PSA deep and rapid decline, OS for a long time "K" period, advanced prostate cancer with multiple bone metastases, apalutamide + ADT brings PSA deep response, long-term tumor control effect is obvious classic case

*For reference only for medical professionals This case is an elderly patient with metastatic hormone-sensitive prostate cancer (mHSPC) with multiple bone metastases
.

The patient was treated with apalutamide + androgen deprivation therapy (ADT) for only 1 month, and the patient's prostate-specific antigen (PSA) decreased by as much as 99.
8%, with a deep PSA response
.

During subsequent treatment, the patient's PSA further decreased and stabilized between 0.
048-0.
021ng/ml
.

The patient has been receiving drug therapy for 6 months and is still being followed up
.

Patients with combination therapy strategy achieved deep PSA response, and sustained tumor remission brought new hope to patients
.

Case Review Basic information: The patient was 86 years old and was admitted to hospital for "sacrococcygeal pain for more than 7 months"
.

Diagnosis and treatment process: The patient developed severe pain in the sacrococcygeal region without obvious incentive more than 7 months ago, and was immediately admitted to the hospital for examination
.

On digital rectal examination, the prostate gland was significantly enlarged, and the lobes on both sides were firm in texture
.

PSA: 309.
228ng/ml, Free PSA (F-PSA): 35.
26ng/ml
.

MRI examination revealed diffuse enlargement of the prostate, multiple nodules on both sides of the lobe, and invasion of bilateral seminal vesicles and the posterior wall of the bladder neck
.

There were multiple enlarged lymph nodes adjacent to bilateral internal iliac vessels and obturator vessels, and several enlarged lymph nodes on the left side of abdominal aorta
.

Prostate biopsy on September 1, 2021: (one needle for each of the left and right lobes of the prostate) prostate acinar adenocarcinoma (Gleason score: 4+5=9, grade group: 5), tumor burden is 100%
.

Figure 1 Results of prostate biopsy on September 3, 2021.
PET-CT examination showed that there were multiple proliferative bone metastases in the T3 vertebral body, the right pedicle of T10 and the sacrum, and the bone metabolism was active.
Considering the possibility of bone metastases
.

The axillary segment of the second rib on the right and the metabolically active foci of the anterior rib on the seventh rib on the left were considered as possible bone metastases
.

The bone metabolism active foci on the right side of the lumbar 3 vertebral body and the thoracic 6 vertebral body are not excluded
.

Fig.
2 Diagnosis of PET-CT examination results: mHSPC with multiple bone metastases
.

Tumor stage: T4N1M1b, high risk/high tumor burden
.

Treatment plan: From September 4, 2021, the patient started to use ADT + apalutamide 240mg QD combination therapy
.

Efficacy evaluation: After 1 month of treatment, the patient's PSA decreased from 309.
228ng/ml before treatment to 0.
91ng/ml on October 13, 2021, a decrease of 99.
8%, and the PSA was in deep response
.

PSA decreased further and stabilized between 0.
048-0.
021 ng/ml during subsequent treatment
.

She has been treated for 6 months and is still being followed up
.

Figure 3 Adverse reaction management of PSA follow-up results during treatment: During the treatment period, the patient only experienced mild gastrointestinal discomfort
.

It gradually improved and the treatment was well tolerated
.

Case analysis The case is an elderly male patient who was admitted to hospital for "sacrococcygeal pain for more than 7 months"
.

On digital rectal examination, the prostate gland was significantly enlarged, and the lobes on both sides were firm in texture
.

Admission PSA: 309.
228ng/ml, free PSA (F-PSA): 35.
26ng/ml
.

After biopsy and PET-CT examination, the diagnosis was: mHSPC with multiple bone metastases
.

Tumor stage: T4N1M1b, high risk/high tumor burden
.

According to the "2020 CSCO Prostate Cancer Diagnosis and Treatment Guidelines", ADT alone is not recommended for mHSPC patients with high tumor burden, but a combination therapy should be given early
.

Therefore, according to the guideline, patients should be given ADT + apalutamide 240mg QD combination therapy from September 04, 2021
.

After only 1 month of treatment, the patient's PSA decreased from 309.
228ng/ml before treatment to 0.
91ng/ml on October 13, 2021, a decrease of 99.
8%, and a deep PSA response
.

PSA decreased further and stabilized between 0.
048-0.
11 ng/ml during subsequent treatment
.

She has been treated for 6 months and is still being followed up
.

During the treatment, the patient's sacrococcygeal pain symptoms were significantly relieved, and the urination condition was significantly improved
.

In the treatment of this real-world elderly mHSPC patient, it can be seen that the combination of ADT and apalutamide brought a significant PSA decrease and sustained control to the patient
.

During the patient's treatment, the symptoms related to bone metastases and primary lesions were significantly improved, highlighting the excellent efficacy and safety of ADT + apalutamide combination therapy
.

