Turning the "gland" into barbarians, showing its strength, apatamide escorts NM-CRPC patients

*Only for medical professionals to read the reference introduction.
Advanced prostate cancer innovative drug "apatamide" is China's first and only new androgen receptor approved for "all types" of metastatic endocrine therapy-sensitive prostate cancer (mHSPC) indications AR inhibitors are also China’s first new type of AR inhibitors approved for high-risk non-metastatic castration-resistant prostate cancer (NM-CRPC) indications.
Through the treatment concept of early active intervention, it will bring to the treatment of prostate cancer.
The survival benefit of comprehensive innovation
.

Apataamide can significantly reduce the risk of death in mHSPC patients by 48%, greatly increase the four-year survival rate by 27% (from 38% to 65%), and it is also the only drug that achieves OS for high-risk NM-CRPC patients for more than 6 years
.

At present, it has been first-line recommended by many authoritative guides at home and abroad for mHSPC and high-risk NM-CRPC
.

Apataamide is the "pillar" of hope among thousands of families, and the patient's expectation for a better life
.

Please support the listing of "apatamide" in the National Medical Insurance Catalog, and contribute to the realization of the 5-year survival rate target for healthy China in 2030! The medical history introduced the patient, a 68-year-old male, and was first diagnosed in May 2012.
The main complaint was "frequent urination with dysuria worsened for more than one week after three months
.
"
▎History of present illness: The patient had no obvious cause before three months and had nocturia, hesitancy in urination, thinning of urine line, dribbling and other symptoms of progressive dysuria, no painful urination and no gross hematuria
.

One week ago, the patient’s symptoms worsened compared to before.
B-ultrasound examination indicated prostate hyperplasia.
Prostate-specific antigen (PSA) examination showed that PSA was 81.
2ng/ml, and symptoms improved after anti-inflammatory and symptomatic treatment
.

At present, the patient comes to the hospital for further treatment, and the outpatient clinic plans to be admitted to the hospital for "prostatic hyperplasia, prostate cancer waiting to be discharged"
.

Admission examination▎ Blood PSA examination: total prostate specific antigen (TPSA) is 81.
35ng/ml, free prostate specific antigen (FPSA) is 3.
29ng/ml, FPSA/TPSA (F/T) is 0.
04
.

▎Digital rectal examination: the size of an egg in the prostate
.

The texture is hard, the surface is smooth, no nodules are reached, no tenderness, the central groove is flattened, and the seminal vesicles are not reached
.

▎B-ultrasound (May 28, 2012): The prostate has a left-right diameter of 4.
5cm, a anteroposterior diameter of 3.
9cm, and a vertical diameter of 3.
5cm.
The shape is normal and the capsule is intact
.

The echo is uniform, and a solid mass of lower echo can be seen in it, the size is about 1.
2cm*1.
2cm, and the realm is not clear
.

Color Doppler showed that there was no obvious blood flow signal inside the mass
.

▎CT (May 29, 2012): The bladder is well filled, the wall is intact, and there are no obvious signs of space occupation
.

The shape of the prostate is normal and the volume is enlarged, about 4.
6cm*4.
2cm*3.
5cm.
There is no obvious abnormal density shadow in the marginal and central lobes
.

The seminal vesicle glands are thickened and uniform in density, and the seminal vesicle angle of the bladder is present
.

There was no swollen lymph node shadow and accumulation of liquid low-density shadow in the pelvis
.

▎Needle biopsy: A needle biopsy of prostate tissue was performed on May 30, 2012.
The pathological results of the upper left, lower left, upper right, and lower right needles of the prostate were all prostate cancer, and the Gleason score was 8 points
.

Figure 1.
Needle biopsy results ▎ECT (June 4, 2012): No obvious signs of bone metastasis, lumbar degeneration
.

Figure 2.
Diagnosis results of ECT ▎ high-risk localized prostate cancer (T2cN0M0)
.

After the treatment, the patient initially received three months of androgen deprivation treatment (ADT).
On September 17, 2012, he underwent B-guided transperineal prostate seed implantation, and the ADT treatment was suspended after the operation
.

After the PSA increased in September 2014, the ADT treatment was continued, and the PSA remained at a low level.
In February 2018, the PSA began to continue to increase
.

Intercepted from May 15, 2019 to May 20, 2020, the patient's PSA doubling time (PSADT) = 8.
44 months <10 months, the patient has a high risk of metastasis, and more effective treatment is required
.

Figure 3.
PSA changes from May 15, 2019 to May 20, 2020.
On May 21, 2020, ECT indicated that there was no abnormality in the whole body bone imaging
.

At this time, the patient belongs to NM-CRPC with a high risk of metastasis
.

Figure 4.
ECT results.
On July 2, 2020, the patient started taking apatamide, and PSA decreased significantly
.

After taking the medicine for three months, the patient reported a rash with mild symptoms and slight itching.
After applying topical steroid ointment, the symptoms were mild and no topical medication was used.
Blood routine and liver function were normal
.

On April 15, 2021, PSA<0.
006ng/ml and testosterone at 0.
13ng/ml
.

Figure 5.
PSA changes from February 19, 2020 to April 15, 2021.
On July 15, 2021, the latest inspection results showed that PSA <0.
006ng/ml and testosterone <0.
1ng/ml
.

Case analysis This patient was first diagnosed with high-risk localized prostate cancer.
After three months of ADT treatment, seed implantation was performed, and ADT treatment was stopped after the operation
.

After PSA increased, ADT continued to be used, PSA decreased and remained at a low level, and then began to continue to increase
.

PSADT ≤10 months, the whole body bone scan of the patient showed no obvious metastasis.
At this time, the patient belongs to NM-CRPC with a high risk of metastasis.
The risk of bone metastasis in such patients increases by 12 times, and the risk of death increases by 4 times [1]
.

Intervention treatment at the NM-CRPC stage to delay the patient's entry into the clinical stage of metastatic castration-resistant prostate cancer (mCRPC) with the worst prognosis is a breakthrough in solving NM-CRPC metastasis
.

The reactivation of the androgen receptor (AR) signaling pathway is a key driving factor for the progress of CRPC.
Delaying the occurrence of metastasis is the therapeutic goal of NM-CRPC, and AR inhibitors are the key to NM-CRPC therapy [2]
.

Compared with ADT treatment, traditional AR inhibitors (such as bicalutamide) have limited benefits for patients, and long-term use can transform the inhibitory effect of AR into an agonistic effect, thereby promoting the proliferation of prostate cancer cells [3-6]
.

A new generation of non-steroidal AR inhibitor apatamide triple-blocks the activation of AR signaling pathways, which is expected to break this dilemma.
A number of guidelines recommend apatamide as the standard treatment for patients with high-risk metastasis risk NM-CRPC [7- 11]
.

Apataamide can significantly delay the patient's entry into the metastasis stage and further prolong the overall survival (OS) of this patient
.

As a new type of anti-androgen that does not require a combination of hormones, apatamide has more convenient clinical management and controllable adverse reactions.
It is the preferred solution for the elderly in China with elderly patients
.

Figure 6.
Throughout the treatment process, the PSA change curve Expert commented that 1NM-CRPC is an objective and independent clinical disease state.
This concept was developed by the Prostate Cancer Collaborative Group (PCWG) in the third standard update working meeting in 2016 For the first time, it is proposed that the diagnosis needs to meet: "castration resistance" and "traditional imaging without metastasis" two key points [12]
.

14.
3% of CRPC patients in China are NM-CRPC, but for a long time in the past, not only did not receive enough clinical attention, but also lacked good treatment methods [13]
.

Early identification of NM-CRPC and timely intervention can help delay the progression of the disease and prolong the survival time of patients [14]
.

Before 2018, international authoritative guidelines had no standard treatment recommendations for NM-CRPC
.

Since the launch of a new generation of powerful AR inhibitors-apatamide, it has opened a new era of NM-CRPC treatment
.

A new generation of antiandrogens represented by apatamide has been recommended by multiple international guidelines.
For example, the 2018 American Urological Association (AUA) guidelines recommended that clinicians should provide apatam to NM-CRPC patients with high-risk metastasis Amine (Level of Evidence Level A); In 2019, the guidelines for the management of castration-resistant prostate cancer issued by the Canadian Urological Association (CUA) and the Canadian Urological Oncology Group (CUOG) recommend the use of Apata for NM-CRPC patients with high-risk metastases (Strongly recommended); The 2020 National Comprehensive Cancer Network (NCCN) guidelines list apatamide as a level 1 recommendation for patients with NM-CRPC with PSADT ≤ 10 months; the 2020 Chinese Society of Clinical Oncology (CSCO) guidelines list A Paltamide is listed as a Grade 1 recommendation for NM-CRPC patients with PSADT ≤ 10 months (Class 1A evidence); the 2021 CUA/CUOG guidelines also recommend apatamide for NM-CRPC patients with high risk of metastasis (strong recommendation) [ 7-11]
.

