Case sharing Early use, more benefits!

Metastatic hormone-sensitive prostate cancer (mHSPC) is a type of metastatic prostate cancer with a better prognosis, but patients at this stage will turn into metastatic castration-resistant prostate cancer (mCRPC), and the prognosis of patients is worse
.

How to improve the prognosis of mHSPC patients and delay the onset of castration resistance has attracted much attention from the academic community
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At present, Zeke® (abiraterone acetate) has become the first-line treatment option for mHSPC and mCRPC recommended by domestic and foreign guidelines
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This time, I will bring you 2 cases from the real world for readers to communicate and discuss
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Case 1 is a 69-year-old male patient with medical history
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Main complaint: Difficulty urinating, physical examination found that the prostate is occupying space
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Past history: 5 years of symptoms of progressive dysuria, manifested as waking up 5-6 times at night
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Digital rectal examination: the mass can be reached, and the texture is nasal tip-like
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Auxiliary examination laboratory examination: total prostate specific antigen (T-PSA): 971.
93 ng/ml, combined prostate specific antigen (C-PSA)>500.
00ng/mL, carcinoembryonic antigen: 5.
42ng/mL
.

Needle biopsy pathology (September 7, 2020): 1.
(Left bottom internal test, left bottom lateral, left middle internal test, left middle lateral, left tip internal test, left tip lateral, right bottom lateral, right middle Internal test, lateral right apex) prostate cancer, Gleason score 4+4=8 points (ISUP: level 4); 2, (internal test at right bottom, lateral right, and internal right apex) prostate cancer, Gleason score 4 +3=7 points (ISUP: Level 3)
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ECT examination: multiple bone metastases are more than 3 (left maxillary area, right 11th costal joint, right sacroiliac joint, left ilium bone metabolism enhancement)
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The diagnosis result is high-risk mHSPC (T4N0M1b stage IV)
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After treatment on September 3, 2020, the T-PSA was 971.
93 ng/dl, and the patient was treated with androgen blockade therapy (ADT) + abiraterone acetate + prednisone
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October 14, 2020 (1 month after receiving ADT + abiraterone acetate + prednisone treatment): The tumor volume was significantly reduced, urination symptoms improved, and rectal compression symptoms were significantly relieved; T-PSA dropped to 9.
51ng/dl; review MRI: prostate cancer with invasion of left neurovascular bundles (NVBs), seminal vesicle invasion may be
.

