Professor Yang Bin: Preoperative neoadjuvant treatment of prostate cancer lined up

Introduction Radical prostatectomy (RP) is more and more widely used in prostate cancer, but there are problems with a high positive rate of postoperative resection margins and a high recurrence rate
.

More and more clinical studies have shown that giving neoadjuvant therapy before RP can reduce tumor stage, reduce tumor focus, reduce prostate specific antigen (PSA), and reduce lymph node metastasis
.

Research on neoadjuvant therapy for prostate cancer is in full swing.
Let us follow Professor Yang Bin to take a look at the current formation
.

Expert profile Associate Professor Yang Bin Associate Chief Physician of the Department of Urology, Shanghai Tenth People's Hospital Member of the Oncology Group of the Youth Committee of the Urology Branch of the Medical Association Member of the Science Popularization and Communication Group of the Youth Committee of the Urology Branch of the Chinese Medical Association Specializes in fusion targeted precision biopsy for early diagnosis of prostate cancer, laparoscopic minimally invasive radical resection of localized prostate cancer with reserved nerve and early urinary control function, and laparoscopic minimally invasive radical resection/open radical resection of high-risk locally advanced prostate cancer As well as enlarged/ultra-enlarged lymph node dissection, primary tumor reduction surgery for oligometastatic prostate cancer and enlarged/ultra-enlarged lymph node dissection, salvage pelvic and retroperitoneal lymph node dissection for biochemical recurrence after radical prostatectomy, based on molecular/ gene individualized comprehensive treatment of advanced prostate cancer detection
.

Neoadjuvant chemotherapy Since the TAX-327 study confirmed the sensitivity of prostate cancer to chemotherapy, research on neoadjuvant chemotherapy for prostate cancer has been carried out in an orderly manner
.

As early as 2004, Dreicer and others conducted a single-arm, phase II study, which for the first time confirmed that patients received neoadjuvant chemotherapy before RP, and the PSA of patients decreased significantly [(12.
00±1.
86)ng/ml and (8.
42±1.
63)ng/ ml, P<0.
03], 20 cases did not need further treatment intervention after an average follow-up of 23 months1
.

Although neoadjuvant chemotherapy has a certain effect, the effect is limited, and most of the current studies are phase II, single-arm studies, and few studies incorporate long-term survival indicators such as OS for evaluation.
Therefore, neoadjuvant chemotherapy does not meet clinical needs
.

Neoadjuvant endocrine therapy is the earliest neoadjuvant treatment for prostate cancer.
A large number of studies have explored neoadjuvant endocrine therapy, but the results indicate that there is no significant benefit to survival outcomes
.

Shelley et al.
analyzed 14 studies on neoadjuvant endocrine therapy from 1966 to 2007, and the results showed that it can reduce the positive rate of resection margins, the tumor stage of T3 patients, and the positive rate of lymph nodes, but the OS and tumor-specific survival rate (CSS) No improvement; Kumar et al.
's study included a neoadjuvant endocrine therapy study for localized or locally advanced prostate cancer from 1996 to 2006, and the results still suggest that there is no significant benefit for OS1
.

In the previous Meta-analysis 2, the efficacy of neoadjuvant androgen deprivation therapy (ADT) combined with RP versus RP alone was evaluated in patients with localized prostate cancer
.

The results showed that after 3 months of neoadjuvant ADT treatment, there was no improvement in recurrence-free survival (RFS) (HR=0.
90, 95% CI: 0.
74-1.
11) and overall survival (OS) (HR=1.
22, 95% CI: 0.
62-2.
41), but significantly reduced the positive rate of surgical margins (RR=0.
48, 95% CI: 0.
41-0.
56) and pathological staging
.

Therefore, neoadjuvant endocrine therapy can reduce tumor volume and reduce postoperative tumor residues, but it cannot improve patient survival and increase benefit.
Therefore, it has not been included in the recommendations of major guidelines. .

Neoadjuvant chemotherapy combined with endocrine therapy alone has no clinical outcome benefit, but neoadjuvant chemotherapy combined with endocrine therapy shows good results
.

CHAARTED/GETUG 12 Study 1 evaluated the benefit of neoadjuvant docetaxel + estramustine + ADT regimen compared to neoadjuvant ADT alone on survival after local radical treatment.
The results of a median follow-up of 8.
8 years showed that the two groups of RFS There is a significant difference (62% vs 50%, HR=0.
71)
.

As early as 2014, Renji Hospital in China conducted a three-arm trial of neoadjuvant chemotherapy combined with endocrine therapy vs.
neoadjuvant ADT vs.
blank control.
The results showed that neoadjuvant chemotherapy combined with endocrine therapy can improve postoperative PSA undetectable levels and biochemical progression-free survival.
(BPFS) 1
.

The above two studies show that neoadjuvant chemotherapy combined with endocrine therapy can benefit patients with high-risk localized prostate cancer
.

Neoadjuvant new endocrine therapy combined with ADT In recent years, new endocrine therapy drugs such as enzalutamide and abiraterone have been developed rapidly, and have shown excellent efficacy in the treatment of advanced prostate cancer.
Some of these drugs have participated in clinical research on neoadjuvant therapy of prostate cancer.

.

In 2020 EAU Guidelines 3, a new study of neoadjuvant new endocrine therapy combined with ADT has been added
.

This study compared the efficacy of neoadjuvant new endocrine therapy combined with ADT vs neoadjuvant ADT for high-risk localized prostate cancer patients.
The results showed that the combined treatment plan significantly reduced tumor volume compared with neoadjuvant ADT alone
.

At the same time, the follow-up results for more than 4 years showed that the smaller the tumor volume after neoadjuvant therapy, the lower the biochemical recurrence rate (BCR) (P=0.
0014)
.

The previous guidelines did not recommend neoadjuvant endocrine therapy, mainly based on research focusing on luteinizing hormone-releasing hormone (LHRH) drugs or a generation of antiandrogens.
Nowadays, research on new endocrine therapy drugs is springing up, and it is very promising to be included in the future.
Guide recommendation
.

References: 1.
Liu Ming, Hou Huimin.
The progress of neoadjuvant chemotherapy combined with endocrine therapy in the treatment of prostate cancer[J].
Chinese Journal of Urology, 2020, 41 (Supplement): 14-16.
2.
Ameeta L Nayak, Anathea S Flaman ,Ranjeeta Mallick,et al.
Do androgen-directed therapies improve outcomes in prostate cancer patients undergoing radical prostatectomy? A systematic review and meta-analysis.
Can Urol Assoc J.
2021 Jan 8.
3.
EAU-EANM -ESTRO-ESUR – SIOG Guidelines on Prostate Cancer (2020).
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