Apartamide + ADT in the treatment of mHSPC has a rapid onset and full strength in classic cases

*Only for medical professionals to read for reference, the new multiple bone metastases mHSPC treated with apatamide + ADT for 2 months PSA decreased by 99.
6%, showing its strength
.

The medical history introduced the patient, a 74-year-old male, with bilateral low back pain and urinary frequency and urgency in February, and was admitted to the hospital on February 7, 2021
.

History of present illness: The patient had bilateral low back pain and discomfort with no obvious cause before 2 months, accompanied by frequent urination, dysuria occasionally, and nocturia 10 times per night
.

Past history: nothing special
.

 Diagnosis and treatment after 2021-02-04 other specialist outpatient MRI scans: thoracolumbar osteoporosis and partial compression fractures of the vertebral body, considering the possibility of myeloma, further examination is recommended
.

2021-02-05 PSMA-PET: 1.
Massive high-uptake lesions (1.
3*0.
7 cm) are seen in the right posterior lobe of the prostate, which is considered to be prostate cancer, invading the right seminal vesicle gland; 2.
The right side of the external iliac blood vessel, right Multiple lymph node enlargement can be seen near the side common iliac vessels, retroperitoneum area, deep feet of the bilateral diaphragm, left supraclavicular fossa, and left lower neck.
Consider multiple lymph node metastases; 3.
Multiple vertebrae of the occiput, cervical thoracic and lumbar spine Body and its accessories, left ulna, bilateral humerus, bilateral multiple ribs, bilateral clavicle, bilateral scapula, pelvic bones, bilateral iliac bones, bilateral femoral heads, and bilateral femurs.
Destroy, consider the extensive transfer of bones throughout the body
.

Figure 1.
PET-CT examination 2021-02-06 blood examination Total prostate specific antigen (tPSA) 1035 ng/mL, free prostate specific antigen (fPSA)> 50 ng/ml
.

Admission to Department of Urology on February 7, 2021.
Digital rectal examination (DRE) on February 08, 2021: The prostate is soft, the central sulcus disappears, and no induration is palpable
.

B-ultrasound: The prostate is enlarged, the shape is full, the echo is uniform, and the size is about 5.
5*5.
0*4.
5cm
.

B-guided transrectal prostate biopsy, postoperative pathology: benign prostatic hyperplasia with chronic inflammation (0/6)
.

 Figure 2.
Results of needle biopsy on February 08, 2021.
Considering that the patient's PSA is abnormally elevated, combined with PSMA-PET, considering the possibility of prostate cancer with multiple metastases throughout the body, patients and their families have a strong willingness to treat
.

2021-02-10 Goserelin 3.
6 mg and zoledronic acid 4 mg were given
.

On March 10, 2021, the patient complained that bilateral low back pain and urination symptoms were significantly relieved.
The tPSA was 190.
1 ng/mL and the fPSA was 18.
57 ng/ml
.

 Figure 3.
TPSA levels before and after treatment with goserelin + zoledronic acid.
On March 11, 2021, ultrasound-guided transrectal prostate biopsy (systemic puncture) was performed again.
Postoperative pathology: prostate hyperplasia with chronic inflammation (0/12) )
.

 Figure 4.
Results of needle biopsy on 2021-03-11 2021-03-11 After discussion of urinary tumor MDT, it is recommended that the patient undergo a pathological biopsy of pelvic lymph nodes to confirm the diagnosis
.

After obtaining the consent of the patient and family members, 3D laparoscopic bilateral pelvic lymph node biopsy was performed on March 17th, 2021.
During the operation, bilateral pelvic lymphadenopathy was seen.
Postoperative pathology: Adenocarcinoma metastasis was seen in bilateral pelvic lymph nodes (3 /4, 2/2), combined with immunophenotype, consistent with prostate acinar adenocarcinoma metastasis
.

 Figure 5.
Bilateral pelvic lymph node biopsy results under 3D laparoscopic clinical diagnosis: prostate cancer with multiple metastases throughout the body (cT3bN1M1b) adrenal adenoma (left side) renal cyst (bilateral) lung bullae and emphysema (bilateral) cavity Reflux esophagitis with intermittent cerebral infarction on March 22, 2021, adjust the treatment plan to apatamide 240mg once/day orally + goserelin 10.
8mg once/monthly subcutaneous injection + zoledronic acid 4mg once /Month intravenous drip
.

 2021-04-22 review: tPSA7.
37 ng/mL, fPSA 1.
64 ng/ml, testosterone 0.
44 ng/mL
.

2021-05-27 review: tPSA 0.
81 ng/mL, fPSA 0.
26 ng/ml, testosterone 0.
44 ng/mL
.

