Clinical trial NCT01148069: Surgery Combined With Intensity Modulated Radiation Therapy - Image-Guided Radiation Therapy (IMRT-IGRT) in Locally-advanced Prostate Cancers
Official title: Surgery Combined With IMRT-IGRT in Locally-advanced Prostate Cancers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Prostate Cancer
Prostate Adenocarcinoma
Keywords: IMRT-IGRT
radiotherapy toxicity
seminal vesicles
Lead sponsor: Rennes University Hospital
Sponsor class: OTHER
Collaborators: name: Center Eugene Marquis
First posted: 2010-06-22
Enrollment: 63
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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).

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.

Eligibility criteria: 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

Primary outcomes:
measure: Rate of bladder and/or rectal grade ≥2 toxicity (late toxicity)
timeFrame: between 6 months and 3 years
Secondary outcomes:
measure: Dose received by the rectum and the bladder with and without seminal vesicles irradiation
timeFrame: Before treatment
measure: Quality of life
timeFrame: 3 years
measure: Erectile troubles
timeFrame: 3 years
measure: Onset of biological signs evocating a recidive
timeFrame: 3 years
measure: Onset of clinical signs evocating a recidive
timeFrame: 3 years
measure: Specific and global survival
timeFrame: 3 years
measure: Rate of bladder and/or rectal grade ≥2 toxicity (CTCAE V4.0) (early toxicity)
timeFrame: 6 months
Other outcomes:
Locations:
city: Rennes
country: France
facility: Service d'Urologie - Hôpital de Pontchaillou
city: Rennes
country: France
facility: Centre Eugène Marquis - CRLCC
Study officials:
affiliation: Rennes CRLCC Eugène Marquis
name: Renaud DE CREVOISIER, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Rennes University Hospital
name: Sebastien VINCENDEAU, MD
role: STUDY_DIRECTOR
affiliation: Rennes University Hospital
name: Eric BELLISSANT, MD, PhD
role: STUDY_CHAIR
References: