Combined, Intensified and Modulated Adjuvant Therapy in Prostate Carcinoma

Not Applicable

Completed

• Conditions: Prostate Cancer
• Interventions: Radiation: Combined, intensified and modulated adjuvant radiotherapy

• Registration Number: NCT03169933
• Lead Sponsor: IRCCS Azienda Ospedaliero-Universitaria di Bologna

Brief Summary

Patients with high risk prostate cancer may benefit from radiotherapy after radical prostatectomy. The investigators postulated that adjuvant androgen deprivation therapy (ADT), radiation dose escalation, and selective pelvic irradiation may improve outcome. A phase II trial was designed to prove that combined-intensified-modulated-adjuvant (CIMA) treatment may improve 5-year biochemical relapse free survival (bRFS) from 75% to 90% in high risk patients. The delivered dose to tumor bed and pelvic nodes was 64.8-70.2 Gy and 45 Gy (57% of patients), respectively, and 69% received ADT.

Detailed Description

Prostate cancer patients at high risk of loco-regional recurrences may benefit from postoperative radiotherapy (RT) following radical prostatectomy (EORTC trial 22911). However, despite an improvement in biochemical relapse-free survival (bRFS), the risk of recurrences remained high for those patients. The investigators postulated that adjuvant androgen deprivation therapy (ADT), radiation dose escalation, and selective pelvic irradiation for patients at risk for regional failures may improve the outcome. The combined-intensified-modulated-adjuvant (CIMA) as described may improve survival through a reduction of loco-regional and systemic failures.

A phase II trial was designed to test the hypothesis that CIMA treatment may improve 5-year bRFS by 15%. Patients less than 80 years old, with a histological diagnosis of prostate adenocarcinoma without distant metastases, stage pT2-4 N0-1, no previous treatments and an ECOG performance status of 0-2 were selected. All patients had at least one of these pathologic features: extracapsular extension, positive surgical margins, or seminal vesicle invasion. Radiation dose to the tumor bed ranged from 64.8 to 70.2 Gy. Pelvic lymph nodes were treated to 45 Gy in selected patients at risk of regional failures (57%). Selected patients at risk for distant metastases (69.1%) received hormonal therapy.

Study Timeline

• Study Start: 2004-01-02
• Primary Completion: 2009-01-10
• Study Completion: 2017-01-02
• Study First Submitted: 2017-05-17
• Study First Submitted QC: 2017-05-25
• Study First Posted: 2017-05-30
• Status Verified: 2018-03
• Last Update Submitted: 2018-03-05
• Last Update Posted: 2018-03-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 123

Inclusion Criteria

• < 80 years old
• histological diagnosis of prostate adenocarcinoma
• no distant metastases
• stage pT2-4
• N0-1
• ECOG performance status of 0-2
• One of these pathologic features: extracapsular extension, positive surgical margins, or seminal vesicle invasion. extracapsular extension, positive surgical margins or seminal vesicle invasion, or positive lymph-nodes
• No surgical complications such as pelvic infections or lymphocele, intraoperative rectal injury or severe urinary incontinence
• Preoperative and postoperative PSA test, bone scan and CT-scan or MRI of abdomen and pelvis prior to enrolment
• Normal bone marrow function

Exclusion Criteria

• Previously treated with Radiotherapy
• Previously treated with androgen deprivation therapy
• Previously treated with chemotherapy for prostate cancer. They also had to be free

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
intensified and modulated adjuvant RT	Combined, intensified and modulated adjuvant radiotherapy	All patients underwent combined, intensified and modulated adjuvant radiotherapy for 5 days a week with the following doses: 1) pelvic node irradiation (45 Gy; 1.8 Gy/fraction) followed by boost on the prostate bed (19.8-25.2 Gy; 1.8 Gy/fraction; total dose: 64.8-70.2 Gy) or 2) exclusive prostate bed irradiation (64.8 -70.2 Gy; 1.8 Gy/fraction).

Primary Outcome Measures

Name	Time	Method
Biochemical relapse free survival	Five years	Survival free from increase of PSA level exceeding 0.2 ng/mL for those with postsurgical PSA level of 0.2 ng/mL or lower, and as two consecutive PSA increases for patients with a postsurgical PSA level of \> 0.2 ng/ml

Secondary Outcome Measures

Name	Time	Method
Incidence of early treatment-emergent adverse events	< 90 days.	Adverse events after radiotherapy . Acute side effects were scored according to the Radiation Therapy Oncology Group (RTOG) scale.
Incidence of late treatment-emergent adverse events were assessed with Radiation Morbidity Scoring Scheme of the RTOG/European Organization for Research and Treatment of Cancer (EORT)	5 years	Late complications were assessed with the Late Radiation Morbidity Scoring Scheme of the RTOG/European Organization for Research and Treatment of Cancer (EORT)
First evidence of any pelvic recurrence	5 years	First evidence of any pelvic recurrence
Metastasis-free survival	5 years	The first evidence of any extra pelvic recurrence of disease.