Figure 1 Results of imaging examination on October 14, 2020.
April 06, 2021 (receiving ADT + abiraterone acetate + prednisone for 6 months): Symptoms improved (dysuria symptoms improved significantly than before, and the number of night urinations Increase, about 5-6 times, not much urine output, but no special discomfort)
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T-PSA decreased to 0.
06ng/dl; re-examination of MRI: the tumor volume did not change significantly from the front; re-examination of ECT: abnormally active bone metabolism in the nasopharynx, right posterior eleventh rib, and right iliac bone
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Figure 2 Results of imaging examination on April 6, 2021.
On April 12, 2021, the patient underwent endoscopic radical prostatectomy + pelvic lymph node dissection.
During the operation, it was found that the volume of the prostate tumor was significantly reduced and the seminal vesicles were atrophy
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Postoperative pathology: prostate adenocarcinoma Gleason score 4+3=7 points (ISUP: level 3), there is no cancer in the tumor capsule, the tumor tissue is scattered on both sides, and the tumor is about 10%
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After the operation, the patients continued to maintain the ADT+abiraterone acetate+prednisone regimen
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On August 1, 2021, PSA fell below 0.
03ng/ml
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Figure 3 PSA follow-up after treatment with ADT + abiraterone acetate + prednisone.
Case thinking: This patient was diagnosed with high-risk mHSPC.
The patient was first treated with ADT + abiraterone acetate + prednisone.
The symptoms improved and PSA decreased significantly
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Six months later, the patient underwent laparoscopic radical prostatectomy + pelvic lymph node dissection + pelvic adhesion lysis + laparoscopy
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After the operation, the ADT+abiraterone acetate+prednisone regimen was continued, and the T-PSA fell below 0.
03ng/ml
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Abiraterone acetate is a new type of endocrine therapy drug, which can completely inhibit the CYP17 enzyme, completely block the production of testosterone and continue to eliminate the "fuel" of prostate cancer tumor progression 1-3
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The results of the LATITUDE study show that early application of abiraterone acetate in the mHSPC stage can bring better clinical benefits: compared with the control group (placebo + ADT), the experimental group (abiraterone acetate + prednisone + ADT) The median OS was significantly prolonged (53.
3 months vs 36.
5 months), and the risk of death was reduced by 34%; the median imaging progression-free survival (rPFS) was extended to 33 months, and the risk of progression was reduced by 53%4,5
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Figure 4 LATITUDE research results LATITUDE post-hoc analysis found that the abiraterone acetate-based program can allow more high-risk mHSPCs to achieve high PSA reduction, and the lowest median PSA value is lower6
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Figure 5 LATITUDE post-hoc analysis results Case provider: Prof.
Song Chao, expert profile Prof.
Song Chao, deputy director of the Second Department of Urology, Wuhan University People’s Hospital, deputy chief physician, double Ph.
D.
from Queen’s University and Sichuan University West China Medical Center, Chinese Medical Association Laser Medicine Committee Member, Hubei Province Integrated Traditional Chinese and Western Medicine Andrology Branch Member, Hubei Provincial Medical Association Urology Branch Committee Member, International Urolithiasis Federation Youth Committee National Health Industry Business Management Association Translational Medicine Industry Branch (CCTMlS) Urinary Stone Prevention Expert Committee Standing Committee Comment ( Wu Tianpeng) Among the newly diagnosed mHSPC patients in China, there are a high proportion of high-risk factors such as more than 3 bone metastases, high Gleason score, and high PSA level
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Due to the limited clinical benefits of combined androgen blockade (CAB) compared to ADT alone, neither the EAU guidelines nor the NCCN guidelines recommend CAB as a routine treatment for high-risk mHSPC
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In this case, after the patient was diagnosed as a high-risk mHSPC patient, the new endocrine drug abiraterone acetate was used as the first-line treatment.
Positive rate of resection margin)
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The patient continued to receive new endocrine therapy after the operation, the condition improved, and the PSA has been maintained at a low level
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In the follow-up treatment, we still need to continue to pay attention to PSA.
The lower the minimum PSA value of the patient, the better the prognosis will be, and the patient is expected to have a better survival period
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Reviewer: Professor Wu Tianpeng Expert Profile Professor Wu Tianpeng Doctor of Medicine, Chief Physician of Urology, Wuhan People's Hospital, Master's Tutor, Member of the Male Reproductive Committee of the Chinese Society of Sexual Medicine, Member of the Male Reproductive Committee of the Chinese Society of Integrative Medicine, Member of the Andrology Branch of the Chinese Society of Integrative Medicine, Member of the Urology Professional Committee of the Chinese Medical Association Standing Committee Member of the Urogenital Branch, Standing Committee Member of Hubei Provincial Sexual Society, Deputy Chairman, Hubei Provincial Medical Association Andrology Branch, Deputy Chairman, Hubei Province Integrated Traditional Chinese and Western Medicine Andrology Branch, Case 2 Male with medical history, 76 years old
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Main complaint: Lower urinary tract symptoms such as frequent urination, urgency, dysuria, etc.

