Original Study
Bone Metastases as the Only Metastatic Site in Patients With Urothelial Carcinoma: Focus on a Special Patient Population

These data were presented, in part, as a poster at the 2017 annual meeting of the European Society for Medical Oncology, Madrid, Spain, September 8-12, 2017
https://doi.org/10.1016/j.clgc.2017.10.012Get rights and content

Abstract

Background

Patients with exclusive bone metastatic spread from urothelial carcinoma (UC) throughout their disease course represent a rare subgroup with unique clinical features. These patients deserved special consideration in a retrospective multicenter study.

Patients and Methods

Analyses were made from a pool of 1911 patients with a diagnosis of metastatic UC, from 23 centers. Baseline characteristics, access to treatment, and outcomes were analyzed according to metastatic spread. Univariable and multivariable Cox analyses were performed.

Results

A total of 128 evaluable patients (6.7%), diagnosed between February 1997 and April 2013, were identified. Eastern Cooperative Oncology Group performance status (PS) was ≥ 2 in 33.3% versus 17.7% of the remaining patients. Seventy-three (57%) received first-line chemotherapy, that was platinum-based in 50 patients (69%). Twenty-eight (21.9%) received second-line chemotherapy (vs. 75.9% and 32.2%, respectively, of the remaining patients). In multivariable analyses, no clinical factor was significantly associated with overall survival (OS). Among platinum chemotherapy-treated patients (total evaluable n = 972), significantly different relapse-free survival (RFS) and OS were observed according to bone metastases status (no bone metastases vs. bone metastases only vs. bone and other sites, P < .001). In these groups, 2-year RFS was 37.4%, 28.8%, and 25.9%, respectively. Two-year OS was 35.5%, 15.8%, and 23%, respectively.

Conclusion

Patients with metastatic UC and bone-only metastases are less likely to receive systemic therapy than those with other metastases, likely because of their lower PS. The prognostic effect of having exclusive bone metastases or additional sites seems to be equally poor. These patients deserve new effective and tolerable agents, and improvements in the knowledge of their disease.

Introduction

The development of metastases from urothelial carcinoma (UC) represents a relatively rare but deadly event, except for patients who present with a regional lymph node involvement, who might be suitable for combined modality treatment.1 Overall survival (OS) outcomes with conventional, platinum-based, chemotherapy depend on the possibility of administering cisplatin versus carboplatin-based regimens, in addition to key baseline factors.2, 3, 4 For cisplatin-ineligible patients, the possibility of administering immune checkpoint inhibitors as an alternative to carboplatin-based chemotherapy might further improve prognosis.5, 6 However, the median OS of patients with metastatic UC might vary from < 10 to > 15 months, according to the treatment. During the past 2 decades, we have learned that OS probability is closely dependent on baseline patient- and disease-related factors. Conventionally, the presence of bone metastases, with or without liver or pulmonary involvement (LLB), is defined as “visceral metastases” from UC, and it is recognized as a negative prognostic factor in a model developed at the Memorial Sloan Kettering Cancer Center, together with Karnofsky performance status (PS), in patients receiving cisplatin-based chemotherapy.7 Subsequently, these factors have been augmented with additional factors like albumin, leukocyte count, hemoglobin level, and the number of metastatic sites.8, 9 In more recent years, the presence of LLB metastases was included in a nomogram for OS calculation that was developed by the authors of the current study on the basis of the data obtained from the Retrospective International Study of Invasive/Advanced Cancer of the Urothelium (RISC) database.10 Interestingly, none of the 3 factors was an independent prognostic indicator of OS, although hepatic involvement in patients receiving second-line chemotherapy was independently prognostic for OS.11 There is a small subgroup of patients with metastatic UC whose tumor shows an exquisite bone tropism and who develop predominant or exclusive skeletal metastases. Literature about these patients is limited to a few case reports, and discordant findings have been reported regarding the clinical course and prognosis of such patients.12, 13 However, these patients should constitute a special population because of their unique clinical course, including the occurrence of bone metastases-related complications, that are likely to cause early deterioration of PS and low rates of access to chemotherapy. Also, because of the lack of measurable disease according to the Response Evaluation Criteria in Solid Tumors (RECIST) in most cases,14 the likelihood of enrollment of such patients in clinical trials is very low. Consequently, access to effective systemic therapy that might prolong survival is frequently prevented by multiple factors, and the outcome is generally poor. This limitation might be well perceived nowadays, because the shifting therapeutic landscape of metastatic UC prompted investigators to develop a huge number of clinical trials that are combining various novel agents, with or without immunotherapy.15 We aimed to retrospectively analyze the population of patients with bone-limited metastatic UC in a multicenter study.

Section snippets

Patient Population

We performed a retrospective study encompassing individual patient-level data from patients with muscle-invasive or advanced UC or nonurothelial histology who have received systemic therapy during the course of their disease. This contemporary database includes data gathered from hospitals in the United States, Europe, Israel, and Canada. The RISC study was approved by the ethics committee at each participating institution. In March 2017, data were extracted to select patients with the

Patient, Disease, and Treatment Characteristics and Outcomes

The study flow chart, with patient selection and reasons for study exclusion, is presented in Figure 1. Among the 1911 patients diagnosed with metastatic UC, a total of 128 evaluable patients (6.7%; ie, the study group) were identified, diagnosed between February 1997 and April 2013, from 23 contributing centers. Table 1 presents the baseline characteristics of the study group, coupled with those of patients from the remaining RISC population (n = 1781; control group). There were no substantial

Discussion

In this report we present, for the first time to our knowledge, an analysis of patients with metastatic UC whose disease spread was limited to the bones throughout their clinical course. Such patients constitute an intriguing and rare subgroup who might deserve special focus for several reasons, which we attempted to analyze. Despite that skeletal involvement from UC is a frequent event, occurring in the range of 25% to 47% of patients with an advanced UC diagnosis,16, 17, 18 the development of

Conclusion

To our knowledge, this study represents the largest clinical assessment of the characteristics, treatments, and outcomes of patients with bone-exclusive metastatic UC. Results showed that access rates for chemotherapy in this subgroup are lower than for the general population of patients with metastatic UC. Among those who received first-line, platinum-based chemotherapy, the outcomes were poor despite the administration of cisplatin chemotherapy, and notwithstanding the presence of additional

Disclosure

The authors have stated that they have no conflicts of interest.

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