Patients with mHSPC with multiple metastases and high tumor burden were treated with apalutamide-based regimen, and their PSA levels were rapidly and deeply reduced, with significant efficacy. Case 1 in this article is an elderly mHSPC with a high tumor burden, a Gleason score of

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Patients with mHSPC with multiple metastases and high tumor burden received apalutamide-based treatment, and their PSA levels were rapidly and deeply reduced, with significant efficacy.

The cases in this article were selected from a real-world study of apalutamide treatment at Yantai Yuhuangding Hospital. This study enrolled 41 patients, 31 of whom were patients with metastatic hormone-sensitive prostate cancer (mHSPC), who received apalutamide + androgen stripping. After ADT treatment, the median time for prostate-specific antigen (PSA) to decrease by ≥90% was only 1.3 months (the median time for PSA to decrease by ≥90% in the TITAN study was 1.9 months), and patients with bone pain were relieved very quickly.

Case 1 in this article is an elderly mHSPC with high tumor burden (T3aN1M1b), Gleason score 9, multiple metastases throughout the body, and was treated with goserelin + apalutamide + denosumab. After 30 days of treatment, the PSA dropped from 874 ng/ml to 3.4 ng/ml, and the PSA dropped by more than 90%. After 3 months of treatment, the PSA dropped to 0.2 ng/ml or less, the overall safety is good, and follow-up is ongoing. Case 2 is an elderly male patient who was diagnosed with mHSPC with high tumor burden (T4N1M1b) and a Gleason score of 9. He received goserelin + apalutamide + denosumab treatment. After 2 months of treatment, the PSA dropped to less than 0.2 ng/ml, and after 5 months, the PSA dropped to less than 0.02 ng/ml and continues to be followed up. A rash occurred during this period, but was effectively relieved about 1 month after the intervention.

Case 1 review: High tumor burden mHSPC

▌ Medical history information

The patient is a 71-year-old male who was admitted to the hospital on March 30, 2022. A physical examination 2 weeks ago found that the PSA reached 711ng/ml, and the current PSA is 8 74ng/ml (March 30, 2022). The prostate MRI examination showed abnormal prostate signals and was highly suspected of prostate cancer. Multiple enlarged lymph nodes were displayed in the bilateral inguinal area and around the bilateral iliac vessels. The pelvic bone signal was uneven. ECT examination was recommended for early external metastasis.

▌ Diagnosis and treatment experience

Based on the prostate MRI examination results, B ultrasound guided transperineal prostate puncture biopsy was performed on March 31, 2022. The puncture result was a Gleason score of 9 points;

ECT examination results: multiple metastases throughout the body, with more than 10 metastases;

▌ disease diagnosis

The patient was diagnosed with high tumor load mHSPC (T3aN1M1b);

▌ treatment plan

goserelin 10.8mg + apalutamide 240mg/qd + desulfate Monoclonal antibody 120mg, apalutamide use time April 11, 2022;

▌ efficacy evaluation

30-day review of PSA on May 11, 2022: from 874 ng/ml dropped to 3.4 ng/ml, and the PSA dropped by more than 90%;

continued to follow up on PSA and took medication for 3 months, and PSA dropped below 0.2 ng/ml, and continued to follow up;

Figure 1 PSA changes

Case 2 review:

High tumor load mHSPC, rash management

▌ Medical history information

71-year-old, elderly male, frequent urination3 months, found pelvic mass occupied for 7 days, admitted to the hospital as "prostate malignant tumor" in the outpatient department on February 28, 2022, PSA: 915ng/ml

▌ After the diagnosis and treatment

7 days ago, the MR from the hospital showed: a huge space in the pelvis, which is considered to be prostate cancer combined with invasion of the bladder, bilateral seminal vesicles, , and the rectum; a space in the back of the right pelvic side with invasion of surrounding muscles, considered to be a metastasis; multiple enlarged lymph nodes in the pelvis and bilateral inguinal areas, and multiple abnormal bone signals are considered to be transferred Migration;

