Professor Li Yonghong: Mid-year inventory - 2022 prostate cancer memorabilia

"An "Medicine" Happy Industry" is a humanistic case collection project
cooperated by Beijing Chen Jumei Public Welfare Foundation and Yimaitong.
The series of interviews with urology doctors will focus on the field of prostate cancer, discuss the significance of standardized diagnosis and treatment paths and whole-course management of prostate cancer to clinical patients based on the real clinical needs, and highlight the research spirit and professionalism of urological oncologists
.

September cold dew white, six levels of autumn grass yellow
.
Unconsciously, most of 2022 has passed, and ASCO-GU, ASCO, EAU, ESMO and other conferences have been held and ended
.
This year, prostate cancer from diagnosis to treatment, continuous innovation, advanced prostate cancer dual therapy to triple therapy, so that the treatment of prostate cancer into a new era
.
In this issue, we invite Professor Li Yonghong of the Affiliated Cancer Hospital of Sun Yat-sen University to share the frontier progress of prostate cancer in 2022 and take stock of the major events in the field of prostate cancer in this year for the benefit of readers
.

Expert profile

Professor Li Yonghong

Deputy Director of the Department of Urology, Affiliated Cancer Hospital of Sun Yat-sen University, and Director of the Third District of Urology

Chief Physician Master Supervisor

Prostate cancer single disease specialist

Outstanding young medical talents in Guangdong Province

Member of the Prostate Cancer Expert Committee of the Chinese Society of Clinical Oncology (CSCO).

He is a member of the Andrology Group of the Urology Branch of the Chinese Medical Association

Member of the Standing Committee of the Asian Society of Cryotherapy

Leader of the Urological Tumor Ablation Professional Group of the Tumor Ablation Treatment Technical Expert Group of the Chinese Medical Doctor Association

Secretary of the Professional Committee of Genitourinary Oncology of Guangdong Anti-Cancer Association

Senior Training Instructor in Leonardo da Vinci Robotic Urology

Specializes in the diagnosis and treatment
of prostate cancer.
He has published more than 20 papers in journals such as "European Urology", "Clinical Cancer Research", "Prostate", "Prostate Cancer and Prostatic Disease", "Urology" and other journals, and his research results have been published by the NCCN Guide in the United States, the CSCO Guide in China and Campbell Urology.
Citing a number of research funds such as the projects of the Natural Science Foundation of the People's Republic of China

Memorabilia 1: The development of diagnosis and tumor markers has set a new benchmark for the diagnosis and treatment of prostate cancer

The accurate diagnosis of prostate cancer and the accurate assessment of tumor burden help to formulate accurate and effective treatment plans, with the development of precision medicine, the limitations of traditional diagnostic methods have gradually emerged, and the research of new diagnostic methods has blossomed, bringing new basis
for clinical diagnosis.

Professor Li Yonghong introduced that there are many research advances in PSMA-PET/CT, and many studies suggest that PSMA can be used to predict the prognosis
of patients.
As the study at the ASCO-GU conference suggested, PSMA PET and FDG PET can be used as predictors of treatment response and prognosis; Another study suggested that the RECIP 1.
0 standard for PSMA-PET/CT could be used as a reactive biomarker to monitor the efficacy of ¹⁷⁷Lu-PSMA in patients with metastatic castration-resistant prostate cancer (mCRPC); Studies at the ASCO conference also showed that PSMA PET stratification predicts the biochemical recurrence (BCR-FS) after radical prostatectomy (RP) in patients with medium- and high-risk prostate cancer
.

Professor Li Yonghong said that PSMA detects metastases with high sensitivity and is receiving more and more attention in clinical practice
.
In the clinical center where Professor Li Yonghong is located, it is recommended that patients with biochemical recurrence after RP, or biochemical residues, use PSMA-PET/CT examination, which is also a widely used indication internationally
.
At the same time, in patients with high-risk localized prostate cancer, PSMA-PET/CT can detect metastases that cannot be detected by conventional imaging examination, thereby changing clinical treatment strategies
.
On July 4, 2022, the journal Nature Reviews Urology published a review stating that PSMA PET and whole-body magnetic resonance imaging (WB MRI) are considered next-generation imaging (NGI) methods
for prostate cancer.
However, because the test is not available in many places, and ^{the 177}Lu-PSMA drug has not yet been approved in China, PSMA is not widely used
in the country.

In addition, at this year's International Congress, a number of studies explored gene mutations as prognostic factors for prostate cancer, such as high-risk (HiRi) mutation characteristics, and the deletion of tumor suppressor genes (TSG) TP53, RB1 and PTEN
.
Because prostate cancer patients are treated for a period of time, heterogeneity will occur, resulting in PSA can not accurately reflect changes in the condition, so biomarkers such as CEA/CA199 will also be used in the clinic to guide clinical decision-making
.