Compared with prostate cancer patients without metastasis, the 5-year survival rate of patients with distant metastasis was significantly lower, and the progression-free survival time was only half of that of patients without metastasis
.

Therefore, how to prolong the time for patients to progress from mHSPC to metastatic castration-resistant prostate cancer (mCRPC) and prolong survival is the main goal of the treatment of such patients
.

As a new generation of androgen receptor inhibitor (ARi), apalutamide has better binding affinity to AR and better antitumor activity
.

The final analysis of the TITAN study[1] presented at the 2021 American Society of Clinical Oncology Symposium on Genitourinary Oncology (ASCO-GU 2021) showed that apalutamide plus ADT significantly reduced the risk of cancer by 48% compared with ADT alone.
The 4-year survival rate was 65.
2%
.

OS was 52.
2 months (P<0.
0001) and not reached (control vs apalutamide), respectively
.

Since 40% of patients in the control group were cross-enrolled to receive apalutamide after the first interim analysis, if the factor of later cross-enrollment was excluded, the median OS of mHSPC patients who received ADT alone was only 39.
8 months
.

Therefore, the combination therapy based on apalutamide + ADT brings good survival benefit to patients
.

Case Provided Expert Profile Professor Di Jinming Director, Chief Physician, Doctoral Supervisor of Urology Department of the Third Affiliated Hospital of Sun Yat-sen University Member of the Robotics and Minimally Invasive Group of the Branch Chairman of the Minimally Invasive Urology Oncology Committee of the Guangdong Provincial Primary Medicine Association Vice Chairman of the Oncology Branch of the Guangdong Genitourinary Association Vice Chairman of the Andrology Branch of the Guangdong Genitourinary Association Deputy Director of the Lower Urinary Tract Disease Special Committee of the Society, Corresponding Editor of the Chinese Journal of Urology, Deputy Director of the Editorial Department and Editorial Board of the Chinese Journal of Endoscopic Urology (Electronic Edition) Its incidence ranks first in male malignant tumors in the world
.

In China, the incidence of prostate cancer is increasing at an annual rate of 2.
75%.
Epidemiological data in 2020 show that prostate cancer has become the sixth most common malignant tumor in men in China, seriously threatening men's health
.

However, the screening and early diagnosis of prostate cancer has not been fully popularized in China, and the early diagnosis rate is significantly lower than that of European and American countries
.

Despite the continuous iteration of anti-tumor treatment methods, more than 70% of advanced prostate cancer patients still develop bone metastases and bone-related events (SREs) caused by bone metabolism disorders
.

SREs not only reduce the quality of life of patients, but also increase the economic burden and mortality of patients
.

Active treatment of the primary disease is an important prerequisite for solving bone metastases and bone-related diseases
.

Therefore, how to take active and effective treatment in the early stage of mHSPC, reduce the symptoms of patients with bone metastases, control the metastatic lesions, and delay the time of castration resistance in patients is very important for improving the prognosis of patients
.

The 2019 TITAN study data was published for the first time, and new endocrine therapy (NHA) showed excellent efficacy and safety in the treatment of mHSPC patients
.

At 2021 ASCO-GU, the final analysis results of the TITAN study were announced.
After nearly 4 years of follow-up, apalutamide combined with ADT can significantly reduce the risk of death by 48% compared with ADT alone, and the 4-year survival rate is 65.
2%.

.

The combined regimen brought significant survival benefits to patients in the treatment of mHSPC
.

At present, the domestic and international authoritative guidelines for the diagnosis and treatment of prostate cancer all recommend the use of ADT + apalutamide drug combination therapy in the treatment of mHSPC patients, and the combination therapy regimen has become a consensus
.

After receiving ADT + apalutamide treatment, this patient had a deep response of PSA, which decreased by 99.
8% in only one month, and maintained a very low level in the follow-up treatment
.

The patient's bone metastases resulted in significant relief of sacrococcygeal pain.
The excellent efficacy and reliable safety of ADT + apalutamide treatment were well reflected in the treatment of this patient
.

At present, the patient has been continuously followed up for more than 6 months, and it is expected that the combination therapy with apalutamide will bring more survival benefits to the patient in the future
.

Case Comments Expert Profile-Professor Liao Hong Vice President of Sichuan Cancer Hospital, Chief Physician of Urology Department, Master Supervisor Member of the Prostate Cancer Expert Committee of the Chinese Society (CSCO) Member of the Prostate Cancer Group of the Urogenital Oncology Committee of the China Anti-Cancer Association Member of the Prostate Cancer Group of the Sichuan Anti-Cancer Association Urogenital Oncology Committee Deputy Director of the Urology Committee of the Sichuan Geriatrics Association Chairman of the Association Deputy Chairman of the Urology Specialized Committee of the Sichuan Rehabilitation Medical Association Member of the Urology Specialized Committee of the Sichuan Medical Association Deputy Head of the Urology Oncology Group of the Sichuan Medical Association Member of the Urology Branch of the Sichuan Medical Association Member of the Management Committee, Member of the Urology Branch of Chengdu Medical Association, Deputy Head of the Advanced Renal Cancer Group, and Expert Commentary on the Editorial Board of JCO-Urinary and Male Genital Tumors The traditional CAB regimen of calutamide, flutamide) combined with ADT has been the main treatment method for the treatment of metastatic prostate cancer
.

