echemi logo
Product
  • Product
  • Supplier
  • Inquiry
    Home > Active Ingredient News > Urinary System > 【2022 ESMO】Excellence│Research Progress on Precision Treatment of Prostate Cancer

    【2022 ESMO】Excellence│Research Progress on Precision Treatment of Prostate Cancer

    • Last Update: 2022-10-01
    • Source: Internet
    • Author: User
    Search more information of high quality chemicals, good prices and reliable suppliers, visit www.echemi.com

    *For medical professionals only



    The 2022 European Society for Internal Oncology (ESMO) Annual Meeting was held



    1413P[1] Tumor transcriptome analysis of patients with metastatic hormone-sensitive prostate cancer (mHSPC) who do not achieve an optimal PSA response with intensive androgen deprivation therapy (ADT-I).



    For mHSPC patients, the latest international guideline, EAU guidelines, the NCCN guidelines, further emphasize the combination therapy of ADT in combination with androgen receptor axis-targeted therapy (ARAT) (ADT-I) in the update of the 2022 edition



    This is a study



    Figure 1 PSA-H vs PSA-L results


    The above results show that there are differences in the tumor gene expression profiles of PSA-H and PSA-L patients, and these data help to identify mHSPC patients who can obtain PSA≤0.



    1373P[4] SPOP mutation (mtSPOP) is a biomarker guiding treatment options for patients with newly diagnosed metastatic castration-sensitive prostate cancer (dn-mHSPC).



    ADT in combination with docetaxel or ARAT (abiteron, apatamine, enzalumine) is currently the standard of care for patients with mHSPC


    The study used de-identification data
    from the FH-FMI CGDB database across the United States.

    Patients with dn-mHSPC were enrolled in tissue biopsy within 90 days of diagnosis, and treatment
    with ARAT or docetaxel + ADT was started within 120 days after diagnosis.

    The main study endpoints were Time to Caercisure Resistance (TTCR) and OS
    .

    Figure 2 Study design flowchart

    The results of the study showed that of the 4089 patients with FH-FMI CGDB, 423 met the inclusion criteria
    .

    215 patients were treated with ADT+ARAT and 208 were treated
    with ADT+docetaxel.

    Thirty-seven patients (8.
    7%) had mt SPOP
    .

    Compared with wild-type SPOP (wtSPOP), there was improvement
    in both MTTCR and OS in patients receiving ARAT.

    Conversely, SPOP status is independent of the outcome of docetaxel treatment (Figures 3, 4
    ).

    Figure 3 mtSPOS vs wtSPOP TTCRPC and OS results and correlation analysis

    Figure 4 mtSPOS vs wtSPOP TTCRPC and OS results

    This real-world retrospective study reveals that mtSPOP is a relevant factor
    suggesting a good prognosis with ADT+ARAT regimens in patients with dn-mHSPC.

    Based on these results, mtSPOP may be a predictive biomarker guiding treatment options for dn-mHSPC
    .

    1378P[5] Gene expression profiles for high-risk prostate cancer biopsies predict survival benefit after long-term versus short-term ADT therapy: an analysis of three randomized phase III studies was included

    The NRG/RTOG 9202, 9413, and 9902 studies were all three randomized controlled trials exploring the use of radiotherapy (RT) + long-term ADT + short-term ADT for localized high-risk prostate cancer, and the results showed that patients receiving long-term ADT (LT-ADT) therapy achieved longer disease-specific survival (DSS) and OS
    .

    The study performed a total transcriptome array analysis
    on biopsy samples from patients enrolled in the above three studies.

    The predictive power of PSCs was assessed using a multivariate Cox model (MVA), including biochemical failure (BF), distant metastases (DM), metastasis-free survival (MFS), prostate cancer-specific mortality (PCSM), and OS
    .

    The aim of the study was to explore whether it could predict long-term (LT; 24-28 months) vs short-term (ST; 4 months) survival benefit
    of ADT therapy.

    Analysis of 265 samples (40% basal, 60% luminal) showed better predictive power for MFS (HR 1.
    8 [1.
    3-2.
    5], p<0.
    001), PCSM (HR 2.
    8 [1.
    5-5.
    0], p<0.
    001), and OS (HR 1.
    8 [1.
    3-2.
    6], p<0.
    001) for PSC substrate type (Figure 3<b10>).

