PSA depth rapidity, OS long-term "coerc" stage, ADT+ apatamide combination therapy for mHSPC patients to win the chance of survival in classic cases

*For medical professionals only

Classic case sharing ~

The following two patients are both cases of metastatic hormone-sensitive prostate cancer (mHSPC), and both were treated with apatamide + androgen deprivation therapy (ADT) after a definitive diagnosis, and the PSA dropped below 0.
2 ng/ml for about 2 months, achieving a rapid decline in
PSA depth.
In subsequent ongoing treatment, PSA further decreased to <0.
001 ng/ml and remained stable and radiographic results improved significantly
.
Gives patients hope
for long-term survival.

▎Basic information

• male patient, 66 years old;

• On October 8, 2021, the patient was admitted to the hospital for examination after the disaster due to "a significant increase in PSA found during the physical examination for more than 4 months (abnormally elevated PSA was found to be in June 2021, due to the flooding and epidemic in Zhengzhou, which was not treated in time)";

• Current medical history: before 4 months, the patient found that tPSA was elevated, no urinary frequency, urgency, dysuria, no gross hematuria, and the PSA was shown by checking the PSA: tPSA: 369.
  250ng/ml, fPSA: 73.
  260ng/ml, F/tPSA: 0.
  18%.
  
  Perfect ultrasound tip: prostate volume enlargement and echo is extremely uneven, prostate mixed echo
  .
  After admission, the tPSA was reviewed as high as 759.
  220ng/ml, and it was admitted to the department
  .
  Spontaneous illness, the patient's weight loss compared to the previous about 2kg;

• Digital rectal diagnosis: increased prostate volume, disappearance of the central groove, hardness, failure to touch specific nodules, poor mobility, no obvious tenderness, strong contraction of the sphincter, no blood staining of the fingertips;

• Past history: history of hypertension for 10 years, maximum hypertension to 180/140 mmHg, self-reported oral drug control is good;

▎Diagnosis and treatment

Tips for completing MRI on October 8, 2021:

• The right peripheral band and central band of the prostate gland can see irregular clump shadows, ranging from about 6.
  3cmx3.
  1cmx4.
  5cm, T1WI is an equal signal, T2WI is a slightly lower signal, DWI is a high signal, ADC is a low signal, and the uneven reinforcement of the enhancement scan is considered prostate cancer;

• Multiple abnormal bone signals in the right acetabular mortar, right ischia, sweeping and lumbosacral vertebrae and bilateral proximal femur, suggesting bone metastasis;

• Slightly larger lymph nodes in the pelvic and bilateral groin;

Figure 1 MRI examination on October 08, 2021

On October 08, 2021, the patient perfected the chest + abdomen + pelvic CT examination prompts:

• Multiple small and micro nodules in both lungs, bone destruction of the 10th rib on the left side and surrounding soft tissue patches;

• Sternal stalk and right 4th rib abnormalities, combined with ECT examination;

• The prostate gland is enlarged and calcified, and the strengthening is less uniform, please combine with MRI;

• Abnormal density of the right acetabular mortar, ischia, iliac bone and part of the vertebral body, bone metastasis is possible;

• Small lymph nodes in the pelvic and inguin;

October 12, 2021 Patient Perfect Bone Scan Findings:

The skeleton of the whole body is clear and morphologically intact, and the skull, sternum, ribs on both sides, shoulder blades, spinal bones, pelvic bones and long bones of the limbs can be seen in many places
.
Examination tips: multiple radioactive hyperactive foci of bone uptake throughout the body, multiple bone metastases (more than 5 places).

