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As one of the most common malignant tumors in men in the world, the incidence of prostate cancer in China has increased year by year in recent years, which is seriously threatening the health of
middle-aged and elderly men in China.
At present, domestic and foreign guidelines consistently recommend androgen deprivation therapy (ADT) as the first-line regimen for prostate cancer treatment, and the main purpose of ADT therapy is to reduce prostate-specific antigen (PSA) and reduce serum testosterone (T) content to maintain it below
castration levels.
Triptorelin, as a commonly used ADT drug, can alleviate PSA levels and deeply reduce testosterone levels, bringing more benefits
to prostate cancer patients.
In order to improve the clinical diagnosis and treatment level of doctors related to genitourinary tumors, Yimaitong invited Professor Wang Jie from Hunan Cancer Hospital to provide prostate cancer cases, and invited Professor Dong Qiang from West China Hospital of Sichuan University to comment
.
Professor Wang Jie
Deputy Chief Physician, Department of Abdominal/Lymphoma Radiotherapy, Hunan Cancer Hospital
Focus on the combination of standardized treatment and individualized treatment of tumors
Proficient in three-dimensional conformal intensity-modulated radiotherapy for malignant tumors
He is especially good at high-precision radiotherapy for abdominal tumors such as prostate cancer, rectal cancer, bladder cancer, lymphoma and other malignant tumors
medical history
Patient male, 43 years old; In April 2018, he was treated in an external hospital due to "gross hematuria and dysuria in March
".
Ancillary examination
Laboratory tests: tPSA=16.
6 ng/mL, T=550 ng/dL
.
Digital rectal examination: prostate III-degree enlargement, hard texture, palpable multiple nodules, central sulcus disappeared, tenderness is not obvious
.
MRI: enlarged prostate, bilateral seminal vesicles and bladder invasion, bilateral iliac paravascular swelling of lymph nodes, and no abnormalities
in systemic bone imaging.
ECOG score: 0 points
.
Diagnostic results
Prostate cancer acinar adenocarcinoma (cT4N1M0), Gleason score 5+5=10 points
.
After the treatment
1.
From May to September 2018, the patient underwent goserelin + bicalutamide treatment, during which PSA decreased to 14 ng/mL, T decreased significantly, T was 32 ng/dL, and the patient's symptoms of hematuria and dysuria continued to worsen, and symptoms of lower abdominal distension and pain
appeared.
Table 1 Changes in PSA and T during the first stage of treatment
2.
In September 2018, he visited our hospital, complaining of obvious symptoms of gross hematuria and dysuria, accompanied by swelling and pain in the lower abdomen, ECOG score of 2 points, tPSA=14 ng/mL, T was 32 ng/dL, pelvic MRI showed that the prostate mass and iliac paravascular lymph nodes were significantly larger
than before.
3.
From September to October 2018, the patient underwent local radiotherapy in the emergency department, replaced the ADT drug with triptorelin treatment, and corrected anemia symptomatically, and the patient's gross hematuria disappeared after 5 radiotherapy sessions, and then the microscopic hematuria gradually disappeared, and the dysuria improved
.
During treatment, the patient's PSA decreased significantly
.
Table 2 Changes of PSA and T during the second stage of treatment
4.
At the end of December 2019, the patient re-examined ECOG score of 0 points, anemia correction, urine red blood cells (-), ADT + docetaxel + cisplatin treatment for 6 cycles, PSA decreased significantly
.
In March 2022, the patient's last follow-up, tPSA<0.
003 ng/mL, HB=135 g/L, no abnormalities were seen in whole-body bone scintigraphy, no abnormalities were found on chest and abdominal CT, and no obvious abnormalities<b11> were found on pelvic MRI.
Table 3 Changes in PSA and T during the third stage of treatment
Case analysis
This case is a limited-stage high-risk prostate cancer patient with a Gleason score of up to 10, which is highly aggressive and prone to castration-resistant prostate cancer (CRPC)1
。 After the diagnosis of the patient, the first choice of goserelin + biscarutamide treatment, testosterone and PSA levels decreased unsatisfactory, and hematuria, dysuria symptoms continued to worsen, and lower abdominal distension and pain symptoms, considering that the clinical symptoms were not relieved, so goserelin was replaced with triptorelin treatment, the follow-up results showed that the patient's testosterone content was always maintained at <13 ng/dL, and PSA was well controlled<b12>.
In patients with CRPC, testosterone content and serum PSA control are important factors
affecting subsequent overall survival.
In a retrospective analysis, a reduction of T<20 ng/dL and T by ≥480 ng/dL resulted in higher overall <b11>survival2
.
ADT is the basic treatment plan for locally progressive and metastatic prostate cancer, and it is also the basis for various new combination treatment regimens, and often needs to run through the follow-up treatment of patients, and has been unanimously recommended
by domestic and foreign guidelines and consensus.
At present, ADT often represents luteinizing hormone-releasing hormone (LHRH) agonists (LHRHa) and LHRH antagonists, of which LHRHa is the most commonly used ADT drug in clinical practice, and triptorelin is a typical representative of
this type of drug.
In one study evaluating the efficacy and safety of triptorelin in patients with locally advanced or metastatic prostate cancer,3 median PSA levels persisted below 4 ng/mL after 8 weeks of treatment until the end of the study; PSA levels decreased by 96.
0% at 26 weeks of treatment, and 90% of patients maintained T<20 ng/dL, suggesting that triptorelin can sustainably and steadily reduce PSA and testosterone levels<b11> in prostate cancer patients.