    Analysis of BF (p=0.
    02) and PCSM (p=0.
    007) shows that there is an intercorrelation between PSC and ADT durations (Figures 4 and 5).


    Compared with ST ADT, the basal type significantly benefits from LT ADT therapy (10-year PCSM 5% [95% CI 0-11%] vs 42% [29-56%], p<0.
    001), while there is no difference between the results of the lumen type and the duration of ADT treatment (p=0.
    72) (Figure 6).
    <b14>

    Fig.
    5 Results of biochemical failure (BF) subgroup analysis

    Fig.
    6 Prostate cancer specific mortality (PCSM) subgroup analysis results

    Figure 7 Relationship between PSC and LT-ADT &ST-ADT

    Based on the above results, the basal-lumen typing PSC of biopsy samples can predict the survival benefit of patients with high-risk prostate cancer receiving long-term ADT and short-term ADT, and patients with basal type can obtain better survival benefits
    through long-term ADT treatment.

    86p[6] Plasma exosome AKR1C3 mRNA expression is a predictive and prognostic biomarker for patients with metastatic castration-resistant prostate cancer

    Aldehydor Degrading Enzyme Family 1 member 3 (AKR1C3) is a potential biomarker for metastatic castration resistance to prostate cancer (mCRPC) and plays an important role
    in the disease progression of prostate cancer.

    Previous studies of AKR1C3 have been based primarily on tissue samples
    .

    This is a prospective study
    using plasma-based liquid biopsy to verify the prognosis and predictive value of AKR1C3 in patients with mCRPC.

    A total of 62 mCRPC patients were recruited, all of whom underwent multiple prostate biopsies at the time of diagnosis of mCRPC, and immunohistochemical (IHC) staining detected the expression
    of AKR1C3 protein in tissues.

    Simultaneous blood is collected from patients and the expression level
    of AKR1C3 in exosomes is detected by droplet digital PCR (ddPCR).

    Detected plasma and tissue AKR1C3 expression levels for analysis of OS and progression-free survival (PFS)
    after first-line use of abiraterone.

    Results showed that 15/62 (24.
    2%) enrolled patients were positive for AKR1C3-EXO (≥20 copies/20 μL) and 25/62 patients (40.
    3%) were positive for
    AKR1C3-IHC.

    Positive AKR1C3-EXO expression is associated with reduced patient survival [PFS: 3.
    9 vs.
    10.
    1 months, P<0.
    001; OS: 16.
    2 vs.
    32.
    5 months, P<0.
    001].
    <b12>
    AKR1C3-IHC positive is also associated with PFS and OS (P=0.
    010, P=0.
    016) (Figure 8).


    When AKR1C3-EXO was positive, patients with higher baseline alkaline phosphatase (ALP), lactate dehydrogenase (LDH) levels, lower hemoglobin (HB) levels, and ISUP/WHO<4 had poorer OS outcomes (Figure 9).
    <b16>

    Figure 8 Kaplan-Meier curve

    A,B AKR1C3-EXO expression prediction ABI-PSF and OS; C,D AKR1C3-IHC expression predicts ABI-PSF and OS

    Figure 9 HR>1 represents a worse OS

    It can be seen that AKR1C3-EXO is associated with the prognosis of patients with OS and ABI-PFS and can be used as a biomarker for mCRPC
    .

    Expert comments:
    In recent years, the incidence and mortality of prostate cancer in Asia have increased
    significantly.

    The incidence of prostate cancer in China is increasing year by year, and the incidence rate in first-tier cities, especially Shanghai and Guangzhou, has exceeded 12/100,000[7
    ].

    Endocrine therapy is the main treatment method for mHSPC, in recent years, with the use of a new generation of AR inhibitors such as apatamide, abiraterone, enzalumine, the survival of patients has been greatly extended, but there are still some patients with poor prognosis, especially mHSPC patients with high tumor burden who progress quickly and have a short
    survival time.

    Therefore, it is particularly important
    to identify patients with poor prognosis early so that more precise treatment can be used as early as possible.

    Common prognosis-related factors in patients with metastatic prostate cancer (mPC) include: prostate-specific antigen, Gleason score, type of metastasis (bone metastases, visceral metastases), tumor load/risk stratification, alkaline phosphatase, lactate dehydrogenase, etc.
    [8], but these still do not fully meet clinical needs
    .