Commenting expert 1 Xu Renfang, Chief Physician, Director of the Department of Urology, Changzhou First People's Hospital, Deputy Director of General Surgery, Professor of Soochow University, Master's Supervisor, Member of the Chinese Society of Clinical Oncology (CSCO) Prostate Cancer Committee, Chinese Medical Association Urology Branch Kidney Member of the Transplantation Group Member of the Urinary and Reproductive Branch of China Association for the Promotion of International Medical Care and Standing Member of the Jiangsu Study Group Standing Committee Member of the Professional Committee of Urinary and Male Reproductive Tumors of the Anti-Cancer Association Member of the Jiangsu Provincial Society of Sexuality Chairman of the Urology Professional Committee of Changzhou Medical Association Chairman of the Andrology Professional Committee of Changzhou Medical Association Member of the 13th and 14th CPPCC of Changzhou Jiangsu Province "333" talent project training object Changzhou "831 Project" key talent training object has been engaged in clinical, teaching and scientific research of urology for more than 30 years.
I have studied systematically in the trauma center, participated in many international academic exchanges, and have the ability to independently deal with difficult and major diseases in urology, especially in the radical surgery of urinary system tumors (large renal tumors, adrenal tumors, local high-risk prostate cancer, etc.
) and kidneys He has rich experience in transplantation, endocavity, and minimally invasive urinary tract surgery
.

Take the lead in carrying out Da Vinci robotic surgery for urinary system diseases in Changzhou
.

Performed more than 16,000 specialized urological operations (including hundreds of kidney transplant operations), and the quality of the operations reached the domestic advanced level
.

  Published more than 30 academic papers in SCI, Chinese-level, and provincial-level core journals
.

Presided over 5 scientific research projects and won more than ten provincial and municipal awards
.

Cultivate more than ten postgraduates
.

Experts commented that the results of the 2SPARTAN study completely broke the NM-CRPC treatment pattern.
The study is an international multi-center randomized controlled double-blind clinical study of apatamide in the treatment of NM-CRPC.
The study randomly assigned patients to a 2:1 ratio.
The apatamide group and the placebo group were given apatamide + ADT treatment and placebo + ADT treatment, respectively
.

The results of the study showed that after excluding patients who crossed over to the apatamide group, the median OS of patients in the treatment group was 73.
9 months, while that in the control group was 52.
8 months (P=0.
0003)
.

The apatamide regimen in the treatment of high-risk NM-CRPC patients is currently the only metastasis-free survival (MFS) prolonged> 2 years, and currently the only new generation AR inhibitor with an OS> 6 years.
A subgroup analysis found that apatamide is in the Asian population There is no significant difference between the curative effect in non-Asian population and it can reduce the risk of metastasis by 71% and 72% respectively [15]
.

This means that our Chinese NM-CRPC population will also have a satisfactory effect when using apatamide
.

After this patient received apatamide treatment, the curative effect was indeed very significant, the PSA dropped rapidly and maintained a deep response, and the adverse reactions were slightly controllable
.

Adhering to the treatment of apatamide will surely continue to maintain a good state of survival and delay the occurrence of metastasis and progression to the greatest extent
.

Expert profile 2 Professor Feng Ninghan, Director and Deputy Dean of Urology, Wuxi Second Hospital Affiliated to Nanjing Medical University, Professor, Chief Physician, Doctoral Tutor of Nanjing Medical University, Postdoctoral Fellow of Karolinska University in Sweden, Leading Medical Talent of Jiangsu Province, Jiangsu Province Six top talents, training objects of the "333" project in Jiangsu Province
.

Member of the International Exchange Committee of the Urology Branch of the Chinese Medical Association, member of the Oncology Committee of the Urology Branch of the Chinese Medical Doctor Association, member of the Urology and Male Instrument Committee of the Chinese Medical Device Industry Association, good at urological laparoscopic surgery, presided over the National Natural Science Foundation of China One project, 25 SCI papers published as the first author or corresponding author
.

