Professor Ye Dingwei's interpretation of "Expert Consensus on Clinical Diagnosis and Treatment of Bone Metastasis and Bone-related Diseases in Prostate Cancer (2021 Edition)"

Foreword Prostate cancer patients are prone to bone metastases, and they are relatively insidious.
For newly diagnosed prostate cancer patients who have developed bone metastases, the median survival time is only 4 to 5 years
.

Despite the continuous improvement of anti-tumor treatment methods, more than 70% of patients with advanced prostate cancer have bone metastases and bone-related events (SREs) caused by bone metabolism disorders, which greatly increases the burden of disease
.

The "Experts Consensus on the Clinical Diagnosis and Treatment of Bone Metastasis and Bone-related Diseases in Prostate Cancer (2021 Edition)" (hereinafter referred to as "Consensus"), compiled by Professor Ye Dingwei from the Cancer Hospital of Fudan University, was published recently, which is the norm for bone metastasis of prostate cancer in China.
Diagnosis and treatment provide a new reference
.

In order to promote the standardized diagnosis and treatment of bone metastases from prostate cancer, we have sorted out the key contents of the "Consensus", and specially invited Professor Ye Dingwei to conduct key interpretations for readers
.

Expert profile Prof.
Ye Dingwei, Deputy Dean of Fudan University Cancer Hospital, Chief Expert of Urological Oncology MDT Director, Shanghai Urological Oncology Institute Director, Fudan University Prostate Cancer Institute, Chinese Anti-Cancer Association Urinary Male Reproductive Tumor Committee (CACA-GU ) Chairman Chinese Society of Clinical Oncology (CSCO) Prostate Cancer Expert Committee Chairman, Chinese Medical Association Urology Branch (CUA) Oncology Group Deputy Chairman Chinese Society of Clinical Oncology (CSCO) Urothelial Cancer Expert Committee Vice Chairman Chinese Clinic Vice Chairman of the Renal Cancer Expert Committee of the Society of Oncology (CSCO) Vice Chairman of the Immunotherapy Expert Committee of the Chinese Society of Clinical Oncology (CSCO) Chairman of the Urinary Oncology Group (UCOG) of the Chinese Cancer Hospital Executive Director of the Chinese Anti-Cancer Association, Executive Director of the Chinese Society of Clinical Oncology Director, Chinese Anti-Cancer Association Urology and Male Reproductive Tumors Committee (CACA-GU) Prostate Cancer Group Leader NCCN Kidney Cancer Diagnosis and Treatment Guide China Edition Deputy Group Leader NCCN Prostate Cancer, Kidney Cancer, Bladder Cancer Asian Consensus Expert Committee on Diagnosis and Treatment Member, Advanced Prostate Cancer Asia-Pacific Consensus Expert Committee Member, Shanghai Medical Doctor Association, Urology Branch, Vice President, Former Chairman of Shanghai Anti-Cancer Association, National Science Gold Second Review Expert, Asia-Pacific Prostate Society (APPS), Vice President, Asia-Pacific Society of Cryosurgery The key contents of the "Consensus" list the pathogenesis.
95% of prostate cancer bone metastases are osteogenic lesions, 5% are mixed lesions, and simple osteolytic metastasis is relatively rare
.

Osteogenic bone metastasis of prostate cancer is manifested by an increase in the number of pathological irregular bone trabeculae, but at the same time the markers of bone resorption also increase, indicating that both osteogenic changes and osteolytic changes exist simultaneously
.

Osteogenic alteration prostate cancer cells may secrete factors that increase the activity of osteoblasts, including bone morphogenetic proteins (BMPs), transforming growth factor β (TGF-β), endothelin-1, fibroblast growth factor family, etc.
, to promote growth Proliferation and differentiation of bone cells
.

Osteolytic alteration of prostate cancer cells metastasizes into the bone marrow through the blood, tumor cytokines stimulate osteoblasts to highly express RANKL (receptor activator of NF-κB ligand), RANKL and the surface of osteoclasts RANK (nuclear factor-κB receptor activator factor) binds to activate osteoclasts, degrade the bone matrix and cause osteolytic changes
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Osteolysis releases growth factors such as TGF-β to promote the growth of prostate cancer cells and form a vicious circle
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Therefore, the RANK-RANKL signaling pathway is closely related to bone metastasis of prostate cancer
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The clinical manifestations of prostate bone metastasis are more common in the pelvis, followed by the spine.
Skull metastasis is rare, and it is most likely to be metastasized to the femur in the peripheral bones
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Most patients with prostate bone metastases have no obvious early manifestations, so they are easily overlooked
.