In previous clinical studies, total survival (OS) was often used as the endpoint of clinical studies, but this endpoint often required longer follow-up to be obtained
.
Professor Li Yonghong introduced that this year's ASCO conference has proposed whether it is possible to use indirect clinical endpoints (ICE) as an alternative endpoint, and the results show that if ICE is used as the research endpoint, the follow-up time is shortened by half compared with OS, which is conducive to the faster entry into clinical application
of research drugs.

Timeline II: Advancement of radiotherapy and neoadjuvant therapy in localized prostate cancer

For the treatment of localized prostate cancer, surgery, radiation therapy, and active monitoring are the mainstream treatments
.
This year's ASCO-GU Conference pointed out that receiving early salvage radiotherapy after RP is associated with improved survival without metastasis (MFS), to which Professor Li Yonghong said that salvage radiotherapy should be involved as early as possible, generally when PSA < 0.
5ng/ml<b11>.

Adverse effects also varied between different radiation therapy modalities, with one real-world study showing better outcomes of urinary incontinence, sexual function, and hormonal function in the low-dose (LDR) brachytherapy (BT) group compared with external radiation therapy (EBRT), but there was no significant difference
between EBRT and EBRT+BT or high-dose (HDR) BT.

Chemotherapy combined with endocrine therapy also provides a survival benefit
.
Preliminary results from the RADIICS-HD trial at the just ESMO conference showed that androgen deprivation therapy (ADT) for 6 months and 24 months on top of postoperative radiotherapy for RP improved MFS
in patients.

In China, high-risk limited and locally advanced prostate cancer patients account for a relatively high proportion, due to the difficulty of surgical treatment of such patients, the benefits of traditional ADT treatment is not ideal, Professor Li Yonghong said, neoadjuvant therapy has become the current research hotspot
.
Previous retrospective studies have provided evidence-based medical evidence for neoadjuvant therapy for prostate cancer, and large sample sizes of prospective phase III studies such as neoadjuvant ADT+apalatamide and neoadjuvant ADT+riveramide have MFS as the primary endpoint
。 However, Professor Li Yonghong believes that the benefits of MFS alone are not convincing enough, because the control group of these two studies is ADT treatment alone, rather than the current standard treatment regimen (no neoadjuvant therapy, direct RP), so it is still unable to challenge the current status of standard treatment for limited prostate cancer, and more convincing evidence-based medical evidence
is needed.

Timeline 3: Changes in the treatment pattern of advanced prostate cancer

Metastatic prostate cancer is the focus and difficulty of clinical treatment, and there are few effective treatment drugs in the past for a long period of time, and the prognosis of patients is poor
.
In recent years, with the vigorous development of targeted drugs such as new endocrine drugs, chemotherapy, nuclide therapy and PARP inhibitors, the treatment of advanced prostate cancer has ushered in the dawn
.
Professor Li Yonghong said that one of the biggest changes in advanced prostate cancer this year is the shift
from dual therapy to triple therapy in metastatic hormone-sensitive prostate cancer (mHSPC).

From ASCO-GU we see that the PEACE-1 study and the ARASENS study show the benefits of triple therapy, i.
e.
the addition of chemotherapy
to ADT+ novel endocrine drugs.
Simultaneous meta-analyses have shown that triple therapy is most likely to improve radiographic progression-free survival (rPFS) and OS, but with increased toxicity, so the dual combination may still be the best option
for older patients with low tumor load.
Based on the significant benefits of the above two studies, this year's CSCO prostate cancer diagnosis and treatment guidelines, the triple therapy is included in the guidelines, to which Professor Li Yonghong said, which represents the concept of our national CSCO prostate cancer guidelines in line
with the latest international research.

However, due to the high toxicity of triple therapy, clinical application still needs to be cautious
.
An exploratory, hypothetical analysis at the ASCO conference suggests that triplet versus dual regimens may not delay disease progression or prolong survival; The I.
B.
Riaz team presented a systematic review of mHSPC combination therapy at this year's ESMO conference, which noted that triple therapy appears to be reliable in patients with high tumor load, and that dual therapy may be the first choice
for patients with low tumor load.
Professor Li Yonghong believes that some patients will benefit from triple therapy, and we need to find better biomarkers to screen out patients who are more suitable for triple therapy, so as to achieve higher treatment benefits
.

The triple protocol was not only applied to the mHSPC phase, but at the mCRPC stage, the PRESIDE study at the ASCO-GU conference evaluated the efficacy and safety of docetaxelic + enzalulamine + prednisolone in mCRPC patients who did not receive chemotherapy and progressed with enzalumine therapy, and the results showed a significant improvement in progression-free survival (PFS) compared with docetaxel chemotherapy, which was maintained for 9.
53 months in combination with docetaxel PFS, a 28% reduction Risk of disease progression (HR = 0.
72).

