Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

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Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

65 patients will receive the immediate treatment with focal HIFU in order to destroy the cancer without causing side effects. HIFU treatment will be conducted with the Focal One® device. The treatment area will be defined using MRI data and 3D biopsies. A safety distance of at least 9 mm will be defined around the tumor. An intraoperative contrast echocardiographic control will be performed to evaluate the necrotic area. If necessary, additional HIFU lesions will be performed during the same session. In case of residual tumor demonstrated during control biopsies, additional treatment of this tumor with focal HIFU may be proposed.

Patients randomized in this arm will also have PSA dosage, MRI exam, questionnaires and prostatic biopsies during their follow up.

65 patients will be randomized to active surveillance and will have exactly the same follow-up as treated patients excepting the HIFU treatment.

Active surveillance is a therapeutic option that shifts the eventual moment of curative treatment while remaining within a window of curability of the disease.

Patients randomized in this arm will also have PSA dosage, MRI exam, questionnaires and prostatic biopsies during their follow up.

HIFU treatment will be conducted with the Focal One® device. The treatment area will be defined using MRI data and 3D biopsies. A safety distance of at least 9 mm will be defined around the tumor. An intraoperative contrast echocardiographic control will be performed to evaluate the necrotic area. If necessary, additional HIFU lesions will be performed during the same session. In case of residual tumor demonstrated during control biopsies, additional treatment of this tumor with focal HIFU may be proposed.

treatment with focal HIFU

PSA dosage will be regularly performed during patient follow up thanks to blood sampling.

PSA dosage

MRI exam will be regularly performed during patient follow up.

Patients will have to complete five questionnaires during their follow up : QLQ-C30 (Quality of Life questionnaire), EPIC-26 (The Expanded Prostate Cancer Index Composite), IPSS (International Prostate Score Symptom), IIEF-5 (The International Index of Erectile Function), STAI-YB (State-Trait Anxiety Inventory)

Questionnaires

Prostatic biopsies will be regularly performed during patient follow up.

Prostatic biopsies

The percentage of malignant prostate tumors detected very early is constantly increasing and the number of well differentiated tumors, with small volume and low risk of progression increases. When a tumor of this type is identified, radical prostatectomy remains the reference treatment, but this treatment is not without side effects. Active surveillance is a strategy which aims at detecting an early development of the cancerous disease in order to propose curative treatment in a timely manner and thus improve specific survival. Patients are therefore re-evaluated each year by rectal examination, PSA (Prostate-Specific Antigen) assay. Active surveillance remains difficult to manage psychologically for both the patient and the practitioner, because of the lack of treatment on the one hand and a rate of non-curable cancers close to 50% when signs of progression trigger a radical treatment.

The aim of the focal treatment HIFU (High Intensity Focused Ultrasound) is to destroy the cancer without causing side effects in contrast to radical treatments. It is in this sense that it is positioned both as an alternative to radical surgery and as an alternative to active surveillance.

Phase 3, Multicenter, Randomized Study, Evaluating the Efficacy and Tolerability of Focused HIFU (High Intensity Focused Ultrasound) Therapy Compared to Active Surveillance in Patients With Significant Low Risk Prostate Cancer

Phase 3, Multicenter, Randomized Study, Evaluating the Efficacy and Tolerability of Focused HIFU Therapy Compared to Active Surveillance in Patients With Significant Low Risk Prostate Cancer

The primary endpoint is the comparison between the 2 groups of the proportion of patient converting to a radical treatment at 48 months of follow-up. Conversion to a radical treatment is define as a medical decision based on the following criteria:

* An increase in Gleason score to a score 7 (3 + 4) with bilateral involvement (Gleason 6 or 7).
* An increase in the Gleason score to a score 7 (3 + 4) with tumor whose location is not compatible with a focal treatment (impossibility to apply safety margins of 9mm).
* An increase in Gleason score to a score of 7 (4 + 3) or higher.
* Risk of lymph node invasion\> 5% (calculated with the MSKCC nomogram)
* An extension of the tumor beyond the prostatic capsule (MRI and / or biopsies).
* Appearance of pelvic ganglion metastases.

The objective is to compare between the 2 groups the proportion of patients needing additional treatment (focal or radical) at 24 months. This includes patients who wish or require radical treatment (prostatectomy, radiotherapy), total focal treatment, focal treatment for patients in the active surveillance group or additional treatment for patients in the treatment group.

The objective is to compare between the 2 groups the proportion of patients needing additional treatment (focal or radical) at 48 months. This includes patients who wish or require radical treatment (prostatectomy, radiotherapy), total focal treatment, focal treatment for patients in the active surveillance group or additional treatment for patients in the treatment group.

