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A high-risk mHSPC patient with hypertension and multiple bone metastases received long-term treatment with apatamide + ADT, which has a significant effect and is expected to achieve long-term high-quality survival.

Brief medical history Patient, male, 68 years old.

In February 2017, due to poor urination, he underwent a prostate resection in an outside hospital.
Postoperative pathology revealed prostate adenocarcinoma.
The Gleason score was 4+5=9.

There was no discomfort such as frequent urination, urgency, dysuria, dysuria, etc.
after the operation.

He had hypertension for more than 10 years, did not take the medicine regularly, and then took one tablet of compound reserpine and methotrexate (po qd); he denied the history of diabetes, epilepsy, stroke, and coronary heart disease.

Admission examination Gleason score: 4+5=9 points.

PSA (Prostate Specific Antigen): 82.
28 ng/ml.

Auxiliary imaging examination: whole body bone imaging: multiple bone metastases throughout the body, involving the sternum, right scapula, upper left humerus, multiple ribs on both sides, multiple vertebral bodies of the spine, bones of the pelvis, and bilateral femurs.

CT whole abdomen + chest scan + enhancement: the prostate protrudes into the bladder; there are multiple lymph nodes in the abdomen and pelvis, and some are enlarged; multiple bone density is uneven, not except for metastases.

Figure 1: SPECT (2017.
03): Whole body bone imaging, multiple bone metastases Figure 2: MRI (2017.
03): The prostate and bladder are not clearly demarcated; bilateral seminal vesicle glands and rectum are affected Figure 3: Whole abdomen + chest CT (2017.
03) ): The prostate protrudes into the bladder, and multiple lymph nodes in the abdomen and pelvis.
Diagnosis: Metastatic hormone-sensitive prostate cancer (mHSPC), T4N1M1. After treatment in March 2017, the patient began to receive goserelin acetate 10.
8mg + apatamide (Ansenke) 240mg QD treatment, 2 months later, PSA decreased to 20.
56ng/ml; in September 2017, PSA decreased To 0.
92ng/ml, in January 2019, PSA continued to drop to 0.
06ng/ml.

In May 2020, that is, 38 months of follow-up, the testosterone value remained below 0.
69ng/ml, and the PSA fell below 0.
02ng/ml.

Figure 4: PSA changes during the treatment of apatamide + goserelin Figure 5: Changes of testosterone during the treatment of apatamide + goserelin Since receiving the new endocrine therapy drug apatamide in March 2017, 24 Months later, the patient’s PSA has been maintained below 0.
02ng/ml, reflecting the rapid, deep and lasting effect of reducing PSA, and the testosterone level has been maintained below 0.
69ng/ml.

In terms of safety, the patient only had a slight rash.
Afterwards, he used compound dexamethasone acetate cream for external use, and took 5 prednisone acetate tablets daily.
After 2 weeks, the patient recovered completely from the rash.
After 1 month, the patient stopped using the hormone.

No other symptoms of discomfort.

The patient's imaging showed no progress after treatment, and the primary and metastatic lesions shrank.

The results of whole body bone imaging in August 2017 showed that bone metastases were significantly weaker than before.

A CT examination in September 2018 showed that the size of the prostate was reduced, and the boundary between the prostate and the bladder was clear, and there has been no change so far; the pelvic lymph nodes have been significantly reduced.

Figure 6: Comparison of whole body bone imaging after 5 months of treatment.
Figure 7: Comparison of pelvic CT results in September 2018.
Case provided by Doctor Zhang Shun, Attending physician, Drum Tower Hospital, Nanjing University School of Medicine, Attending urologist, Doctor of Medicine, specializing in advanced prostate cancer , Urothelial cancer, kidney cancer and other drug treatments.
Good at targeted therapy of urinary system tumors and full-process standardized management.
Responsible for more than 30 clinical trials and research in urology.
Familiar with the latest developments of various international cutting-edge new drugs.
Published multiple SCI papers.
Case analysis.
Once prostate cancer patients With metastasis, the risk of disease progression and death is greatly increased. According to the results of the three RCT studies TITAN, CHAARTED, and LATITUDE [1-3], for patients with high tumor burden/high-risk mHSPC, the average progression-free survival (rPFS) after androgen deprivation therapy (ADT) treatment is only Approximately 1.
15 years.

In addition, the use of traditional combined androgen blockade (CAB) therapy also has limited benefits, and new androgen receptor (AR) inhibitors are urgently needed for active intervention.

In this case, the patient was diagnosed as mHSPC (T4N1M1) immediately after admission, with multiple bone metastases throughout the body, with a Gleason score of 9 points, and a history of hypertension for many years, which is a typical high-risk mHSPC type.

For such patients, effective treatments need to be taken immediately to delay the metastasis of the patient's disease and prolong life.

In recent years, with the emergence of more and more high-level evidence-based medicine evidence, new treatment methods based on ADT combined with new endocrine therapy drugs have continued to emerge, bringing more significant survival benefits to mHSPC patients.

The TITAN study [4] is a randomized, placebo-controlled, double-blind study, enrolling 1052 mHSPC patients from 260 treatment centers around the world.

The study enrolled "All Comers" patients, including low-risk/low tumor burden, high-risk/high tumor burden mHSPC patients, newly diagnosed patients, and mHSPC patients with localized prostate cancer recurrence and metastasis.

The primary endpoint results showed that compared with the control group, the risk of imaging progression or death in the apatamide treatment group was reduced by 52% (HR=0.
48; 95%CI 0.
39-0.
60; P<0.
0001); compared with the control group, the treatment group died The risk was reduced by 33% (HR=0.
67; 95%CI 0.
51-0.
89; P=0.
0053).