The Gleason score of the puncture result on March 31, 2023 was 9 points;

ECT examination results: abnormal radioactive concentration was visible in the upper segments of the bilateral femurs, left ischium , left sacroiliac joint and left 9th posterior rib;

▌ Disease diagnosis

The patient was diagnosed with high tumor Loaded mHSPC (T4N1M1b);

▌ treatment plan

goserelin 10.8 mg + apalutamide 240 mg/qd + denosumab 120 mg apalutamide usage time March 16, 2022;

April 20, 2022, the patient's 34-day review PSA results: from 915 ng/ml dropped to 1.09 ng/ml, and PSA dropped by more than 90%, reaching PSA90 ng/ml;

▌ Efficacy evaluation

After 2 months of follow-up PSA medication, PSA dropped to less than 0.2 ng/ml, and 5 months later, PSA dropped to less than 0.02 ng/ml and continues to be followed up;

Figure 2 PSA changes

The patient's family reported on June 6 that the patient had a rash on his back and lower limbs for more than 10 days. It was less at first and then increased significantly 2 days ago, with itching.

According to the rash classification, the patient's rash was upgraded to grade three. The treatment plan is: oral cetirizine (1 tablet in the morning) ± ebastine (1 tablet in the evening) + topical mometasone furoate cream (ailosone), for one week There was no improvement after that, so the patient was switched to 10 mg prednisone bid + topical mometasone furoate cream. The patient's rash was relieved within two weeks. The prednisone dose was gradually reduced and the drug was gradually discontinued + topical mometasone furoate cream. After one month, the rash was completely relieved, and prednisone and mometasone furoate cream were stopped. The patient is still under follow-up.

case analysis

Case 1 is an elderly mHSPC with high tumor burden (T3aN1M1b), with a Gleason score of 9, multiple metastases throughout the body, and more than 10 metastases. Tumor burden is a key factor in determining the prognosis and treatment options of mHSPC patients. The time and OS of mHSPC patients with high tumor burden to progress to castration-resistant prostate cancer (CRPC) are significantly shorter, and active treatment is required. The patient received goserelin + apalutamide + denosumab treatment. After 30 days of treatment, the PSA dropped from 874 ng/ml to 3.4 ng/ml. The PSA dropped by more than 90%. After 3 months of treatment, the PSA dropped to less than 0.2 ng/ml. The patient is currently being followed up. It is suggested that apalutamide can bring benefits to mHSPC with high tumor burden and has good safety profile.

Case 2 is an elderly male patient. When he was admitted to the hospital for "malignant prostate tumor", his PSA was 915ng/ml. The patient was diagnosed with high tumor load mHSPC (T4N1M1b), GLeas. On score was 9 points, and abnormal radioactive accumulation was seen in the upper femoral segments, left ischium, left sacroiliac joint, and left 9th posterior rib. The patient received goserelin + apalutamide + denosumab treatment. The patient's PSA was reviewed after 34 days of treatment. From 915 ng/ml dropped to 1.09 ng/ml, and PSA dropped by more than 90%, reaching PSA90. After taking the medicine for 2 months, the PSA dropped to below 0.2 ng/ml, and after 5 months of medication, the PSA dropped to below 0.02 ng/ml and the patient is still being followed up. Three months later, the patient developed grade three rash. After symptomatic treatment, the patient's rash was completely relieved in more than a month and is currently being followed up. Doctors and patients are reminded to actively intervene starting from mild rashes, pay more attention to patients, and seek medical treatment immediately if they experience any discomfort to avoid secondary severe rashes. However, it is generally preventable and curable.

