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Editor's note
As one of the common male malignant tumors, prostate cancer has the characteristics
of late staging when the disease is diagnosed and the incidence rate has increased rapidly in recent years.
Androgen deprivation therapy (ADT) is one of the most important basic treatments for prostate cancer, and its main goal is to reduce and stabilize serum testosterone (T) below
castration levels.
Testosterone is closely related to the occurrence and development of prostate cancer, and since the release of the Chinese Expert Consensus on Testosterone Management in Prostate Cancer [1] (hereinafter referred to as the "Consensus"), the scientific management model of testosterone has become more and more important
in clinical practice.
Recently, we are honored to invite Professor Zhou Liqun from Peking University First Hospital and Professor Wei Qiang from West China Hospital of Sichuan University to interpret the 2021 edition of the "Consensus" for our readers
Professor Zhou Liqun
Director of the Institute of Urology, Peking University
Head of Department of Urology, Peking University Health Science Center
Honorary President and Past President of Urologist Branch of Chinese Medical Doctor Association
Member of the Standing Committee of the Urology Branch of the Chinese Medical Association
Vice Chairman of the Urology Branch of Beijing Medical Association
Executive Vice Chairman of the Professional Committee of Medical Education Surgery (Urology) after graduation of Chinese Medical Doctor Association
Professor Wei Qiang
Standardize the whole process, a new concept in the new era
Professor Zhou Liqun:
The "Consensus" was first released in 2017, based on the current clinical application status of testosterone management in China, combined with the update of guidelines, consensus and literature evidence in various countries in recent years, the Urology Branch of the Chinese Medical Association (CUA), the Urologist Branch of the Chinese Medical Doctor Association (CUDA) and the Urogenital Oncology Professional Committee of the Chinese Anti-Cancer Association (CACA-GU) jointly organized experts to update, and launched a new version of the "Consensus"
in April 2021.
Compared with the old version of the expert consensus, the new version of the testosterone management consensus highlights four core ideas:
● Testosterone management needs to run through the whole process: including diagnosis, evaluation, treatment and efficacy evaluation;
● Monitoring testosterone at important disease nodes: including diagnosis, recurrence, new metastases, castration-resistant prostate cancer (CRPC), curative therapy, changes in ADT methods, chemotherapy, and other treatments at the initiation;
● Simultaneous testosterone testing and PSA: especially at the onset of important disease, treatment switch, or disease progression, testosterone and PSA need to be monitored in a timely manner;
● T<20 ng/dL is a better prognostic indicator: deep ketone lowering (lower testosterone < 20 ng/dL) during ADT can be used as a reference indicator
for better clinical treatment prognosis and adjustment of treatment.
It can be seen that this "consensus" update emphasizes the importance of standardized management of testosterone, and in the context of the normalized management of the new crown epidemic, more standardized means better prognosis
.
Professor Wei Qiang:
Testosterone management runs through the diagnosis, evaluation, treatment and prognosis evaluation of prostate cancer, and is of great significance
for patients with different stages of the disease.
Several studies have shown that baseline serum testosterone levels correlate with the risk of prostate cancer and disease outcome, so monitoring baseline testosterone values at important nodes of the disease (disease stage initiation and treatment switching point) is important
for the prognosis of patients.
In addition, the significance of testosterone management should be educated to patients and their families to obtain cooperation
.
Figure 1 Key time points for testosterone management
Deep ketone reduction, a new option under new technology
Professor Wei Qiang:
Domestic and foreign guidelines recommend that testosterone should be regularly monitored during ADT treatment, and testosterone should reach and stably maintain below
castration levels.
However, in the past, due to the limitation of detection technology, "T<50 ng/dL" was used as the castration criterion<b21> for testosterone.
In recent years, with the development of medical technology, clinicians have come to realize that lowering testosterone to deeper levels can lead to better outcomes for patients
.
Univariate analysis of patients with metastatic prostate cancer showed that patients with testosterone levels ≤ 25 ng/dL at the first month of ADT had a lower risk of progression to CRPC (HR=1.
46, 95% CI: 1.
08-1.
96, P=0.
013); At 6 months of ADT, the time to progression to CRPC was significantly longer in patients with testosterone levels ≥< 20 ng/dL compared with those with testosterone levels of 20 ng/dL (48 versus 24 months, P = 0.
025).
<b20> Multivariate analysis confirmed that testosterone levels <20 ng/dL were independent predictors<b21> of longer overall survival (OS).
Based on a number of evidences, the new version of EAU, Canadian Consensus, etc.
have recommended "T<20 ng/dL" as a new castration standard<b20>.
For the first time, the consensus recommends that a decline in testosterone levels during ADT is associated with
better disease outcomes and outcomes.
