The paper interviewed Prof. Na Yanqun, Chairman of the Chinese Medical Association Urology Section, and invited Associate Professor Gong Kan, National Youth Member of the Chinese Medical Association Urology Section, to give a detailed interpretation of the literature. Interview with Prof. Na Yanqun, Director of the Chinese Medical Association Urology Section, Director of the Chinese Medical Association Urology Section, Director of the Beijing Medical Association Urology Section, President of Peking University Shougang Hospital, Professor of Urology of Peking University People’s Hospital, Editor-in-Chief of the Chinese Journal of Urology, Professor of the Chinese Journal of Urology. He is the chief editor of Chinese Journal of Urology, deputy chief editor of Chinese Journal of Surgery, and executive editorial board member of Chinese Medical Journal. As the leader, he is currently undertaking many special researches such as National 11th Five-Year Plan, National Natural Science Foundation of China, and major projects of National Education Commission. He has received several awards from the Ministry of Science and Technology, the Ministry of Health, the Ministry of Health Outstanding Thesis Award for Young People, the Beijing Science and Technology Achievement Award, and the Beijing Medical University Science and Technology Achievement Award. Prostate cancer: high incidence, bone metastasis is often the final destination The incidence of prostate cancer in the past differs greatly between the East and West. In Europe and the United States, the incidence of prostate cancer is the second highest among all tumors, second only to lung cancer, and the mortality rate is also very high, while the incidence rate in Eastern countries is low, so previous studies believe that the incidence of prostate cancer is related to race and living environment. The incidence of prostate cancer in Eastern countries has increased dramatically in recent years as the dietary differences between the East and West have decreased. 2002 data from Shanghai showed that the incidence of prostate cancer was as high as 11.5 cases per 100,000 people. Prostate cancer may evolve to become the most threatening disease for older Chinese men. Bone metastasis is often the final outcome of prostate cancer. Bone pain and pathological fractures caused by bone metastases seriously affect the quality of life of patients. Diagnosis and treatment of prostate cancer bone metastasis Bone scan is commonly used for diagnosis, but it often reveals pseudo-metastases, which may be inflammation or injury in the joint area. X-rays, MRI and pathological methods can also be used. Currently, comprehensive treatment is mostly used, including endocrine therapy, radiation therapy, radionuclide and drug therapy. Prostate cancer is androgen-dependent, and surgical debulking (orchiectomy) is simple and effective, but is less commonly used at present. Early stage of bone metastasis is sensitive to endocrine therapy and is mostly treated by pharmacological debulking; some patients in the later stage will turn to be androgen non-dependent and not respond to endocrine therapy. It is generally accepted that patients with bone metastases at any stage of treatment can be treated with bisphosphonate medication. Drug therapy can relieve bone pain, prevent and reduce bone-related events including pathological fractures, and improve patients’ quality of life. Clodronate: improved survival and ease of administration Clodronate is a better choice for the treatment of prostate cancer bone metastases. According to a recent article published in The Lancet? Oncology reported in a recent article that clodronate improves survival in patients with bone metastases from prostate cancer. Therefore, clodronate should be used routinely and long-term in the presence of bone metastases from prostate cancer, allowing more Chinese patients to benefit. In 2009, the Chinese Society of Urology formulated a new version of the guidelines for the management of prostate cancer, in which In 2009, the Chinese Medical Association Urological Society formulated a new guideline for the treatment of prostate cancer, which mentioned that oral agents are convenient for long-term use. Bisphosphonates Pyrophosphonate analogues, drug classification depends on the type of side chain. Can be used to treat hypercalcemia and bone-related events caused by bone metastases from malignant tumors. Nitrogen-free bisphosphonates A class of bisphosphonates whose side chains do not contain nitrogen, mainly clodronates. Both oral and intravenous forms are available. Nitrogen-containing bisphosphonates A class of bisphosphonates with nitrogen in the side chain, available only in intravenous form. Clodronate improves the survival rate of prostate cancer patients with bone metastasis Literature Interpretation Gong Kan, Department of Urology, Peking University First Hospital National Youth Member of the Chinese Medical Association Urology Branch, International Advisory Committee of the International Association of Lin Island Syndrome (VHL), Member of the European Association of Urology. He is the secretary of the preparation group of the Guidelines for the Diagnosis and Treatment of Prostate Cancer of the Urology Branch of the Chinese Medical Association. From January to July 2009, he was sent to Rochester and UCLA Medical Center in the United States as a visiting clinical scholar, sponsored