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CT examination of the urinary system: prostate cancer is associated with lymph node metastasis, and the possibility of bone metastasis is high
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Auxiliary examination laboratory examination: PSA: 75ng/mL
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MRI: prostate cancer with invasion of the bladder, seminal vesicle gland, anterior rectum, and pelvic floor, multiple metastases in the pelvic cavity and retroperitoneal lymph nodes, multiple bone metastases
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ECT: T10, abnormal radioactivity distribution in the right sacroiliac joint and the fifth anterior rib on the left, considering the possibility of bone metastasis (3 bone metastases)
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Pathological biopsy: Gleason score of prostate adenocarcinoma 5+3=8 points
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Diagnosis results First diagnosis (September 2020): mHSPC, cT4N1M1b
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Second diagnosis (February 2021): mCRPC
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After the treatment in September 2020, the PSA was 75ng/ml, and then the original abiraterone acetate regimen was first recommended, but due to the patient's own economic reasons, the CAB regimen was finally used
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In December 2020, patient review: PSA dropped from 75ng/ml to 2.
24ng/ml, which did not reach the ideal value; testosterone was 0.
13ng/ml, reaching the castration level
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After admission in February 2021, testosterone was found to be castrated, PSA significantly increased to 19.
2ng/ml, whole body bone scan revealed multiple bone metastases throughout the body (more than or equal to 2 new lesions), and there was bone related bone pain such as paraplegia In the event, consider the patient's progression from the mHSPC stage to the mCRPC stage; switch to the original abiraterone acetate + prednisone + ADT regimen
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Figure 6 Patients with PSA level after CAB regimen were switched to the original abiraterone acetate + prednisone + ADT regimen for 2 months.
The symptoms of bone pain were relieved and the lower limbs recovered consciousness
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Case thinking This patient was diagnosed with mHSPC for the first time.
After using the CAB protocol, the disease progressed and PSA was significantly increased.
The bone scan revealed more than 2 new bone metastases, and there were bone-related events such as paraplegic bone pain, which was converted to mCRPC.
Switching to the original abiraterone acetate + prednisone + ADT regimen, the patient's bone symptoms were relieved and the lower limbs recovered consciousness
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For patients with high-risk mHSPC, traditional endocrine therapy will progress to mCRPC7 in a relatively short period of time
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After conventional endocrine therapy is ineffective, patients will face problems such as disease progression, reduced quality of life, and shortened survival time8
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When the patient enters the mCRPC stage with spinal metastasis and paraplegia, what should be the next treatment? A Canadian RCT study found that: mCRPC first-line abiraterone acetate and second-line enzalutamide significantly prolonged the progression of PSA in patients and provided patients with more treatment possibilities9
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The combination of two new endocrine therapies with different mechanisms did not bring additional benefits and decreased PSA10
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Figure 7 RCT study results AQUARiUS prospective study showed that among the adverse events reported by mCRPC patients, the proportion of abiraterone acetate fatigue and deterioration of cognitive impairment was significantly lower than that of enzalutamide group11
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Figure 8 AQUARiUS study results Case provider: Prof.
Li Jin expert profile Prof.
Li Jin, chief physician, director of urology department of Xiangtan Central Hospital, a doctoral student of Central South University, vice chairman of Hunan Traditional Chinese Medicine and Urology Committee of the Integrative Medicine Society of Hunan Province Medical Association Member of the Andrology SocietyMember of Hunan Urinary and Male Reproductive Tumor Association The vice chairman of the Andrology Committee, Xiangtan Medical Association, commented (Wang Yinhuai) Traditional endocrine therapy for high-risk mHSPC patients, and the median failure-free survival time is less than 1 year 12
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Delaying metastasis and delaying castration resistance are important treatment strategies for prostate cancer
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The guidelines recommend apatamide to delay the progression of mHSPC and NM-CRPC to mCRPC8
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Among them, for patients with high-risk mHSPC, new endocrine therapy should be used earlier in clinical practice
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The patient in this case gave up the original abiraterone acetate regimen after being diagnosed as high-risk mHSPC for the first time, the disease progressed rapidly, and was subsequently diagnosed as mCRPC
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The EAU guidelines (2020) point out that the diagnosis of mCRPC needs to be met: serum testosterone reaches the castrated level (<50ng/dl or 1.
7nmol/L) + 3 consecutive PSA rises at an interval of 1 week or more, and two consecutive increases of 50% from the lowest value Above, and PSA>2 ng/L or two or more new bone scan lesions appear, or new soft tissue lesions appear according to RECIST standards13
.

For the treatment of mCRPC patients, how can we "remedy the situation"? Studies have confirmed that compared with placebo + prednisone, mCRPC patients receiving abiraterone acetate + prednisone treatment significantly prolonged the median survival to 34.
7 months and reduced the risk of death by 19% (HR=0.
81, P=0.
0033) 14
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In addition, studies have found that abiraterone acetate + prednisone significantly delays the progression of tumor imaging metastasis, bone destruction and pain deterioration 15
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After the case was converted to mCRPC, he switched to the original abiraterone acetate+prednisone+ADT regimen for 2 months and the bone symptoms were relieved, and the lower limbs recovered consciousness
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Therefore, it is emphasized that patients in the mCRPC stage should use abiraterone acetate as soon as possible to prolong survival and delay progression
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Commenting expert: Prof.
Wang Yinhuai Expert Profile Prof.
Wang Yinhuai Chief Physician Professor Doctoral Supervisor Director of Department of Urology, Xiangya Second Hospital of Central South University Director of Minimally Invasive Urology Clinical Research Center of Hunan Province Member of Urology Branch of Chinese Medical Association Member of Urology Branch of Chinese Medical Doctor Association Member of the Andrology and Sexual Medicine Branch of the Chinese Physician AssociationDeputy Chairman of the Urology Committee of the Hunan Medical Association Standing Committee Member of the Urology Professional Committee of the Chinese Research Hospital Association Member of the International Urolithiasis Federation Member of the World Chinese Andrologist Association Member of the Editor's Handbook For the treatment of high-risk mHSPC and mCRPC patients, the efficacy and safety of Zeke® (abiraterone acetate) have been obtained Widely recognized clinically
.

The above two cases remind us that abiraterone should be used as soon as possible for the treatment of mHSPC and mCRPC patients, especially mHSPC patients, so as to delay the progression of the disease and give patients a chance of long-term survival
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