24 Gy in One Fraction Urethral-sparing "HDR Like" SBRT for Prostate Cancer

Official title

24 Gy in One Fraction Urethral-sparing "High-Dose-Rate Like" Stereotactic Body RadioTherapy for Prostate Cancer: a Single-center Non-randomized Prospective Clinical Study (PRO-FAST)

Overview

Patients with prostate cancer who are candidates for stereotactic radiotherapy to the prostate and seminal vesicles will undergo staging exams, which will include prostate specific membrane antigen (PSMA) positron emission tomography-computed tomography (PET-CT). If the PET scan is negative and the uroflowmetry is acceptable, the patients will perform the treatment, after fiducial implantation, simulation CT and magnetic resonance (MR), in a single fraction, delivered with a high-dose-rate (HDR)-like urethral sparing technique. In 70 patients, acute and late toxicity, biochemical control, overall survival, cancer specific-survival, and quality of life (through specific questionnaires) will be evaluated.

Detailed description

This is an interventional prospective non-randomised single-center trial that will enroll, 13 patients for the first phase of the study, according to the optimal design of Simon. The hypothesis is that the proportion of patients free from acute cumulative G3-G4 toxicity (Common Terminology Criteria for Adverse Events-CTCAE v5.0 scale) 1 month after the end of treatment must be \< 85% to suspend treatment and \> 95% to consider the treatment as safe.

The treatment will be interrupted if G3-G4 toxicities and/or biochemical recurrences are recorded within a month in 2 or more patients; otherwise the study will continue with the second phase. Another 52 patients will be added, for a total of 65 patients. The treatment consists in a single fraction of 24 Gy with the "urethral sparing HDR like" technique. Assuming a minimal drop-out, given that the primary endpoint is toxicity one month after treatment, we will enroll 5 more patients in total, thus reaching a total number of 70 patients (65 necessary + 5 for any drop-outs).

In the absence of worse subsequent toxicity, and with biochemical control comparable to that in the literature as well as historical treatments in our Radiation Oncology, the scheme will be considered safe, and the enrollment will continue open label.

Patients with negative lymph nodes and without distant metastases will be enrolled and treated on the prostate/prostate and tumor vesicles (depending on the stage) at a total dose of 24 Gy delivered in a single fraction, sparing the urethra and with a dose distribution similar to high dose rate brachytherapy. Androgen Deprivation Therapy (ADT) will be prescribed according to the guidelines for the stages of the disease.

Short-term cortisone and alpha lytics will be prescribed, for prophylactic purposes. Follow-up visits will be performed at 1, 3, 6,12,18, 24, 36, 48, 60 months with blood tests including prostate specific antigen (PSA) and testosterone (performed every 3 months in the first two years, every 6 months in the next 3 years), imaging, when needed, and quality of life questionnaires: European Organization for Research and Treatment of cancer (EORTC) quality of life questionnaire (QLQ) C30 and QLQ-PR25, International Prostate symptoms score (IPSS), International Index of Erectile Function (IIEF)-5, Expanded Prostate Cancer Index Composite (EPIC)- 26.

Interventions

• Radiation prostate SBRT
  Patients with prostate cancer will be treated with high-dose SBRT to prostate and seminal vesicles, delivered in one fraction, sparing the urethra and generating a dose distribution similar to HDR brachytherapy

Primary outcome measures

• Acute toxicity [Time frame: one month]

Secondary outcome measures (12)

• Biochemical control [Time frame: 5 years (with interim analyzes at 1 and 3 years)]
• Biochemical relapse [Time frame: 5 years (with interim analyzes at 1 and 3 years)]
• Local Control [Time frame: 5 years (with interim analyzes at 1 and 3 years)]
• Distant Disease Control [Time frame: 5 years (with interim analyzes at 1 and 3 years)]
• Survival [Time frame: 5 years (with interim analyzes at 1 and 3 years)]
• Subacute Toxicity [Time frame: 3 months]
• Late Toxicity [Time frame: 5 years (with interim analyzes at 1 and 3 years)]
• Incidence of Treatment-Emergent Adverse Events as assessed with general quality of life questionnaires [Time frame: 5 years]
• Incidence of Treatment-Emergent Adverse Events as assessed with prostate specific quality of life questionnaires [Time frame: 5 years]
• Incidence of Treatment-Emergent Adverse Events as assessed with urinary quality of life questionnaires [Time frame: 5 years]
• Incidence of Treatment-Emergent Adverse Events as assessed with erectile quality of life questionnaires [Time frame: 5 years]
• Incidence of Treatment-Emergent Adverse Events as assessed with composite quality of life questionnaires [Time frame: 5 years]

Eligibility criteria

Inclusion criteria

• Histological diagnosis of prostate adenocarcinoma, International Society of Urological Pathology (ISUP) grade groups 1-5
• Patients over 18 years of age
• Signed informed consent
• Negative lymph nodes confirmed by imaging (PSMA PET/CT and/or pelvic MRI with and without contrast medium) where recommended by guidelines (intermediate and high risk patients, according to National Comprehensive Cancer Network (NCCN) guidelines) in the previous 3 months
• Clinical M0 (PSMA PET/CT and/or bone scan and/or pelvic MRI with and without contrast medium in suspected patients and unfavorable intermediate and high risk patients, according to NCCN guidelines), in the previous 3 months
• Acceptable uroflowmetry: peak urine flow index (peak flow preferably ≥ 15 ml/s), post voiding residue (PVR) ≤50 cc. If lower, acceptable if, by carrying out 3 months of neoadjuvant hormone therapy + alpha-lytic for the reduction of prostate volume, uroflowmetry is reset to at least ≥ 12 ml/s.
• PS (ECOG) ≤2
• No previous pelvic radiotherapy
• Other conditions necessary for the correct execution of the proposed treatment (ability to fill in the questionnaires for the evaluation of the Quality of Life EORTC QLQ-C30, EORTC QLQ-PR25, IPSS, IIEF-5, EPIC 26)

