This is A Multi-centre, Single-arm, Prospective, Interventional Study to Assess Efficacy and Safety of Neoadjuvant Hormone Therapy using Zoladex (Goserelin) and Casodex (Bicalutamide) in Patients with Advanced Prostate Cancer Undergoing Radical Prostatectomy, to assess the efficacy by resectability rate of neoadjuvant hormone therapy (NHT) in subjects with advanced prostate cancer.
Neoadjuvant hormonal treatment (NHT) for clinically localised prostate cancer consists of complete androgen blockade (CAB) preceding either radiotherapy or surgery. The rational for this approach is based on the assumption that NHT will reduce both the tumour and normal prostatic tissue volume, and induce cancer regression by the mechanism of apoptosis \[1\]. Most randomized clinical trials show that NHT reduces the incidence of positive surgical margins after radical prostatectomy and apparently determines tumour downstaging, however no advantage has been documented in terms of biochemical disease progression \[for example, time to prostate specific antigen (PSA) increase\] between treated and untreated patients \[2-8\]. Because of relatively low biological aggressiveness of prostatic carcinoma, many patients will need to be followed for a considerable time before drawing significant conclusions on the effects of NHT on survival \[2,4,7,10\]. A large sample of 393 radical prostatectomy specimens were evaluated in 3 treatment groups, which were immediate surgery, 12 weeks of NHT (Zoladex and Casodex), and 24 weeks of NHT. Patients included clinical stage B (T2a and T2b) and stage C (T3a and T3b). Systemic hormonal treatment, whether 12 weeks or 24 weeks of NHT, is able to "downstage" the primary tumour and decrease the positive margin rate before definitive localised treatment \[11\]. Currently treatment of patients with oligometastatic prostate cancer is undergoing dramatic changes \[12\]. The local treatment of the primary tumour might provide a survival benefit to men with metastatic and lymph node-positive disease. Similar observations have been made in treatment of metastatic lesions with life-prolonging, rather than palliative intent \[13-17\]. This study is proposed primarily to observe the efficacy and safety of 24-week NHT (Zoladex and Casodex) in patients with locally advanced or oligometastatic prostate cancer. Progression status and survival will be followed-up for up to 2 years after NHT. This is a multi-centre, single-arm and prospective study to explore the efficacy and safety of neoadjuvant hormone therapy (NHT) for advanced prostate cancer patients undergoing radical prostatectomy (RP). A total of 104 subjects with locally advanced and oligometastatic prostate cancer at clinical stage of T3 and T4 will be enrolled at almost 20 centres in China. The eligible subjects will receive Casodex 50 mg orally per day in combination with Zoladex 10.8 mg implant subcutaneously every 12 weeks as neoadjuvant therapy for 24 weeks, and then will be assessed for resectability of the primary tumour. The subjects will undergo a RP \[RALP (robot-assisted laparoscopic prostatectomy), laparoscopic RP or RRP (radical retropubic prostatectomy)\] plus eLND thereafter if the primary tumour is assessed as resectable. Surgical margin status and involvement of bilateral pelvic lymph nodes will be evaluated. Subjects will be prescribed post-surgical treatment such as continuous ADT and metastasis-directed therapy upon investigator's discretion and be followed-up for up to 2 years. Progression free survival (PFS) and overall survival (OS) will be collected during this study. For the subjects with unresectable primary tumour after NHT, PFS and OS will also be collected in the follow-up for up to 2 years after 24 weeks of CAB.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
9
The eligible subjects will receive Casodex 50 mg orally per day in combination with Zoladex 10.8 mg implant subcutaneously as neoadjuvant therapy per 12 weeks for up to 24 weeks.
Research Site
Beijing, China
Research Site
Changsha, China
Research Site
Changsha, China
Resectability rate for primary tumour (the resectability will be assessed by central review using a digital rectal examination and confirmed by CT or MRI)
To assess the efficacy by resectability rate of neoadjuvant hormone therapy (NHT) in subjects with advanced prostate cancer
Time frame: at 24 week
Radical prostatectomy rate
Which will be derived using the number of patient who will conduct the radical prostatectomy at 24 week.
Time frame: From baseline to 24 week
The mean PSA by the end of NHT
which will be derived using the value of mean PSA by the end of NHT
Time frame: From baseline to 24 week
Percentage of positive surgical margin for primary tumour
Which will be derived using the number of positive surgical margin at 24 week
Time frame: From baseline to 24 week
Incidence of seminal vesicle invasion
Which will be derived using the value of incidence of seminal vesicle invasion at 24 week
Time frame: From baseline to 24 week.
Percentage of pathological downstaging
Which will be derived using the number of pathological downstaging at 24 week.
Time frame: From baseline to 24 week
surgical-related variables at 12 weeks, potent rates in erectile function at 12 weeks after surgery
Which will be derived using the value of observe surgical-related variables and complications at week 36
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Research Site
Chengdu, China
Research Site
Guangzhou, China
Research Site
Guangzhou, China
Research Site
Hangzhou, China
Research Site
Hangzhou, China
Research Site
Hefei, China
Research Site
Shanghai, China
...and 5 more locations
Time frame: From 24 week to 36 week
PFS
Which will be derived using the number of PFS at the end of study
Time frame: From baseline to the end of study
AEs/SAEs
To evaluate the safety of NHT using goserelin and bicalutamide
Time frame: From baseline to 28 week
PSA change from baseline
Which will be derived using the value of PSA at the baseline.
Time frame: From baseline to 24 week
Involvement of bilateral pelvic lymph nodes
Which will be derived using the value of involvement of bilateral pelvic lymph nodes at 24 week.
Time frame: From baseline to 24 week
OS
Which will be derived using the number of OS at the end of study.
Time frame: From baseline to the end of study