    With the increasing research of biomarkers related to genomics, proteomics and transcriptomics, the continuous improvement of basic research and molecular technology, the means of mPC prognosis and prediction are also increasing and improving
    .

    At the ESMO conference, the researchers revealed differences in tumor gene expression profiles of PSA-H and PSA-L through RNAseq analysis of pre-treatment biopsy samples, and the discovery of relevant biomarkers helps identify patients who
    may not respond to treatment before ADT-I treatment.

    A PSA of ≤0.
    2 ng/ml after treatment suggests a better prognosis [2], which in turn suggests that treatment regimens
    may need to be changed as soon as possible.

    For mtSPOP mHSPC patients, treatment with ADT+ARAT will result in better OS and longer time
    to CRPC.

    Gene expression analysis of biopsy samples showed that basal-lumen typing predicted long- and short-term ADT efficacy, with basal patients benefiting
    from longer duration of ADT therapy.

    In addition to updates on biomarkers in the mHSPC phase, the conference also covered updates related to the mCRPC phase
    .

    AKR1C3-EXO is associated with prognosis in patients with OS and PFS, suggesting that AKR1C3-EXO can be used as a biomarker for the prognosis
    of treatment with abiraterone in patients with mCRPC.

    Synthesizing the above content, with the development of genomics, proteomics and transcriptomics, more and more biomarkers have been discovered, which not only has great help for the diagnosis, development and prognosis prediction of prostate cancer, but also has great help for the choice of treatment drugs and the decision of treatment order
    .

    However, due to the limitations of small sample sizes in many prospective explorations at present, more and larger sample sizes are still needed for verification in the
    future.

    Expert profile

    Professor Wei Wei

    Chief Physician, Ningbo Huamei Hospital, University of Chinese Academy of Sciences

    Master tutor of Ningbo University and Zhejiang Wanli University

    He is a member of the Andrology Branch of Zhejiang Medical Association

    He is a member of the Andrology Branch of Zhejiang Medical Doctor Association

    Young member of the Radioactive Particle Committee of Zhejiang Anti-Cancer Association

    He is a member of the Urology Branch of Zhejiang Mathematical Medicine Association

    Member of the Pelvic Integration Committee of Zhejiang Mathematical Medicine Association

    Member of Zhejiang Minimally Invasive Alliance Urology Branch

    Member of the Urology Branch of Ningbo Medical Association

    He is a member of Ningbo Integrative Traditional Chinese and Western Medicine Urology Branch

    Member of Andrology Branch of Ningbo Medical Association

    Published 8 SCI national utility model patents

    Presided over 1 major project of Ningbo 2025 science and technology innovation (2019)

    "The essence of diagnosis and treatment of common diseases in urology" and "Diagnosis and treatment of urological diseases", associate editor

    References:

    [1].
    Abstract 1413p, 2022 ESMO Congress

    [2].
    Abstract 1281,2021 AUA Congress

    [3].
    Swami U, et al.
    Eur Urol.
    2020; 78(5):652-656

    [4].
    Abstract 1373p, 2022 ESMO Congress

    [5].
    Abstract 1378p, 2022 ESMO Congress

    [6].
    Abstract 86p, 2022 ESMO Congress

    Ye Dingwei, et al.
    Chinese Journal of Surgery, 2015,53:249-252.

    Liang Peng, et al.
    Shandong Medical Sciences, 2022, 62(19): 96-100.

    *This article is for the sole purpose of providing scientific information to medical professionals and does not represent the views of this platform

    This article is an English version of an article which is originally in the Chinese language on echemi.com and is provided for information purposes only. This website makes no representation or warranty of any kind, either expressed or implied, as to the accuracy, completeness ownership or reliability of the article or any translations thereof. If you have any concerns or complaints relating to the article, please send an email, providing a detailed description of the concern or complaint, to service@echemi.com. A staff member will contact you within 5 working days. Once verified, infringing content will be removed immediately.

    Contact Us

    The source of this page with content of products and services is from Internet, which doesn't represent ECHEMI's opinion. If you have any queries, please write to service@echemi.com. It will be replied within 5 days.

    Moreover, if you find any instances of plagiarism from the page, please send email to service@echemi.com with relevant evidence.