▎ Expert comment 1: Patients with mHSPC with high tumor burden can benefit from apalutamide

The two cases in this article are both patients with mHSPC with high tumor burden, which are characterized by multiple metastases. Once metastasis occurs in prostate cancer, the risk of disease progression and death is greatly increased. Specific studies have shown that for prostate cancer patients with distant metastasis, the 5-year relative survival rate is reduced to 30%, and the median progression-free survival (PFS) is only half of that of patients without metastasis.[1,2]. Tumor burden is a key factor in determining the prognosis and treatment options of patients with mHSPC. The time to progression to CRPC and overall survival (OS) of patients with high tumor burden mHSPC are significantly shorter. The treatment goal is to prolong the time for the disease to progress to CRPC, thereby prolonging OS. The

TITAN study shows that apalutamide, as a new androgen receptor inhibitor, can significantly delay disease progression and reduce the risk of death in patients with mHSPC without adding additional adverse event burden. At the same time, the TITAN study also confirmed the benefit of the apalutamide regimen for "all types" of mHSPC patients, including newly diagnosed high- and low-tumor mHSPC and patients who have been previously treated and are still in the mHSPC stage.[3]. In the TITAN study, subgroup analysis of OS showed that apalutamide can bring obvious or even significant therapeutic benefits to patients with various types of mHSPC. Among them, apalutamide can significantly reduce the risk of death by 30% in patients with high tumor burden, and by 48% in patients with low tumor burden. Apalutamide can significantly reduce the risk of death by 50% in patients with only bone metastasis at initial diagnosis.

Therefore, apalutamide-based treatment is a suitable treatment for these two patients with high tumor burden. Studies suggest that the lower the PSA nadir, the longer the disease, the lower the risk of progression to mCRPC, and the greater the survival benefit. After using apalutamide-based treatment regimen, patients' PSA decreased by more than 90%, suggesting that apalutamide-based treatment regimen is a good choice for delaying the progression of mHSPC.

▎ Expert comment 2: Apalutamide has stable and reliable safety data, but it is necessary to improve patients’ self-management awareness

Judging from clinical research data [3], in terms of adverse event (AE) data, apalutamide does not increase the incidence of treatment-related adverse events (TEAE) in patients as a whole. Whether it is the overall AE incidence or the incidence of grade 3 to 4 AEs, apalutamide is consistent with the control group. Common AEs of apalutamide, such as rash, are mostly grade 1-2, indicating that apalutamide has a good safety profile. It was also observed in long-term follow-up that apalutamide treatment did not increase the risk of decreased quality of life in patients.

Table 1 Adverse events of apalutamide

The overall safety of case 1 in the article was good after taking the drug, but case 2 developed a grade three rash, but it was overall controllable after treatment. The exposure of apalutamide and N-desmethylapalutamide is significantly correlated with rash and weight loss, and it is possible to effectively control the rash by reducing the dose; relevant studies suggest [4] that about 21% of patients in the apalutamide group had dose adjustments due to AEs, and the average daily dose was 209 mg. The dose adjustment did not affect the plasma concentration of APA and its active metabolites; dose reduction/interruption of administration to manage adverse events is not expected to reduce the efficacy of apalutamide.

Looking back on the patient’s experience of developing rash, it is actually possible to avoid developing it into grade three. When mild itching and a little rash initially occurred, the patient did not pay attention, and then a third-grade rash developed. This reminds clinicians and patients that rashes of any grade cannot be ignored. Patients should be educated and paid more attention to, and active intervention should be initiated from mild to early intervention to avoid secondary severe rashes.

case provides expert introduction:

Wu Jitao Professor

Yantai Yuhuangding Hospital

  • Director of the Department of Urology and Deputy Director of the General Surgery Department of Yantai Yuhuangding Hospital,

  • MD, chief physician, master's degree tutor,

  • Taishan Scholar Young Expert,

  • Chinese Medical Doctor Association Young Committee on Men's Surgery,

  • Youth Vice Chairman of the Urology Branch of Shandong Provincial Medical Association,

  • Youth Vice Chairman of the Organ Transplantation Society of Shandong Provincial Medical Association.