The rate of positive biopsies in the untreated lobe and treated lobe evaluated and will be used to evaluate the oncological evolution at 24 months.

The rate of positive biopsies in the untreated lobe and treated lobe will be measured and will be used to evaluate the oncological evolution at 48 months.

The clinically significant cancer rate (Gleason 7 or invasion of more than 3 biopsies or invasion\> 3 mm regardless of Gleason) in the untreated lobe and the treated lobe will be measured and will be used to evaluate the oncological evolution at 24 months.

The clinically significant cancer rate (Gleason 7 or invasion of more than 3 biopsies or invasion\> 3 mm regardless of Gleason) in the untreated lobe and the treated lobe will be measured and will be used to evaluate the oncological evolution at 48 months.

Evolution of the Gleason score (appearance of Gleason ≥7) will be measured and will be used to evaluate the oncological evolution at 24 months.

Evolution of the Gleason score (appearance of Gleason ≥7) will be measured and will be used to evaluate the oncological evolution at 48 months.

Appearance of another cancerous focus in the other half of the prostate will be supervised and will be used to evaluate the oncological evolution at 24 months.

Appearance of another cancerous focus in the other half of the prostate will be supervised and will be used to evaluate the oncological evolution at 48 months.

Appearance of metastases (lymph node or bone) will be supervised and will be used to evaluate the oncological evolution at 24 months.

Appearance of metastases (lymph node or bone) will be supervised and will be used to evaluate the oncological evolution at 48 months.

Appearance of an extra capsular extension will be supervised and will be used to evaluate the oncological evolution at 24 months.

Appearance of an extra capsular extension will be supervised and will be used to evaluate the oncological evolution at 48 months.

Overall survival at 48 months will be measured from the date of inclusion to the date of death, all causes of death combined or the date of last new or point date to 48 months.

Prostate cancer specific survival at 48 months will be measured from the date of inclusion to the date of death related to prostate cancer or the date of last new or point date to 48 months

Prostate cancer specific survival at 48 months will be measured from the date of inclusion to the date of first metastasis , or the date of last new or point date to 48 months

comparison between the 2 groups of the proportion of serious adverse effect at 48 months

quality of life will be compared between the two groups and assessed using the QLQC30 questionnaire

urinary function will be compared between the two groups and assessed using the EPIC-26 questionnaire.

urinary function will be compared between the two groups and assessed using the IPSS questionnaire.

Sexual function will be compared between the two groups and assessed using the IIEF-5 questionnaire

Anxiety will be compared between the two groups and assessed using the STAi-YB questionnaire

Hospices Civils de Lyon

170 patients with prostate cancer of intermediate risk receive the immediate treatment with focal HIFU. The treatment area will be defined using MRI data and 3D biopsies. A safety distance of at least 9 mm will be defined around the tumor. An intraoperative contrast echocardiographic control will be performed to evaluate the necrotic area. If necessary, additional HIFU lesions will be performed during the same session. In case of residual tumor demonstrated during control biopsies, additional treatment of this tumor with focal HIFU may be proposed. Patients will also have PSA (Prostate-Specific Antigen) dosage, MRI (Magnetic Resonance Imaging) exam, questionnaires and prostatic biopsies during their follow up. If the patient decides to participate in the ancillary study, a blood test (for immunological analyzes and detection of CTC (circulating tumor cells)) and a urine test (for PCA3 (The prostate cancer antigen 3 gene) test) will be performed during their follow up.

Patients will have to complete five questionnaires during their follow up : QLQ-C30 (Quality of Life questionnaire), EPIC-26 (The Expanded Prostate Cancer Index Composite), IPSS (International Prostate Score Symptom), IIEF-5 (The International Index of Erectile Function).

if the patient decides to participate in the ancillary study, a blood test (for immunological analyzes and detection of CTC (circulating tumor cells)) will be performed during their follow up.

blood test

if the patient decides to participate in the ancillary study, a urine test (for PCA3 test) will be performed during their follow up.

