Koizumi et al. BMC Cancer 2010, 10:423 http://www.biomedcentral.com/1471-2407/10/423 Page 7 of 9 Figure 5 Kaplan-Meier curves of SRE and CSD in patients with (gray line) and without pain (black line). Upper row figures indicate the analysis using SRE as an event. Lower row figures indicate the analysis using CSD as an event. Left line figures indicate the analysis in patients with a solitary bone lesion at the date of skeletal metastasis diagnosis, and right line figures indicate patients with multiple bone lesions. Starting point was the date of diagnosis of skeletal metastasis. Black lines indicate patients without pain and gray lines indicate patients with pain. A log- rank test in each patient group with solitary bone lesion and SRE event, solitary bone lesion and CSD event, multiple bone lesions and SRE event, and multiple bone lesions and CSD event were performed with c2 values 27.4 (p < 0.0001), 0.8 (p = 0.36), 48.8 (p < 0.0001), and 15.8 (p < 0.0001), respectively. at the end of 2004, and actual use began in 2005. There- fore, there were limited data regarding the use of bisphosphonates in this study and this prevented analy- sis of the impact of bisphosphonate treatment. The strategy of using radiotherapy for treating skeletal metastasis changed during the study period. The inclu- sion of radiotherapy treatment in the SRE classification could result in an overestimation of the incidence of SRE in this study. We have also performed another ana- lysis in which first RT was not regarded as SRE and RT at least three months apart from first RT was counted as SRE. Although the distribution of kinds of SREs has been changed (additional file 5), the results of statistical analyses [Cox analysis (additional file 6) and Kaplan Meier analysis (data not shown)] were similar. Patients were screened using periodic bone scans and more than 50% of patients (396/666, 59.5%) were diagnosed as having skeletal metastasis without pain. This is in contrast to other reports in which only a small percentage of patients were diagnosed with skele- tal metastasis without pain. Front et al. reported that 21/66 (21%) patients did not have bone pain at diagnosis [19]. This difference could be due to the screening pro- tocol used for skeletal metastasis, and advances in ima- ging modalities such as computed tomography and magnetic resonance imaging, which were used to con- firm the presence or absence of skeletal metastasis. Two randomized clinical trials (RCT) regarding breast cancer follow-up were published in 1994, although the studies were conducted almost 20 years ago. They concluded that regular physical examina- tions and annual mammography were as effective as more intensive approaches, based on laboratory and imaging tests in terms of timelessness of recurrence