PSA deep rapid decline, OS long-term "ke" period, apalutamide + ADT long-term tumor control, bringing long-term survival hope to mHSPC patients classic case

*For medical professionals only for reference 19.
54ng/ml, the drop rate is as high as 97%, which truly realizes the deep rapid drop of PSA
.

In the follow-up treatment, the patient's PSA and testosterone levels were controlled and stable, and the patient's tolerance was good and the safety was high
.

This program has long-term tumor control and brings long-term survival hope to patients
.

Case review Basic information: The patient was 74 years old and was admitted to the hospital for "difficulty urinating for half a year, and swelling of the left lower extremity for more than 20 days"
.

The patient has a history of hypertension for 10 years, oral antihypertensive treatment, hyperlipidemia for several years, oral lipid-lowering drugs (unknown)
.

Smoking history: none
.

History of drinking: more than 50 years
.

Diagnosis and treatment process: The patient began to have dysuria half a year ago, accompanied by frequent urination, thinning of the urine line, and increased nocturia, which was not paid attention to and treated
.

Swelling of the left lower extremity occurred more than 20 days ago, without pain and fever, and the urine output was similar to before, so he was admitted to the hospital on September 9, 2021
.

On September 08, 2021, the laboratory examination of the external hospital: serum total PSA (TPSA)>147.
0ng/ml, free PSA (FPSA)>18.
7ug/ml
.

Ultrasound examination of prostate in other hospitals showed: prostate area occupying space, considering malignant tumor lesions; hydronephrosis, multiple cysts in both kidneys; bilateral ureteral dilatation; left external iliac vein and common femoral vein thrombosis with complete occlusion; Blood stasis in the saphenous vein, slow blood flow, and prolonged regurgitation of the right common femoral venous valve
.

Magnetic resonance examination on admission showed that the size of the prostate gland was significantly enlarged, and it was prostrate along the anterior wall of the bladder and rectum, and the boundary was unclear
.

The largest range is about 82×93×99
.

Adjacent seminal vesicles were not shown clearly, and multiple lymphadenopathy with fusion was seen in the pelvis
.

There were scattered nodular abnormal signal shadows from the inside and pubic bone of bilateral hips, a nodular similar signal shadow was seen near the right posterior sacral foramen, and a small piece of exudative change was seen adjacent to the right gluteus medius muscle
.

Diagnostic opinion: Prostate cancer is suspicious, with multiple pelvic lymph node metastasis and multiple pelvic metastasis
.

Metastatic lesions near the right posterior sacral foramen with exudation of the right gluteus medius
.

Figure 1.
MRI examination of the patient on admission.
ECT examination showed that the skeleton of the whole body was clearly imaged, and the radiation distribution in it was uneven.
The occipital bone, left sixth posterior rib, right seventh posterior rib, cervical spine, T10, T12, right sacroiliac joint, left Abnormal radioactive concentrations were seen in the sciatic bones
.

The above abnormal radioactive concentration considers multiple bone metastases of malignant tumor
.

Figure 2.
Multi-point biopsy of the prostate in the patient's ECT examination: all showed prostate acinar adenocarcinoma
.

Immunohistochemistry: P63 (-); CKH (-); PSA (+); P504S (+); Fig.
3 The patient's prostate cancer biopsy results Diagnosis: mHSPC with multiple lymph node and bone metastases
.

Tumor stage: T4N1M1b, high tumor/high risk; treatment plan: From September 28, 2021, the patient will be treated with goserelin + apalutamide combination
.

Efficacy evaluation: After 1 month of treatment, the patient's PSA decreased from 667.
2ng/ml before treatment to 19.
54ng/ml, a decrease of more than 97%
.

PSA decreased further and remained stable during subsequent treatment
.

Recheck PSA=2.
680ng/ml until February 26, 2022
.

Figure 4 PSA follow-up results during treatment During treatment, testosterone levels decreased progressively and remained low
.

It decreased from 5.
90ng/ml before treatment to 0.
21ng/ml after 1 month, and maintained at 0.
16-0.
13ng/ml
.

Figure 5.
Follow-up results of testosterone during treatment.
On January 6, 2022, the re-examination of MRI and MRI showed that: compared with the examination results of 2021-09-11, the scope of the lesions was significantly smaller than before
.

The metastases near the right posterior sacral foramen were smaller than the anterior film
.

