Advanced prostate cancer has always been a difficult point in clinical diagnosis and treatment, especially metastatic castration-resistant prostate cancer (mCRPC). In 2016, abiraterone acetate was approved for first-line treatment of mCRPC in China, officially opening a new era of advanced prostate cancer diagnosis and treatment in China. Today, Abiraterone acetate has accompanied Chinese patients for more than 6 years. In this issue of the "Practice Pre-Gland" column, Medical Pulse invited Professor Zhao Yawei of Xinjiang Production and Construction Corps Hospital and Professor Zhang Zhewei of the Second Affiliated Hospital of Zhejiang University School of Medicine to provide mCRPC cases, and invited Professor Dong Qiang of West China Hospital of Sichuan University and Professor Chen Jimin of the Second Affiliated Hospital of Zhejiang University School of Medicine to comment on it for readers.
Case 1
medical history
Male, 65 years old.
Main complaint: Admitted to hospital in December 2020 for "finding PSA elevated for 1 day".
Adjunctive testing
- Laboratory tests: PSA: 415.9 ng/ml, testosterone: 26.02 nmol/l.
- MRI suggests: abnormal signals in the peripheral areas of the prostate, consistent with prostate cancer, signs of breakthrough of the envelope; Abnormal signals in the middle of the seminal vesicle gland, which does not exclude the possibility of invasion; Bilateral sciatic bone, pubic bone, and acetabular molar multiple abnormal signals, consider bone metastases; enlarged lymph nodes in the left inguinal area, suggesting metastases; Prostatic hyperplasia with partial regional bleeding.
- Pathological findings of puncture biopsy: prostate adenocarcinoma, Gleason score 4 + 4 = 8 points.
Figure 1 Puncture biopsy case report sheet and postoperative pathology report image
Diagnostic results
Metastatic hormone-sensitive prostate cancer (mHSPC) (cT3N1M1b).
Treatment progression
- Stage 1: 2020.12-2021.06, patients underwent radical prostatectomy (RP) + traditional CAB [combined with androgen blockade therapy (leuprolide + bicalutamide)], but testosterone decline was not ideal after treatment with the traditional CAB regimen, and PSA had an upward trend since July 2020. Admission to the hospital in August 2021 for CT showed bone metastases, suggesting disease progression, and after comprehensive consideration, the disease progressed to the mCRPC stage.
Figure 2 Changes in testosterone values during treatment with RP + conventional CAB
- The second stage: 2021.08-2021.10, switch to domestic abiraterone + prednisone + goserelin treatment. After three months, the patient's PSA increased to 8.92 ng/ml, and the bone scan metastases increased, and after clinical evaluation, it was considered that the efficacy of domestic abiraterone was not good rather than pure PSA flickering.
- The third stage: 2021.11-2022.01, replaced by the original research abiraterone acetate + prednisolone + goserelin treatment. At the 3rd month of treatment, PSA decreased to 0.165 ng/ml and radiography improved. A re-examination of bone scans in March 2022 showed that bone salt metabolism was active and slightly lower than the previous metabolism.
Figure 3 PSA and radiographic changes throughout the stage of endocrine therapy in patients
Figure 4 Comparison of bone scan imaging of patients on 2021-10-29 and 2022-03-17
Case analysis
The case was initially diagnosed as a high-risk mHSPC, and the patient was first treated with RP + traditional CAB, but rapidly progressed to the mCRPC stage after 8 months. After communicating with patients, they switched to domestic abiraterone treatment, but PSA continued to rise, and bone scan metastases increased. Finally, the patient's bone pain symptoms were significantly alleviated, and the PSA decreased rapidly and was well controlled. In today's rapidly changing prostate cancer treatment, our expectations for the treatment of anti-cancer drugs are also constantly increasing. Due to the limited survival benefits of traditional CAB, international guidelines such as EAU, NCCN, and AUA no longer recommend traditional CAB as a routine treatment regimen for mCRPC. At the same time, authoritative guidelines at home and abroad also point out that if patients progress to the mCRPC stage, first-line treatment should give priority to new endocrine therapy options such as abiraterone, thereby delaying disease progression and prolonging patient survival. It is satisfactory that after the patient switched to the original research Abitrol acetate, the tolerability and safety were good, and the therapeutic effect was remarkable, which was worthy of further clinical research and promotion.
Case Provider: Professor Yawei Zhao
Professor Yawei Zhao
Deputy Chief Physician of Xinjiang Production and Construction Corps Hospital Master's degree
Member of the Urology Branch of the Medical Association of the Xinjiang Production and Construction Corps
Proficient in the diagnosis and treatment of various urological diseases, especially the standardized diagnosis and treatment of tumors of the reproductive system of urologists, he studied in the Department of Urology of cancer hospital of Chinese Academy of Medical Sciences/National Cancer Center; He has presided over 2 college-level projects, participated in 5 provincial and ministerial projects, 1 national-level project, and published nearly 20 papers and 1 SCI.
