Early use to reverse the decline: the first-line treatment for prostate cancer is not effective, and the addition of disulumab can quickly relieve bone pain and achieve long-term benefits

*Only for medical professionals to read for reference.
Disumab has a rapid effect on the treatment of prostate cancer bone metastases, and the medication is safe and effective! Case brief introduction ■ General situation: A 69-year-old male patient with bone pain at the first visit was diagnosed with urination dripping for half a year.
He complained of urination dripping for half a year.
In the past two months, he developed bone pain in the spine and left pelvic area and gradually worsened.

Past history, personal history, and family history are nothing special.

Specialist physical examination: the volume of the prostate on the digital anus examination was slightly enlarged, the surface was nodular, hard, the edges were clear, and the central groove disappeared.

Pain assessment: NRS (Numerical Pain Score) score 4 points.

■ Auxiliary examination: Prostate cancer and multiple bone lesions found before treatment: Alkaline phosphatase: 75 IU/L.

Radioimmunoassay DPC (isotope) test report (July 22, 2020): Prostate specific antigen (PSA) is 1224ng/mL.

Chest CT: the texture of the two lungs increased, moving towards nature, small nodules on the left apex, subpleural nodules in the dorsal section of the left lower lobe, and small nodules in the lower tongue of the left lung, about 3mm; multiple osteogenesis in the thoracic spine.

Prostate MRI: prostate transition zone hyperplasia, T2W1 signal is uneven, showing mixed signal, local hyperplastic nodules; peripheral zone is slightly compressed and atrophy, signal is uneven, left peripheral zone has sheet-like low signal, diameter 27mm, ADC is low Signal, after enhancement, the lesion is enhanced early, considering the possibility of cancer.

The seminal vesicle structure signal was fair, and no obvious abnormal enhancement was seen.

There was no obvious enlarged lymph nodes in the pelvic wall, but the signals of the bones in the pelvis were not bad.

The prostate PI-RADS score is 5 grades.

Prostate biopsy pathology (July 27, 2020): (outside the right side of the prostate) biopsy tissue immunoenzyme labeling results: tumor cells P63 (-), NKX3.
1 (+), P504S (+); (right prostate) Lateral transition area) puncture biopsy tissue immunoenzyme labeling results: focal acinar P63 (-), P504S (+); (outer, middle, paramedian of the right peripheral area of ​​the prostate, outer, middle, and paramedian of the left peripheral area, (Left transitional area) needle biopsy: prostate cancer, Gleason score 9 points (4+5), with perineural cancer infiltration; (right transitional area of ​​the prostate) needle biopsy: focal atypical small alveolar hyperplasia of the prostate ( ASAP).

Whole body bone imaging (August 6, 2020): The whole body bone imaging is clear, with multiple occurrences of the spine, multiple ribs on both sides, left iliac bones, and right pubic bones with radioactive concentration foci, and no abnormal increase in radioactivity distribution in the remaining bones ( Hot zone) or reduced (cold zone) performance.

Radioactivity in kidney, bladder, etc.
is caused by excretion of imaging agent.

Figure 1 Results of imaging diagnosis of bone metastases in the patient ■ Preliminary diagnosis: metastatic castration sensitive prostate cancer (mHSPC), multiple bone metastases.

 Treatment process ■ Dispel the cloud and see the day-Bone pain was obvious during the first-line treatment, and it was quickly relieved after the addition of desulumab.
From August 2020 to September 2020, the patient was given the first-line treatment with goserelin + abiraterone + prednisone.
The complaint is accompanied by mild bone pain, and the pain score is 2 points.

 Therefore, according to the above situation, disulimab was added to the second-line treatment plan.
From October 2020 until now, goserelin + abiraterone + prednisone + desulimab has been treated.
The patient has bone pain within one month after receiving the treatment.
It disappeared, the PSA dropped below 0.
2ng/ml after six months of treatment, and the patient did not complain of significant discomfort.

 Figure 2 The PSA level changes during the treatment of the patient and the whole body bone imaging (April 6, 2021) see: Multiple bone metabolism abnormalities throughout the body, combined with the medical history, considered as multiple bone metastases, compared with the whole body on August 6, 2020 As a result of bone imaging, bone metabolic activity was significantly reduced, suggesting that disulumab can effectively target bone metastases and control the patient's related symptoms.

 Figure 3 Case summary and consideration of re-examination of bone metastases in the patient after 6 months of desulumab treatment.
This patient was already in the mHSPC stage at the time of diagnosis.
Therefore, the first-line treatment plan is currently the latest standard plan, that is, medical castration plus new endocrine drug treatment Based on the patient’s report that the symptoms of bone pain are obvious, and the bone scan clearly indicates metastases, in order to reduce the symptoms and reduce the risk of bone-related events, the medication was adjusted in the second-line treatment, and the disulumab was added to the original treatment plan.

 During the course of treatment, the patient’s bone pain disappeared within one month of treatment with desulumab.
After six months, the patient’s PSA dropped below 0.
2ng/ml, and the bone scan showed that the metabolism of bone metastases was significantly reduced.

The overall therapeutic effect of desulumab is good, and the patients have not reported side effects.
It is in line with the efficacy and safety of the two previous phase III clinical studies for patients with advanced prostate cancer with bone metastasis [1-2], and reached the expectations of the treatment team The goal, and the medication is safe and convenient.