Figure 1 PFS results of the PRESIDE study

The research design of PRESIDE has been highly recognized by urological oncologists at home and abroad, and Professor Li Yonghong said that the choice of follow-up treatment options for new endocrine treatment advances in the mCRPC stage is still a hot and difficult point
in the clinic.
Because both enzalumide and docetaxel chemotherapy are treatments with high clinical accessibility, the PRESIDE study can provide valuable efficacy and safety data for the triple regimen in post-treatment of
the second line.

In addition to triple therapy, other new treatment options for mHSPC are also being carried out simultaneously, ASCO Conference Abstract 5005 shows that compared with bicalutamide combined with ADT, rveruride combined with ADT significantly improves the rPFS of high tumor load mHSPC, which has received widespread attention from domestic urological oncologists, Professor Li Yonghong said that this drug may become one of the most important treatment options for Chinese patients in the
future.

At the same time, research on novel endocrine therapies has been in full swing in recent years, such as the LATITUDE study of abiraterone, the ARCHES and ENZAMET studies of enzalumine, and the TITAN study of apatamide, which have achieved good OS benefits
for mHSPC patients.

In the preliminary analysis of the ARCHES study, enzalumine + ADT significantly improved rPFS in mHSPC patients, and this year's updated OS results showed that the median OS of enzalumine + ADT and placebo + ADT was not achieved, and the OS rates of 24 months, 36 months and 48 months of enzalumine were 86%, 78% and 71%, respectively, while the placebo group was 82%, 69% and 57%,
respectively 。 The risk of death was reduced by 43% in the Nzalulamine group compared with the placebo group after the potential effects of crossover were corrected by a preset sensitivity analysis model (RPSFT) (HR, 0.
57; P<0.
001;); The median OS was not achieved in the enzalumide group, which was 47.
7 months in the placebo group (95% CI, 43.
3-non-assessed).
<b11>

Figure 2 ARCHES study OS results

PRP inhibitors have made a lot of progress in prostate cancer in recent years, and Professor Li Yonghong shared two research advances
on the application of PARP inhibitors in mCRPC.
The PROpel study revealed the efficacy of abiraterone plus olaparil in patients with mCRPC, and the results showed a significant benefit of rPFS in the olapalli group compared with the placebo group, and the data from the secondary interim analysis at the ESMO conference suggested an increased
trend of OS benefit.
The study showed that both HRR mutants and patients without mutations benefited from PARP combination therapy, but patients without mutations benefited less
from rPFS obtained through combination therapy.

The MAGNITUDE study, which evaluated the efficacy of Nirapalil in combination with abidolone and prednisone (AAP) in patients with mCRPC and homologous recombination repair (HRR) gene mutations, with a BRCA1/2 positive rate of more than 50%, confirmed that PARP inhibitors and novel endocrine combination therapy can bring greater therapeutic benefits to patients with HRR mutations, and MAGNITUDE was the first to explicitly demonstrate the presence of BRCA1/ Clinical trials
in which PARP inhibitors and abiraterone are used in combination therapy with 2-mutation patients for benefit from the mCRPC1 line.

Expert thoughts

With the acceleration of the pace of new drug research and development, the diagnosis and treatment of prostate cancer has developed vigorously in recent years, bringing about changes
again and again.
Nowadays, androgen receptor (AR) pathway has always been a research hotspot in the field of prostate cancer, based on the research of Chinese group is making efforts, we look forward to China's research from a runner to a leader, so that the survival and quality of life of prostate cancer patients can be further improved
.

Past Review

1.
Professor Zhu Yao: The revision of the guidelines is like building a giant ship, carrying the hopes of patients all the way forward

2.
Easy to find Professor | The "growth" of the guide accompanies the breakthrough of diagnosis and treatment, and guides the future to a brighter and smoother road

3.
Professor He Weiyang: The development of anti-androgenic drugs: a clinical "revolution" driven by drug resistance

4.
Director Li Rubing: White clothes, clever hands, red heart - prostate cancer diagnosis and treatment concept and medical spirit

5.
Professor Ma Limin: "Medicine" has a long way to go, and the waves are gushing

6.
Professor Sun Ting: Optimization strategy for the whole process of prostate cancer management from one end to the end

7.
Professor Wang Jianbo: Literature and martial arts are both complete, hundreds of steel, doctors have a long way to go

8.
Professor Fan Xinrong: NHT is booming, mHSPC combined therapy is charging again

Special thanks to: Beijing Astellas Pharmaceutical Co.
, Ltd

Editor: Bingxin

Review: Bingxin

Typesetting: LR