Figure 6.
The PSA value of the patient decreased after treatment.
The doctor's profile.
Professor Tan Wanlong, Director, Chief Physician, and Doctoral Supervisor, Department of Urology, Nanfang Hospital, Southern Medical University, Member of the Urology Branch of the Chinese Medical Doctor Association Member of the Society of Medical Robotic Doctors of Guangdong Province Medicine Deputy Chairman of the Urology Branch of the Association, Chairman of the Urology and Laparoscopy Branch of the Guangdong Urogenital Association, Vice Chairman of the Urology Branch of the Guangdong Medical Physician Association Deputy Chairman of the Urology Branch of the Guangdong Association of Integrated Traditional Chinese and Western Medicine Vice Chairman of the Guangdong Anticancer Association Urology Deputy Chairman of the Reproductive Oncology Committee Deputy Chairman of the Minimally Invasive Surgery Branch of the Guangdong Society of Integrative Medicine and Vice Chairman of the Urology Branch of the Guangdong Medical Education Association Deputy Chairman of the Minimally Invasive Surgery Group of the Urology Branch of the Guangdong Medical Education Association Case analysis The patient presented with bilateral low back pain and discomfort due to no obvious cause, accompanied by frequent urination and urgency, and came to the hospital for treatment for 2 months
.

Biochemical examination and imaging examination revealed prostate cancer with multiple lymph node metastasis and bone metastasis, but needle biopsy (transrectal prostate biopsy guided by B-ultrasound) showed prostatic hyperplasia with chronic inflammation
.

In view of the patient's tPSA and imaging findings, goserelin ADT was given empirically, and zoledronic acid was given for anti-bone metastasis therapy
.

After 1 month of treatment, the patient reported that her back pain and urination symptoms were relieved, and tPSA was also greatly reduced
.

In order to further confirm the diagnosis, a transrectal prostate biopsy under the guidance of B-ultrasound was performed again on March 11, and the results still showed that benign prostatic hyperplasia with chronic inflammation
.

After discussing the urinary tumor MDT, the patient was recommended to undergo pelvic lymph node biopsy.
After obtaining the consent of the patient and family members, a 3D laparoscopic bilateral pelvic lymph node biopsy was performed on March 17, and the results suggested that prostate acinar adenocarcinoma metastasis
.

The final diagnosis was prostate cancer (cT3bN1M1b) with multiple lymph node metastases throughout the body and multiple bone metastases throughout the body
.

 Compared with patients with prostate cancer without metastasis, the median progression-free survival (PFS) of prostate cancer patients with distant metastasis is shortened by nearly half
.

For the treatment of patients with metastatic prostate cancer (mPC), the initial endocrine therapy is mostly effective, which belongs to hormone-sensitive prostate cancer (mHSPC); if patients in the mHSPC stage cannot effectively control the disease progression, once they enter the metastatic castration-resistant prostate Cancer (mCRPC) stage, the prognosis is poor
.

Therefore, our consensus recommends that the treatment goal of mHSPC is to delay the progression of mHSPC to mCRPC and prolong patient survival [1]
.

 The abnormality of the androgen receptor (AR) signaling pathway is the key to the progression of mHSPC to mCRPC.
Early intervention with androgen receptor inhibitors has important clinical value
.

Compared with androgen deprivation (ADT) treatment, patients with traditional AR inhibitors have limited benefits.
The new generation of AR inhibitor apatamide triple potently inhibits androgen-androgen receptor binding ability and prevents the entry of activated androgen receptor The nucleus and androgen receptor bind to DNA in the nucleus
.

 The final analysis results of TITAN showed that mHSPC patients with traditional endocrine therapy will progress to mCRPC stage in "less than 1 year", and the median follow-up of apatamide regimen for nearly 4 years has not reached the median value.
The risk of mHSPC patients entering mCRPC is reduced by 66 %, greatly extending the time from mHSPC to mCRPC
.

After excluding the effect of cross-entry, compared with placebo+ADT treatment, apatamide+ADT treatment can significantly prolong the patient’s overall survival (OS) (HR 0.
52, P<0.
0001), and reduce the patient’s risk of death by 48%, 4 years The survival rate was 65.
2%, which was significantly higher than 37.
9% in the placebo group
.

Subgroup analysis showed that apatamide combined with ADT treatment reduced the risk of death by 50% in newly diagnosed patients with bone metastases (HR 0.
50, 95% CI 0.
37-0.
67) [2]
.

 This patient is a newly diagnosed mHSPC patient with multiple bone metastases.
After 2 months of treatment with apatamide + ADT, the PSA decreased by as much as 99.
6%, which further verified the rapid and deep reduction of PSA level by apatamide + ADT in clinical studies.
Effect
.