And with the progress of the TITAN study, the apatamide regimen has a better trend of benefit.

In the TITAN study, there were 558 patients with bone metastases mHSPC patients, 289 patients received apatamide + ADT treatment, and 269 patients received placebo + ADT treatment.

The results show that treatment with apatamide regimen can more significantly improve overall survival (OS) and rPFS, reduce the risk of death in patients with bone metastases mHSPC by 53%, and reduce the risk of imaging progression by 62%.

Therefore, based on the good efficacy data of the TITAN study, the treatment plan of apatamide combined with ADT can bring satisfactory efficacy to patients with high tumor burden/high-risk mHSPC.

Figure 8: Results of the efficacy of patients with bone metastases in the TITAN study Expert comments 1 In recent years, the emergence of new endocrine therapy drugs has brought many changes to prostate cancer patients, and the treatment of patients has undergone fundamental changes.

Apataamide can potently inhibit AR in triplet, it can not only block the binding of androgens and receptors, but also can effectively block the nuclear transport of AR and the binding of AR to DNA.

In addition, apatamide has a higher affinity for AR, and the probability of AR mutation is lower than that of ADT alone.

According to the TITAN study, apatamide can significantly improve OS and rPFS in patients with bone metastases mHSPC, and long-term use does not increase the incidence of adverse events.

In this case, the patient was initially treated with apatamide regimen after he was diagnosed with mHSPC.
During the treatment, the PSA and testosterone levels decreased rapidly and remained low.

The patient's imaging showed no progress, and the primary and metastatic lesions shrank.

This all reminds us that the treatment of apatamide regimen has achieved a good disease control effect, and the curative effect is better.

During the treatment, the patient only developed a mild rash.

This patient had hypertension for more than 10 years, but during the treatment for nearly 4 years, the safety of use was controllable and well tolerated.

Expert profile Professor Hongqian Guo, Executive Director of Urology, Nanjing Gulou Hospital, Chief Physician, Director of the Institute of Urology, Nanjing University, Professor of Nanjing University, Nanjing University, Doctoral Tutor of Nanjing Medical University, State Council Government Special Allowance, Jiangsu Quality Control Association Urinary System Disease Committee Associate editor of the chairman of "Chinese Journal of Cancer Surgery", editorial board of "Chinese Journal of Andrology", "Journal of Modern Urology", "Chinese Journal of Minimally Invasive Surgery" and other journals won the "National Health System Young Professionals" and "Nanjing Top Ten Outstanding "Youth", "Nanjing City Young and Middle-aged Experts with Outstanding Contributions", and was selected as "Key Talents of the Six Talent Peaks" and "Key Talents of the 333 Project" of Jiangsu Province.
Published more than 60 SCI papers in the past 5 years, and is a national core Published more than 100 papers, won 7 Jiangsu Medical New Technology Introduction Awards, 3 Municipal Science and Technology Progress Awards, etc.
, published 5 works and expert comments 2 Some patients with prostate cancer in China are already in the advanced stage when they are diagnosed, and the treatment goal should be delayed The further progress of the disease will improve the survival benefits of patients, and try to strive for more survival time for patients.

This patient is in the mHPSC stage.
In the early stage of treatment, we should use new endocrine therapy drugs combined with ADT to reduce PSA levels, prolong hormone sensitivity, and delay the progression to mCRPC.

Apataamide is a new endocrine therapy drug that has been proven to be the preferred clinical initial treatment for mHSPC.
The TITIAN study confirmed that apatamide is suitable for "all types" of mHSPC patients, reducing PSA faster and longer, and patients with bone metastasis The benefits are more significant.

The 2020 European Academy of Urology (EAU) guidelines strongly recommend apatamide combined with ADT for patients who have first manifested M1 disease and are suitable for this regimen [6].

The 2020 National Comprehensive Cancer Network (NCCN) guidelines and the American Urological Association (AUA) guidelines also recommend apatamide as one of the treatment options for mHSPC [5-6].

As of the most recent follow-up period, this patient has been treated with apatamide for 38+ months and has received very good efficacy.
The actual efficacy and safety are equivalent to the overall TITAN study.
It is believed that the patient will be expected to achieve long-term survival.
. Expert Profile Professor Ge Jingping, Chief Physician, PhD Supervisor, Deputy Director, Department of Urology, Eastern Theater General Hospital, Member of the Expert Committee on Clinical Application Management of Surgical Robots, National Health Commission, Member of the Robotics Group, Chinese Medical Association Urology Branch, Jiangsu Medical Association Urology Member of the Standing Committee of the Branch and Leader of the Minimally Invasive Department, Deputy Director of the Quality Control Center for Urology, Jiangsu Province, Member of the Standing Committee of the Andrology Branch of the Jiangsu Medical Association, and a member of the Stone Group of the Urology Branch of the Armed Police.
Postoperative pathology revealed prostate adenocarcinoma, with a Gleason score of 4+5=9, and multiple bone metastases throughout the body.
Finally, the patient was diagnosed as mHSPC (T4N1M1). If you were the attending physician, which of the following treatment options would you choose for this patient? References: [1] Chi KN, et al.
Apalutamide for Metastatic, Castration-Sensitive Prostate Cancer.
N Engl J Med 2019; 381 (1): 13-24.
[2] Sweeney CJ, et al.
Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer.
N Engl J Med 2015; 373 (8): 737-746.
[3] Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer[4] Chi K, et al.
Apalutamide for Metastatic, Castration- Sensitive Prostate Cancer.
N Engl J Med.
2019 Jul 4;381(1):13-24.
[5] James LM, et al.
NCCN Clinical Practice Guideline in Prostate Cancer 2020 v1.
[6] Lowrance W, et al.
AUA Guideline.
American Urological Association 2020.