Case provider Dr.
Nailong Cao, Doctor of Urology, Shanghai Sixth People’s Hospital, Visiting Scholar of the University of Pittsburgh, presided over 1 Shanghai Science and Technology Innovation Yang Fan Project, 1 Shanghai Jiaotong University Doctoral Innovation Fund Project, published SCI paper as the first author 11 papers and 4 papers in Chinese core journals.

Experts comment that bone is one of the most common metastatic sites for advanced tumors.
Common cancers such as breast cancer, prostate cancer, and non-small cell lung cancer are prone to bone metastasis, leading to pathological fractures, bone surgery and/or bone radiotherapy, and spinal cord compression.
And other bone-related events (SREs), which seriously affect the daily function and quality of life of patients [3].

 Inhibiting the activity of osteoclasts and reducing bone destruction caused by bone metastasis of cancer cells is the key to reducing and delaying the occurrence of SREs in patients with advanced tumors.
As a fully humanized monoclonal antibody of nuclear factor kappa B receptor activator ligand (RANKL), Desulimab can achieve this therapeutic goal by interfering with the combination of RANK/RANKL.
The mechanism of action is different from that of the original bisphosphonate drugs.
In a number of randomized controlled phase III studies, it has shown that it is better than zoledronic acid.
Good efficacy and safety [4].

Among them, for prostate cancer patients, a study included 1904 castration-resistant prostate cancer patients to compare the SREs preventive effects of disulumab and zoledronic acid in these patients with bone metastases.

The results showed that the median time for the appearance of SREs in the desulumab group was 20.
7 months, which was significantly better than that in the zoledronic acid group (17.
1 months), and the HR value was 0.
82 (P=0.
008) [5].

 Figure 4 The research data dessumab was listed in China in 2020 and included in the national medical insurance catalogue.
Based on the good availability of the drug and the impressive efficacy, the Chinese Society of Clinical Oncology (CSCO) prostate cancer diagnosis and treatment guidelines will be updated in 2021.
The recommended level of Sulimab for the prevention of bone-related events in castration-resistant metastatic prostate cancer (mCRPC) has been upgraded from Type II to Type I, becoming the preferred treatment option for the prevention of SREs in domestic patients.

 In this patient, after adding disulumab to the treatment regimen, the symptoms of bone pain were quickly relieved, the metabolism of bone metastases was significantly reduced, and the PSA level also fell below 0.
2ng/ml, reflecting the effect of disulumab on bone metastasis and bone pain Good efficacy, follow-up follow-up should reflect the efficacy of disulumab in prolonging survival without bone metastasis and delaying bone-related events.

 Commenting expert’s profile, Professor Gu Baojun, Chief Physician, Researcher, and Doctoral Supervisor of Urology at the Sixth People’s Hospital Affiliated to Shanghai Jiaotong University, Ph.
D.
from Shinshu University, Japan, and postdoctoral fellow from Duke University in the United States.
Four general projects of the National Science Foundation, five scientific research projects of the Shanghai Natural Science Foundation and the Ministry of Education, published more than 30 SCI papers as the first author or corresponding author; published a monograph as the first complete person and won the Shanghai Medical Science and Technology Award The third prize is one of the reviewers of the National Natural Science Foundation of China, as the reviewer of THE JOURNAL OF UROLOGY and other SCI journals.
References: [1] Fizazi K, CarducciM, Smith M, et al.
Denosumab versus zoledronic acid for treatment of bonemetastases in men with castration-resistant prostate cancer: a randomised,double-blind study[J].
The Lancet, 2011, 377(9768): 813-822.
[2]Smith MR, Saad F,Coleman R, et al.
Denosumab and bone-metastasis-free survival in men withcastration-resistant prostate cancer: results of a phase 3, randomised,placebo-controlled trial[J].
The Lancet, 2012, 379(9810): 39-46.
[3]Weinfurt KP , LiY, Castel LD, et al.
The significance of skeletal-related events for thehealth-related quality of life of patients with metastatic prostate cancer[J].
Annals of Oncology, 2005, 16(4): 579-584.
[4]Lipton A, FizaziK, Stopeck AT, et al.
Superiority of denosumab to zoledronic acid forprevention of skeletal-related events: a combined analysis of 3 pivotal,randomised , phase 3 trials[J].
European Journal of Cancer, 2012, 48(16):3082-3092.
[5]Fizazi K, CarducciM, Smith M,et al.
Denosumab versus zoledronic acid for treatment of bone metastasesin men with castration -resistant prostate cancer: a randomised, double-blindstudy.
Lancet.
2011;377(9768):813‐822.
doi:10.
1016/S0140-6736(10)62344-6.
*This article is only used to provide science to medical professionals Information, does not represent the views of this platform[5]Fizazi K, CarducciM, Smith M,et al.
Denosumab versus zoledronic acid for treatment of bone metastasesin men with castration-resistant prostate cancer: a randomised, double-blindstudy.
Lancet.
2011;377(9768):813‐822 .
doi:10.
1016/S0140-6736(10)62344-6.
*This article is only used to provide scientific information to medical professionals and does not represent the views of this platform[5]Fizazi K, CarducciM, Smith M,et al.
Denosumab versus zoledronic acid for treatment of bone metastasesin men with castration-resistant prostate cancer: a randomised, double-blindstudy.
Lancet.
2011;377(9768):813‐822 .
doi:10.
1016/S0140-6736(10)62344-6.
*This article is only used to provide scientific information to medical professionals and does not represent the views of this platform