Stereotactic Re-irradiation of Local Recurrences of Prostate Cancer After Radiotherapy

Official title

Phase II Study - Stereotactic Re-irradiation of Local Recurrences of Prostate Cancer After Radiotherapy - PROSTARE (PROstate Cancer STereotActic REirradiation) Trial

Overview

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

• Radiation Stereotactic 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

Primary outcome measures

• Tolerance of salvage SBRT [Time frame: 3 months post-SBRT, 2-years post-SBRT]

Secondary outcome measures (9)

• Tolerance of salvage SBRT [Time frame: 3 months post-SBRT, every 6 months post SBRT up to 3-years post-SBRT]
• Biochemical Control [Time frame: 3 months post-SBRT, 6 months post SBRT, every 6 months thereafter up to 5-years post-SBRT]
• Biochemical Response [Time frame: 3 months post-SBRT, 6 months post-SBRT, every 6 moths thereafter up to 5-years post-SBRT]
• Biochemical Failure-Free Survival (BFS) [Time frame: 3 months post-SBRT, 6 months post SBRT, every 6 months thereafter up to 5-years post-SBRT]
• Metastases-Free Survival [Time frame: 1-year post SBRT, then annually up to 5-years post-SBRT]
• Relapse-Free Survival [Time frame: 1-year post SBRT, then annually up to 5-years post-SBRT]
• Local Control [Time frame: 1-year post SBRT, then annually up to 5-years post-SBRT]
• Overall Surival [Time frame: 3 months post-SBRT, 6 months post-SBRT, every 6 moths thereafter up to 5-years post-SBRT]
• Patients' reported Quality of Life [Time frame: 2-years post SBRT, 3-years post SBRT]

Eligibility criteria

Inclusion criteria

• Local recurrence of prostate cancer after definitive radiotherapy

• biopsy proven or/and
• Consistent MRI and PET-PSMA results and PSA growth dynamics
• Time since primary radiotherapy - at least 2 years
• 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

• Polymetastatic dissemination in distant or regional lymph nodes (N1, M1) or oligometastatic dissemination, but not eligible for local forms of metastasis directed therapy (MDT)
• Tumour volume (GTV) > 14 cc
• Poor tolerability of primary radiotherapy (≥G3 toxicity) or persistent late toxicity ≥G2 interfering with re-irradiation
• Severe dysuria before repeated SBRT (e.g., IPSS ≥19)
• Diseases of the distal part of the rectum or anal canal that may affect SBRT tolerance (e.g., anal fissure)
• Previous prostate brachytherapy
• Substantial risk for further urologic interventions (e.g., TURB/TURP)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Poland · 1 center

• Maria Sklodowska Memorial Research Institute of Oncology — Gliwice

Publications

• Valle LF, Lehrer EJ, Markovic D, Elashoff D, Levin-Epstein R, Karnes RJ, Reiter RE, Rettig M, Calais J, Nickols NG, Dess RT, Spratt DE, Steinberg ML, Nguyen PL, Davis BJ, Zaorsky NG, Kishan AU. A Systematic Review and Meta-analysis of Local Salvage Therapies After Radiotherapy for Prostate Cancer (MASTER). Eur Urol. 2021 Sep;80(3):280-292. doi: 10.1016/j.eururo.2020.11.010. Epub 2020 Dec 11. PMID 33309278
• Miszczyk M, Kraszkiewicz M, Moll M, Kaminiow K, Sobel S, Dolla L, Wojcieszek P, Rajwa P, Yanagisawa T, Nowicka Z, Shariat SF, Goldner G, Miszczyk L, Majewski W. Long-Term Outcomes of Stereotactic Body Radiotherapy (SBRT) for Intraprostatic Relapse after Definitive Radiotherapy for Prostate Cancer: Patterns of Failure and Association between Volume of Irradiation and Late Toxicity. Cancers (Basel). PMID 36831523
• Jereczek-Fossa BA, Marvaso G, Zaffaroni M, Gugliandolo SG, Zerini D, Corso F, Gandini S, Alongi F, Bossi A, Cornford P, De Bari B, Fonteyne V, Hoskin P, Pieters BR, Tree AC, Arcangeli S, Fuller DB, Franzese C, Hannoun-Levi JM, Janoray G, Kerkmeijer L, Kwok Y, Livi L, Loi M, Miralbell R, Pasquier D, Pinkawa M, Scher N, Scorsetti M, Shelan M, Toledano A, van As N, Vavassori A, Zilli T, Pepa M, Ost P PMID 33965893
• Archer P, Marvaso G, Detti B, Colombo F, Francolini G, Vandendorpe B, Thananayagam MA, Baty M, De Crevoisier R, Alongi F, Nicosia L, Scher N, Toledano A, Di Muzio N, Fodor A, Zilli T, Franzese C, Scorsetti M, Shelan M, Triggiani L, Aymes E, Le Deley MC, Jereczek-Fossa BA, Pasquier D. Salvage Stereotactic Reirradiation for Local Recurrence in the Prostatic Bed After Prostatectomy: A Retrospective M PMID 37012102
• Schroder C, Tang H, Windisch P, Zwahlen DR, Buchali A, Vu E, Bostel T, Sprave T, Zilli T, Murthy V, Forster R. Stereotactic Radiotherapy after Radical Prostatectomy in Patients with Prostate Cancer in the Adjuvant or Salvage Setting: A Systematic Review. Cancers (Basel). 2022 Jan 29;14(3):696. doi: 10.3390/cancers14030696. PMID 35158961

Identifiers

NCT: NCT06201078 · nio-kb/430-72/23

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