urine test

The aim of the focal treatment HIFU is to destroy the cancer without causing side effects in contrast to radical treatments. Radical treatments (surgery or radiation therapy) are the standard therapies for patient with intermediate risk localized prostate cancer and good life expectancy (prostatectomy if life expectancy10 years) By destroying only the part of the gland that harbors cancer, it may indeed be possible to provide efficient cure of the disease while minimizing treatment-induced morbidity (incontinence and loss of potency). Around 20% of patients presented with a unilateral tumor: this patients are currently treated radically. No study published papers reported outcomes of a large population (\>100) with intermediate risk cancers treated with Focal-HIFU (conducted with the Focal One® device). Focal therapy must be only offer within clinical trial setting (EAU (European Association of Urology) Guidelines ). The aim of this cohort will be to determine the success rate of Focal-HIFU in this intermediate risk population. The result the study will be used for calculation the arms of a future random study

Efficacy Evaluation of Focused HIFU (High Intensity Focused Ultrasound) Therapy in Patients With Localized Intermediate Risk Prostate Cancer

Phase 2, Multicenter, Prospective Cohort Study, Estimating the Efficacy of Focused HIFU Therapy in Patients With Localized Intermediate Risk Prostate Cancer

The main objective is the estimation of FOCAL HIFU treatment efficacy defined as the percentage of positive biopsies in the treated lobe at 12 months after inclusion.

The objective is to determine the proportion of patients needing additional treatment (focal or radical) at 12 months. This includes patients who wish or require radical treatment (prostatectomy, radiotherapy), total focal treatment, or additional focal treatment.

The objective is to determine the proportion of patients needing additional treatment (focal or radical) at 48 months. This includes patients who wish or require radical treatment (prostatectomy, radiotherapy), total focal treatment, or additional focal treatment.

The objective is to determine the proportion of patients needing additional radical treatment at 12 months. This includes patients who wish or require prostatectomy or radiotherapy total focal treatment.

The objective is to determine the proportion of patients needing additional radical treatment at 48 months. This includes patients who wish or require prostatectomy or radiotherapy total focal treatment.

The rate of positive biopsies in the untreated lobe and treated lobe evaluated and will be used to evaluate the carcinologic evolution at 12 months.

The rate of positive biopsies in the untreated lobe and treated lobe evaluated and will be used to evaluate the carcinologic evolution at 24 months.

The rate of positive biopsies in the untreated lobe and treated lobe evaluated and will be used to evaluate the carcinologic evolution at 48 months.

The clinically significant cancer rate (Gleason 7 or invasion of more than 3 biopsies or invasion\> 3 mm regardless of Gleason) in the untreated lobe and the treated lobe will be measured and will be used to evaluate the carcinologic evolution at 48 months.

Evolution of the Gleason score (appearance of Gleason ≥7) will be measured and will be used to evaluate the carcinologic evolution at 12 month.

The Gleason score is a prognosis factor for prostate cancer. It is based prostate cancer cells architecture from biopsies. The more the architectures of prostate cancer cell is destroyed, the worse is the prognosis. The score grades from 3 to 5, 5 being the more destroyed, the score 1 and 2 being normal cells. When there is more than one tumor cells population in the prostate, the score is composed of the sum of the most 2 frequents grade. For example a Gleason 7 tumor could be 3+4 or 4+3, the 4+3 being more aggressive.

Evolution of the Gleason score (appearance of Gleason ≥7) will be measured and will be used to evaluate the carcinologic evolution at 24 month.

The Gleason score is a prognosis factor for prostate cancer. It is based prostate cancer cells architecture from biopsies. The more the architectures of prostate cancer cell is destroyed, the worse is the prognosis. The score grades from 3 to 5, 5 being the more destroyed, the score 1 and 2 being normal cells. When there is more than one tumor cells population in the prostate, the score is composed of the sum of the most 2 frequents grade. For example a Gleason 7 tumor could be 3+4 or 4+3, the 4+3 being more aggressive.

Evolution of the Gleason score (appearance of Gleason ≥7) will be measured and will be used to evaluate the carcinologic evolution at 48 month.

The Gleason score is a prognosis factor for prostate cancer. It is based prostate cancer cells architecture from biopsies. The more the architectures of prostate cancer cell is destroyed, the worse is the prognosis. The score grades from 3 to 5, 5 being the more destroyed, the score 1 and 2 being normal cells. When there is more than one tumor cells population in the prostate, the score is composed of the sum of the most 2 frequents grade. For example a Gleason 7 tumor could be 3+4 or 4+3, the 4+3 being more aggressive.

Appearance of another cancerous focus in the other half of the prostate will be supervised and will be used to evaluate the carcinologic evolution at 12 months.

Appearance of another cancerous focus in the other half of the prostate will be supervised and will be used to evaluate the carcinologic evolution at 24 months.

Appearance of another cancerous focus in the other half of the prostate will be supervised and will be used to evaluate the carcinologic evolution at 48 months.