Big coffee reviews
With the development of new endocrine therapeutic drugs such as abiraterone acetate, the status of traditional endocrine therapeutic drugs has gradually replaced. After the patient entered the mCRPC stage, he was first treated with domestic abiraterone, but it was not effectively controlled, and the subsequent patient adjusted the treatment plan in time and switched to the treatment of abiraterone acetate, and the PSA was deeply relieved. As an original drug, it needs to go through phase II and phase III clinical trials before marketing, as well as more extensive phase IV observation after marketing. However, generic drugs lack sufficiently strong clinical data before marketing, resulting in differences in clinical efficacy between some generic drugs and original drugs1. A retrospective study of western real-world patient use of generic drugs found that 8% to 34% of patients reported suboptimal efficacy and/or new adverse effects2. The efficacy of the original drug is more clear, and the course of treatment can be predicted from long-term clinical experience, and then the drug cost may be predicted, and the cost performance is higher. The above case reminds us that under the premise of conditions, the choice of abiraterone acetate can be preferred to obtain the maximum benefit.
Review expert: Professor Dong Qiang
Professor Dong Qiang
Chief Physician/Professor of Urology, West China Hospital, Sichuan University, Doctoral Supervisor
Director of the Department of Urology, West China Hospital, Sichuan University
Director of the Urology and Andrology Research Office of the Institute of Urology, West China Hospital, Sichuan University
Visiting Professor of Surgery, Cao Guangbiao, Chinese University, Hong Kong
Academic and technical leader of Sichuan Province
Winner of the 4th "Famous Doctor of the Nation and Excellent Style"
Incumbent:
Member of the Standing Committee of the Andrology Branch of the Chinese Medical Association
Deputy Leader of the Prostatology Group of the Andrology Branch of the Chinese Medical Association
Deputy Leader of the Andrology Group of the Urology Branch of the Chinese Medical Association
Member of the International Exchange Committee of the Urology Branch of the Chinese Medical Association
Member of the Standing Committee of the Andrologist Branch of the Chinese Medical Doctor Association
Member of the Expert Committee on Prostate Health Consultation and Management of the Andrologist Branch of the Chinese Medical Doctor Association
Member of China Urology and Andrology Medical Technology and Equipment Innovation Alliance
Member of the Standing Committee of the Asian Andrology Society
Member of the Committee for the Preparation of Disease Guidelines of the Asian Andrology Society
Chairman-designate of the Andrology Committee of Sichuan Medical Association and Chairman of the Youth Committee
Member of the Minimally Invasive Urology Specialty Group of the Urology Committee of Sichuan Medical Association
Member of the Standing Committee of the Day Surgery Physician Committee of Sichuan Medical Doctor Association
Case 2
medical history
Male, 72 years old.
Main complaint: Admitted to the hospital in September 2015 due to "frequent urination with dysuria for more than 1 year, aggravated by 1 week".
Past history
- Previously underwent transurethral electroresection of the prostate (TURP).
- Diabetes 2 years.
Adjunctive testing
- Laboratory test: PSA is 934 ng/ml.
- MRI suggests: prostate cancer, invasion of the bladder and seminal vesicles, multiple lymph node metastases in the pelvic cavity.
- Bone scan suggests: abnormal metabolism of the T10 vertebral body and right sciatic bone.
- Prostate puncture (11/12) suggests: Prostate acinoma acinoma, Gleason 9, ISUP 5 group.
Diagnostic results
Prostate cancer (cT4aN1M1b).
Treatment progression
- From 2015.09 to 2017.06, patients were treated with traditional CAB, and after two months of treatment, PSA dropped to 48ng/dl. In July 2017, the disease progressed to the mCRPC phase.
- Since 2017.07, the patient was treated with abiraterone acetate instead, and during the treatment, the patient had PSA flickering. The initial PSA of the switch to Abiraterone rose to 3.39 ng/dl, and after the PSA decreased rapidly, it remained at 0.008 ng/dl.
- In October 2018, the patient underwent tumor-reducing laparoscopic prostatectomy. Postoperative pathological prompts: only small foci of prostate adenocarcinoma components were seen, and Gleason scored 3 + 3 = 6 points; Upper and lower urethral and left and right vasectomy margins are negative; Left and right seminal vesicle glands are not involved in tumor involvement; Left pelvic lymph nodes: 0/2 lymph nodes positive; Right pelvic lymph nodes: 0/1 lymph node positive.
- In the follow-up from 2020 to the present, the patient's PSA value has always been 0, and the overall control of the disease is satisfactory.
Case analysis
Patients were first treated with traditional CAB in this case, but after 1 year, the disease progressed rapidly to the mCRPC stage. After clinical evaluation, the PSA rose to 3.39 ng/dl after switching to abiraterone acetate, and the PSA decreased rapidly to 0.008 ng/dl. This suggests that the patient may have psa flicker. PSA flickering refers to the phenomenon in which a patient is treated with a PSA value that first rises relative to baseline PSA levels, but then begins to decline and falls below baseline PSA levels. According to studies, PSA flickering occurs in a variety of treatment modalities during mCRPC treatment, including 8-20% of chemotherapy patients, 5-30% of ADT treatment patients, and 11.9% of radium-223 treatment patients have PSA flicker3. PSA is one of the important indicators of follow-up monitoring of patients with advanced prostate cancer, but it must be emphasized that it is unreliable to assess the change in mCRPC with PSA changes alone, and should be evaluated comprehensively in conjunction with PSA, imaging, and clinical symptoms. From this case, it can be concluded that pSA flicker does not mean that the drug needs to be stopped immediately and does not affect clinical outcome, and clinicians should carefully identify and insist on continuing treatment so as not to prematurely terminate treatment that benefits patients.
Case provider Professor Zhang Zhewei
Professor Zhang Zhewei
Chief Physician of the Department of Urology, Second Affiliated Hospital of Zhejiang University School of Medicine
Vice Chairman of the Youth Branch of Zhejiang Urology Society
Graduated from Zhejiang University, he has been engaged in the treatment of urological tumors and stones
Completed 1,000 cases of laparoscopic surgery, including radical prostate cancer, total bladder resection, radical renal cancer resection, partial renal resection, retroperitoneal lymphatic dissection, pelvic lymphatic dissection
He has presided over more than 40 kidney transplants. Good at treating urinary system tumors, good at minimally invasive surgery combined with radiotherapy and immunotherapy for urinary tumors, health concept "minimally invasive, accurate and all-round treatment of urinary system tumors"
Big coffee reviews
For patients at the mCRPC stage, the American Urological Association (AUA), the Prostate Cancer Clinical Trials Working Group (PCWG3), and the St. Gallen Consensus unanimously recommend that imaging and/or clinical progression need to be met to indicate disease progression after PSA progression has been confirmed. PCWG3 recommends that the PSA progress criteria should be based on the baseline, which is divided into two cases: decreasing PSA and continuing to rise. In the first case, if serum PSA exceeds 25% of the lowest value of PSA during treatment, and the ≥ 2 ng/ml, and repeated confirmation after ≥3 weeks, PSA progression can be judged. In the second case, PSA progression is judged to be measured after 12 weeks of disease treatment when PSA is elevated by more than 25% of baseline and ≥ 2 ng/mL4. It is important to note that the date of reporting PSA progression may not represent the need to stop treatment. In summary, clinicians are advised to continue treatment in cases where there is a separate rise in PSA after the initial decline in PSA until there is significant radiographic or clinical progression.
Figure 5 mCRPC criteria for disease progression
With the development of new endocrine drug treatments such as abiraterone acetate, it has gradually replaced the status of traditional endocrine therapy and become a first-line treatment plan recommended by authoritative guidelines and consensus at home and abroad.
Review expert: Professor Chen Jimin
Professor Jimin Chen
Deputy Chief Physician of the Department of Urology, Second Affiliated Hospital, Zhejiang University School of Medicine
Standing Committee Member of Andrology of Zhejiang Province
Member of the Andrology Committee of Integrated Traditional Chinese and Western Medicine
Deputy leader of the provincial urinary control (prostate disease) group, a medical identification expert in Zhejiang Province
He has presided over a number of projects of the Provincial Department of Science and Technology, the Department of Education and the Department of Health, published many SCI papers, and won the third prize of the Zhejiang Provincial Department of Health Science and Technology Progress
Specialized urology, andrology, kidney transplantation, focusing on the accurate diagnosis and treatment of professional urological male germline tumors, female pelvic floor repair, female stress urinary incontinence sling surgery application research, praised by experts
SUI sling surgery domestic forefront, DCD kidney transplant surgery in the province forefront
Editor's Codex
Abiraterone acetate is a first-line novel endocrine therapy drug recognized in the field of urological tumors for mCRPC patients, and its safety and efficacy have been widely recognized clinically. In both cases, elevated PSA early in treatment was present, but clinical treatment decisions were very different. The enlightenment given to us is that for the treatment of mCRPC patients, we should use abiraterone acetate as much as possible to select evidence-based and sufficient evidence, full treatment, ensure tolerance, reduce the complexity of clinical judgment, so that both doctors and patients can be more at ease, not bothered, confident in treatment, keep the first use of the time, and keep the "last line of defense" of advanced prostate cancer.
bibliography
1.Zeng Junfen, Song Jinchun. Herald of Medicine, 2019, 038(007):884-887.
2.Helle Hakonsen, et al. A review of patient perspectives on generics substitution: what are the challenges for optimal drug use. Generics and Biosimilars Initiative Journal (GaBI Journal). 2012;1(1):28-32.
3.Ceci F, et al. Eur J Nucl Med Mol Imaging. 2018 Dec;45(13):2253-2255.
4.Scher HI,et al. J Clin Oncol. 2016;34(12):1402-1418.
Edit: yt Reviewer: Bing Xin
Typography: LR
More practical cases of prostate cancer are waiting for you to see.