome in patients with bone metastasis [10, 11].…”

Lack of evidence regarding bone metastases of genitourinary cancers: interventions by surgery, radiotherapy, and bone-targeted systemic therapy

“…Therefore, preventing SREs is vital for the management of patients with BMs. Our previous large retrospective study revealed that 72.5% of patients with BMs of RCC developed SRE at least once and that the median time to first SREs in these patients was 10 months after the diagnosis of BMs (17). An Italian multicenter-based survey (18) reported a similar finding, in which 71% of 398 patients with BMs of RCC developed SREs.…”

“…Moreover, in a subgroup analysis of patients with RCC, the estimated reduction rate for first SREs was 29% in the denosumab group compared to that in the ZA group. In our previous retrospective study on the clinical benefit of early treatment with BMAs, defined as the administration of BMAs within 6 months from the diagnosis of BM, the median time to first SRE in the early treatment group (87 months) was significantly longer than that in non-user group (6 months) (P=0.003) in mRCC patients with BMs (17).…”

“…Moreover, a recent review by von Moos et al (20) suggested that BMAs could relieve pain, prolong the time to first analgesic medication and opioid use, and improve patient quality of life. Although the incidence of SREs is significantly higher in RCC than that in PCa (17,18), evidence supporting the efficacy of BMAs in patients with mRCC is still limited. A retrospective subset analysis of patients with mRCC enrolled in a multicenter, randomized, placebo-controlled study revealed that ZA significantly reduced the incidence of SREs (37% vs. 74% for placebo; P=0.015) and prolonged the median time to first SREs (not reached vs. 72 days for placebo; P=0.006).…”

Incidence and Prognosis of Bone Metastases in Common Solid Cancers at Initial Diagnosis: A Population-Based Study

“…The earlier bone metastases are diagnosed and treated, the greater the bene t to the patient. The treatment of bone metastases aims to relieve symptoms, preserve or reconstruct function and improve the quality of life, but it requires a deep understanding of the underlying diseases [5,14,15]. In most literature, data on bone metastases are based on a single tumor.…”