A new era of prostate cancer treatment with ADT as the cornerstone from 2022 ASCO-GU

The 2022 American Society of Clinical Oncology Annual Meeting on Genitourinary Oncology (ASCO-GU) has come to a close
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The theme of this conference is "Leading Breakthroughs in the Development of Urogenital Tumors", providing a platform for academic discussion and cutting-edge knowledge exchange for urologic oncologists around the world
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Drugs are booming, and various new combination therapies emerge in an endless stream, but the treatment of prostate cancer is inseparable from the development of androgen deprivation therapy (ADT)
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At this year's ASCO-GU conference, there has been a lot of progress in endocrine therapy for prostate cancer.
Let's review the highlights of ADT together
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Rock-solid, solid ADT cornerstone Androgen-deprivation therapy (ADT) is the basic treatment for locally advanced and metastatic prostate cancer, as well as the basis for various novel combination therapy regimens, and is often required throughout the patient's follow-up treatment
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ADT treatment includes various embodiments, of which simple castration (surgical or medical) is the most widely accepted core treatment modality
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This year's ASCO-GU conference updated the research results of multiple new therapeutic drug combination therapy, but the status of ADT as a basic treatment is unbreakable
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1.
Abs 13: The results of the phase III ARASENS trial showed that darotamide combined with ADT plus docetaxel significantly improved overall survival (OS) in metastatic hormone-sensitive prostate cancer (mHSPC) and reduced the risk of death by 32.
5% (HR= 0.
68, 95% CI 0.
57-0.
80; P<0.
001) [1]; 2.
Abs 115: Post hoc analysis of the ARCHES trial suggested that in mHSPC patients with high and low disease burden and initial diagnosis of M0 or M1, Enzalu The long-term survival benefit of amine (E) combined with ADT compared to placebo is consistent [2]; 3.
Abs 132: This review evaluated the efficacy of 9 combination therapies, including abiraterone combined with prednisone-ADT ( AAP-ADT), E-AAP-ADT, AAP-docetaxel (D)-ADT and other therapies, the conclusions suggest that triple therapy is most likely to improve imaging progression-free survival (rPFS) and OS, but the toxicity has increased [ 3]
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At present, first-line castration drugs mainly include luteinizing hormone-releasing hormone (LHRH) agonists and LHRH antagonists, among which LHRH agonists are the most commonly used ADT drugs in clinical practice, including triptorelin, goserelin and leuprolide
.

At this ASCO-GU conference, the third analysis of the FINITE trial of LHRH agonist (LHRHa) combined with abiraterone (AA) in the treatment of biochemically recurrent non-metastatic hormone-naïve prostate cancer (M0HNPC) patients confirmed the efficacy of LHRHa + AA.
Benefit (Abs 135) [4]
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In preoperative studies, short-term LHRHa+AA treatment of high-risk prostate cancer can significantly reduce tumor, but in M0HNPC patients, androgen signaling inhibitor (ASI) is only suitable for patients with short PSA doubling time (PSADT)
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The researchers concluded that patients with preoperative LHRHa+AA debulking may benefit from short-term HRHa+AA therapy after PSA recurrence
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The trial was a phase III trial that randomized 199 patients 1:1 to LHRHa alone (n=99) or LHRHa+AA+prednisone (n=98) with a median PSA of 0.
95ng/dL , the median testosterone was 342.
5ng/dL
.

The primary endpoint was 12-month PSA-free survival (<0.
1 ng/dL)
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As of October 1, 2021, patients who received LHRHa+AA had a higher proportion of PSA-free survival at 12 months after completing treatment (34% vs 19%, P=0.
02)
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PSA progression occurred in 168 patients (85%), and the overall population median time to PSA progression (TTPP) was 24.
3 months
.

The duration of TTPP was longer in the LHRHa+AA group compared with LHRHa alone (27.
2 vs 19.
9 months, P=0.
003)
.

