CACA Guidelines for Clinical Management of Patients with Advanced Prostate Cancer

During the 2021 CCO conference, the intensive reading conference of "China Integrated Tumor Diagnosis and Treatment Guidelines-Prostate Cancer" was held online
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At the meeting, Professor Zeng Hao from West China Hospital of Sichuan University explained the clinical management of patients with advanced prostate cancer according to the CACA guidelines based on the leading cases of advanced prostate cancer provided by Professor He Liru of Sun Yat-sen University Cancer Center
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Let's take a look
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Basic information of case guidance: Male, 53 years old, admitted to hospital due to "difficulty urinating, accompanied by dysuria".
He was healthy in the past
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PSA: 74.
38ng/ml
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MRI: Prostate mass, considering prostate cancer invading the bladder, bilateral seminal vesicles and prostate urethra, and around the rectum, beside the bilateral iliac vessels, multiple inguinal lymphadenopathy
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Prostate biopsy: acinar adenocarcinoma of the prostate, GS 4+4
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PET CT: Abnormal radioactive concentrated foci in the sacrum and left subscapular angle, considering metastasis; multiple nodules in both lungs, slightly active metabolism, and metastatic cancer to be excluded
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Clinical diagnosis: T4N1M1, stage IV
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This is a case of a patient with advanced metastatic prostate cancer who was diagnosed with advanced metastatic prostate cancer by complete examination
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The patient was initially diagnosed with total androgen deprivation therapy and achieved a rapid decrease in PSA
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Subsequent patients experienced aggravation of bone pain, and achieved long-term control for more than 2 years through chemotherapy and new endocrine therapy
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In subsequent patients with tumor progression, target mutations were found through genetic testing, and further control of symptoms was achieved through targeted therapy combined with appropriate local radiotherapy
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The successful diagnosis and treatment of this patient fully demonstrates that for patients with advanced metastatic prostate cancer, multi-drug combination and timely local treatment can still achieve the purpose of prolonging the patient's survival time and improving the patient's quality of life
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So how should clinicians treat patients with advanced prostate cancer? How are the CACA guidelines recommended? Let us listen to Professor Zeng Hao's interpretation
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Expert interpretation of the diagnosis and treatment of metastatic hormone-sensitive prostate cancer (mHSPC) Metastatic prostate cancer is an advanced stage of prostate cancer.
In theory, all treatment methods cannot achieve curative effects
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However, the overall progress of prostate cancer at this stage is relatively slow, which also gives clinicians a relatively long preparation time to create "miracles"
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mHSPC tumors have metastasized, and patients are at increased risk of disease progression and death (16% of all-cause mortality risk), but the disease is still manageable in the long term
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Therefore, an integrated medical model is needed to delay the disease progression of patients and prolong the overall survival time of patients
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With the deepening of clinicians' understanding of the molecular characteristics of mHSPC, new drugs and new treatment methods are constantly being applied to the treatment of this stage of the disease
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At present, the new combination therapy mode has extended the overall survival time of prostate cancer patients to more than 60 months, and has also played a good effect on mHSPC
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Prostate cancer is a malignant tumor closely related to androgen, so all treatment options are based on anti-androgen therapy
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On this basis, superimposing other treatment modes can maximize the treatment effect of patients
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According to the results of clinical trials, risk stratification of patients, China's national conditions and current status of diagnosis and treatment, the CACA guidelines make different levels of recommendations for the treatment of mHSPC patients
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Faced with numerous treatment options, how can clinicians rationalize their application in real diagnosis and treatment? An effective means to guide clinicians to rationally select treatment options is to classify prostate cancer patients
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Based on the current clinical evidence, the CACA guidelines stratify advanced metastatic prostate cancer.
The stratification is based on the number of bone metastases and the presence of visceral metastases.
Patients are divided into high tumor burden and low tumor burden to guide clinical medication.

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There is a special group of patients with metastatic prostate cancer, which CACA guidelines define as patients with oligometastatic prostate cancer
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These patients may obtain better therapeutic effects from the process of systematic treatment + local treatment, and even achieve an effect that is infinitely close to clinical cure
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Oligometastatic prostate cancer was defined as: no visceral metastases; ≤3-5 metastatic lesions; excluding lymph node metastases
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Optimizing patient population selection and systematic treatment in this setting can maximize the therapeutic effect of some metastatic prostate cancers
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The treatment of metastatic prostate cancer, especially oligometastatic prostate cancer, is through the integration of multiple disciplines and the combination of drugs, surgery, radiotherapy and interventional therapy to comprehensively improve the overall efficacy and achieve the MDT to HIM diagnosis and treatment model
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Diagnosis and treatment of castration-resistant prostate cancer (CRPC) After receiving anti-androgen therapy for a certain period of time, some patients will develop drug resistance.
At this time, clinicians need to consider whether the tumor develops into CRPC
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At this time, the tumor has entered the terminal stage, and the overall prognosis of the patient is poor even if there are abundant clinical treatment methods.
Therefore, the clinical treatment of CRPC is extremely complicated, and rational drug use by clinicians is very important
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Compared with mHSPC, the tumor lethality of metastatic castration-resistant prostate cancer (mCRPC) is significantly higher, even reaching 56%
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At the same time, more than 90% of metastatic patients also have bone metastases and bone pain
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Therefore, in the treatment of CRPC patients, while prolonging the life of the patients, it is also necessary to pay attention to the quality of life of the patients
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The CACA guidelines summarize 4 major characteristics of CRPC patients
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1 Attention should be paid to the treatment of patients in the non-metastatic stage.
The treatment goal of patients with non-metastatic castration-resistant prostate cancer (nmCRPC) is to delay the time node when patients develop metastasis
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The diagnostic and definition criteria of nmCRPC in CACA guidelines: the patient is in castration state; serological PSA has not progressed; imaging has not progressed (the most critical)
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The guidelines recommend that for this part of patients: firstly, it is necessary to delay tumor metastasis, while maintaining the quality of life of patients, and ultimately improving the overall survival of patients
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When the PSA doubling time (PSADT) of nmCRPC patients is less than or equal to 10 months, the guidelines recommend the use of new anti-androgen drugs such as apalutamide, dalotamide, and enzalutamide to delay the occurrence of metastasis; patients with PSA doubling time (PSADT) >10 At 12 months, the guidelines recommend observational follow-up of patients
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2CRPC diagnosis and treatment is one of the best application scenarios of MDT to HIM.
In the CRPC stage, clinicians especially need to pay attention to the diagnosis and treatment mode of MDT to HIM
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At present, the overall efficacy of the CRPC stage at home and abroad needs to be improved
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The Chinese urological tumor consultation platform has been established in China, allowing as many Chinese advanced mCRPC patients as possible to participate in clinical trials through this platform and obtain better curative effect from the MDT to HIM diagnosis and treatment model
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The data from West China Hospital shows that the diagnosis and treatment model of MDT to HIM can provide better survival benefits for patients with CRPC stage
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3.
Precise treatment studies under the guidance of genetic testing have found that the changes in the condition of CRPC patients are related to a variety of abnormal signals, including androgen signaling, cell cycle signaling, and DNA damage repair
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Research data show that about 90% of CRPC patients have clinically significant gene mutations; 25%-30% of patients carry pathogenic DNA repair pathway gene mutations
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Some new targeted drugs, such as olaparib and pembrolizumab, have been validated in clinical trials and have been used in the clinical treatment of CRPC, showing good efficacy in specific patient populations
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4 Patients with common bone metastases 90% of mCRPC patients have bone metastases and bone pain.
Therefore, during the treatment process, clinicians need to pay attention to the treatment of bone metastases
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The treatment of bone metastases in the CRPC stage is divided into two levels: first, the use of therapeutic drugs (new anti-androgen drugs, chemotherapeutic drugs, radionuclide radium-233, etc.
) to control the tumor and delay the occurrence of bone-related adverse events; second, appropriate use of bone protection Agents (denosumab, zoledronic acid, etc.
) are used to protect bone, and ultimately achieve the results of bone health management and prolonged survival of patients
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Conclusion Due to the lack of data from the Chinese population, domestic guidelines still prefer to use high-quality foreign evidence to guide the treatment of CRPC in the Chinese population
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Therefore, we advocate that more clinicians and CRPC patients work together to participate in clinical trials and obtain data belonging to the Chinese population
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Finally, Professor Ye Dingwei from Fudan University Affiliated Cancer Hospital made a summary of the above content
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Professor Ye pointed out that there are four key points in the treatment of advanced prostate cancer: systemic therapy is the foundation, molecular targeting is advanced, local therapy can be explored, and precise evaluation is needed to see the efficacy
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Only by doing these four points can clinicians finally achieve the MDT to HIM diagnosis and treatment model, improve the curative effect of prostate cancer patients, and benefit more patients
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Expert Introduction Dr.
He Liru, Chief Physician, Doctoral Supervisor Visiting Scholar at MD Anderson Cancer Center, USA Member of the Special Committee of the Urology Oncology Group of the Radiotherapy Branch of the Chinese Medical Association Member of the National Health and Health Commission Capacity Building and Continuing Education Oncology Special Committee Youth Committee Member of Guangdong Anti-Cancer Association Urogenital Oncology Youth Committee Vice Chairman Professor Zeng Hao Standing Committee Member of Radiation Oncology Branch of Guangdong Women's Physician Association Mentor Member of the CSCO Prostate Cancer Expert Committee Member of the CSCO Urothelial Cancer Expert Committee Member of the Youth Committee of the Urological Branch of the Chinese Medical Association Member of the International Exchange Committee of the Urological Branch of the Chinese Medical Association Head of the Rare Type Kidney Cancer Collaboration Group of the Urogenital Cancer Special Committee of the Cancer Society Professor Ye Dingwei Director of the Institute of Prostate Cancer, Fudan University Director of the Shanghai Institute of Urology and Oncology Director of the Urology and Male Genital Oncology Committee of the China Anti-Cancer Association Executive Director of the China Anti-Cancer Association Executive Director of the Oncology Group of the Urology Branch of the Chinese Medical Association Asia Pacific Prostate Society (APPS) President-elect Editor: LR Reviewer: Mia Executive: LR