However, relevant studies have confirmed that there is almost no difference in the survival benefit of patients with CAB regimen and ADT alone
.

As the second-generation ARi represented by apalutamide is widely used in clinical practice, major international and domestic authoritative guidelines no longer recommend CAB as a long-term treatment for mHSPC
.

For patients with mHSPC, the mCRPC stage usually occurs soon after PSA progression, and mCRPC is the terminal stage of prostate cancer disease development with a significantly increased risk of disease progression and death
.

Therefore, delaying the progression of mHSPC into mCRPC and improving the quality of life of the patients are the two most important goals in the treatment of mHSPC patients
.

Data from the TITAN study showed that when PSA progression occurred at a median of 12.
9 months in the placebo group, the apalutamide group did not achieve PSA progression at a median follow-up of 44 months, significantly reducing the risk of PSA progression by 74%
.

PSA is a convenient, rapid, and easily monitored indicator of disease progression, and the importance of apalutamide has been confirmed by numerous studies and clinical practices
.

Apalutamide can rapidly, deeply and lastingly reduce PSA decline in prostate cancer patients, which is of great value for long-term survival benefits
.

A post hoc analysis of the TITAN study also found that patients with a PSA of 0.
2 ng/mL had an 83% lower risk of death compared with those who did not (HR 0.
17, P < 0.
0001)
.

The Gleason score in the pathological examination of the above patients reached 4+5=9 points, and only one month after receiving the combination therapy, the PSA decreased rapidly by 99.
8%, and maintained a very low level (<0.
2ng/ml) in the follow-up treatment.

.

Currently, the patient continues to have stable PSA control at follow-up lasting more than 6 months
.

It fully reflects the good efficacy of the apalutamide combination therapy strategy for mHSPC patients with high Gleason score, and the corresponding mHSPC patients will also significantly delay disease progression and significantly prolong their survival
.

It also significantly prolongs the time for patients to progress to mCRPC, winning the hope of "long survival" for patients
.

TITAN study: apalutamide reduces the risk of mHSPC conversion to mCRPC by 66%
.

Apalutamide does not need to be used with glucocorticoids during the medication process to avoid adverse reactions caused by long-term use of glucocorticoids; such as: hypertension, hyperglycemia, stress ulcers, osteoporosis, low immunity, etc.
etc.
, which results in a better quality of life for patients and easier long-term management of patients
.

Data from the final analysis of the TITAN study were included in a meta-analysis that systematically compared the efficacy of multiple mHSPC treatment modalities
.

A total of 17,641 patients from 18 randomized controlled trials were included in the study
.

The results showed that apalutamide can reduce the risk of death by 50% in patients with prostate cancer with bone metastases
.

In terms of improving the overall survival (OS) and failure-free survival (FFS) of patients, the combination of apalutamide and ADT with the highest probability of treatment effect (OS: 92.
9%; FFS: 68.
0%)
.

And in the treatment comparison of apalutamide, abiraterone, and enzalutamide, the treatment effect of apalutamide + ADT in improving OS and FFS of the general population and different subgroups is the most prominent
.

Therefore, if objective conditions allow, apalutamide + ADT as a common clinical treatment for mHSPC is expected to bring more survival benefits to patients
.

Case Comments and Expert Profile II Prof.
Liu Xiaodong Deputy Director, Chief Physician, Doctoral Supervisor, Department of Urology, The First Affiliated Hospital of Kunming Medical University, Chief Physician, Doctoral Supervisor, Postdoctoral Fellow in Urology Pathology Chief MDT Expert of Urological Tumors, The First Affiliated Hospital of Kunming Medical University China Anti-Cancer Society Member of the Urological and Male Genital Tumors and Kidney Cancer Group Member of the Urology Professional Committee of Chinese Integrative Medicine Committee Member of the Urology Branch of the China Research Hospital Association Deputy Director of the Urology Branch of the Provincial Anti-Cancer Association Member of the Yunnan Provincial Hospital Association Urology Management Committee Member of the Ministry of Health Urology Specialist Access Expert Committee Member of the Yunnan Provincial Medical Malpractice Expert Library Member American Urological Society Member International Continence Society Member References: [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*This article is only used to provide scientific information to medical professionals and does not represent the views of this platform