The size of the prostate is slightly enlarged, about 44x34x49mm.
The structure of the central zone and the peripheral zone is unclear.
There are scattered nodules and patchy abnormal signals.
The boundary is not clear.
The structure of the bilateral seminal vesicles is unclear.
Multiple enlarged lymph nodes were seen in the bilateral inguinal region, the larger ones were about 12x17.
5 in diameter, located next to the left iliac vessels
.

A nodule about 9x13mm in size was seen in the right posterior sacral foramen
.

Multiple nodular low signals on T1WI and T2WI were seen on bilateral ilium, ischium and acetabulum
.

Figure 6 Adverse reaction management of re-examination MRI results on January 6, 2022: During the treatment process, the patient's compliance was good, the drug was well tolerated, and no serious adverse events occurred
.

Summary: PSA decreased by more than 97% after 1 month of treatment, and the prostate volume was reduced by more than half after 4 months of treatment
.

The patient is currently in good general condition, without dysuria, and in good mental state
.

Case Analysis The case is an elderly patient who was admitted to the hospital for "difficulty urinating for half a year and swelling of the left lower extremity for more than 20 days"
.

Imaging and various laboratory examinations were perfected.
After pathological examination, the diagnosis was: mHSPC with multiple lymph node and bone metastases
.

Tumor stage: T4N1M1b
.

According to the "2021 CSCO Prostate Cancer Diagnosis and Treatment Guidelines", tumor burden stratification should be performed for patients with advanced prostate cancer who have not received endocrine therapy when metastases are found
.

The patient had >4 bone metastases (>1 bone metastases outside the pelvis and spine) confirmed by imaging studies and should be classified as high tumor burden mHSPC according to the CHAARTED study
.

The final analysis of the TITAN study [1] showed that after nearly 4 years of follow-up, apalutamide combined with ADT significantly reduced the risk of death by 48% compared with ADT alone, and the 4-year survival rate was 65.
2% , Once the TITAN results were announced, apalutamide combined with ADT was quickly recommended by domestic and foreign guidelines as the standard treatment for mHSPC patients
.

The apalutamide regimen reduced the risk of developing metastatic castration-resistant prostate cancer (mCRPC) in mHSPC patients by 66%
.

At a median follow-up of 44 months, patients had not yet reached the median time to CRPC (11.
4 months in the control group)
.

Subgroup analysis showed that apalutamide treatment benefited the vast majority of mHSPC patients, and the high tumor burden group significantly prolonged overall survival (OS) and reduced the risk of death by 30% compared with the placebo group
.

In addition, apalutamide regimen treatment of mHSPC patients with bone metastases reduced the risk of death by 50%, and the risk of radiographic progression was also reduced by 62%
.

Based on the above considerations, starting from September 16, 2021, patients were given ADT + apalutamide combined therapy, and after only one month, the patient's PSA decreased from more than 667.
2ng/ml before treatment to 19.
54ng/ml, a decrease of 97%
.

In the follow-up treatment, the PSA further stabilized and continued to decline, and the re-examination PSA=2.
680ng/ml on February 26, 2022
.

During the treatment period, the testosterone level of the patients was also stably controlled
.

Testosterone decreased from 5.
90ng/ml before treatment to 0.
21ng/ml after 1 month of treatment, and maintained at 0.
16-0.
13ng/ml
.

In this case, the combined treatment of ADT and apalutamide resulted in a deep rapid decline in PSA
.

MRI re-examination 3 months after treatment showed that compared with the results of imaging examination before treatment, the range of primary tumor lesions was significantly reduced, and the prostate volume was reduced by more than half
.

The metastases near the right posterior sacral foramen were significantly smaller than before
.

It shows that the combination therapy of apalutamide + ADT brings significant imaging improvement to the patients, and the tumor control is good
.

Although the patients were old and had underlying diseases, no obvious adverse reactions occurred during the follow-up treatment of the patients, and the treatment was well tolerated, which further confirmed the good safety of apalutamide in the real world
.

Case providing expert Professor Yu Kaiyuan The Second Affiliated Hospital of Wenzhou Medical University, Deputy Director of the Department of Urology, Chief Physician, Doctoral Student Engaged in Urology for more than 20 years, from 2018.
8 to 2020.
1, served as the chief expert in the First People's Hospital of Aksu, Xinjiang, Director of the Department of Urology Zhejiang Member of the Urology Branch of the Provincial Medical Association Member of the Urology Branch of the Wenzhou Medical Association of Zhejiang Province Member of the Urology and Andrology Professional Committee of the Zhejiang Provincial Rehabilitation Medicine Association Member of the Urological Oncology Professional Committee of the Zhejiang Mathematical Medical Association The members of the bureau's expert database presided over and participated in a number of provincial, ministerial, municipal and projects, and published more than 10 expert comments on Chinese series and SCI papers as the first author or corresponding author.
In view of the popularization of early screening of prostate cancer in China, we are not satisfied
.

