Local Recurrence of Malignant Tumor of Prostate, Radiotherapy
Conditions
Keywords
local recurrence, prostate, radiotherapy, salvage
Brief summary
The goal of this clinical study is to evaluate the toxicity and efficacy of re-irradiation using focal stereotactic body radiotherapy (SBRT) in patients with local recurrence of prostate cancer after definitive or post-operative radiotherapy. The main question is the tolerance of such treatment, concerning the incidence of Grade ≥ 2 and Grade ≥ 3 GU and GI toxicity. Also the efficacy of SBRT will be measured in terms of Biochemical Control with other secondary endpoints which include: Biochemical Response, Biochemical Failure-Free Survival, Metastases-Free Survival, Relapse-Free Survial, Local Control, Overall Survival and patients' reported tolerance measured with Quality of Life questionnaires (QoL C-30 and PR-25). The evaluation of the tolerance and effectiveness of stereotactic radiotherapy (SBRT) will be performed in 3 subgroups: in patients with local recurrence after conventionally fractionated/moderately hypofractionated definitive radiotherapy (Group A) or ultrahypofractionated definitive SBRT (Group C) or after prostatectomy and post-operative radiotherapy (Group B). The study group is planned to include 55 patients.
Detailed description
The diagnosis of local recurrence after radiotherapy in patients with prostate cancer is a serious clinical problem. Interventional salvage treatment in the previously irradiated area is difficult with safety issues of special concern. According to the MASTER meta-analysis the effectiveness of various local salvage methods turned out to be comparable in patients with local recurrence after definitive radiotherapy. Stereotactic radiotherapy (SBRT) had the best toxicity profile, so this non-invasive treatment may be a suitable alternative to other methods. A particular problem is local recurrences after post-prostatectomy radiotherapy. The data on SBRT in such setting are even more scarce than in the case of relapses after definitive radiotherapy. Still, they show a low percentage of serious adverse events of grade ≥3 and good treatment tolerance. Considering the own experience with re-irradiation of patients with prostate cancer, it was decided that re-irradiation should be carried out in the form of focal SBRT. With the objective of enhancing the safety and quality of salvage re-irradiation, and a comprehensive evaluation of the efficacy of this treatment it was determined that it should be implemented as a prospective phase II study- PROSTARE (PROstate cancer STereotActic Reirradiation). The evaluation of the tolerance and effectiveness of stereotactic radiotherapy (SBRT) will be performed in patients with local recurrence after conventionally fractionated/moderately hypofractionated definitive radiotherapy (Group A), ultrahypofractionated definitive SBRT (Group C), or after prostatectomy and postoperative radiotherapy (Group B). The study will be conducted as a single-centre study. The evaluation of the safety and effectiveness of such treatment could help develop qualification criteria for repeated irradiation. As a consequence, this should allow for the implementation of this form of treatment into radiotherapy protocols and then, in a controlled and safe way, into clinical practice. The total sample size will comprise 55 patients. The expected recruitment period is 6 years (10 patients per year). Requirements for reirradiation with SBRT: 1. Both PET-PSMA and MR of the prostate or prostate bed are required in patients with recurrence after definitive radiotherapy or surgery followed by radiotherapy 2. Fiducial implantation is not routinely required 3. Empty rectum and partially empty/partially filled bladder (improved reproducibility)\* during treatment planning and during each fraction of stereotactic radiotherapy 4. Treatment with a linear accelerator is preferred 5. CBCT must be performed before each fraction of SBRT with verification for tumour location (GTV)\*\* 6. Focal radiotherapy, i.e., irradiation of only the visible tumour with an appropriate margin 7. Hormonal treatment is not routinely recommended (according to the ESTRO ACROP consensus) - up to the decision of the attending physician * Principles of preparation with laxatives - Bisacodyl is advocated 4-5 hours before SBRT. If the diameter of the rectum on the CT for treatment planning exceeds 4 cm in diameter, the procedure should be repeated after appropriate preparation of the patient. * If stereotactic radiotherapy is conducted on the CyberKnife - KV imaging and Tracking verification are required; additionally an assessment of bladder filling in ultrasonography should be performed
Interventions
RADIATIONStereotactic Body Radiotherapy
Salvage SBRT will be performed in three subgroups of patients with local recurrence: Group A - after conventionally fractionated/moderately hypofractionated definitive radiotherapy; Group B - after prostatectomy and postoperative radiotherapy; Group C - after ultrahypofractionated definitive SBRT Target volumes: GTV- tumour visible on MRI and PET-CT; CTV- 1-3 mm margin around GTV PTV- 3 mm around CTV\* \*- in cases in which very high accuracy and reproducibility of SBRT are ensured, and the margin overlaps the rectum and/or bladder, it is possible to reduce the margin from these organs to 1 mm. Dose constrains: The criteria for limiting the dose in nearby organs are not well-defined for repeated irradiation - the following doses should be aimed: * Maximum rectal dose ≤103% of the prescribed dose (optimal ≤100%) * Maximum bladder dose ≤105% of the prescribed dose (optimal ≤103%) Dose-volume constrains: Rectum: • D30% \<15Gy Bladder: • D30% \< 15 Gy
Sponsors
Maria Sklodowska-Curie National Research Institute of Oncology
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Local recurrence of prostate cancer after definitive radiotherapy 1. biopsy proven or/and 2. Consistent MRI and PET-PSMA results and PSA growth dynamics 2. Time since primary radiotherapy - at least 2 years 3. Good performance status (ZUBROD 0-1) * If the results of the MRI and PET PSMA are inconsistent, and if there is no technical possibility of performing an MRI biopsy, the treatment is acceptable, but repeated imaging (PET or MRI) should be performed to assess the dynamics of the recurrence.