Figure 2 Bone scan on October 12, 2021

On 13 October 2021, the patient underwent ultrasound-guided perineal prostate biopsy under general anesthesia:

• Pathological return tips: prostate acinar adenocarcinoma, Gleason score: 4+5=9, WHO grading group 5;

• Immunohistochemistry: CK34BE12(-), P504S(+);

Figure 3 Pathological examination

▎Disease diagnosis

High hazard and high load mHSPC; Clinical staging: T4N1M1b (T4: tumor invasion of the pelvis; N1: lymphatic metastases; M1b: Multiple bone metastases throughout the body)

▎Treatment plan and efficacy evaluation

The patient began treatment with ADT+apatamine 240mg QD + sodium ibanphosphonate in October 2021; After nearly 2 months of treatment, the patient's tPSA decreased from >759.
22 ng/ml before treatment to 3.
35 ng/ml, a decrease of more than 99%, achieving a deep response to
PSA.
In subsequent treatment, the patient's tPSA further decreased to <0.
001 ng/ml and remained
stable.
Testosterone levels have also decreased significantly compared to before treatment and remain at very low levels
.
As of March 2022, the patient has been receiving combination drug therapy for more than 5 months, and the follow-up tPSA remains at <0.
001ng/ml
.

Figure 4 PSA follow-up results during treatment

2022-04-09 (treatment for 6 months) patients re-examination MRI examination tips:

• After prostate cancer treatment: the lesion is significantly smaller than that of 2021-10-08 tablets;

• Multiple bone signals in the right acetabular and ischia, lumbosacral vertebrae and bilateral proximal femur, which are reduced in scope compared with the anterior;

• Slightly larger lymph nodes in the bilateral groin;

Figure 5 MRI examination was reviewed on April 09, 2022 (6 months of treatment).

Bone scan for patients on April 11, 2022 (6 months of treatment) re-examination:

• For multiple bone metastatic carcinoma in the whole body, compared with the 2021-10-12 tablets, the degree of radioactive uptake was significantly reduced, and the change
  after treatment was considered.
  

Figure 6 Bone scan for follow-up on April 11, 2022 (treatment for 6 months).

▎Management of adverse reactions: During the treatment of patients, the drug is well tolerated and no adverse events occur
.

▎Basic information

• male patient, 66 years old;

• On July 22, 2021, the patient was admitted to the hospital for examination due to "a significant increase in tPSA found during physical examination for more than 4 months";

• Current medical history: tPSA>100ng/ml, no dysuria, no frequent urination, no gross hematuria, no special treatment, no special treatment
  was found during physical examination.
  After a follow-up at the local hospital 1 week ago, tPSA still > 100 ng/ml
  .
  Perfect prostate MRI shows: prostate abnormal signals, prostate cancer is suspect
  .
  Lumbar 4 and 5 vertebral abnormal signals, consider bone metastasis, pelvic enlargement lymphadenopathy, consider the possibility of metastasis
  .
  In order to seek further diagnosis and treatment, the outpatient clinic is admitted to the department of "prostate cancer with bone metastasis to be discharged";

• Digital rectal diagnosis: increased prostate volume, disappearance of the central groove, hardness, failure to touch specific nodules, poor mobility, no obvious tenderness, strong contraction of the sphincter, no blood staining of the fingertips;

• Past history: no history of exceptional disease;

• Admission laboratory tests: tPSA: 918.
  2.
  ng/ml, testosterone: 5.
  6ng/ml;

▎Diagnosis and treatment

October 2021, 07 Patient Perfect Bone Scan Findings:

• Left about the 1st rib, 7th posterior rib, 4thoracic vertebrae, 12th thoracic vertebrae uptake radioactive hyperactive foci, bone metastasis is not excluded, it is recommended to combine with other examinations;

• Increased radioactive uptake of the right knee, considering arthritic lesions;

• abnormal development of the right kidney and right ureter, considered to be associated with hydropreservation;

Figure 7 Bone scan on October 2021, 07

Patients in July 2021 complete SPECT/CT examination prompts:

• positive for PSMA development;

• Prostate morphology irregularity with soft tissue mass shadow, increased uptake of PSMA, consider prostate cancer, please combine clinical;

• Multiple enlarged lymph node shadows in the pelvis, increased uptake of PSMA, consideration of lymph node metastasis;

• Osteogenic bone destruction is seen in many places in the bones, PSMA uptake is increased to varying degrees, and bone metastasis is considered;

• Right pyel-ureteral dilated effusion;

Figure 8 SPECT/CT examination in July 2021

On July 27, 2021, the patient underwent ultrasound-guided biopsy under local anesthesia:

• Pathological return tips: prostate acinar adenocarcinoma, Gleason score: 4+5=9, WHO grading group 5;
• Immunohistochemistry: CK34BE12(-), P504S(+);

Figure 9 Pathological examination

▎Disease diagnosis

High hazard and high load mHSPC; Clinical stage: T3N1M1b

▎Treatment plan and efficacy evaluation

The patient began treatment with ADT+Apatamide 240mg QD+zoledronic acid in July 2021; After nearly 2 months of treatment, the patient's tPSA decreased from >918.
2 ng/ml before treatment to 12.
57 ng/ml, and rapidly decreased to 0.
1 ng/ml after the subsequent 2 months of treatment, a decrease of more than 99%, achieving a deep response to
PSA.
In subsequent treatment, the patient's tPSA further decreased to <0.
001 ng/ml and remained
stable.
Testosterone levels have also decreased significantly compared to before treatment and remain at very low levels
.
As of February 2022, the patient has been receiving combination drug therapy for more than 7 months, and the follow-up tPSA remains at <0.
001 ng/ml
.

Figure 10 Follow-up results of tPSA and testosterone during treatment

▎Management of adverse reactions: During the treatment of patients, the drug is well tolerated and no adverse events occur
.

Case analysis

While improving the 5-year survival rate of cancer patients, their quality of life is also worthy of attention; Not only to let them live longer, but also to live better; From the level of scientific evidence, current research has confirmed that the deep rapidity of PSA that can be achieved early in the treatment of the disease can be used as a "strong predictor" of long-term survival benefits, and the lower the trough, the more studies indicating longer OS support PSA 0.
2ng/mL as the threshold value to distinguish between prognosis ^[12-15], and the above two patients with high tumor load and high-risk patients choose ADT+apatamide regimen to 0.
2ng/ml in 2 months after choosing ADT+apatamide regimen.
Both patients quickly perceived the effectiveness of the treatment plan, improved treatment confidence, and reduced psychological stress
.

Expert profiles are provided for the case PROFILE

Professor Wang Xiangyang

Deputy Chief Physician of Department of Urology, Henan Provincial People's Hospital

Vice Chairman of the Youth Committee of the Urology Branch of Henan Medical Association

Vice Chairman of Urology Branch of Henan Medical Informatics Society

Vice Chairman of the Special Committee of Urinary Stones of Henan Geriatrics Association

He is a member of the Urological Stone Group of Henan Medical Association

Young member of the Urology Surgeon Branch of Henan Medical Doctor Association

He is a member of Henan Provincial Branch of Urology of Combining Chinese and Western Relations

Expert comment one

In recent years, a number of authoritative outlines/white papers have put forward the requirements for the survival rate and quality of life of tumor patients, and put forward the requirements of "providing the whole life cycle health management for the people" and have clear goals for cancer prevention and control and the survival rate of cancer patients: by 2030, the overall 5-year survival rate of cancer will increase by 15%, and the treatment plan chosen by the above 2 cases according to the current guidelines, drug accessibility and patient condition has brought confidence to patients to actively fight prostate cancer.
It is believed that the 5-year survival rate of prostate cancer will be significantly improved after more active treatment options are applied to clinical trials
.

The treatment of 28 cases of advanced prostate cancer in our hospital also brings confidence to patients in the fight against prostate cancer because of the choice of a more aggressive treatment plan, and the details of our cases are as follows:

Henan Provincial Cancer Hospital Experience:

Figure 11 Baseline of real-world cases in Henan Provincial Cancer Hospital

All of these patients were given standard ADT+apatamide in combination
.
During the follow-up process, the average time of PSA90 and bone pain relief was observed to be about 1 month, because the rapid and deep decline of PSA and the rapid relief of symptoms in patients reduced the psychological pressure caused by tumors, life treatment was improved, and they were more confident of maintaining the existing treatment regimen, and they were full of expectations
for future life.

Figure 12 Real-world follow-up results of Henan Provincial Cancer Hospital + TITAN research results^[11].

Review Expert One Introduction PROFILE

Professor He Chaohong

Ph.
D.
Master supervisor

Director of the Department of Urology, Henan Provincial Cancer Hospital

Member of the Urinary Androgenic Department of Cancer Professional Committee of the Chinese Anti-Cancer Association

Vice Chairman of Urology Branch of Henan Medical Association

He has deep knowledge in the diagnosis and treatment of adrenal tumors, kidney tumors, ureteral tumors, bladder tumors, prostate tumors, and male germline tumors, and is good at minimally invasive urological techniques
.
He has presided over 1 project of Henan Provincial Science and Technology Research Program, 3 projects of Henan Provincial Medical Science and Technology Research Program, 1 project funded by young and middle-aged backbone teachers in Henan Province, 1 cooperation project of the National Natural Science Foundation of China, 1 sub-project of the national "973" Program Project, 1 second prize of Henan Provincial Science and Technology Progress Award, and 1 department-level scientific and technological achievement
.

Expert comment two

In recent years, with the intensification of Chinese aging and other reasons, the incidence and death of prostate cancer in China have shown a significant upward trend, and the burden of disease has become increasingly serious
.
Prostate cancer has gradually entered the public eye
from the traditional "rare disease".
According to GLOBOCAN 2020 China data, the incidence of prostate cancer in 2020 ranked sixth and seventh among male cancers[^10], and the total incidence of prostate cancer in China showed a rapid upward trend year by year, and about 30% of the clinical patients with prostate cancer in China have experienced distant metastases much higher than in Western countries ^[8,9].

。 The 2000-2017 SEER database statistics show that the 3-year survival rate for patients with prostate cancer who are first diagnosed with M1 is less than 50%, and the 5-year survival rate is only 30.
6%, which is much lower than that of localized and locally progressive prostate cancer ^[5].

The above two patients with mHSPC were diagnosed with a significant increase in PSA during routine physical examination, and they were confirmed by further examination, and they did not have any typical symptoms
before the onset of the disease.
This is also consistent
with the characteristic that prostate cancer has an insidious onset and atypical symptoms.
Although these patients are advanced at first diagnosis, there is a longer survival benefit
with aggressive treatment.

How to choose from the many active treatment options available? In comparison of real-world studies of the efficacy of apatamide, abiraterone, and enzalumide in patients with mHSPC, the proportion of patients treated with apatamine for mHSPC who achieved PSA90 and PSA decreased to <0.
2 ng/mL was higher and more rapid than that of abiterol and enzarucide ^[4].

Figure 13 A retrospective longitudinal cohort study - a review of real-world data

In clinical research and real-world diagnosis and treatment practice, the apatamide + ADT protocol can achieve deep rapidity of PSA and maintain it at a low level for a long time, bringing greater survival benefits
to patients.
The depth of PSA dropping (<0.
001 ng/ml) in both cases allowed patients to quickly perceive the effectiveness of the treatment regimen, improve treatment confidence, and reduce psychological stress ^[16-18].

Review Expert Two Expert Profile PROFILE

Professor Hu Zhiquan

Deputy Director of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology

Doctor of Medicine, Professor, Chief Physician, Doctoral Supervisor

He is a member of the Oncology Group of the Urology Branch of the Chinese Medical Association

Member of the Standing Committee of the Urological Male Genital Department Tumor Professional Committee of the Chinese Anti-Cancer Association and Deputy Leader of the Minimally Invasive Research Group

Member of the Standing Committee of the Prostate Cancer Expert Committee of the Chinese Society of Clinical Oncology

Member of the Standing Committee of the Urology Professional Committee of the Cross-Strait Medical and Health Exchange Association

Chairman of the Urinary Male Genital Tumor Branch of Hubei Anti-Cancer Association

Deputy Leader of Oncology Group of Urology Branch of Hubei Medical Association

Director of Oncology Research Office of Hubei Institute of Urology

He is a member of the Urology Branch of Hubei Medical Association

Member of the Urology Branch of Hubei Medical Doctor Association

Vice Chairman of Urology Branch of Wuhan Association of Integrative Traditional Chinese and Western Medicine

SIU Commissioner

He is a member of the editorial board of Journal of Cancer Prevention and Treatment, Journal of Modern Genitourinary Oncology, Clinical Urology, and Chinese Journal of Physicians (Electronic Edition).

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