The early diagnosis rate is significantly lower than that of European and American countries and Japan
.

Most patients were diagnosed at an advanced stage and lost the opportunity for surgical treatment
.

Relevant studies have shown that once localized prostate cancer metastasizes, the 5-year survival rate of patients will drop to about 30%, and the progression-free survival (PFS) is less than half of that of patients with limited-stage tumors
.

Once the mHSPC patients progress to mCRPC, the treatment will be more difficult, and the prognosis of the patients will be more affected
.

Therefore, it is very important to take active and effective treatment in the early stage of mHSPC to delay the time when patients enter castration resistance as much as possible for improving the prognosis of patients
.

However, the traditional CAB regimen for the treatment of metastatic prostate cancer has extremely limited therapeutic goals.
With the release of data from the LATITUDE study in 2017 [2] and the TITAN study in 2019, both domestic and foreign guidelines have eliminated the previous recommendations for traditional CAB regimens
.

The apalutamide+ADT regimen has been unanimously recommended by international/domestic authoritative guidelines as the standard treatment regimen for mHSPC patients
.

In this case, after the use of ADT combined with apalutamide treatment, the PSA achieved a deep rapid decline, and the imaging review also suggested that the patient had obvious imaging remission
.

The excellent efficacy and reliable safety of ADT combined with apalutamide have been confirmed again in real-world treatment cases
.

It is expected that more mHSPC patients can benefit from apalutamide treatment
.

Case review expert Professor Wang Shuo Deputy Director of the Department of Urology, The First Affiliated Hospital of Zhejiang University School of Medicine, Director of the Minimally Invasive Center of Urology Surgery, Member of the Robotics Group and Deputy Secretary General of the Urology Branch of the Chinese Medical Association, Zhejiang Medical Association Expert Commentary 2, Chairman
of the Andrology Society
New endocrine therapy drugs represented by abiraterone and apalutamide continue to bring benefits to advanced prostate patients in major clinical studies, and also push the diagnosis and treatment of advanced prostate cancer in China into a new era
.

In authoritative guidelines such as EAU, NCCN and AUA, ADT + new endocrine therapy drugs have become the first-line drug treatment for mHSPC patients
.

In the TITAN study, the median time to PSA90 was only 1.
9 months, and 67% of patients could reduce PSA to ≤0.
2ng/mL, truly achieving a deep and rapid PSA decline
.

In the study, it was also confirmed that the apalutamide regimen has considerable safety and is suitable for long-term use
.

What is commendable is that the study also included the data of Chinese people, which confirmed the efficacy and safety of Chinese patients
.

Let us have some confidence in the extrapolation of the research results
.

It is precisely because of this that apalutamide has obtained the indication of mHSPC "full population" in China
.

During the diagnosis and treatment of this patient, ADT + apalutamide not only brought about a deep control of PSA and an effective decrease in testosterone levels, but also brought about obvious tumor regression, and the benefits of the above treatments are still ongoing
.

It is hoped that with the advancement of standardized diagnosis and treatment of mHSPC in the future, the excellent efficacy and good safety of apalutamide will benefit more advanced prostate cancer patients
.

Case review expert Prof.
Zhixian Er Yu, Chief Physician, Master's Tutor, Department of Urology, The First Affiliated Hospital of Wenzhou Medical University, Director of the Department of Urology, Member of the Prostate Cancer Group of the Chinese Anti-Cancer Association Urogenital Oncology Committee Member of the Urology Branch of the Chinese Medical Doctor Association (CUDA) Member of the Bladder Cancer Collaborative Group Member of the Chinese Medical Doctor Association Urology Branch (CUDA) Kidney Cancer Collaborative Group Member Vice-chairman of the first committee of the Andrology Rehabilitation Professional Committee Vice-chairman of the Minimally Invasive Group of the Zhejiang Urological Society Vice-chairman of the Urological Tumor Professional Committee of the Zhejiang Mathematical Medical Association References for members of the Society of Surgery: [1]Chi KN, Agarwal N, Bjartell A, Apalutamide for Metastatic, Castration-Sensitive Prostate Cancer.
N Engl J Med.
2019 Jul 4;381(1):13-24[2]Fizazi K , Tran N, Fein L, Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer.
N Engl J Med.
2017 Jul 27;377(4):352-360 represent the views of this platform