Cystoprostatectomy Versus Radiotherapy Combined With ADT for the Treatment of cT4 Prostate Cancer With Bladder Invasion (CRADT)

• ClinicalTrials.gov Identifier: NCT03482089
• Recruitment Status: Recruiting
• First Posted: March 29, 2018
• Last Update Posted: October 21, 2022
• Sponsor: Tongji Hospital
• Collaborators: Chinese PLA General Hospital; Xiangya Hospital of Central South University; Hubei Cancer Hospital
• Information provided by (Responsible Party): Tongji Hospital

Study Description

Brief Summary:

Prostate cancer is the most common male cancer in global, which accounts for 19% of the total and poses great hazards to male health. Unfavorable factors including prostatic specific antigen (PSA) >20 ng/ml, Gleason score >8, and T3/4 are significantly associated with biological recurrence, metastatic progression and poor survival in prostate cancer. In clinical T4(cT4) prostate cancer with bladder invasion patients, symptoms of hematuria, urinary urgency, bladder outlet and ureteral obstruction, and pelvic pain led to a poor quality of life.

Radical prostatectomy is crucial for the multimodal treatment of prostate cancer, but limited proof demonstrated enough advantages of the surgery in T4 tumor with bladder invasion. Radical prostatectomy could hardly meet both demands of local tumor control and urinary function. Treatment trends suggest that patients with T4 prostate cancer be treated with radiotherapy combined with androgen deprivation therapy (ADT). However, surgery enables a full pathological assessment of the tumor characteristics and thus a better estimation of the risk of recurrence. Cystoprostatectomy offers an option of surgical treatment for T4 prostate cancer with bladder invasion，which can well remove the bladder and urethra, decrease the risk of positive surgical margins and avoid urination complications.

There is no consensus regarding optimal treatment of T4 prostate cancer and no evidence of oncological outcomes of cystoprostatectomy from clinical trials. A randomized clinical trial comparing two multimodal treatment regimens of cystoprostatectomy and radiotherapy for T4 prostate cancer with bladder invasion is therefore warranted.

Condition or disease	Intervention/treatment	Phase
Prostate Cancer	Procedure: Cystoprostatectomy; Radiation: external beam radiotherapy	Not Applicable

Detailed Description:

1. Determine the subjects

Patients were determined in strict accordance with the inclusion and exclusion criteria, and the trial process and significance were explained to the patients, and informed consent was signed.

2 Randomization

The patients were randomly assigned to surgery group or radiotherapy group according to the random number table.

3 Implementation Process

The intervention measures were divided into operation group and non-operation group. The operation group was given cystoprostatectomy + expanded pelvic lymph node dissection + urinary diversion. The non-operation group received radiotherapy plus androgen deprivation therapy.

4 Follow-up Process

Follow-up was performed once a month (12 times in total) in the first year after surgery or radiotherapy, once every 3 months (4 times in total) in the second year, and once every six months after 2 years. Follow-up items included the presence of complications, digital rectal examination, PSA and testosterone levels, liver and kidney function. If digital rectal examination is positive and serum PSA continues to rise, pelvic MRI and bone scan should be performed. Bone pain, regardless of PSA level, should be scanned.

FunctionalAssessment of Cancer Therapy-General (FACT-G; FunctionalAssessment of Cancer Therapy-Prostate, FACT-P) and color Doppler ultrasonography of bilateral kidney and ureter were performed once every six months after 1 year.

Pelvic MRI, bone scan, chest radiograph, and color ultrasound of abdomen (liver, bile, pancreas and spleen) were examined once a year after surgery or radiotherapy.

Other follow-up examination items or follow-up time can be selected according to special circumstances. The patients were followed up for at least 10 years after surgery or after the end of radiotherapy.

5. Monitoring and management of recurrence, metastasis and complications

If biochemical recurrence after surgery (PSA level two consecutive acuity 0.2 ng/ml, two test interval of 2 weeks) or local recurrence, choose save radiotherapy, 8 Gy single, range is the whole pelvic, continued progress or control again after recurrence after radiotherapy are endocrine therapy, and its solution for than carew amine (50 mg 1 time, 1 times a day, Orally) + Goserelin (3.6mg once every 28 days, subcutaneously injected into the anterior abdominal wall); Patients with extensive metastasis after surgery were treated directly with endocrine therapy (bicalutamide 50mg once daily, orally) plus gosererin (3.6mg once every 28 days, subcutaneously injected into the anterior abdominal wall). The remaining tumor progression was managed according to the recommendations of authoritative guidelines at home and abroad.

