Prof. Liping Xie and Prof. Junhua Zheng: Prospects for prostate cancer screening and treatment in the era of precision medicine

In recent years, the incidence of prostate cancer in China has shown a continuous and rapid increase, and it has become the tumor with the highest incidence of the genitourinary system in Chinese men.

Compared with the United States and other developed countries, the overall survival rate of prostate cancer patients in my country is poor, and more effective screening and diagnosis and treatment strategies are urgently needed to improve the prognosis of patients.

With the advent of the era of precision medicine, "tumor" has become the most important and recent target of precision medicine.

Recently, on the occasion of "2021 AstraZeneca Prostate Cancer Summit Forum and Prostate Cancer Diagnosis and Treatment Integration Summit Forum" on January 16, Yimaitong had the honor to interview Professor Xie Liping, Director of Urology Department of the First Affiliated Hospital of Zhejiang University School of Medicine, and Shanghai Professor Zheng Junhua, Deputy Dean of the First People's Hospital, shared the "Prospects of mCRPC Targeted Therapy and Precision Therapy" and "The Current Status and Future of Prostate Cancer Screening in China".

Prof.
Liping Xie • The First Affiliated Hospital of Zhejiang University School of Medicine • Chief Physician, Doctoral Supervisor • Doctor of Medicine in Germany, and obtained a German medical license • Director of Urology Department of Zhejiang University First Hospital • Member of the Presidium of the Urological Society • International Collaborative Organization for Innovative Diagnosis of Urinary Tumor Co-Chairman•Deputy Secretary-General of Asian Urological Society•Vice Chairman of the Chinese Medical Association Urology Branch, Leader of the Minimally Invasive Group•Chairman of the Urology Branch of Zhejiang Medical Association Professor Zheng Junhua•Shanghai First People’s Hospital Vice President • Vice Chairman of the Chinese Medical Association Urology Branch • Standing Committee Member of the Urology Specialist Branch of the Chinese Medical Doctor Association • Chairman of the Urology Specialty Branch of the Shanghai Medical Association • Director of the Shanghai Hospital Association and Deputy Chairman of the Medical Quality and Safety Management Committee • Shanghai's leading talent and Shanghai outstanding academic leader.
Prospects for mCRPC targeted therapy and precision therapy Professor Xie Liping shared based on the current epidemiological characteristics of metastatic castration-resistant prostate cancer (mCRPC) and unmet clinical needs His vision for mCRPC targeted therapy and precision therapy.01 mCRPC's epidemiological characteristics and clinical unmet needs Professor Xie Liping said that the incidence of prostate cancer in my country is increasing year by year.
A large number of patients have already metastasized to cancer when they see a doctor.
They have lost the opportunity for radical treatment and almost eventually will develop into mCRPC.

Although the treatment of mCRPC has made a lot of progress in recent years with the application of new endocrine therapy drugs and chemotherapy such as paclitaxel, the overall survival time is still only 2-3 years.

About 90% of mCRPC patients carry genetic mutations, of which 20%-30% are homologous recombination repair (HRR) gene mutations, and 10% are BRCA mutations.
Studies have found that patients with HRR mutations have rapid disease progression and poor prognosis.
The standard treatment of the disease has low sensitivity and high tumor-specific mortality.

Therefore, there is an urgent need for new treatments to help these patients improve their survival, which is an important medical need for advanced prostate cancer at this stage.

02 The value and prospects of HRR gene detection in mCRPC Professor Liping Xie believes that HRR gene mutations can predict the efficacy of PARP inhibitors.
The detection of HRR genes can be initiated in newly diagnosed mCRPC, and patients who can benefit from targeted therapies can be identified early and let them Receive targeted treatment at the first time to maximize clinical benefit.

At present, multiple guidelines and expert consensus at home and abroad have recommended tests that include HRR genes for metastatic prostate cancer.

However, there is currently no HRR gene detection kit and analysis software approved by NMPA in my country, and there is a lack of relevant technical evaluation guidelines.

At the same time, the test panels of different laboratories vary greatly, the quality is uneven, and the interpretation standards are not uniform, all of which affect the use of HRR genetic testing in clinical practice.

03HRR test guided mCRPC molecular targeted therapy Professor Xie Liping pointed out that studies have confirmed that prostate cancer with HRR gene mutations is sensitive to PARP inhibitor treatment.
Compared with new endocrine therapy drugs, PARP inhibitors can significantly improve the survival of patients including OS.
Prognostic indicators. With the approval of PARP inhibitors for mutant prostate cancer indications in Europe and the United States, PARP inhibitors have become the standard treatment for patients with mutant prostate cancer, which is a huge boon for the majority of advanced prostate cancer patients.

Finally, Professor Liping Xie concluded that the precision medicine model has brought many possibilities for improving the prognosis of mCRPC.

With the development of molecular detection technology, it is expected that in the future, under the guidance of multiple biomarkers such as genetic mutations, proteomics, and big data analysis, molecular targeted drugs can be accurately selected, and precise treatment plans can be formulated for patients to truly achieve Individualized treatment.