Professor Zhou Liqun:
Current commonly used drugs for ADT include luteinizing hormone-releasing hormone agonists (LHRHa) and luteinizing hormone-releasing hormone antagonists (LHRH antagonist), which are two classes of drugs
that inhibit testosterone production.
They inhibit testosterone secretion by inhibiting LHRH secretion
, which in turn inhibits testosterone secretion in the testes.
At present, LHRHa is more widely used in domestic clinical use, including triptorelin, goserelin and leuprolide.
In a retrospective analysis [2], there was some difference in testosterone levels reduction between the three agents, with triptorelin lowering testosterone levels to <20 ng/dL at six and nine months, and triptorelin reducing testosterone levels to <10 ng/dL in the 3-month form in the highest proportion of patients (P<0.
001<b11>).
From theory to practice, new exploration under the new journey
Professor Wei Qiang:
CRPC is a characteristic disease stage of prostate cancer and an important time node
for switching clinical treatment strategies.
Castration levels of testosterone are required to diagnose CRPC and should be maintained
in subsequent treatment with CRPC.
In recent years, longer-acting LHRHa dosage forms have gradually gained clinical recognition
compared with traditional single-month dosage forms.
Especially during the new coronavirus pneumonia epidemic, the application of 3-month dosage form reduces the travel risk of patients under the premise of ensuring the same testosterone control level, and its clinical application advantages have been fully reflected
.
At present, triptorelin has entered the medical insurance, but has not yet entered the National Essential Drugs List (referred to as the "Basic Drug List"), and we also look forward to the inclusion of triptorelin in the "Basic Drug List" as soon as possible, so that patients can get better treatment
at a lower cost.
Professor Zhou Liqun:
In this "consensus", in view of the important clinical value of testosterone management during ADT, the expert group developed a standardized flow chart of testosterone monitoring and management, which is convenient for clinicians to quickly understand and easily apply
.
The "consensus" recommends regular monthly testosterone testing before the start of ADT and within 6 months of treatment; After the condition enters a stable state, the interval between testosterone tests can be extended to once every 3~6 months
.
It should be noted that while emphasizing testosterone monitoring, do not forget the detection of PSA, PSA and testosterone are monitored together, double standard parallel, can maximize the benefits of castration therapy for patients
.
As one of the commonly used ADT drugs, triptorelin can not only effectively reduce the PSA level of prostate cancer patients to <4 ng/ml [<b11>3], but also deeply reduce testosterone levels [4], making "double standard parallelism" not only a slogan, but a real benefit
for patients.
Therefore, we also call for "triptorelin acetate for injection 3.
75mg", "triptorelin dihydroxynaphthalate 15mg for injection" and other LHRHa to be included in the "basic drug list", so that patients in grassroots areas can also be treated guaranteed
.
Fig.
2 Standardized process of testosterone monitoring and management during ADT treatment[1].
postscript
Testosterone management is an important part of the whole process of prostate cancer management, the update of the new version of "consensus" will establish a scientific testosterone management model for China, improve the standardized management of testosterone in the era of new endocrine therapy, and strive
to improve the overall survival level of prostate cancer patients.
References:
[1] Urology Branch of Chinese Medical Association, Urogenital Oncology Professional Committee of Chinese Anti-Cancer Association, Urology Physician Branch of Chinese Medical Doctor Association.
Chinese expert consensus on testosterone management in prostate cancer(2021 edition)[J].
Chinese Journal of Urology,2021,42(04):241-245.
)
[2] Shim M, Bang WJ, Oh CY, et al.
Effectiveness of three different luteinizing hormone-releasing hormone agonists in the chemical castration of patients with prostate cancer: Goserelin versus triptorelin versus leuprolide .
Investig Clin Urol.
2019 Jul; 60(4):244-250.
[3] LI Ningchen, SONG Yi, JIANG Haowen, DING Qiang, GAN Weidong, GUO Hongqian, SUN Zeyu, HU Zhiquan, YE Zhangqun, WEI Qiang, NA Yanqun.
Efficacy and safety of long-acting gonadotropin-releasing hormone analogues in the treatment of metastatic prostate cancer[J].
Chinese Journal of Surgery,2008(21):1653-1657.
)
[4] Lebret T, Rouanne M, Hublarov O,et al.
Efficacy of triptorelin pamoate 11.
25 mg administered subcutaneously for achieving medical castration levels of testosterone in patients with locally advanced or metastatic prostate cancer.
Ther Adv Urol.
2015 Jun; 7(3):125-34.
Typesetting: Huang Lingling
Editor: Huang Lingling
Review: Qiu Jia
"Physician Daily" submission public mailbox: yishibao2017@163.
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