Figure 1 The TTPP results of the FINITE trial focused on the frontier.
The ketone-lowering effect of ADT was obvious.
As early as 1941, Huggins et al.
[5] observed that orchiectomy or estrogen therapy can effectively control metastatic prostate cancer, and first proposed the inhibition of testosterone (T) levels can be used to treat metastatic prostate cancer, and in follow-up studies, ADT treatment that suppresses testosterone levels can reduce PSA levels and directly reduce the risk of death
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At this year's ASCO-GU conference, the published results of the subgroup analysis of the Phase III HERO study confirmed that GnRH has a significant ketone-lowering effect (Abs 105) [6]
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The study is a randomized, global, multicenter, randomized controlled study to compare the efficacy and safety of GnRH experimental and control groups in advanced prostate cancer
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Previous results suggest that 96.
7% of patients in the experimental group achieved and maintained castration levels of testosterone within 48 weeks of follow-up, compared with 88.
8% in the control group, compared with the control group.
This conference mainly reports on a subgroup of black patients Analysis results
.

The results showed that both the test group and the control group maintained the castration level (<50ng/dL) rate of 93.
3% at 48 weeks.
The suppression of testosterone castration levels at 15 days (97% vs 13%) and the rate of deep ketone reduction at day 15 (67% vs 6%) were superior
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In parallel with double-labeling, triptorelin has a higher benefit of deep ketone reduction.
Both testosterone and PSA are important predictors of survival in patients with prostate cancer.
The early research and clinically recognized castration level standard is T<50 ng/dL
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With the accumulation of evidence-based medical evidence, the researchers found that the clinical outcome of T levels in the range of 20-50 ng/dL was worse than that of patients with T < 20 ng/dL, so it is recommended to define the standard of castration level as T < 20 ng/dL
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At present, the European Association of Urology (EAU) has specified in the latest guidelines that control of T < 20 ng/dL can benefit more prostate cancer patients than T levels of 20-50 ng/dL [7]
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Among the many ADT drugs, the LHRH agonist triptorelin has a more pronounced effect of deep ketone reduction while reducing PSA levels
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A retrospective analysis [8] compared the changes in testosterone levels within 9 months of triptorelin, leuprolide, and goserelin treatment, and the results suggested that in 125 patients, the triptorelin treatment group (regardless of All patients, whether in the overall population or in the monotherapy subgroup), were able to reduce testosterone levels to <20 ng/dL at 6 and 9 months
.

In addition, among the three drugs, triptorelin had the highest proportion of patients in reducing testosterone levels to <10ng/dL in 3 months, which was significantly better than goserelin (P<0.
001)
.
Figure 2.
Summary of the efficacy comparison of triptorelin ,
goserelin and leuprolideThe diagnosis and treatment of prostate cancer is developing rapidly.
Looking at the new era of prostate cancer treatment from the 2022 ASCO-GU, the cornerstone of ADT remains unshakable
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In clinical practice, PSA value is often used as a treatment evaluation criterion, while testosterone level cannot be ignored.
Deep ketone reduction (T < 20 ng/dL) can significantly delay the progression of prostate cancer and significantly prolong the progression to castration-resistant prostate cancer (CRPC).
Time is an important predictor of survival in prostate cancer patients
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Double standard parallel, go to be bound to reach! Only by focusing on the simultaneous management of PSA and testosterone in the diagnosis and treatment of prostate cancer can it bring long-term survival benefits to patients
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References: [1] Matthew Raymond Smith, Maha HA Hussain, Fred Saad, et al.
2022 ASCO-GU, abstract 13.
[2] Andrew J.
Armstrong, Taro Iguchi, Arun Azad, et al.
2022 ASCO-GU, abstract 115.
[3] Irbaz Bin Riaz, Syed Arsalan Ahmed Naqvi, Waleed Ikram,et al.
2022 ASCO-GU,abstract 132.
[4] Andrew Warren Hahn, Xuemei Wang, Eleni Efstathiou,et al.
2022 ASCO-GU, abstract 135.
[5] HUGGINS C.
Studies on prostatic cancer: Ⅱ.
The effects of castration on advanced carcinoma of the prostate gland［J］.
Arch Surg, 1941, 43(2): 209-223.
[6] Daniel J .
George, Fred Saad, Christopher Michael Pieczonka, et al.
2022 ASCO-GU, abstract 105.
[7] CORNFORD P, VAN DEN BERGH RCN, BRIERS E, et al.
EAU-EANM-ESTRO-ESUR-SIOG guidelines on prostate cancer.
part Ⅱ-2020 update: treatment of relapsing and metastatic prostate cancer［J］.
Eur Urol, 2021, 79(2): 263282.
[8] 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.
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