As the disease progresses, bone metastases can cause pain, pathological fractures, spinal cord compression and other SREs; patients with extensive bone metastases can also be accompanied by systemic symptoms such as fatigue, weight loss, and anemia; patients with hypercalcemia can affect the whole body more systems, such as the nervous system, cardiovascular system, gastrointestinal tract, digestive system, urinary system
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Diagnosis: Bone metastasis should be suspected when the patient has the following conditions: (1) bone pain or fracture; (2) symptoms of spinal cord or nerve compression; (3) elevated blood alkaline phosphatase; (4) hypercalcemia Disease
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If the Gleason score of newly diagnosed prostate cancer patients is ≥8 or the clinical stage is ≥T3, they can also be regarded as a population at high risk of bone metastasis
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In addition, bone metastasis of prostate cancer requires a joint judgment based on medical history, symptoms, signs, and imaging examinations, and a biopsy can be performed when the clinical diagnosis is in doubt
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The treatment of bone metastasis of prostate cancer currently includes drug therapy, conventional analgesia, external radiotherapy, radionuclide, orthopedic surgery and minimally invasive interventional therapy, among which drug therapy is the main treatment modality
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Drug therapy is further divided into systemic therapy drugs for tumor cells and bone protective agents for bone-related events.
The former includes endocrine therapy and chemotherapeutics, and the latter includes bisphosphonates and RANKL inhibitor desulumab
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Experts have written the "Consensus" under the general trend.
New thinking in the new environment.
With the continuous improvement and update of anti-tumor treatment methods, the survival time of patients with malignant tumors has been continuously extended.
The publication of the Expert Consensus on the Clinical Diagnosis and Treatment of Bone Metastasis and Bone-related Diseases of Prostate Cancer is the general trend
.

As far as advanced prostate cancer is concerned, bone metastasis and SREs are common problems that patients are exposed to after prolonged survival
.

SREs not only reduce the quality of life of patients, but also increase the economic burden of patients and the risk of death
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Early diagnosis can prevent and treat SREs in time, and reduce or delay the adverse effects of SREs on patients
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As prostate cancer treatment drugs become more abundant, there are more treatment options for bone modification drugs
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This "Consensus" was released under this clinical background, aiming to improve clinicians' awareness of bone metastasis treatment, standardize the diagnosis and treatment of prostate cancer bone metastasis, and provide clinicians with more reasonable prostate cancer bone metastases.
The multidisciplinary diagnosis and treatment strategy is to reduce or delay the occurrence of SREs, improve the quality of life of patients, while reducing the impact of anti-tumor therapy, and prolong the survival time of patients
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Bone-targeted drugs are included in the "Consensus", a new choice in the new era.
The "Consensus" covers bone metastasis mechanisms, diagnosis, treatment and other aspects.
The content is comprehensive and detailed, and it is systematically updated in conjunction with the latest advances in diagnosis and treatment
.

In terms of treatment, the RANKL inhibitor desulumab, which was approved last year, was also included in the "Consensus
.
"
Desulimab is the first precisely targeted RANKL inhibitor.
It is a fully human monoclonal antibody used to prevent SRE in solid tumors.
Its mechanism of action is unique.
It targets the RANKL-RANK-OPG axis and blocks the effects of RANK and RANKL.
Combined to inhibit the activity of osteoclasts, reduce bone resorption, promote bone remodeling, and reduce the incidence of fractures, it can be described as a true bone-targeted drug
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A number of clinical studies have shown that, compared with zoledronic acid, disulumab can greatly reduce the occurrence of SREs, and at the same time can greatly delay the occurrence of SREs
.

In the Phase III clinical study, the median time to the first occurrence of SREs in the desulumab group was 20.
7 months, which was 3.
6 months longer than that in the zoledronic acid group (P=0.
008), and significantly reduced the risk of first or recurrence of SREs by 18 %(P=0.
008)
.

In addition, desulumab can significantly delay the progression of pain up to 8.
3 months, which is 1.
4 months longer than zoledronic acid (P=0.
02)
.

Disulumab is not metabolized by the kidneys, and renal adverse reactions are relatively small, without the need to monitor renal function and adjust the dose; the method of use is subcutaneous injection, which is more convenient to use than zoledronic acid, which can improve patient compliance and improve patient’s health The level of bone health improves the quality of life of patients
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Working together to promote the "Consensus", the new target diagnosis and treatment norms under the new background is a gradual process.
The update of diagnosis and treatment technology and the enrichment of treatment methods will gradually change clinical practice, but these require an industry consensus to promote and promote
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The release of the "Consensus" can further increase clinicians' recognition and understanding of the latest advances in diagnosis and treatment, and form standardized diagnosis and treatment in the clinic
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At the same time, the "Consensus" can increase the importance of clinicians on prostate cancer bone metastasis, and implement disease intervention as soon as possible to minimize the impact of the disease on patients
.

I believe that with the promotion of the "Consensus", the quality of life of patients with prostate cancer and bone metastases can be greatly improved.
I hope that colleagues across the country can work together to make patients' health even better
.

Reference: Professional Committee of Urinary and Male Reproductive System Tumors of Chinese Anti-Cancer Association.
Expert consensus on clinical diagnosis and treatment of bone metastasis and bone-related diseases of prostate cancer (2021 edition)[J].
Chinese Journal of Oncology,2021,43(10):1016-1026.