Looking back at the anterior "gland" and exploring a new realm——the choice for accurate diagnosis and treatment of mCRPC patients

*For medical professionals to read for reference only, the experts in the field will show you the current situation and prospects of the field of prostate cancer diagnosis and treatment, and see how PARP inhibitors combined with abiraterone can become the accurate choice for the diagnosis and treatment of patients with metastatic castration-resistant prostate cancer (mCRPC)
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On February 26, 2022, AstraZeneca's "Legend of the Legend, Ascension to the New Realm" Prostate Cancer Summit Forum was successfully held
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National experts in the field of prostate cancer diagnosis and treatment gathered online and offline to take stock of the latest progress and discuss diagnosis and treatment strategies
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At the meeting, Prof.
Huang Jian from Sun Yat-sen Memorial Hospital of Sun Yat-sen University and Prof.
Wei Qiang from West China Hospital of Sichuan University respectively published the titles of "Looking Back at the Footprints of the Prostate Gland and Joining Hands to Explore the New Realm" and "Professional New Students: The Choice for Accurate Diagnosis and Treatment of MCRPC Patients Treated by NHA" ' excellent speech
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After the meeting, the medical community specially invited two academic leaders to take stock of the latest research results of 2022 ASCO-GU for us, and look forward to the future development prospects of the field
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Let's have a sneak peek! Accurate early diagnosis and personalized treatment throughout the whole process—a new trend in prostate cancer diagnosis and treatment Prostate cancer—one of the most common malignant tumors in the genitourinary system of elderly men worldwide
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In the global male malignant tumor, the incidence and mortality of prostate cancer ranked the second and fifth respectively [1]
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In China, prostate cancer has become a male malignant tumor with the fastest growing incidence and rising mortality rates in China in the past decade
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Prof.
Huang Jian's interview video Prof.
Huang Jian said: "After decades of development, China has made great progress in the diagnosis and treatment of prostate cancer
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In the diagnosis of prostate cancer, China is moving towards two directions of 'early diagnosis' and 'precise diagnosis' Great strides
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” In recent years, with the popularization and application of prostate cancer early screening technology in China, the early diagnosis rate of prostate cancer patients has increased significantly
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Early diagnosis of "localized prostate cancer" has won patients a valuable surgical opportunity
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At the same time, with the vigorous development of imaging technology, molecular pathology and genetic testing technology
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The diagnosis and tumor biology of prostate cancer have become more precise
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In the treatment of prostate cancer, it is also progressing in the direction of "minimally invasive" and "multidisciplinary diagnosis and treatment"
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Professor Huang Jian said that for patients with limited-stage prostate cancer, the advancement of surgical techniques is of great significance
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Radical surgery for prostate cancer has developed from "open surgery" to "laparoscopic surgery" and now to "robot surgery"
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For patients, this means less trauma and better preservation of organ function while maintaining efficacy
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At the same time, as a systemic disease, the multidisciplinary collaborative diagnosis and treatment model provides patients with an "all-round" and "individualized" diagnosis and treatment plan "the best solution"
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Improve patient survival time and quality of life
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In 1941, Professor Charles Huggins first discovered and reported the important role of androgens in the occurrence and progression of prostate cancer
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This major discovery opens a new era in the treatment of prostate cancer targeting the androgen axis
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Professor Charles Huggins also won the Nobel Prize in Medicine
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After more than half a century of development, the iterative update of anti-androgen drugs at various stages of androgen synthesis and secretion has further strengthened the role of the "androgen axis" in prostate cancer, and the drug treatment of prostate cancer has gradually moved towards "precision".
The direction of "diversification"
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The video of Prof.
Wei Qiang's interview was accompanied by the advent of new endocrine therapy (NHA) drugs represented by abiraterone, and patients who progressed to mCRPC ushered in a rare opportunity for treatment
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"For some mCRPC patients who still progress after NHA treatment, the disease progression will become very rapid, and the treatment will become very difficult!" Professor Wei Qiang said, under normal circumstances, such patients are switched to another Sequential treatment of NHA drugs, due to the existence of cross-resistance among NHA drugs, the median treatment duration is only about 3 months, and the benefit of patients is very limited
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Clearly, sequential use of NHA drugs is not an ideal option
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At the 2019 and 2020 annual meetings of the European Society for Medical Oncology (ESMO), the PROfound study [2], as a blockbuster research in the field of prostate cancer, made a shocking appearance
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This study evaluated the efficacy and safety of the PARP inhibitor (PARPi) olaparib in patients with mCRPC who have progressed after receiving NHA drugs and carry mutations in genes related to the homologous recombination repair (HRR) pathway
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The study showed that compared with the sequential treatment of NHA drugs, olaparib significantly improved the overall survival time of BRCA1/2 and ATM-mutated mCRPC patients when 67% of the patients in the control group crossed over to the olaparib group ( OS)
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Reduced risk of radiographic progression or death by 66% in all BRCA-mutated patients
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"Olaparib shows obvious therapeutic advantages for mCRPC patients with HRR pathway-related gene mutations who progress after NHA treatment
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" 2022 ASCO-GU's latest study PROpel - first-line treatment of mCRPC with olaparib + abiraterone The "golden partner" of olaparib is based on the unique therapeutic advantages demonstrated by olaparib in the STUDY-08 study [3] and the PROfound study
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The researchers wanted to know whether olaparib combined with abiraterone could benefit patients in the first-line treatment of mCRPC without NHA
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At the just-concluded ASCO-GU annual meeting, the results of the PROpel study [4] were published
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Professor Wei Qiang explained the study in detail
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The PROpel study enrolled 796 patients with mCRPC in the first-line treatment worldwide, and divided them into olaparib + abiraterone treatment group and placebo + abiraterone treatment group 1:1
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The primary endpoint of the study: imaging progression-free survival (rPFS) assessed by the investigator, and the key secondary endpoint was OS
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The results of the study showed that, for the primary endpoint of the study, olaparib + abiraterone compared with placebo + abiraterone, and the median rPFS assessed by the investigator was 24.