The current status and future of prostate cancer screening in China Professor Zheng Junhua analyzed the current status and future development trends of prostate cancer screening in China.

01 Purpose of prostate cancer screening Professor Zheng Junhua pointed out that early detection of tumors, early diagnosis and early treatment is the first principle.
The earlier the detection, the greater the chance of a patient being cured.

If prostate cancer has entered the middle and advanced stages when it is first diagnosed, the treatment options are limited, which affects the prognosis.

Therefore, the purpose of prostate cancer screening is to reduce the mortality rate of prostate cancer without affecting their quality of life.

Mass screening can increase the diagnosis rate of prostate cancer and find more patients with early-stage prostate cancer.

02 The current status of prostate cancer epidemiology and screening in China Professor Zheng Junhua said that the incidence of prostate cancer in men in my country is lower than in western developed countries.
However, in recent years, with the improvement of my country's economic level, the improvement of people's living standards and the extension of life expectancy The incidence of prostate cancer in my country has shown a significant upward trend, and it has become the tumor with the highest incidence of male urinary system in my country.

In addition, the staging of newly diagnosed prostate cancer patients in my country is very different from that of developed countries in the West.

Take the United States as an example.
Among the new cases of prostate cancer, nearly 81% of cases are localized, and lymph node metastasis and distant metastasis account for only 12% and 4% respectively2.

Data from multicenter studies in my country show that only one-third of newly diagnosed prostate cancer patients are clinically localized prostate cancer, and most patients are already in the middle and advanced stages when they are first diagnosed3.

Compared with Western countries, the overall survival rate of prostate cancer patients in my country is significantly poorer.

According to an analysis of the prevalence of malignant tumors in China released by the National Cancer Center in 2015, the 5-year survival rate for prostate cancer in my country was only 66.
4%4, while the 5-year survival rate for prostate cancer in the United States from 2006 to 2012 reached 99%5.

Professor Zheng Junhua believes that the incidence and diagnostic data of prostate cancer in China remind us that the current situation in China is insufficient screening.
As a result, a high proportion of patients are initially diagnosed with locally advanced or metastatic patients, and the best time for treatment is lost.

In addition, the public’s insufficient awareness of prostate cancer and preventive measures, and there are still certain differences in the level of medical care between urban and rural areas and between different levels of hospitals, resulting in the overall prognosis of prostate cancer patients in my country is far worse than those in Western countries.

03 The future of prostate cancer screening in China Professor Zheng Junhua pointed out that based on the current status of prostate cancer screening in my country, the government, medical institutions, enterprises, and society will need to work together in the future to build a province-wide model of early prostate cancer screening and diagnosis.

In addition, my country has a vast territory, and it can be promoted to the whole country starting from the pilot area to achieve "unified standards, unified methods, and unified platforms", and use information technology to conduct comprehensive analysis.

Professor Zheng Junhua emphasized that people at high risk of prostate cancer should carry out prostate cancer screening based on serum prostate-specific antigen (PSA) testing as soon as possible.

The high-risk population for screening refers to men with good physical condition and life expectancy ≥10 years who meet one of the following three conditions: (1) age> 50 years old; (2) age> 45 years old and have a family history of prostate cancer; or ( 3) Age>40 years old and baseline PSA>1ng/ml.

Although PSA has certain shortcomings, such as low specificity and sensitivity, it is still the most mature screening marker at this stage.

Recently, some emerging prostate cancer markers, such as PCA3, P2PSA, 4K score, etc.
, have been confirmed to have higher specificity and sensitivity than PSA.

However, group screening requires fast, simple, and inexpensive inspection methods.
Therefore, these new markers and imaging inspection methods are not suitable for routine screening populations, but only for specially restricted populations.
For example, PSA cannot be clarified and needed.
Patients undergoing further investigation. Professor Zheng Junhua concluded that the further promotion of prostate cancer screening among high-risk groups and the detection and active treatment of early prostate cancer patients will be expected to improve the late stage of prostate cancer in my country and the overall poor prognosis.

In addition, it is also important to raise the public’s awareness of diseases.
Through the power of the whole society, the public will be promoted for early screening and diagnosis of tumors, in order to reduce public fear and rejection, and truly achieve scientific prevention and treatment for the whole people. References: 1.
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Ma Chunguang, Ye Dingwei , Li Changling, et al.
Epidemiological characteristics of prostate cancer and analysis of advanced first-line endocrine therapy[J].
Chinese Journal of Surgery, 2008, 46(12): 921-9254.
Zheng Rongshou, Sun Kexin, Zhang Siwei, et al.
Analysis of the prevalence of malignant tumors in China in 2015[J].
Chinese Journal of Oncology,2019,41(1):19 -28.
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Jemal A, Ward EM, Johnson CJ, et al.
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Statement: It is for reference only for disease education and not for any promotion purposes.