Surgery Combined With Intensity Modulated Radiation Therapy - Image-Guided Radiation Therapy (IMRT-IGRT) in Locally-advanced Prostate Cancers (TARGET)

Surgery Combined With IMRT-IGRT in Locally-advanced Prostate Cancers

Standard treatment of locally-advanced prostate cancers consists in the association of radiotherapy of prostate and seminal vesicles (SV) and androgen deprivation (AD) for 3 years. This treatment is usually preceded by pelvic lymphadenectomy to assess the possible extension to lymph nodes of prostatic cancer and to avoid irradiating the pelvis in case of no lymph node involvement. However, radiotherapy leads usually to about 30% of grade ≥2 risk of bladder and/or rectal toxicity. This risk particularly depends on the radiation volume. In the aim of lowering the toxicity, the treatment in this study will associate:

• pelvic lymph node dissection and resection of seminal vesicles, allowing decreasing the radiation target volume to the prostate only (and not to irradiate the SV);
• a high-precision radiotherapy technique combining Intensity Modulated Radiation Therapy (IMRT) and Image-Guided Radiation Therapy (IGRT).

Study Overview

• Status: Completed
• Conditions: Prostate Cancer; Prostate Adenocarcinoma
• Intervention / Treatment: Procedure: Surgery combined with IMRT-IGRT

Detailed Description

This study targets non metastatic prostatic locally-advanced adenocarcinomas which are at high risk of both local progression and metastases. The standard treatment of these tumours associates external beam radiation therapy (EBRT) and 3 years of androgen deprivation (AD) with LH-RH analogue. In the absence of AD and mainly when prostate specific antigen (PSA) is >10 ng/ml, several randomized studies have shown that high doses of EBRT increase biochemical control. Nevertheless, escalating the doses of radiation significantly increases the risk of rectal and/or urinary toxicities. In order to lower the toxicity of irradiation in locally-advanced prostate cancers, and to improve the quality of life of patients, this study aims at decreasing the volume of irradiated healthy tissues. To carry out this objective, we will use a double strategy:

• Limiting the target volume to prostate only by removing seminal vesicles at the time of lymph node dissection,
• Using a technique of high-precision radiation combining Intensity Modulated Radiation Therapy (IMRT) and Image-Guided Radiation Therapy (IGRT).

Based on the literature, we may assume a toxicity rate of 30% during the three years of hormonotherapy with standard treatment (i.e. without removing seminal vesicles). We make the hypothesis of a 20% absolute reduction of toxicity with our protocol.

• Study Type: Interventional
• Enrollment (Actual): 63
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Rennes, France, 35033
    • Service d'Urologie - Hôpital de Pontchaillou
  • Rennes, France, 35042
    • Centre Eugène Marquis - CRLCC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Age > 18,
• Prostate adenocarcinoma (histologically proven),
• Locally-advanced (T3a or Gleason > 7 or PSA ≥ 20 ng/mL),
• Distal half of seminal vesicles unaffected on MRI,
• Non metastatic cancer: negative extension assessment (on prostatic and pelvic MRI and bone scintigraphy),
• Radiotherapy and hormonotherapy indication,
• Medical insurance affiliation,
• Written informed consent.

Non-inclusion criteria:

• Co-morbidity or medical history contraindicating surgery (pelvic lymphadenectomy and seminal vesicle ablation),
• Contraindication to pelvic irradiation,
• Hip prosthesis,
• History of cancer for the last 5 years (except baso-cellular epithelioma),
• History of pelvic irradiation,
• Person deprived of freedom or under guardianship,
• Participation in another biomedical research.

Exclusion Criteria:

• Surgery showing lymph nodes involvement (pelvic radiation indication)
• Surgery without ablation of seminal vesicles
• Surgery with positive margins in seminal vesicles

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Surgery combined with IMRT-IGRT	Procedure: Surgery combined with IMRT-IGRT; Patients will have surgery consisting in extensive pelvic dissection and ablation of seminal vesicles. Surgery will be followed by prolonged hormonotherapy (3 years) associated, after 2 months, with prostatic only irradiation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of bladder and/or rectal grade ≥2 toxicity (late toxicity)	Rate of bladder and/or rectal grade ≥2 toxicity (CTCAE V4.0) observed between 6 months and 3 years after the beginning of the radiotherapy.	between 6 months and 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose received by the rectum and the bladder with and without seminal vesicles irradiation	Assessed using a dose-volume histogram	Before treatment
Quality of life	Assessed with EORTC questionnaires (QLQ-C30, QLQ-PR25)	3 years
Erectile troubles	Assessed with erectile troubles questionnaire (IIEF-5)	3 years
Onset of biological signs evocating a recidive	Assessed with PSA levels	3 years
Onset of clinical signs evocating a recidive		3 years
Specific and global survival		3 years
Rate of bladder and/or rectal grade ≥2 toxicity (CTCAE V4.0) (early toxicity)	Rate of late bladder and/or rectal grade ≥2 toxicity (CTCAE V4.0) observed 6 months after the beginning of the radiotherapy.	6 months

Collaborators and Investigators

• Sponsor: Rennes University Hospital
• Collaborators: Center Eugene Marquis
• Investigators: Principal Investigator: Renaud DE CREVOISIER, MD, PhD, Rennes CRLCC Eugène Marquis; Study Director: Sebastien VINCENDEAU, MD, Rennes University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 30, 2010
• Primary Completion (Actual): July 4, 2018
• Study Completion (Actual): July 4, 2018

Study Registration Dates

• First Submitted: June 18, 2010
• First Submitted That Met QC Criteria: June 18, 2010
• First Posted (Estimate): June 22, 2010

Study Record Updates

• Last Update Posted (Actual): December 19, 2018
• Last Update Submitted That Met QC Criteria: December 18, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Keywords: IMRT-IGRT; radiotherapy toxicity; seminal vesicles
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms
• Other Study ID Numbers: ID RCB 2009-A01336-51; LOC/09-07 (Other Identifier: Rennes University Hospital); CIC0203/128 (Other Identifier: Rennes Clinical Research Center)