8 months, compared with placebo + abiraterone treatment.
The rPFS of the group was 16.
6 months, prolonged by 8.
2 months (R=0.
66, 95%CI 0.
54-0.
81, P<0.
0001), and the risk of radiographic progression or death was reduced by 34%
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In the subgroup analysis, the combination of olaparib and abiraterone was beneficial in all prespecified subgroups, especially in the subgroup with HRR mutation
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Although the study OS data is not yet mature, olaparib + abiraterone has shown a trend of benefit in the key efficacy endpoint OS
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In terms of safety and adverse reaction management, Professor Wei Qiang emphasized that from the safety analysis of the PROpel study, it can be seen that the combination of olaparib and abiraterone did not increase the adverse reactions of patients compared with monotherapy.
incidence
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At the same time, according to the experience in the use of olaparib as a single drug, almost all adverse reactions appear in the first half year of medication.
During these six months, as long as possible adverse reactions are detected in a timely manner through close inspection and early intervention, patients can obtain better drug treatment.
tolerance
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The PROpel study, as the first large-scale phase III clinical study of PARP inhibitor combined with NHA therapy in the whole first-line population of mCRPC, showed excellent efficacy and safety
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It is expected to become the "new standard" of first-line treatment for mCRPC patients in the future
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"Precision" and "AI" Dual Drive - Helping the Comprehensive Development of Prostate Cancer Diagnosis and Treatment The STUDY-08 study for the first time confirmed the "mechanical synergy" between PARPi and NHA drugs
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The PROfound study, published later, is the first large-scale phase III clinical study of prostate cancer that uses molecular typing to guide precise targeted therapy and achieves positive results
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Opened the era of precise targeted therapy for advanced prostate cancer
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Professor Wei Qiang said that the popularization of prostate cancer genetic testing is of great significance for the realization of precise treatment
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The significance of genetic testing is not only to predict the response and prognosis of a patient's drug therapy, but also to guide the patient's choice of therapeutic drugs based on the results of genetic testing
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At present, major global authoritative guidelines recommend early genetic testing for patients with metastatic or castration-resistant stages
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In the future, more research will seek to find some specific intervention targets for prostate cancer patients, which is expected to allow more patients to benefit from precision targeted therapy
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Regarding the future development of prostate cancer diagnosis and treatment and the application of artificial intelligence technology, Professor Huang Jian said that artificial intelligence technology has been increasingly used in the medical field
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From scientific research exploration to clinical practice, the shadow of artificial intelligence can be seen
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In terms of diagnosis, current related research shows that in the future, artificial intelligence is expected to help doctors to carry out various tasks such as rapid tumor disease screening, non-invasive tumor diagnosis, imaging and pathological reading assistance, reducing the burden on doctors and improving work efficiency
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In terms of treatment, surgical robots have been widely used in clinical practice.
In the future, with artificial intelligence technology, it is expected to realize the functions of intraoperative tissue structure identification and early warning, fine operation assistance, and become a powerful "assistant" for doctors
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References: [1] Sung H, Ferlay J, Siegel RL, et al.
Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries.
CA Cancer J Clin.
2021 May;71(3): 209-249.
doi: 10.
3322/caac.
21660.
Epub 2021 Feb 4.
PMID: 33538338.
[2] Maha Hussain 1, Joaquin Mateo 1, Karim Fizazi.
Survival with Olaparib in Metastatic Castration-Resistant Prostate Cancer.
2020 Dec 10; 383(24):2345-2357.
doi: 10.
1056/NEJMoa2022485.
Epub 2020 Sep 20.
[3]Noel Clarke 1, Pawel Wiechno 2, Boris Alekseev .
Olaparib combined with abiraterone in patients with metastatic castration-resistant prostate cancer: a randomised , double-blind, placebo-controlled, phase 2 trial.
2018 Jul;19(7):975-986.
doi: 10.
1016/S1470-2045(18)30365-6.
Epub 2018 Jun 4.
[4]Fred Saad, Andrew J.
Armstrong, Antoine Thiery-Vuillemin, PROpel:Phase III trial of olaparib (ola) and abiraterone (abi) versus placebo (pbo) and abi as first-line (1L) therapy for patients (pts) with metastatic castration-resistant prostate cancer (mCRPC).
Meeting Abstract | 2022 ASCO Genitourinary Cancers Symposium*This article is for the purpose of providing scientific information to medical professionals only and does not represent the views of this platform