Appearance of metastases (lymph node or bone) will be supervised and will be used to evaluate the carcinologic evolution at 12 months.

Appearance of metastases (lymph node or bone) will be supervised and will be used to evaluate the carcinologic evolution at 24 months.

Appearance of metastases (lymph node or bone) will be supervised and will be used to evaluate the carcinologic evolution at 48 months.

Appearance of an extra capsular extension will be supervised and will be used to evaluate the carcinologic evolution at 12 months.

Appearance of an extra capsular extension will be supervised and will be used to evaluate the carcinologic evolution at 24 months.

Appearance of an extra capsular extension will be supervised and will be used to evaluate the carcinologic evolution at 48 months.

Prostate cancer specific survival at 48 months will be measured from the date of inclusion to the date of first metastasis , or the date of last new or point date to 48 months.

comparison of the proposition of serious adverse effect at 48 months

quality of life will be assessed using the QLQC30 (Quality of Life questionnaire) questionnaire.

It is a specific questionnaire to determine the quality of life a patient with cancer. It is composed of 30 questions with 4 potential answers going from: not at all, a little, enough or a lot, within 28 questions and with a visual scale going from 1 to 7 (7 being excellent and 1 being very bad) for the last 2 questions. The raw score is established by adding the score of each question and a linear transformation range it from 0 to 100. The higher the score, the better the quality of life.

urinary function will be assessed using the EPIC-26 (The Expanded Prostate Cancer Index Composite) questionnaire.

The EPIC-26 is a self-reported scale health-related quality of life questionnaire for prostate cancer patients . It is composed of 26 items in 4 different domains: urinary incontinence, urinary irritation/obstruction, bowel, sexual, and vitality/hormonal.

Response options for each EPIC item form a Likert scale, and multi-item scale scores are transformed linearly to a 0-100 scale. Each items as a standardized value from 0 to 100. Then the average of the standardized value is determined in each domain to crate the summary score. The higher the score, the better the quality of life.

urinary function will be assessed using the IPSS (International Prostate Score Symptom) questionnaire.

The IPSS questionnaire is based on the answers to seven questions concerning urinary symptoms and one question concerning quality of life. Each question concerning urinary symptoms allows the patient to choose one out of six answers indicating increasing severity of the particular symptom. The answers are assigned points from 0 to 5. The total score can therefore range from 0 to 35. The score is then categorized as follow: Mild (symptoms score less than or equal to 7), Moderate (symptom score range 8-19), Severe (symptom score range 20-35). The higher the score, the worse the symptoms.

Sexual function will be assessed using the IIEF-5 (The International Index of Erectile Function) questionnaire.

The IIEF-5 Questionnaire is composed of 5 items with 5 possible answers rating from 1 to 5 (very low, low, moderate, high, very high).

The score is the sum of the ordinal responses to the 56 items. It is then categorized as follow: 22-25: No erectile dysfunction, 17-21: Mild erectile dysfunction, 12-16: Mild to moderate erectile dysfunction, 8-11: Moderate erectile dysfunction, 5-7: Severe erectile dysfunction. The higher the score, the better the sexual function.

The main objective is the estimation of FOCAL HIFU treatment efficacy defined as the percentage of positive biopsies in the treated lobe at 48 months after inclusion.

The consequences of HIFU treatment over immune anti-tumoral induction will be estimated by the description of Programmed death-ligand 1/ligand 2 (PDL1/L2) overexpression on immune cells and overexpression of Programmed cell death 1 (PD-1) on T lymphocytes (T-cells).

The consequences of HIFU treatment over Messenger RNA (mRNA) will be estimated by measure of CTC number reduction.

The consequences of HIFU treatment over PCA3 will be estimated by measure of ncRNA PCA3 level reduction.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Phase 3, Multicenter, Randomized Study, Evaluating the Efficacy and Tolerability of Focused HIFU (High Intensity Focused Ultrasound) Therapy Compared to Active Surveillance in Patients With Significant Low Risk Prostate Cancer	NCT03531099	Prostate Cancer	treatment with ... PSA dosage MRI Questionnaires Prostatic biops...	50 Years - 80 Years	Hospices Civils de Lyon
Efficacy Evaluation of Focused HIFU (High Intensity Focused Ultrasound) Therapy in Patients With Localized Intermediate Risk Prostate Cancer	NCT03568188	Prostate Cancer	treatment with ... PSA dosage MRI Questionnaires Prostatic biops... blood test urine test	50 Years - 80 Years	Hospices Civils de Lyon

Spots Global Cancer Trial Database for prostatic biopsies