Exclusion criteria
1. Polymetastatic dissemination in distant or regional lymph nodes (N1, M1) or oligometastatic dissemination, but not eligible for local forms of metastasis directed therapy (MDT) 2. Tumour volume (GTV) \> 14 cc 3. Poor tolerability of primary radiotherapy (≥G3 toxicity) or persistent late toxicity ≥G2 interfering with re-irradiation 4. Severe dysuria before repeated SBRT (e.g., IPSS ≥19) 5. Diseases of the distal part of the rectum or anal canal that may affect SBRT tolerance (e.g., anal fissure) 6. Previous prostate brachytherapy 7. Substantial risk for further urologic interventions (e.g., TURB/TURP)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tolerance of salvage SBRT | 3 months post-SBRT, 2-years post-SBRT | Assessment of early and late radiation toxicity: Grade ≥ 3 radiation-induced bladder/urethral (GU) and bowel/rectal (GI) adverse events toxicity or other, according to CTCAE criteria |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Surival | 3 months post-SBRT, 6 months post-SBRT, every 6 moths thereafter up to 5-years post-SBRT | Overall Survival is the time interval between SBRT and patient death irrespective of the cause |
| Tolerance of salvage SBRT | 3 months post-SBRT, every 6 months post SBRT up to 3-years post-SBRT | Rate of moderate or worse early and late radiation toxicity: Grade ≥ 2 radiation-induced bladder/urethral (GU) and bowel/rectal (GI) adverse events toxicity or other, according to CTCAE criteria |
| Biochemical Control | 3 months post-SBRT, 6 months post SBRT, every 6 months thereafter up to 5-years post-SBRT | Biochemical Control will be defined as observations without biochemical recurrence defined as PSA concentration: a. \>2 ng/mL above the nadir (according to Phoenix) for groups A and C b. \>0.2 ng/ml (according to AUA) for group B |
| Biochemical Response | 3 months post-SBRT, 6 months post-SBRT, every 6 moths thereafter up to 5-years post-SBRT | Decrease in PSA level below baseline (pre-SBRT) |
| Patients' reported Quality of Life | 2-years post SBRT, 3-years post SBRT | Evaluation of EORTC QLQ-C30 and PR-25 questionnaires |
| Metastases-Free Survival | 1-year post SBRT, then annually up to 5-years post-SBRT | Metastases-Free Survival is the time interval between SBRT and occurrence of distant metastases or death irrespective of the cause |
| Relapse-Free Survival | 1-year post SBRT, then annually up to 5-years post-SBRT | Relapse-Free Survival is the time interval between SBRT and occurrence of clinical relapse: local recurrence, regional or distant metastases, start of hormonal therapy, or death irrespective of the cause |
| Local Control | 1-year post SBRT, then annually up to 5-years post-SBRT | Local Control is defined as the observations without local failure (within prostate or prostate bed): 1. in-field 2. out-field |
| Biochemical Failure-Free Survival (BFS) | 3 months post-SBRT, 6 months post SBRT, every 6 months thereafter up to 5-years post-SBRT | Biochemical Failure Free Survival (BFS) is defined as the time interval between SBRT and biochemical, local, regional failure, distant metastasis or death irrespective of the cause |
Countries
Poland
Contacts
Primary ContactWojciech Majewski, MD, PhD
Backup ContactAleksandra Napieralska, MD, PhD
Outcome results
None listed