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

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.

Sex

Male

Minimum age

18 Years

Maximum age

80 Years

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)

• BACKGROUNDValle 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
• BACKGROUNDMiszczyk 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). 2023 Feb 13;15(4):1180. doi: 10.3390/cancers15041180. PMID 36831523
• BACKGROUNDJereczek-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; on the behalf of the European Society for Radiotherapy, Oncology Advisory Committee on Radiation Oncology Practice (ESTRO ACROP). Salvage stereotactic body radiotherapy (SBRT) for intraprostatic relapse after prostate cancer radiotherapy: An ESTRO ACROP Delphi consensus. Cancer Treat Rev. 2021 Jul;98:102206. doi: 10.1016/j.ctrv.2021.102206. Epub 2021 Apr 20. PMID 33965893
• BACKGROUNDArcher 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 Multicenter Study. Eur Urol Oncol. 2023 Jun;6(3):303-310. doi: 10.1016/j.euo.2023.03.005. Epub 2023 Apr 1. PMID 37012102