Exclusion criteria

• Serious systemic diseases
• Psychic or other disorders that may prevent the patient from signing the informed consent
• Previous invasive cancer, except skin cancer (excluding melanoma) unless patient free of disease for at least 3 years (e.g. carcinoma in situ of the oral cavity or bladder)
• Lymph node disease (N1)
• Evidence of distant metastases (M1)
• IPSS questionnaire data > 20 points
• Uroflowmetry with maximum basal flow ≤ 11 ml/sec and/or PVR >100 ml
• Concomitant urinary/gastrointestinal inflammatory diseases (e.g. ulcerative colitis, Crohn's disease)
• Overactive bladder
• Impossibility of implantation of fiducials
• Inability or refusal to place bladder catheter for simulation CT and MR
• Inability to perform simulation MRI
• Contraindication for hormonal treatment for patients with unfavorable intermediate, high or very high risk disease
• Non-compliance with dose limits established in the treatment plan

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

Italy · 1 center

• San Raffaele Scientific Institute — Milan

Publications

• Hamdy FC, Donovan JL, Lane JA, Mason M, Metcalfe C, Holding P, Davis M, Peters TJ, Turner EL, Martin RM, Oxley J, Robinson M, Staffurth J, Walsh E, Bollina P, Catto J, Doble A, Doherty A, Gillatt D, Kockelbergh R, Kynaston H, Paul A, Powell P, Prescott S, Rosario DJ, Rowe E, Neal DE; ProtecT Study Group. 10-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Localized Prostate Cancer. N E PMID 27626136
• Donovan JL, Hamdy FC, Lane JA, Mason M, Metcalfe C, Walsh E, Blazeby JM, Peters TJ, Holding P, Bonnington S, Lennon T, Bradshaw L, Cooper D, Herbert P, Howson J, Jones A, Lyons N, Salter E, Thompson P, Tidball S, Blaikie J, Gray C, Bollina P, Catto J, Doble A, Doherty A, Gillatt D, Kockelbergh R, Kynaston H, Paul A, Powell P, Prescott S, Rosario DJ, Rowe E, Davis M, Turner EL, Martin RM, Neal DE; PMID 27626365
• Prada PJ, Cardenal J, Blanco AG, Anchuelo J, Ferri M, Fernandez G, Arrojo E, Vazquez A, Pacheco M, Fernandez J. High-dose-rate interstitial brachytherapy as monotherapy in one fraction for the treatment of favorable stage prostate cancer: Toxicity and long-term biochemical results. Radiother Oncol. 2016 Jun;119(3):411-6. doi: 10.1016/j.radonc.2016.04.006. Epub 2016 Apr 22. PMID 27118583
• Prada PJ, Ferri M, Cardenal J, Blanco AG, Anchuelo J, Diaz de Cerio I, Vazquez A, Pacheco M, Raba I, Ruiz S. High-dose-rate interstitial brachytherapy as monotherapy in one fraction of 20.5 Gy for the treatment of localized prostate cancer: Toxicity and 6-year biochemical results. Brachytherapy. 2018 Nov-Dec;17(6):845-851. doi: 10.1016/j.brachy.2018.06.002. Epub 2018 Jul 18. PMID 30030111
• Pollack A, Zagars GK, Starkschall G, Antolak JA, Lee JJ, Huang E, von Eschenbach AC, Kuban DA, Rosen I. Prostate cancer radiation dose response: results of the M. D. Anderson phase III randomized trial. Int J Radiat Oncol Biol Phys. 2002 Aug 1;53(5):1097-105. doi: 10.1016/s0360-3016(02)02829-8. PMID 12128107
• Kuban DA, Tucker SL, Dong L, Starkschall G, Huang EH, Cheung MR, Lee AK, Pollack A. Long-term results of the M. D. Anderson randomized dose-escalation trial for prostate cancer. Int J Radiat Oncol Biol Phys. 2008 Jan 1;70(1):67-74. doi: 10.1016/j.ijrobp.2007.06.054. Epub 2007 Aug 31. PMID 17765406
• Hall MD, Schultheiss TE, Smith DD, Tseng BP, Wong JY. The impact of increasing dose on overall survival in prostate cancer. Radiat Oncol. 2015 May 21;10:115. doi: 10.1186/s13014-015-0419-3. PMID 25990489
• Dearnaley D, Syndikus I, Mossop H, Khoo V, Birtle A, Bloomfield D, Graham J, Kirkbride P, Logue J, Malik Z, Money-Kyrle J, O'Sullivan JM, Panades M, Parker C, Patterson H, Scrase C, Staffurth J, Stockdale A, Tremlett J, Bidmead M, Mayles H, Naismith O, South C, Gao A, Cruickshank C, Hassan S, Pugh J, Griffin C, Hall E; CHHiP Investigators. Conventional versus hypofractionated high-dose intensity-m PMID 27339115

Identifiers

NCT: NCT05936736 · PRO-FAST

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