The time of occurrence, name of complication, patient status, Clavien-Dindo complication classification, treatment measures and procedures, and treatment results were recorded. Complications were managed according to the recommendations of the guidelines and the experience of our unit.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 70 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Cystoprostatectomy Versus Radiotherapy Combined With Androgen Deprivation Therapy for the Treatment of Clinical T4 Prostate Cancer With Bladder Invasion: a Multicentre, Prospective, Open, Randomized Clinical Trial
• Actual Study Start Date: June 12, 2018
• Estimated Primary Completion Date: June 12, 2023
• Estimated Study Completion Date: June 12, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Cystoprostatectomy; (Open, laparoscopic or robot-assisted ) cystoprostatectomy with urinary diversion surgery and extended pelvic lymph node dissection; without adjuvant androgen deprivation therapy;	Procedure: Cystoprostatectomy; Patients with bladder infiltrating T4 prostate cancer receive cystoprostatectomy with urinary diversion surgery and extended pelvic lymph node dissection
Active Comparator: Radiotherapy; Radiotherapy by external beam radiotherapy (81 Gy，2.4-4 Gy per fraction over 4-6 weeks); with adjuvant androgen deprivation therapy for the least 3 years	Radiation: external beam radiotherapy; Patients with bladder infiltrating T4 prostate cancer are treated with adjuvant androgen deprivation therapy

Outcome Measures

Primary Outcome Measures :

1. Overall survival (OS) [ Time Frame: 10 years ]
   The percentage of subjects in a study who have survived at the the endpoint of the observation since randomization or the interval between randomization and death from any cause.

Secondary Outcome Measures :

1. Biochemical progression-free survival (BPFS) [ Time Frame: 10 years ]
   the interval between randomization and biochemical recurrence or death from any cause or the percentage of subjects in a study who have survived without biochemical recurrence at the endpoint of the observation since randomization
2. Cancer-specific survival (CSS) [ Time Frame: 10 years ]
   the interval between randomization and tumor recurrence, metastasis, or death from any cause, or the percentage of subjects in a study who have survived without tumor recurrence or metastasis at the endpoint of the observation since randomization
3. Functional Assessment of Cancer Therapy-General (FACT-G) score [ Time Frame: 10 years ]
   This is a score system assessing cancer patients' quality of life, including four aspects of physical status, social status, emotional status and functional status. The total score ranges from 0-108 and a higher score indicates a better outcome.
4. Functional Assessment of Cancer Therapy-Prostate (FACT-P) score [ Time Frame: 10 years ]
   This is a score system assessing prostate cancer patients' quality of life. The total score ranges from 0-48 and a higher score indicates a better outcome
5. complications [ Time Frame: 10 years ]
   the complications and the incidence

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Age ≤75, at the time of randomization
2. Newly diagnosed primary prostatic adenocarcinoma confirmed by pathological examination of biopsy；diagnosed within 6 months prior to randomization
3. Untreated for surgery, radiotherapy, or androgen deprivation therapy
4. Eastern Cooperative Oncology Group (ECOG) performance status 0- 2; American Standards Association (ASA) classification I-III
5. A life expectation of at least 10 years
6. Tumor stage (T, M, N): Clinical T4N0M0 with bladder invasion (confirmed by MRI)
7. Eligible for either treatment of cystoprostatectomy or radiotherapy
8. Signed informed consent should be obtained from both the patient or one authorized legal relative.

Exclusion Criteria:

1. Patients with a history of other cancer diagnoses except non-melanoma skin cancer
2. Patients with pelvic surgery
3. Patients with severe systemic diseases
4. severe kidney function -glomerular filtration rate (GFR) < 30 ml/min or elevated liver transaminases above > 10 upper limit of normal (ULN)
5. Patients who are not able comply with scheduled follow-up visits and examinations with the consideration of patients' physical or mental condition

Contacts and Locations

Contacts

Contact: Zhiqiang Chen, M.D.,Ph.D; 008613995512271; zhqchen8366@163.com

Contact: Peng Yuan, M.D.; 008615927679790; mwyuanpeng@163.com

Locations

China, Hubei

Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology; Recruiting

Wuhan, Hubei, China, 430030

Contact: Zhiqiang Chen, M.D.,Ph.D

Sponsors and Collaborators

Tongji Hospital

Chinese PLA General Hospital

Xiangya Hospital of Central South University

Hubei Cancer Hospital

Investigators

• Study Chair: Zhiqiang Chen, M.D.,Ph.D; Tongji Hospital

More Information

• Responsible Party: Tongji Hospital
• ClinicalTrials.gov Identifier: NCT03482089
• Other Study ID Numbers: CZQ5208
• First Posted: March 29, 2018
• Last Update Posted: October 21, 2022
• Last Verified: October 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases