Clinical trial NCT06941363: Salvage Ultrahypofractionated Postoperative External Radiotherapy For Biochemical Recurrence
Official title: Salvage Ultrahypofractionated Postoperative External Radiotherapy For Biochemical Recurrence
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Prostate Cancer (Post Prostatectomy)
Keywords: biochemical recurrence; salvage RT; toxicity profile; oncological outcomes; linac-based SBRT
Lead sponsor: University of Milano Bicocca
Sponsor class: OTHER
First posted: 2025-04-23
Enrollment: 50
Sex: MALE
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with biochemical relapse following radical prostatectomy

Brief summary: Recently, the Radiation Oncology Department at Fondazione IRCCS San Gerardo dei Tintori has been renovated and has been equipped with cutting edge technologies to treat prostate cancer. Specifically, the now available technology can track organ motion in real time, thus allowing improved precision in radiation delivery, with increased protection of the surrounding organs at risk. These facilities have already enabled the kickoff of two prospective observational trials, the ABRUPT and the POPART, which are currently ongoing in the treatment of intact prostate and the biochemical recurrence, respectively. Taken together, these observations provide the basis for the prospective clinical study herein proposed. Patients enrolled in the study will undergo salvage single stereotactic RT to the prostate bed by means of image guided volumetric intensity-modulated arc technique (IGRT-VMAT) and state-of-the-art treatment-planning and quality assurance procedures, with emphasis on normal tissue sparing and and pinpoint delivery accuracy via the use of devices that ensure stability and beam location reproducibility

Detailed description: Patients enrolled in this observational prospective trial undergo image-guided, intensity-modulated radiotherapy using the same equipment, techniques, and treatment-planning procedures as per clinical practice. Eligible patients are those with (1) persistently detectable PSA post-operatively or (2) developing biochemical recurrence after prostatectomy with initially undetectable PSA, without evidence of macroscopic local relapse and/or regional and distant metastases at restaging, proposed for receiving up to 15 Gy in a single session to the prostate bed.

As per current practice, in case of PSMA positivity at the level of prostate bed, the treatment will be intended to cover this area up to 110% of the prescribed dose yet respecting the OARs constraints.

Patients will be followed at approximately one month, then approximately every 3 months for the first 12 months and every 6 months thereafter. At follow-up visit patients will be evaluated for urinary, rectal, and sexual toxicity. Baseline measures of these domains will be obtained prior to treatment. Serum PSA values will be drawn on the same schedule as clinical follow-up.

Eligibility criteria: Inclusion Criteria:

* Subjects of male sex ≥ 18 years of age.
* Subjects have freely signed the pertinent informed consent before the beginning of the study

  * Adenocarcinoma of the prostate treated with radical prostatectomy (any type of radical prostatectomy is permitted including retropubic, perineal, laparoscopic or robotically assisted; there is no time limit for the date of radical prostatectomy)
  * Detectable post-prostatectomy PSA of ≥ 0.1 - \< 2.0 ng/mL either (1) persistently detectable post-operatively or (2) developing biochemical recurrence after prostatectomy (initially undetectable)
  * No evidence of N1 and/or M1 disease assessed by PSMA PET-CT within 90 days prior to registration
  * Negative Magnetic Resonance Imaging (MRI) of the pelvis in case of equivocal evidence of local relapse on PSMA PET-CT
  * Androgen deprivation therapy (ADT) allowed as per physician's discretion
  * ECOG performance status of 0-1
  * Ability to complete the questionnaires

Exclusion Criteria:

* N1 and or M1 patients
* Macroscopic local relapse at pelvic MRI.
* Prior radiation of any kind to the prostate gland or pelvis
* Prior brachytherapy
* History of inflammatory colitis or other active severe comorbidities
* Patients who are on immunosuppressant medication

Primary outcomes:
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v. 5.0
timeFrame: 60 months
Secondary outcomes:
measure: QUALITY OF LIFE (QOL) assessed by Expanded Prostate Cancer Index Composite (EPIC-CP) Questionnaire. For each domain minimum symptom score (=0) means best QOL and maximum symptom score (=12) means worst QOL
timeFrame: 60 months
measure: Number of participants with urinary incontinence assessed by International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF), ranging from 0 (best) to 21 (worst)
timeFrame: 60 months
measure: Number of participants with erectile dysfunction assessed by International Index of Erectile Function Questionnaire ranging from 5 (worst ) to 25 (best)
timeFrame: 60 months
measure: Number of participants with biochemical relapse assessed by PSA (cut off 0.20 ng/mL)
timeFrame: 60 months
Other outcomes:
Locations:
city: Monza
country: Italy
facility: Radiation Oncology, Fondazione IRCCS San Gerardo dei Tintori (University of Milan Bicocca)
Study officials:
References:
citation: Dess RT, Sun Y, Jackson WC, Jairath NK, Kishan AU, Wallington DG, Mahal BA, Stish BJ, Zumsteg ZS, Den RB, Hall WA, Gharzai LA, Jaworski EM, Reichert ZR, Morgan TM, Mehra R, Schaeffer EM, Sartor O, Nguyen PL, Lee WR, Rosenthal SA, Michalski JM, Schipper MJ, Dignam JJ, Pisansky TM, Zietman AL, Sandler HM, Efstathiou JA, Feng FY, Shipley WU, Spratt DE. Association of Presalvage Radiotherapy PSA Levels After Prostatectomy With Outcomes of Long-term Antiandrogen Therapy in Men With Prostate Cancer. JAMA Oncol. 2020 May 1;6(5):735-743. doi: 10.1001/jamaoncol.2020.0109.
citation: Burdett S, Fisher D, Parker CC, et al. LBA64 duration of androgen suppression with post-operative radiotherapy (DADSPORT): a collaborative meta-analysis of aggregate data. Ann Oncol. 2022;33(7):S1428-S1429
citation: Ferrario F, Franzese C, Faccenda V, Vukcaj S, Belmonte M, Lucchini R, Baldaccini D, Badalamenti M, Andreoli S, Panizza D, Magli A, Scorsetti M, Arcangeli S. Toxicity profile and Patient-Reported outcomes following salvage Stereotactic Ablative Radiation Therapy to the prostate Bed: The POPART multicentric prospective study. Clin Transl Radiat Oncol. 2023 Nov 25;44:100704. doi: 10.1016/j.ctro.2023.100704. eCollection 2024 Jan.
citation: Lucchini R, Franzese C, Vukcaj S, Purrello G, Panizza D, Faccenda V, Andreoli S, Poli GL, Baldaccini D, Lo Faro L, Tomatis S, Cazzaniga LF, Scorsetti M, Arcangeli S. Acute Toxicity and Quality of Life in a Post-Prostatectomy Ablative Radiation Therapy (POPART) Multicentric Trial. Curr Oncol. 2022 Nov 30;29(12):9349-9356. doi: 10.3390/curroncol29120733.
citation: Buyyounouski MK, Pugh SL, Chen RC, Mann MJ, Kudchadker RJ, Konski AA, Mian OY, Michalski JM, Vigneault E, Valicenti RK, Barkati M, Lawton CAF, Potters L, Monitto DC, Kittel JA, Schroeder TM, Hannan R, Duncan CE, Rodgers JP, Feng F, Sandler HM. Noninferiority of Hypofractionated vs Conventional Postprostatectomy Radiotherapy for Genitourinary and Gastrointestinal Symptoms: The NRG-GU003 Phase 3 Randomized Clinical Trial. JAMA Oncol. 2024 May 1;10(5):584-591. doi: 10.1001/jamaoncol.2023.7291.