Commentary 1 Introduction Professor Ye Dingwei, Deputy Dean of Fudan University Cancer Hospital, Leader of Urology, Chief Expert of Urological Oncology MDT, Chief Physician, Doctoral Supervisor Director of Shanghai Urological Oncology Institute Director of Prostate Cancer Institute, Fudan University China Anti-Cancer Association Chairman of the Committee on Urinary and Male Reproductive Cancer Committee of the Chinese Society of Clinical Oncology (CSCO) Committee on Prostate Cancer, Vice Chairman of CSCO Committee on Urothelial Cancer, Vice Chairman of Committee on Renal Cancer CSCO, CSCO Immunotherapy Vice-Chairman of the Special Committee China Cancer Hospital Urinary Oncology Cooperative Group (UCOG) Chairman, Standing Council Member of China Anti-Cancer Association CSCO Standing Council Member Expert Comment 1 The incidence of prostate cancer among Chinese men has been on the rise in recent years, which is a serious threat to men’s health
.

For the treatment of mHSPC patients, a study published in 2020 showed that ADT-based combination therapy is more effective than ADT alone
.

The 2021 version of the European Association of Urology (EAU) guidelines also emphasizes: For patients who are first diagnosed with mHSPC, if there are no contraindications to combination therapy, sufficient life expectancy to benefit from combination therapy, and willingness to accept the increased risk of side effects, they Combine other treatments on the basis of ADT
.

Based on this, the 2021 version of the Chinese Society of Clinical Oncology (CSCO) prostate cancer guidelines no longer recommends ADT alone for mHSPC patients
.

 In this case, the treatment plan of apatamide + ADT was used, which was in line with the recommendations of domestic and foreign guidelines
.

According to the TITAN study, the apatamide + ADT regimen has a good effect in Chinese patients, and apatamide has been approved for the treatment of mHSPC patients in China.
In the future, with the continuous exploration of the research, it will be a good effect for the prostate in China.
Cancer patients bring more benefits
.

Review Expert 2 Introduction Professor Wei Qiang, Director of Urology, West China Hospital, Sichuan University, Vice Chairman, Chinese Medical Association Urology Branch (CUA), Vice Chairman, Chinese Medical Doctor Association Urology Branch (CUDA), and Chinese Medical Doctor Association, Standing Committee Member of Medical Robotic Physician Branch CUDA Leader of the Adrenal Hypertension Surgery Collaboration Group Vice Chairman of the Chinese Society of Clinical Oncology (CSCO) Prostate Cancer Specialty Committee Chairman of the Urology Specialty Committee of Sichuan Medical Association Chairman of the Chinese Medical Journal English Edition (CMJ) Editorial Board Member of the Chinese Journal of Urology Editor's comment 2 Compared with European and American countries, the early diagnosis rate and 5-year survival rate of prostate cancer patients in our country are lower.
About 2/3 of patients are in the middle and advanced stage when they are first diagnosed.
[3], the newly diagnosed prostate cancer should be standardized.
, Individualized treatment helps delay the progression of the disease to CRPC, thereby promoting the overall five-year survival rate and the improvement of the patient’s quality of life
.

 Studies have shown that compared with placebo, treatment with apatamide can significantly improve the progression of OS and PSA in mHSPC patients, whether they are newly diagnosed mHSPC patients or patients with primary mHSPC progression [4]
.

Moreover, the use of apatamide will not increase the incidence of AR mutations in common resistance mechanisms related to the AR signaling pathway, which also provides a guarantee for the subsequent treatment of patients
.

Based on the latest evidence-based medical evidence, the new version of the CUA guidelines also newly added apatamide regimen recommended for newly diagnosed metastatic prostate cancer patients who can tolerate apatamide therapy (level 1 evidence) [5]
.

 In this newly diagnosed mHSPC patient with multiple bone metastases, the PSA decreased by 96% after 1 month of treatment with apatamide + ADT, and after 2 months of treatment, the PSA decreased by 99.
6%
.

Apataamide + ADT can quickly and deeply reduce PSA levels, and is a good choice for delaying the progress of mHSPC
.

Apatamide is approved for marketing in China, which will help promote the realization of the "chronic disease" of prostate cancer in China
.

Reference materials: [1] 2019 Chinese Expert Consensus on Chemotherapy for Metastatic Prostate Cancer (2019 Edition).
[2] Chi KN, et al.
Presented at ASCO-GU 2021 Virtual Scientific Program.
[3] Ma Chunguang, Ye Dingwei, Li Changling, etc.
.
Epidemiological characteristics of prostate cancer and analysis of advanced first-line endocrine therapy[J].
Chinese Journal of Surgery, 2008, 46(12): 921-925.
[4] Kim N.
Chi et al.
EAU 2020.
Poster556.
[5 ] Chinese Guidelines for Diagnosis and Treatment of Urology and Andrology Diseases.
Guidelines for Diagnosis and Treatment of Prostate Cancer (2019 Edition).
*This article is only used to provide scientific information to medical professionals and does not represent the views of this platform