Professor Dong Qiang
Chief Physician/Professor of Urology Doctoral supervisor
Director of Department of Urology, West China Hospital, Sichuan University
Director of the Laboratory of Urology, Institute of Urology, West China Hospital, Sichuan University
Visiting Professor of Surgery at Chinese University of Hong Kong, Cao Guangbiao
Academic and technical leader in Sichuan Province
Winner of the 4th "National Famous Doctor, Excellent Style"
Incumbent:
Member of the Standing Committee of Andrology Branch of Chinese Medical Association
Deputy leader of the prostate group of the Andrology Branch of the Chinese Medical Association
Deputy leader of Andrology Group, Urology Branch of Chinese Medical Association
Member of the International Exchange Committee of the Urology Branch of the Chinese Medical Association
Member of the Standing Committee of Andrologist Branch of Chinese Medical Doctor Association
Member of the Prostate Health Consultation and Management Expert Committee of Andrologist Branch of Chinese Medical Doctor Association
Member of China Urology andrology Medical Technology and Equipment Innovation Alliance
Member of the Standing Committee of the Asian Andrology Society
Member of the Disease Guidelines Writing Committee of the Asian Andrology Society
Chairman-elect of Andrology Committee and Chairman of Youth Committee of Sichuan Medical Association
Member of the Minimally Invasive Urology Professional Group of the Urology Special Committee of Sichuan Medical Association
Member of the Standing Committee of the Day Surgeon Special Committee of Sichuan Medical Doctor Association
With the improvement of people's living standards, the incidence of prostate cancer in Chinese men has also increased year by year, and compared with Europe and the United States and other countries, the probability of prostate cancer patients in China is already advanced at the time of initial diagnosis, which brings greater challenges
to the treatment and prognosis of prostate cancer patients in China 。 At present, domestic and foreign guidelines unanimously recommend ADT therapy as a first-line basic treatment plan for locally advanced prostate cancer and metastatic prostate cancer, and the key to evaluating the efficacy of ADT is the management of testosterone levels in patients, the guidelines point out that testosterone management should run through the whole process of diagnosis and treatment of prostate cancer and prognosis, and the patient's testosterone levels must be monitored throughout the treatment process to delay the progression
of the patient's disease.
The Chinese Expert Consensus on the Management of Testosterone in Prostate Cancer (2021 Edition)4 recommends that testosterone levels should be maintained at <20 ng/dL<b20> in the treatment of patients with advanced prostate cancer.
In this case, the patient consistently < 20 ng/dL of testosterone and therefore benefited well<b21>.
ADT treatment is a cornerstone in the clinical treatment of prostate cancer, and LHRHa represented by triptorelin, goserelin and leuprolide is commonly used ADT drugs
in clinical practice.
The case was well controlled with triptorelin after poor treatment with goserelin, suggesting that triptorelin can not only be used for first-line treatment of prostate cancer, but also provides significant benefit
to patients when other LHRHa are less effective.
castration levels.
A retrospective analysis5 of 125 patients with prostate cancer divided into triptorelin, leuprorelin, and goserelin investigated changes in testosterone levels within nine months of ADT treatment
.
Results showed that all patients in the triptorelin-treated group reduced testosterone levels to less than 20 ng/dL
at 6 and 9 months.
Of the three drugs, triptorelin had the highest proportion of patients with a 3-month reduction in testosterone levels to <10 ng/dL<b15>.
Fig.
4 Results of the control of testosterone levels by triptorelin, goserelin and leuprolide
In the past, clinicians may have focused more on changes and controls in patients' PSA levels than on changes and management of testosterone
.
In order to enhance clinicians' attention to testosterone management, the Chinese Expert Consensus on Testosterone Management in Prostate Cancer (2021 Edition)4 has standardized and recommended
the whole process of testosterone management.
The consensus recommends regular monthly testosterone
testing prior to initiation of ADT and for 6 months of treatment.
As the condition enters a stable state, the interval between testosterone tests can be extended to once every 3~6 months, or testosterone testing can be synchronized with PSA testing
.
Regular monitoring of a patient's testosterone can not only determine whether current treatment regimens are working for the patient, but also monitor the patient for disease progression
.
We know that testosterone below castration levels is necessary to diagnose CRPC
.
Therefore, testosterone monitoring is necessary
for patients with advanced prostate cancer to undergo ADT treatment at the same time.
The concept of "deep ketone reduction" is gradually being paid attention to by urologists and used in clinical practice, and many clinical studies have confirmed that triptorelin can significantly reduce testosterone levels
in patients with advanced prostate cancer.
At present, Chinese clinicians are still in the stage of continuous exploration of "deep ketone reduction", and we hope that through this case sharing, Chinese clinicians can realize the importance of testosterone monitoring during ADT treatment and further improve the quality of life of
prostate cancer patients in China.
References:
1.
Robinson D, et al.
Integrative clinical genomics of advanced prostate cancer.
Cell.
2015 May 21; 161(5):1215-1228.
2.
Yamamoto S, et al.
Testosterone Reduction of ≥ 480 ng/dL Predicts Favorable Prognosis of Japanese Men With Advanced Prostate Cancer Treated With Androgen-Deprivation Therapy.
Clin Genitourin Cancer.
2017 Dec; 15(6):e1107-e1115.
3.
Lebret T, 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.
4.
Urology Branch of Chinese Medical Association, Urogenital Tumor 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.
)
5.
Shim M, 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.
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