by the China Scholarship Council and Peking University’s “Young Faculty Training Program”. He was sent to Rochester and UCLA Medical Center as a visiting clinical scholar. Since 1994, a multicenter randomized double-blind placebo-controlled trial (PR05) was conducted by the Medical Research Council (MRC) to evaluate the effect of clodronate disodium on the progression of prostate cancer bone metastases. The Lancet? This article in Oncology reports the final analysis on long-term survival based on a follow-up study to the PR05 trial. Study Methods The PR05 trial from 1994 to 1998 included 311 patients with bone metastases from prostate cancer (M1), all of whom received standard endocrine therapy. Patients were grouped by a central randomization method with stratification factors including: treatment center, time to start long-term hormone therapy (≤6 weeks or >6 weeks), type of hormone therapy (monotherapy or complete androgen blockade therapy), and patient World Health Organization (WHO) general status classification. After grouping patients were randomized to adjuvant therapy and received oral clodronate disodium 4 capsules daily or placebo for 3 years, respectively. Long-term survival was evaluated for patients registered in England and Wales with an intention to treat (278 patients) based on data from the National Health Information Centre, UK. The median follow-up was 11.5 years. 258 (93%) of the 278 patients with bone metastases from prostate cancer died. The 5-year survival rates were 30% and 21% in the clodronate group and the 10-year survival rates were 17% and 9% in the placebo group, respectively. Patients in the clodronate disodium-treated group benefited in terms of 10-year overall survival compared with the placebo group [hazard ratio (HR)=0.77, 95% confidence interval (CI) 0.60-0.98, P=0.32]. Conclusions Long-term clinical trial data suggest that the nitrogen-free bisphosphonate drug clodronate disodium improves long-term survival in patients with hormone-treated prostate cancer bone metastases. Overall survival is an important long-term assessment for patients with bone metastases from prostate cancer and has clear clinical relevance. Based on the results of the PR05 trial, Professor Deanley previously reported that disodium clodronate in patients with bone metastases from prostate cancer was effective in prolonging disease-free survival in patients with bone metastases (HR=0.71, 95% CI 0.56-0.92), increasing the time between progression of symptoms requiring further treatment and maintaining alkaline phosphatase and serum prostate-specific antigen (PSA) at The time to the lowest point was increased. In particular, early treatment with disodium clodronate may be beneficial in patients with poor prognostic indicators (e.g., elevated alkaline phosphatase and creatinine levels). Patients with elevated alkaline phosphatase levels are usually thought to have increased osteogenic activity, and Professor Deanley speculates that patients with progressive disease also have high levels of osteoclast activity and osteolysis, which may be improved by early treatment with bisphosphonates. Elevated creatinine levels may reduce the excretion of bisphosphonates, thus resulting in higher concentrations of the relevant drugs and potentially better biological effects. The main action of bisphosphonates is to reduce osteoclast activity and promote bone resorption. Their effects also include reduction of tumor growth factor production, inhibition of tumor cell adhesion to the bone matrix, and induction of apoptosis. It can also treat multiple myeloma, metastatic breast cancer and hypercalcemia caused by malignant tumors. Prostate cancer is characterized by osteogenic metastasis, and is osteoclast activity a prerequisite for bone metastasis or a consequence of its presence? There is still controversy. Professor Deanley’s study suggests that clodronate disodium efficacy appears to be limited to the progressive stage of bone metastases, thus lending more support to the latter. However, a 2006 randomized placebo-controlled study of patients with operable breast cancer without bone metastases treated with clodronate for 2 years and followed for 10 years found that clodronate reduced the incidence of bone metastases (HR=0.692, p=0.043) and improved overall survival (HR=0.768, p=0.048) in patients with breast cancer without bone metastases. This study suggests that nitrogen-free clodronate has a “preventive” effect on bone metastases from breast cancer. We expect that the NSABP-34 study, which is currently underway in North America and includes more than 3,000 patients with operable breast cancer without bone metastases who are treated with clodronate, will provide a satisfactory answer. The early addition of clodronate to patients with bone metastases from prostate cancer receiving standard endocrine therapy improved overall patient survival, and PR05 was the first trial to confirm its effectiveness. The effectiveness of clodronate in patients with metastasis-free prostate cancer is expected to be further confirmed by data from additional clinical trials. As a nitrogen-free bisphosphonate, clodronate is the only phosphonate currently focused on “improving patient survival” and has shown encouraging results in prostate and breast cancers. We have reason to believe that more comprehensive clinical studies on clodronate will bring more surprises to the medical community.