  • presided over 2 National Natural Science Foundation of China general projects, 5 scientific research fund projects of Shandong Provincial Health and Family Planning Commission and Department of Science and Technology, won 1 third-class Science and Technology Progress Award of the Chinese Medical Association, two second-class Science and Technology Progress Awards of Shandong Province, and published more than 30 SCI papers.
  • In 2016-2017, Cleveland Medical Center (Cleveland) ranked first in urology in the United States. Clinic) as a postdoctoral visiting scholar for 1 year,

  • focusing on robotic minimally invasive surgery in urology and the diagnosis and treatment of prostate cancer and renal tumors.

Comments from experts:

Professor Qi Lin

  • Central South University Professor, Chief Physician, Doctoral Supervisor of the First "Xiangya Famous Doctors"

  • Director of the Institute of Urology, Central South University

  • Deputy Chairman of the Urology Branch of the Chinese Medical Association

  • Leader of the Laser Group of the Urology Branch of the Chinese Medical Association

  • Academic Leader of the National Key Clinical Specialties of the National Health Commission

  • Standing Member of the Urological and Male Reproductive System Tumors Professional Committee of the Chinese Anti-Cancer Association

  • Hunan Expert Group of the National Health Commission Urology Surgeon Admission Expert Committee Team leader

  • Chairman of the Urology Professional Committee of the Hunan Provincial Medical Association

  • Leader of the Oncology Group of the Urology Professional Committee of the Hunan Provincial Medical Association

  • Chairman of the Urology and Male Reproductive System Tumors Professional Committee of the Hunan Anti-Cancer Association

  • Hunan Provincial Urology Director of the Medical Quality Control Center for Surgical Diseases

  • Winner of the 2015 " Wu Jieping Urological Medicine Award "

  • Winner of the 2019 "Huatuo Award" of the Urology Branch of the Chinese Medical Association

  • Director of the Institute of Urology, Central South University

  • 《 International Journal of Urology " Chief Editor, " Modern Journal of Urology " Deputy Editor, " Chinese Journal of Urology " Standing Editorial Member

Comments from Expert Two Introduction:

Professor Wang Shaogang

Chief Physician, Doctoral Supervisor

  • Director of the Department of Urology, Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology Director of the Department of Urology

  • Standing Committee Member of the Urology Branch of the Chinese Medical Association

  • President of the Urology Branch of the Chinese Geriatrics Society

  • Vice President of the Urology Branch of the Chinese Medical Equipment Association

  • Graduate of the Chinese Medical Doctor Association Deputy Chairman of the Professional Committee of Post-professional Education Urology

  • Standing Committee of the Medical Robotic Physician Branch of the Chinese Medical Doctor Association

  • Standing Committee of the Laparoscopic and Robotic Surgery Branch of the Chinese Anti-Cancer Association

  • Chairman of the Andrology Branch of the Hubei Provincial Medical Association

  • Director-elect of the Urology Branch of the Hubei Provincial Medical Association Member

  • Deputy Chairman of the Urology Branch of Hubei Medical Association

  • Director of Hubei Province Urological Surgery Minimally Invasive Treatment Clinical Medical Research Center

  • Chairman of the Robotic and Laparoscopic Surgery Branch of Wuhan Medical Association

References:

[1] Jemal A,Siegel R,Xu J,Ward E.Cancer Statistics,2010.CA:A Cancer Journal for Clinicians.2010;60(5):277-300.

[2]Ross RW,Xie W,Regan MM,et al.Efficacy of androgen deprivation therapy(Adt) in patients with advanced prostate cancer:Association between Gleason score,prostate-specific antigen level,and prior ADT exposure with duration of ADT effect.Cancer.2008;112(6):1247-1253.

[3]Feng FY,et al.ASCO-GU oral present 2020;abstract 5535.

[4]Perez-Ruixo C,et al.Clin Cancer Res.2020;26(17):4460-4467

*This article is only used to provide scientific information to medical professionals and does not represent the views of this platform
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