Profile of the doctor providing the caseProfessor Wei Xia, deputy chief physician of the Department of Urology, Changzhou First People's Hospital Diagnosis and Comprehensive Treatment Specializes in comprehensive diagnosis and treatment of prostate cancer (precision biopsy, minimally invasive surgical treatment, multidisciplinary comprehensive treatment, individualized precision treatment) and minimally invasive surgical treatment of prostatic hyperplasia with holmium laser enucleation in Shanghai Renji Hospital in 2016 HoLEP Academy has trained transurethral holmium laser enucleation of the prostate.
So far, more than 450 cases of HoLEP surgery have been performed.
More than 10 urology papers have been published in medical journals at home and abroad, and 3 reference literatures on urology have been participated in the compilation: [1]Metwalli AR, Rosner IL, Cullen J, et al.
Elevated Alkaline Phosphatase Velocity Strongly Predicts Overall Survival and the Risk of Bone Metastases in Castrate-Resistant Prostate Cancer.
Urologic Oncology 2014; 32: 761–768.
[2]Esther J, Maughan BL , Anderson N, et al.
Management of Nonmetastatic Castration-Resistant Prostate Cancer: Recent Advances and Future Direction.
Curr Treat Options Oncol 2019; 20 (2): 14.
[3]Veldscholte J, Berrevoets CA, Ris-Stalpers C, et al.
The androgen receptor in LNCaP cells contains a mutation in the ligandbinding domain which affects steroid binding characteristics and response to antiandrogens.
The Journal of Steroid Biochemistry and Molecular Biology.
1992;41(3-8):665-669.
[4] Jun Liu,,, etc.
.
Research progress on the mechanism of androgen-independent prostate cancer[J].
Chinese Journal of Andrology,2009,23(8):66-69.
[5]Qian Subo,Shen Haibo,Cao Qifeng , Etc.
Analysis of the efficacy of anti-androgen withdrawal in the treatment of castration-resistant prostate cancer[J].
Journal of Modern Urology,2015,20(1): 40—43.
[6]Ishikura N, Kawata H, Nishimoto A, et al.
CH5137291, an androgen receptor nuclear translocation-inhibiting compound,inhibits the growth of castration-resistant prostate cancer cells.
International Journal of Oncology.
2015;46(4):1560-1572.
[7]https:// .
org/guidelines/prostate-cancer-castration-resistant-guideline[8]NCCN Clinical Practice Guidelines in Oncology: prostate cancer 2020 v1.
[9]2020 CSCO prostate cancer guidelines[10]Saad F, Aprikian A, Finelli A, et al.
2021 Canadian Urological Association (CUA)-Canadian Uro Oncology Group (CUOG) guideline: Management of castration-resistant prostate cancer (CRPC).
Can Urol Assoc J.
2021;15(2):E81-E90.
[11]Saad F, Aprikian A, Finelli A, et al.
2019 Canadian Urological Association (CUA)-Canadian Uro Oncology Group (CUOG) guideline: Management of castration-resistant prostate cancer (CRPC).
Can Urol Assoc J.
2019;13(10):307 -314.
[12]Scher HI, Morris MJ, Stadler WM, et al.
Trial Design and Objectives for Castration-Resistant Prostate Cancer: Updated Recommendations From the Prostate Cancer Clinical Trials Working Group 3.
J Clin Oncol.
2016 Apr 20;34 (12):1402-18.
[13]Xu Gao, A real-world study of prostate cancer based on the PC-follow database: Current status of diagnosis and treatment of CRPC patients in China.
2019 National Urology Conference.
Paper ID: 1652944.
[14]Li Yonghong, Chen Dong, Zhou Fangjian.
New advances in the treatment of non-metastatic castration-resistant prostate cancer with antiandrogens[J].
Chinese Journal of Urology, 2021, 42(Z1): 6-9.
[15] Eric Jay Small, FS, Simon Chowdhury,Final survival results from SPARTAN, a phase III study of apalutamide (APA) versus placebo (PBO) in patients (pts) with nonmetastatic castration-resistant prostate cancer (nmCRPC).
ASCO 2020, 2020.
Abstract 5516.
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